FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Langford, L Litts, D Pearson, JL AF Langford, Linda Litts, David Pearson, Jane L. TI Using Science to Improve Communications About Suicide Among Military and Veteran Populations: Looking for a Few Good Messages SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID MENTAL-HEALTH PROBLEMS; MEDIA CAMPAIGN; SERVICE USE; STIGMA; CARE; INTERVENTION; PREVENTION; BARRIERS; ILLNESS; RISK AB Concern about suicide in US military and veteran populations has prompted efforts to identify more effective prevention measures. Recent expert panel reports have recommended public communications as one component of a comprehensive effort. Messaging about military and veteran suicide originates from many sources and often does not support suicide prevention goals or adhere to principles for developing effective communications. There is an urgent need for strategic, science-based, consistent messaging guidance in this area. Although literature on the effectiveness of suicide prevention communications for these populations is lacking, this article summarizes key findings from several bodies of research that offer lessons for creating safe and effective messages that support and enhance military and veteran suicide prevention efforts. (Am J Public Health. 2013;103:31-38. doi:10.2105/AJPH.2012.300905) C1 [Langford, Linda; Litts, David] EDC, Suicide Prevent Resource Ctr, Waltham, MA 02453 USA. [Pearson, Jane L.] NIMH, Bethesda, MD 20892 USA. RP Langford, L (reprint author), EDC, Suicide Prevent Resource Ctr, 43 Foundry Ave, Waltham, MA 02453 USA. EM llangford@edc.org FU NIGMS NIH HHS [R01 GM065830] NR 85 TC 8 Z9 8 U1 2 U2 19 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JAN PY 2013 VL 103 IS 1 BP 31 EP 38 DI 10.2105/AJPH.2012.300905 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 062NZ UT WOS:000312927900009 PM 23153130 ER PT J AU Beninati, S Park, MH Wolff, E Fesus, L Abbruzzese, A Chung, SI Carmassi, F Cocuzzi, E Trawick, ML Piacentini, M AF Beninati, Simone Park, Myung Hee Wolff, Edith Fesues, Laszlo Abbruzzese, Alberto Chung, Soo Ii Carmassi, Franco Cocuzzi, Enzo Trawick, Mary Lynn Piacentini, Mauro TI In memoriam: John E. Folk (1925-2010) SO AMINO ACIDS LA English DT Biographical-Item C1 [Beninati, Simone; Piacentini, Mauro] Univ Rome, Dept Biol, Rome, Italy. [Park, Myung Hee; Wolff, Edith] NIDR, NIH, Bethesda, MD 20892 USA. [Fesues, Laszlo] Univ Debrecen, Dept Biochem & Mol Biol, Hungarian Acad Sci, H-4012 Debrecen, Hungary. [Abbruzzese, Alberto] Univ Naples 2, Dept Biochem & Biophys, Naples, Italy. [Chung, Soo Ii] Kangnung Natl Univ, Dept Oral Pathol, Coll Dent, Kangnung, South Korea. [Carmassi, Franco] Univ Pisa, Dept Internal Med, Pisa, Italy. [Cocuzzi, Enzo] Ctr Vaccines Evaluat Biol & Genet Therapies, Viral Vaccines Div, Directorate Hlth, Ottawa, ON, Canada. [Trawick, Mary Lynn] Baylor Univ, Dept Chem & Biochem, Inst Biomed Studies, Waco, TX 76798 USA. RP Beninati, S (reprint author), Univ Rome, Dept Biol, Rome, Italy. EM beninati@bio.uniroma2.it RI Piacentini, Mauro/I-2411-2016; OI Piacentini, Mauro/0000-0003-2919-1296; Carmassi, Franco/0000-0003-2244-4430; Beninati, Simone/0000-0002-2704-0745 NR 1 TC 1 Z9 1 U1 0 U2 4 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 EI 1438-2199 J9 AMINO ACIDS JI Amino Acids PD JAN PY 2013 VL 44 IS 1 BP 11 EP 18 DI 10.1007/s00726-012-1367-y PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063QW UT WOS:000313015900002 PM 22847781 ER PT J AU Caraglia, M Park, MH Wolff, EC Marra, M Abbruzzese, A AF Caraglia, M. Park, M. H. Wolff, E. C. Marra, M. Abbruzzese, A. TI eIF5A isoforms and cancer: two brothers for two functions? SO AMINO ACIDS LA English DT Review DE eIF5A isoform; Hypusine; Tissue transglutaminase; Cancer; Apoptosis; Prognostic markers; Hypusine synthesis inhibitors ID INITIATION-FACTOR 5A; YEAST SACCHAROMYCES-CEREVISIAE; CELL LUNG-CANCER; PROTEIN-SYNTHESIS; DEOXYHYPUSINE SYNTHASE; HEPATOCELLULAR-CARCINOMA; SUBCELLULAR-DISTRIBUTION; INDEPENDENT PREDICTOR; HYPUSINE MODIFICATION; PROTEOMIC ANALYSIS AB Eukaryotic translation initiation factor 5A (eIF5A) is the only cellular protein that contains the unusual amino acid hypusine [N (epsilon)-(4-amino-2-hydroxybutyl)lysine]. The role of hypusine formation in the eIF5A protein in the regulation of cell proliferation and apoptosis is addressed in the present review. Moreover, vertebrates carry two genes that encode two eIF5A isoforms, eIF5A-1 and eIF5A-2, which, in humans, are 84% identical. However, the biological functions of these two isoforms may be significantly different. In fact, eIF5A-1 is demonstrable in most cells of different histogenesis, whereas eIF5A-2 protein is detectable only in certain human cancer cells or tissues, suggesting its role as a potential oncogene. In this review we focus our attention on the involvement of eIF5A-1 in the triggering of an apoptotic program and in the regulation of cell proliferation. In addition, the potential oncogenic role and prognostic significance of eIF5A-2 in the prediction of the survival of cancer patients is described. eIF5A-1 and/or the eIF5A-2 isoform may serve as a new molecular diagnostic or prognostic marker or as a molecular target for anti-cancer therapy. C1 [Caraglia, M.; Marra, M.; Abbruzzese, A.] Univ Naples 2, Dept Biochem & Biophys, I-80138 Naples, Italy. [Park, M. H.; Wolff, E. C.] NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Caraglia, M (reprint author), Univ Naples 2, Dept Biochem & Biophys, Via Costantinopoli 16, I-80138 Naples, Italy. EM michele.caraglia@unina2.it RI Caraglia, Michele/N-5670-2015 OI Caraglia, Michele/0000-0003-2408-6091 FU National Institute of Dental and Craniofacial Research (NIDCR) FX This paper is dedicated to the memory of Dr. J.E. Folk (Oct 29, 1925-Dec 27, 2010). In addition to his pioneering work on the mechanism of transglutaminase, he and his colleagues discovered the hypusine modification pathway. The research was supported in part by the Intramural Research Program of National Institute of Dental and Craniofacial Research (NIDCR). NR 66 TC 29 Z9 30 U1 0 U2 9 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD JAN PY 2013 VL 44 IS 1 BP 103 EP 109 DI 10.1007/s00726-011-1182-x PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063QW UT WOS:000313015900012 PM 22139412 ER PT J AU Hodder, SL Justman, J Hughes, JP Wang, J Haley, DF Adimora, AA Del Rio, C Golin, CE Kuo, I Rompalo, A Soto-Torres, L Mannheimer, SB Johnson-Lewis, L Eshleman, SH El-Sadr, WM AF Hodder, Sally L. Justman, Jessica Hughes, James P. Wang, Jing Haley, Danielle F. Adimora, Adaora A. Del Rio, Carlos Golin, Carol E. Kuo, Irene Rompalo, Anne Soto-Torres, Lydia Mannheimer, Sharon B. Johnson-Lewis, LeTanya Eshleman, Susan H. El-Sadr, Wafaa M. CA Womens HIV SeroIncidence Study TI HIV Acquisition Among Women From Selected Areas of the United States A Cohort Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BEHAVIORAL SURVEILLANCE SYSTEM; RISK; MEN; SEX; INFECTION; BIAS AB Background: Women account for 23% of newly diagnosed HIV infections in the United States, but there are few recent, well-characterized cohorts of U. S. women in whom behavior characteristics and HIV acquisition have been well-described. Objective: To evaluate HIV incidence and describe behaviors among U. S. women residing in areas of high HIV prevalence. Design: Multisite, longitudinal cohort of women who had HIV rapid testing and audio computer-assisted self-interviews at baseline and every 6 months for up to 12 months. (ClinicalTrials.gov: NCT00995176) Setting: 10 urban and periurban communities with high HIV prevalence and poverty rates, located in the northeastern and southeastern United States. Patients: Venue-based sampling was used to recruit women aged 18 to 44 years who recently had unprotected sex and had 1 or more additional personal or partner risk factors and no self-reported previous HIV diagnosis. Measurements: HIV prevalence and incidence, frequency of HIV risk behaviors, and health status perceptions. Results: Among 2099 high-risk women (85.9% black and 11.7% of Hispanic ethnicity), 32 (1.5%) were diagnosed with HIV infection at enrollment. Annual HIV incidence was 0.32% (95% CI, 0.14% to 0.74%). Older age, substance use, and knowing a partner had HIV were associated with HIV prevalence. Ten women died during the study (0.61% per year). Limitations: Longitudinal assessment of risk behaviors was limited to a maximum of 12 months. There were few incident HIV infections, precluding identification of characteristics predictive of HIV acquisition. Conclusion: This study enrolled a cohort of women with HIV incidence substantially higher than the Centers for Disease Control and Prevention national estimate in the general population of U. S. black women. Concerted efforts to improve preventive health care strategies for HIV and overall health status are needed for similar populations. Primary Funding Source: National Institutes of Health. Ann Intern Med. 2013;158:10-18. C1 [Hodder, Sally L.] Univ Med & Dent New Jersey, Dept Med, Div Infect Dis, Newark, NJ 07101 USA. Columbia Univ, Coll Phys & Surg, Int AIDS Care & Treatment Program, Joseph L Mailman Sch Publ Hlth, New York, NY USA. Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. FHI 360, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Ctr AIDS Res, Atlanta, GA 30322 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Hodder, SL (reprint author), Univ Med & Dent New Jersey, Dept Med, Div Infect Dis, 185 S Orange Ave,MSB I-506, Newark, NJ 07101 USA. EM hoddersa@umdnj.edu RI del Rio, Carlos/B-3763-2012 OI del Rio, Carlos/0000-0002-0153-3517 FU National Institutes of Health; National Institute of Allergy and Infectious Diseases [UM1 AI068619, U01-AI068613, UM1-AI068613]; National Institute on Drug Abuse [UM1 AI068619, U01-AI068613, UM1-AI068613]; National Institute of Mental Health [UM1 AI068619, U01-AI068613, UM1-AI068613]; Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University [5UM1A1069466]; University of North Carolina Clinical Trials Unit [AI069423]; University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award [RR 025747]; University of North Carolina Center for AIDS Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit [5UO1AI069418]; Center for AIDS Research [P30 AI050409]; Clinical and Translational Science Award [UL1 RR025008, ULI RR025008]; Johns Hopkins Adult AIDS Clinical Trials Unit [AI069465]; Johns Hopkins Clinical and Translational Science Award [ULI RR025005]; Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit FX National Institutes of Health.; Grant Support: By the National Institute of Allergy and Infectious Diseases, National Institute on Drug Abuse, and National Institute of Mental Health (cooperative agreement UM1 AI068619, U01-AI068613, and UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman School of Public Health, Columbia University (5UM1A1069466); University of North Carolina Clinical Trials Unit (AI069423); University of North Carolina Clinical Trials Research Center of the Clinical and Translational Science Award (RR 025747); University of North Carolina Center for AIDS Research (AI050410); Emory University HIV/AIDS Clinical Trials Unit (5UO1AI069418), Center for AIDS Research (P30 AI050409), and Clinical and Translational Science Award (UL1 RR025008); Johns Hopkins Adult AIDS Clinical Trials Unit (AI069465) and Clinical and Translational Science Award (ULI RR025008); Johns Hopkins Clinical and Translational Science Award (ULI RR025005); and The Terry Beirn Community Programs for Clinical Research on AIDS Clinical Trials Unit. NR 34 TC 38 Z9 39 U1 0 U2 15 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 JAN 1 PY 2013 VL 158 IS 1 BP 10 EP U53 DI 10.7326/0003-4819-158-1-201301010-00004 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 065AV UT WOS:000313119900003 PM 23277896 ER PT J AU Compton, WM Volkow, ND Throckmorton, DC Lurie, P AF Compton, Wilson M. Volkow, Nora D. Throckmorton, Douglas C. Lurie, Peter TI Expanded Access to Opioid Overdose Intervention: Research, Practice, and Policy Needs SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID UNITED-STATES; NALOXONE; ABUSE; PAIN C1 [Compton, Wilson M.; Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Throckmorton, Douglas C.; Lurie, Peter] US FDA, Silver Spring, MD USA. RP Compton, WM (reprint author), NIDA, 6001 Execut Blvd,MSC 9589, Bethesda, MD 20892 USA. EM wcompton@nida.nih.gov NR 13 TC 15 Z9 15 U1 0 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 JAN 1 PY 2013 VL 158 IS 1 BP 65 EP U147 DI 10.7326/0003-4819-158-1-201301010-00013 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 065AV UT WOS:000313119900011 PM 23277902 ER PT J AU Argiris, A Kotsakis, AP Hoang, T Worden, FP Savvides, P Gibson, MK Gyanchandani, R Blumenschein, GR Chen, HX Grandis, JR Harari, PM Kies, MS Kim, S AF Argiris, A. Kotsakis, A. P. Hoang, T. Worden, F. P. Savvides, P. Gibson, M. K. Gyanchandani, R. Blumenschein, G. R., Jr. Chen, H. X. Grandis, J. R. Harari, P. M. Kies, M. S. Kim, S. TI Cetuximab and bevacizumab: preclinical data and phase II trial in recurrent or metastatic squamous cell carcinoma of the head and neck SO ANNALS OF ONCOLOGY LA English DT Article DE bevacizumab; cetuximab; EGFR; head and neck cancer; VEGF ID GROWTH-FACTOR RECEPTOR; COLORECTAL-CANCER; TYROSINE KINASE; SOLID TUMORS; ACQUIRED-RESISTANCE; ORTHOTOPIC MODEL; ONCOLOGY-GROUP; CHEMOTHERAPY; INHIBITOR; THERAPY AB We evaluated combined targeting with cetuximab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody, and bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, in squamous cell carcinoma of the head and neck (SCCHN). The combination was studied in human endothelial cells and head and neck and lung cancer xenograft model systems. Patients with recurrent or metastatic SCCHN were treated with weekly cetuximab and bevacizumab, 15 mg/kg on day 1 given intravenously every 21 days, until disease progression. Analysis of tumor biomarkers and related serum cytokines was performed. Cetuximab plus bevacizumab enhanced growth inhibition both in vitro and in vivo, and resulted in potent reduction in tumor vascularization. In the clinical trial, 46 eligible patients were enrolled. The objective response rate was 16% and the disease control rate 73%. The median progression-free survival and overall survival were 2.8 and 7.5 months, respectively. Grade 3-4 adverse events were expected and occurred in less than 10% of patients. transforming growth factor alpha, placenta-derived growth factor, EGFR, VEGFR2 increased and VEGF decreased after treatment but did not correlate with treatment efficacy. Cetuximab and bevacizumab are supported by preclinical observations and are well tolerated and active in previously treated patients with SCCHN. C1 [Argiris, A.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, Canc Res & Therapy Ctr, San Antonio, TX 78229 USA. [Kotsakis, A. P.] Univ Crete, Dept Med, Iraklion, Greece. [Hoang, T.; Harari, P. M.] Univ Wisconsin, Dept Med, Div Hematol Oncol, Madison, WI 53706 USA. [Worden, F. P.] Univ Michigan, Ctr Canc, Div Hematol Oncol, Dept Internal Med, Ann Arbor, MI 48109 USA. [Savvides, P.] Case Western Reserve Univ, Dept Hematol Oncol, Cleveland, OH 44106 USA. [Gibson, M. K.] Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA USA. [Gyanchandani, R.] Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, Pittsburgh, PA USA. [Blumenschein, G. R., Jr.; Kies, M. S.] Univ Texas MD Anderson Canc Ctr, Department Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. [Chen, H. X.; Kim, S.] NCI, CTEP, Bethesda, MD 20892 USA. [Grandis, J. R.] Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. RP Argiris, A (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Div Hematol Oncol, Canc Res & Therapy Ctr, 7979 Wurzbach Rd,MC8232,Zeller Building,4th Floor, San Antonio, TX 78229 USA. EM argiris@uthscsa.edu RI Kotsakis, Athanasios/Q-4600-2016 FU NIH [R01 (CA113448)]; Head and Neck SPORE Grant from the National Cancer Institute [P50 (CA097190-06)]; NCI ECOG YIA [CA 87718]; Genentech; Imclone Systems Incorporated; [U01 (CA099168-01)] FX This work was supported in part by U01 (CA099168-01), NIH R01 (CA113448) to P.M.H., and the Head and Neck SPORE Grant No. P50 (CA097190-06) to J.R.G. from the National Cancer Institute, Grant [CA 87718] from NCI & ECOG YIA to T.H., and laboratory grants from Genentech and Imclone Systems Incorporated to P.M.H. NR 38 TC 54 Z9 55 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2013 VL 24 IS 1 BP 220 EP 225 DI 10.1093/annonc/mds245 PG 6 WC Oncology SC Oncology GA 058SI UT WOS:000312653900032 PM 22898037 ER PT J AU Vogtmann, E Li, HL Shu, XO Chow, WH Ji, BT Cai, H Gao, J Zhang, W Gao, YT Zheng, W Xiang, YB AF Vogtmann, E. Li, H. L. Shu, X. O. Chow, W. H. Ji, B. T. Cai, H. Gao, J. Zhang, W. Gao, Y. T. Zheng, W. Xiang, Y. B. TI Dietary glycemic load, glycemic index, and carbohydrates on the risk of primary liver cancer among Chinese women and men SO ANNALS OF ONCOLOGY LA English DT Article DE Chinese men and women; cohort study; diet; glycemic index; glycemic load; primary liver cancer ID CHRONIC HEPATITIS INFECTION; HEPATOCELLULAR-CARCINOMA; DIABETES-MELLITUS; PROSPECTIVE COHORT; METABOLIC SYNDROME; COLORECTAL-CANCER; METAANALYSIS; HEALTH; REPRODUCIBILITY; ASSOCIATION AB Dietary glycemic index (GI) and glycemic load (GL) typically have a positive relationship with obesity and diabetes, which are risk factors for liver cancer. However, studies on their association with liver cancer have yielded inconsistent results. Therefore, we assessed the association of GI, GL, and carbohydrates with liver cancer risk. A total of 72 966 women and 60 207 men from the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health Study (SMHS) were included for analysis. Food frequency questionnaire (FFQ) data were used to calculate daily dietary GI, GL, and carbohydrate intake. These values were energy adjusted and categorized into quintiles. The hazard ratios (HRs) and 95% confidence intervals (CI) were calculated with adjustment for potential confounders. After a median follow-up time of 11.2 years for the SWHS and 5.3 years for the SMHS, 139 and 208 incident liver cancer cases were identified in the SWHS and SMHS, respectively. In multivariable Cox regression models, no statistically significant trends by quintile of GI, GL, or carbohydrate intake were observed. Stratification by chronic liver disease/hepatitis, diabetes, or body mass index (BMI) did not alter the findings. There is little evidence that dietary GI, GL, or carbohydrates affect the incidence of liver cancer in this Asian population. C1 [Vogtmann, E.; Li, H. L.; Gao, J.; Zhang, W.; Xiang, Y. B.] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, State Key Lab Oncogene & Related Genes,Shanghai C, Shanghai 200032, Peoples R China. [Vogtmann, E.; Li, H. L.; Gao, J.; Zhang, W.; Gao, Y. T.; Xiang, Y. B.] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Epidemiol,Shanghai Canc Inst, Shanghai 200032, Peoples R China. [Vogtmann, E.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA. [Shu, X. O.; Cai, H.; Zheng, W.] Vanderbilt Univ, Dept Med, Sch Med, Div Epidemiol,Vanderbilt Epidemiol Ctr,Vanderbilt, Nashville, TN USA. [Chow, W. H.; Ji, B. T.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Xiang, YB (reprint author), Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, State Key Lab Oncogene & Related Genes,Shanghai C, 25,Lane 2200,Xie Tu Rd, Shanghai 200032, Peoples R China. EM ybxiang@shsci.org FU State Key Project Specialized for Infectious Diseases of China [2008ZX10002-015, 2012ZX10002008-002]; United States National Institutes of Health [R37 CA070867, R01 CA82729, R01 HL095931]; Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988-5]; Cancer Prevention and Control Training Program at the University of Alabama at Birmingham through the National Institutes of Health [5R25 CA047888] FX This work was supported by funds from the State Key Project Specialized for Infectious Diseases of China [No. 2008ZX10002-015 and 2012ZX10002008-002]; the United States National Institutes of Health [R37 CA070867, R01 CA82729, and R01 HL095931]; the Fogarty International Clinical Research Scholars and Fellows Program at Vanderbilt University [R24 TW007988-5 to EV and HLL]; and the Cancer Prevention and Control Training Program at the University of Alabama at Birmingham funded through the National Institutes of Health [5R25 CA047888 to EV]. The funding organizations had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. NR 39 TC 4 Z9 5 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2013 VL 24 IS 1 BP 238 EP 244 DI 10.1093/annonc/mds287 PG 7 WC Oncology SC Oncology GA 058SI UT WOS:000312653900035 PM 22898034 ER PT J AU Li, QQ Lee, RX Liang, HS Zhong, YH AF Li, Qingdi Quentin Lee, Rebecca X. Liang, Huasheng Zhong, Yuhua TI Anticancer Activity of beta-Elemene and its Synthetic Analogs in Human Malignant Brain Tumor Cells SO ANTICANCER RESEARCH LA English DT Article DE Apoptosis; brain cancer; Chinese medicine; beta-elemene; A172; U-87MG; CCF-STTG1 cells; synthetic analogs ID UNITED-STATES; CASPASE ACTIVATION; CANCER CELLS; DEATH; APOPTOSIS; TRENDS; GLIOBLASTOMA; MITOCHONDRIA; COMBINATION; MECHANISMS AB Malignant brain tumors are aggressive in both children and adults. Despite recent improvements in diagnostic techniques, therapeutic approaches remain disappointing and unsuccessful. There is an urgent need for promising anticancer agents to improve overall survival of patients with brain cancer. beta-Elemene has been shown to have antiproliferative effects on many types of carcinomas. In this study, we compared the cytotoxic efficacy of beta-elemene and its synthetic analogs in the brain tumor cell lines A172, CCF-STTG1, and U-87MG. beta-Elemene exhibited cytotoxicity towards the tumor lines, effectively suppressing tumor cell survival. The inhibitory effect of beta-elemene was mediated by the induction of apoptosis, as demonstrated by three assays. The annexin V assay showed that beta-elemene increased the percentage of early- and late-apoptotic cells. Apoptotic nuclei were detected in cancer cells in situ by the terminal deoxynucleotidyltransferase-mediated deoxy-UTP-fluorescein nick end labeling (TUNEL) staining, and the number of TUNEL-positive cells was significantly increased at 24-72 h following drug treatment of the cell lines. Cell death enzyme-linked immunosorbent assay (ELISA) gave similar results. Furthermore, beta-elemene increased caspase-3/7/10 activity, up-regulated protein expression of BAX, and down-regulated the one of BCL-2, BCL-XL, and of X-linked inhibitor of apoptosis (XIAP) in the cells, suggesting that apoptotic signaling pathways are involved in the responses triggered by beta-elemene. Compared with beta-elemene, only three of the 10 synthetic beta-elemene analogs studied here, exerted comparable cytotoxic efficacy towards the three brain tumor lines: the analogs Lr-1 and Lr-2 had the same antitumor efficacy, while Lr-3 was less potent than beta-elemene. Thus, some synthetic analogs of beta-elemene may inhibit brain cancer cell growth and proliferation, and the synthetic analogs Lr-1 and Lr-2 may have great potential as alternatives to beta-elemene for anticancer therapy. Overall, this study provides, to our knowledge, the first evidence showing that synthetic analogs of beta-elemene hold promise for patients with brain tumors. C1 [Li, Qingdi Quentin] NCI, NIH, Bethesda, MD 20892 USA. [Li, Qingdi Quentin; Liang, Huasheng; Zhong, Yuhua] Beihai Inst Endocrine & Metab Dis, Beihai, Guangxi, Peoples R China. [Li, Qingdi Quentin; Lee, Rebecca X.] W Virginia Univ, Ctr Canc, Morgantown, WV 26506 USA. RP Li, QQ (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM liquenti@mail.nih.gov; zhongyh111@163.com FU Natural Science Foundation of Science & Technology Department of Guangxi Province [0991294]; Guangxi Scientific Research and Technological Development Program [200901059]; National Institutes of Health [P20RR16440-010003, P20RR16440-020003, P20RR16440-030003, P20RR16440-040003]; West Virginia University School of Medicine Research Grant FX This publication was made possible by grants from the Natural Science Foundation of Science & Technology Department of Guangxi Province (no. 0991294) and the Guangxi Scientific Research and Technological Development Program (no. 200901059), and by grants from the National Institutes of Health (no. P20RR16440-010003, P20RR16440-020003, P20RR16440-030003, P20RR16440-040003) and West Virginia University School of Medicine Research Grant (to Q. Q. Li). NR 38 TC 14 Z9 16 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD JAN PY 2013 VL 33 IS 1 BP 65 EP 76 PG 12 WC Oncology SC Oncology GA 063SR UT WOS:000313021600008 PM 23267129 ER PT J AU Eastman, RT Pattaradilokrat, S Raj, DK Dixit, S Deng, BB Miura, K Yuan, J Tanaka, TQ Johnson, RL Jiang, HY Huang, RL Williamson, KC Lambert, LE Long, C Austin, CP Wu, YM Su, XZ AF Eastman, Richard T. Pattaradilokrat, Sittiporn Raj, Dipak K. Dixit, Saurabh Deng, Bingbing Miura, Kazutoyo Yuan, Jing Tanaka, Takeshi Q. Johnson, Ronald L. Jiang, Hongying Huang, Ruili Williamson, Kim C. Lambert, Lynn E. Long, Carole Austin, Christopher P. Wu, Yimin Su, Xin-zhuan TI A Class of Tricyclic Compounds Blocking Malaria Parasite Oocyst Development and Transmission SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; MULTIDRUG-RESISTANCE; CHLOROQUINE RESISTANCE; ANTIMALARIAL-DRUGS; CANCER-CELLS; IN-VITRO; GENE; KETOTIFEN; TRANSPORTERS; ARTEMISININ AB Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a Plasmodium falciparum ABC transporter (Pf14_ 0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of P. falciparum and the rodent parasite Plasmodium yoelii in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of Plasmodium cynomolgi infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication. C1 [Eastman, Richard T.; Pattaradilokrat, Sittiporn; Raj, Dipak K.; Deng, Bingbing; Miura, Kazutoyo; Yuan, Jing; Tanaka, Takeshi Q.; Jiang, Hongying; Williamson, Kim C.; Long, Carole; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Pattaradilokrat, Sittiporn] Chulalongkorn Univ, Fac Sci, Dept Biol, Bangkok, Thailand. [Dixit, Saurabh; Lambert, Lynn E.; Wu, Yimin] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Bethesda, MD 20892 USA. [Johnson, Ronald L.; Huang, Ruili; Austin, Christopher P.] NHGRI, NIH Chem Genom Ctr, NIH, Bethesda, MD 20892 USA. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM xsu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Divisions of Intramural Research at the National Institute of Allergy and Infectious Diseases; National Human Genome Research Institute; National Institutes of Health; PATH/Malaria Vaccine Initiative FX This work was supported by the Divisions of Intramural Research at the National Institute of Allergy and Infectious Diseases and the National Human Genome Research Institute and by the Director's Challenge Award Program, all at the National Institutes of Health. The PATH/Malaria Vaccine Initiative supported the P. falciparum mosquito membrane feeding assays. NR 68 TC 18 Z9 20 U1 0 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2013 VL 57 IS 1 BP 425 EP 435 DI 10.1128/AAC.00920-12 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 062XS UT WOS:000312958400055 PM 23129054 ER PT J AU Gabay, O Sanchez, C Dvir-Ginzberg, M Gagarina, V Zaal, KJ Song, YJ He, XH McBurney, MW AF Gabay, Odile Sanchez, Christelle Dvir-Ginzberg, Mona Gagarina, Viktoria Zaal, Kristien J. Song, Yingjie He, Xiao Hong McBurney, Michael W. TI Sirtuin 1 enzymatic activity is required for cartilage homeostasis in vivo in a mouse model SO ARTHRITIS AND RHEUMATISM LA English DT Article ID HUMAN OSTEOARTHRITIC CHONDROCYTES; SMALL-MOLECULE ACTIVATORS; SIR2-ALPHA PROTEIN; STEM-CELLS; LIFE-SPAN; MICE; APOPTOSIS; HISTOPATHOLOGY; INFORMATION; DEFECTS AB Objective We and others previously demonstrated that sirtuin 1 (SIRT-1) regulates apoptosis and cartilage-specific gene expression in human chondrocytes and mouse models. This study was undertaken to determine if SIRT-1 enzymatic activity plays a protective role in cartilage homeostasis in vivo, by investigating mice with SIRT-1 mutations to characterize their cartilage. Methods Articular cartilage was harvested from the paws and knees of 5- and 6-month-old wild-type (WT) mice and mice homozygous for SIRT-1tm2.1Mcby (SIRT-1y/y), an allele carrying a point mutation that encodes a SIRT-1 protein with no enzymatic activity (y/y mice). Mice ages 2 days old and 67 days old were also examined. Mouse joint cartilage was processed for histologic examination or biochemical analyses of chondrocyte cultures. Results We found that articular cartilage tissue sections from y/y mice of up to 6 months of age contained reduced levels of type II collagen, aggrecan, and glycosaminoglycan compared to sections from WT mice. In contrast, protein levels of matrix metalloproteinase 8 (MMP-8), MMP-9, and MMP-13 were elevated in the cartilage of y/y mice. In addition, chondrocyte apoptosis was elevated in SIRT-1 mutant mice as compared to their WT littermates. Consistent with these observations, protein tyrosine phosphatase 1b was elevated in the y/y mice. Conclusion Our in vivo findings in this animal model demonstrate that mice with defective SIRT-1 also have defective cartilage, with elevated rates of cartilage degradation with age. Hence, normal cartilage homeostasis requires enzymatically active SIRT-1 protein. C1 [Gabay, Odile] NIAMSD, NIH, Cartilage Biol & Orthoped Branch, Bethesda, MD 20892 USA. [Sanchez, Christelle] Univ Liege, Liege, Belgium. [Dvir-Ginzberg, Mona] Hebrew Univ Jerusalem, Jerusalem, Israel. [Song, Yingjie] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [He, Xiao Hong; McBurney, Michael W.] Ottawa Hosp Res Inst, Ottawa, ON, Canada. RP Gabay, O (reprint author), NIAMSD, NIH, Cartilage Biol & Orthoped Branch, 50 South Dr, Bethesda, MD 20892 USA. EM gabayo@mail.nih.gov OI Dvir-Ginzberg, Mona/0000-0003-3089-6875 FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH FX Supported by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH. NR 35 TC 29 Z9 29 U1 3 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD JAN PY 2013 VL 65 IS 1 BP 159 EP 166 DI 10.1002/art.37750 PG 8 WC Rheumatology SC Rheumatology GA 062RD UT WOS:000312938100018 PM 23124828 ER PT J AU Zuliani, G Morieri, ML Volpato, S Vigna, GB Tch, CB Maggio, M Cherubini, A Bandinelli, S Guralnik, JM Ferrucci, L AF Zuliani, Giovanni Morieri, Mario Luca Volpato, Stefano Vigna, Giovanni B. Tch, Cristina Bosi Maggio, Marcello Cherubini, Antonio Bandinelli, Stefania Guralnik, Jack M. Ferrucci, Luigi TI Determinants and clinical significance of plasma oxidized LDLs in older individuals. A 9 years follow-up study SO ATHEROSCLEROSIS LA English DT Article DE Oxidized LDL; Mortality; Cardiovascular disease; Aging ID LOW-DENSITY-LIPOPROTEIN; CORONARY-HEART-DISEASE; TYPE-2 DIABETIC-PATIENTS; MIDDLE-AGED MEN; ARTERY-DISEASE; BETA-CAROTENE; OXIDATIVE MODIFICATION; METABOLIC SYNDROME; STATIN THERAPY; PREDICTOR AB Oxidized LDLs (ox.LDLs) uptake by macrophages inside the arterial wall is a crucial step in atherosclerotic disease, and some studies suggest that high ox.LDLs plasma levels might be associated with cardiovascular disease (CVD). However, whether high ox.LDLs continue to be a CVD risk factors in older persons is unknown. We investigated the clinical correlates of plasma ox.LDLs, and their role in predicting long-term CVD/cardiac mortality in 1025 older community dwelling individuals (mean age: 75.5 +/- 7.4 years; females: 55%) from the InCHIANTI study. Kaplan-Meier curves were fitted to explore the relationship between tertiles of ox. LDLs (ox.LDL/LDL-C ratio) and time to CVD/cardiac death. Hazard Ratios (HR) were estimated by Cox regression analysis. At multivariate analysis, ox.LDLs were independently associated with LDL-C, triglycerides, and HDL-C (adjusted r(2): 0.42; P = 0.001). The ox.LDL/LDL-C ratio (the extent of LDLs oxidation) was independently correlated with HDL-C, triglycerides, and beta-carotene (adjusted r(2): 0.15, P = 0.001). Among 1025 individuals, 392 died after 9 years, 166 from CVD. The HR for CVD/cardiac mortality was not significantly different across tertiles of ox.LDLs or ox.LDL/LDL-C ratio, both in the whole sample and in individuals with prevalent CVD. We conclude that in an elderly population LDL-C, triglycerides, and HDL-C are the most important determinants of ox.LDLs levels, indirectly suggesting an association between small dense LDLs and LDLs oxidation. No association emerged between higher ox.LDLs levels and 9 years CVD/cardiac mortality, suggesting that in advanced age the prognostic information added by ox. LDLs on CVD/cardiac mortality might be negligible. (C) 2012 Elsevier Ireland Ltd. All rights reserved. C1 [Zuliani, Giovanni; Morieri, Mario Luca; Volpato, Stefano; Vigna, Giovanni B.; Tch, Cristina Bosi] Univ Ferrara, Sect Internal Med Gerontol & Clin Nutr, Dept Clin & Expt Med, I-44100 Ferrara, Italy. [Maggio, Marcello] Univ Parma, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. [Cherubini, Antonio] Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. [Bandinelli, Stefania] ASF Geriatr Rehabil, Florence, Italy. [Bandinelli, Stefania] Tuscany Reg Hlth Agcy, Florence, Iot, Italy. [Guralnik, Jack M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Cherubini, Antonio] Italian Natl Ctr Aging INRCA, IRCCS, Geriatr Hosp, Ancona, Italy. RP Zuliani, G (reprint author), Univ Ferrara, Sect Internal Med Gerontol & Clin Nutr, Dept Clin & Expt Med, Via Savonarola 9, I-44100 Ferrara, Italy. EM gzuliani@hotmail.com RI Vigna, Giovanni/H-2826-2015; VOLPATO, STEFANO/H-2977-2014; OI Vigna, Giovanni/0000-0001-8640-7052; VOLPATO, STEFANO/0000-0003-4335-6034; Zuliani, Giovanni/0000-0003-0969-3184; Cherubini, Antonio/0000-0003-0261-9897 FU Italian Ministry of Health [ICS110.1/RF97.71]; U.S. National Institute on Aging [263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-5-0002]; National Institute on Aging, National Institutes of Health, Baltimore, Maryland FX The InCHIANTI study baseline (1998-2000) was supported as a "targeted project" (ICS110.1/RF97.71) by the Italian Ministry of Health, and in part by the U.S. National Institute on Aging (Contracts: 263 MD 9164 and 263 MD 821336). The follow-up 1 (2001-2003) was funded by the U.S. National Institute on Aging (Contracts: N.1-AG-1-1 and N.1-AG-1-2111); the follow-up 2 and 3 studies (2004-2010) were financed by the U.S. National Institute on Aging (Contract: N01-AG-5-0002). Supported in part by the Intramural research program of the National Institute on Aging, National Institutes of Health, Baltimore, Maryland. NR 37 TC 10 Z9 12 U1 1 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2013 VL 226 IS 1 BP 201 EP 207 DI 10.1016/j.atherosclerosis.2012.10.028 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 060WA UT WOS:000312807700035 PM 23141584 ER PT J AU Hussain, S Garantziotis, S AF Hussain, Salik Garantziotis, Stavros TI Interplay between apoptotic and autophagy pathways after exposure to cerium dioxide nanoparticles in human monocytes SO AUTOPHAGY LA English DT Editorial Material DE autophagy; apoptosis; nanoparticle; cerium dioxide; human monocyte AB Engineered nanomaterials, defined as having at least one dimension smaller than 100 nm, have revolutionized many technology sectors ranging from therapeutics and diagnostics to environmental monitoring and remediation. This has resulted in a rapid increase in their manufacture over the past few years, accompanied by an increased human exposure potential. However, understanding of the interactions of nanomaterials with biological systems is still rudimentary. We have described that an environmentally and medically relevant nano metal (cerium dioxide) can affect primary human monocyte viability and interact with programmed cell death pathways leading to apoptosis and autophagic cell death. Cerium dioxide nanoparticles (CeO2 NPs)-induced autophagy acts as a prodeath mechanism and leads to increased cytotoxicity of human monocytes. A better understanding of the implication and biological significance of CeO2 NPs-induced autophagy and apoptosis will help us understand the risks associated with its uses and develop safer nanomedicine. C1 [Hussain, Salik; Garantziotis, Stavros] NIEHS, Clin Res Program, NIH, Res Triangle Pk, NC 27709 USA. RP Hussain, S (reprint author), NIEHS, Clin Res Program, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM salik.hussain@nih.gov RI Hussain, Salik/O-1687-2016; Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X FU Intramural NIH HHS NR 0 TC 17 Z9 17 U1 7 U2 59 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD JAN PY 2013 VL 9 IS 1 BP 101 EP 103 DI 10.4161/auto.22266 PG 3 WC Cell Biology SC Cell Biology GA 064LY UT WOS:000313077900010 PM 23047327 ER PT J AU Elena, JW Steplowski, E Yu, K Hartge, P Tobias, GS Brotzman, MJ Chanock, SJ Stolzenberg-Solomon, RZ Arslan, AA Bueno-de-Mesquita, HB Helzlsouer, K Jacobs, EJ LaCroix, A Petersen, G Zheng, W Albanes, D Allen, NE Amundadottir, L Bao, Y Boeing, H Boutron-Ruault, MC Buring, JE Gaziano, JM Giovannucci, EL Duell, EJ Hallmans, G Howard, BV Hunter, DJ Hutchinson, A Jacobs, KB Kooperberg, C Kraft, P Mendelsohn, JB Michaud, DS Palli, D Phillips, LS Overvad, K Patel, AV Sansbury, L Shu, XO Simon, MS Slimani, N Trichopoulos, D Visvanathan, K Virtamo, J Wolpin, BM Zeleniuch-Jacquotte, A Fuchs, CS Hoover, RN Gross, M AF Elena, Joanne W. Steplowski, Emily Yu, Kai Hartge, Patricia Tobias, Geoffrey S. Brotzman, Michelle J. Chanock, Stephen J. Stolzenberg-Solomon, Rachael Z. Arslan, Alan A. Bueno-de-Mesquita, H. Bas Helzlsouer, Kathy Jacobs, Eric J. LaCroix, Andrea Petersen, Gloria Zheng, Wei Albanes, Demetrius Allen, Naomi E. Amundadottir, Laufey Bao, Ying Boeing, Heiner Boutron-Ruault, Marie-Christine Buring, Julie E. Gaziano, J. Michael Giovannucci, Edward L. Duell, Eric J. Hallmans, Goran Howard, Barbara V. Hunter, David J. Hutchinson, Amy Jacobs, Kevin B. Kooperberg, Charles Kraft, Peter Mendelsohn, Julie B. Michaud, Dominique S. Palli, Domenico Phillips, Lawrence S. Overvad, Kim Patel, Alpa V. Sansbury, Leah Shu, Xiao-Ou Simon, Michael S. Slimani, Nadia Trichopoulos, Dimitrios Visvanathan, Kala Virtamo, Jarmo Wolpin, Brian M. Zeleniuch-Jacquotte, Anne Fuchs, Charles S. Hoover, Robert N. Gross, Myron TI Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium SO CANCER CAUSES & CONTROL LA English DT Article DE Diabetes; Risk factor; Cohort consortium; Pancreatic cancer ID BASE-LINE CHARACTERISTICS; BLOOD-GROUP ALLELES; BODY-MASS INDEX; CIGARETTE-SMOKING; WOMENS HEALTH; ORIGINAL WHITEHALL; INSULIN-RESISTANCE; MELLITUS; NUTRITION; MORTALITY AB Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan). The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case-control study design. Subjects who were diagnosed with diabetes near the time (< 2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer. Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2-8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52). These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation. C1 [Elena, Joanne W.; Sansbury, Leah] NCI, DCCPS, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Steplowski, Emily] Informat Management Serv Inc, Silver Spring, MD USA. [Chanock, Stephen J.; Amundadottir, Laufey; Hutchinson, Amy] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. [Brotzman, Michelle J.] Westat Corp, Rockville, MD USA. [Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Environm Med, New York, NY USA. [Arslan, Alan A.; Zeleniuch-Jacquotte, Anne] NYU, Inst Canc, New York, NY USA. [Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands. [Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands. [Helzlsouer, Kathy] Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA. [Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Visvanathan, Kala] Johns Hopkins Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Jacobs, Eric J.; Patel, Alpa V.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA. [LaCroix, Andrea; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Petersen, Gloria] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Epidemiol Ctr, Nashville, TN USA. [Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England. [Bao, Ying; Wolpin, Brian M.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Buring, Julie E.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Nuthetal, Germany. [Boutron-Ruault, Marie-Christine] INSERM, Villejuif, France. [Boutron-Ruault, Marie-Christine] Inst Gustave Roussy, Villejuif, France. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Aging, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Phys Hlth Study, Boston, MA 02115 USA. [Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. [Giovannucci, Edward L.; Hunter, David J.; Kraft, Peter; Trichopoulos, Dimitrios] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Giovannucci, Edward L.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Giovannucci, Edward L.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Duell, Eric J.] Catalan Inst Oncol ICO IDIBELL, Unit Nutr Environm & Canc, Barcelona, Spain. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. [Howard, Barbara V.] Georgetown Univ, MedStar Hlth Res Inst, Hyattsville, MD USA. [Hutchinson, Amy] NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA. [Michaud, Dominique S.] Brown Univ, Div Biol & Med, Providence, RI 02912 USA. [Michaud, Dominique S.] Univ London Imperial Coll Sci Technol & Med, Div Epidemiol Publ Hlth & Primary Care, London, England. [Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy. [Phillips, Lawrence S.] Emory Univ, Div Endocrinol, Atlanta, GA 30322 USA. [Phillips, Lawrence S.] Atlanta VA Med Ctr, Decatur, GA USA. [Overvad, Kim] Aarhus Univ, Sch Publ Hlth, Dept Epidemiol, Aalborg, Denmark. [Simon, Michael S.] Wayne State Univ, Dept Oncol, Karmanos Canc Inst, Detroit, MI USA. [Slimani, Nadia] Int Agcy Res Canc, F-69372 Lyon, France. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med Pathol, Minneapolis, MN 55455 USA. RP Elena, JW (reprint author), NCI, DCCPS, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM elenajw@mail.nih.gov RI Boutron, Marie-Christine/K-8168-2013; Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015; Boutron-Ruault, Marie-Christine/H-3936-2014; Amundadottir, Laufey/L-7656-2016; Tobias, Geoffrey/M-4135-2016; OI Amundadottir, Laufey/0000-0003-1859-8971; Tobias, Geoffrey/0000-0002-2878-8253; Duell, Eric J/0000-0001-5256-0163; PALLI, Domenico/0000-0002-5558-2437; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Intramural Research Program of the National Cancer Institute; U.S. Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National Institute of Aging [5U01AG018033]; National Cancer Institute [CA105069, CA73790, P01CA087969, R01CA124908]; European Commission: Public Health and Consumer Protection Directorate; Ligue contre le Cancer; Societe 3 M; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health (Spain); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health, Food Standards Agency; Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity; Hellenic Health Foundation; Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) (Italy); Dutch Ministry of Public Health, Welfare and Sports; Dutch Prevention Funds; LK Research Funds; Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands); Swedish Cancer Society; Swedish Scientific Council; Regional Government of Skane and Vasterbotten (Sweden); World Cancer Research Fund (WCRF); National Institute of Environmental Health Sciences Center [ES000260]; Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics); National Heart, Lung, and Blood Institute [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; National Cancer Institute, National Institutes of Health; [P01CA055075] FX The authors thank the investigators from the PanScan Cohort Consortium centers and the study participants, without whom this study would have not been possible. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. Government. The Alpha-Tocopherol, Beta-Carotene Cancer Prevention Trial was supported by funding provided by the Intramural Research Program of the National Cancer Institute, and the U.S. Public Health Service contracts [(N01-CN-45165, N01-RC-45035, N01-RC-37004]. CLUE II was supported by National Institute of Aging [5U01AG018033] and National Cancer Institute [CA105069, CA73790]. European Prospective Investigation into Cancer and Nutrition was supported by the European Commission: Public Health and Consumer Protection Directorate 1993-2004; Research Directorate-General 2005; Ligue contre le Cancer; Societe 3 M; Mutuelle Generale de l'Education Nationale; Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center, Federal Ministry of Education and Research (Germany); Danish Cancer Society (Denmark); Health Research Fund (FIS) of the Spanish Ministry of Health, The participating regional governments and institutions (Spain); Cancer Research UK, Medical Research Council, Stroke Association, British Heart Foundation, Department of Health, Food Standards Agency, the Wellcome Trust (United Kingdom); Greek Ministry of Health and Social Solidarity, Hellenic Health Foundation and Stavros Niarchos Foundation (Greece); Italian Association for Research on Cancer (AIRC) (Italy); Dutch Ministry of Public Health, Welfare and Sports, Dutch Prevention Funds, LK Research Funds, Dutch ZON (Zorg Onderzoek Nederland) (the Netherlands); Swedish Cancer Society, Swedish Scientific Council, Regional Government of Skane and Vasterbotten (Sweden); World Cancer Research Fund (WCRF). The New York University Women's Health Study is supported by the National Cancer Institute research grants [R01CA034588, R01CA098661, P30CA016087] and the National Institute of Environmental Health Sciences Center grant [ES000260]. The Nurses' Health Study is supported by the National Cancer Institute research grants P01CA087969 and R01CA124908. The Health Professional's Follow-up Study is supported by P01CA055075 and R01CA124908. The Physician's Health Study by R01CA097193 and R01CA124908. The Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial was supported by contracts from the National Cancer Institute [University of Colorado Denver, NO1-CN-25514, Georgetown University NO1-CN-25522, Pacific Health Research Institute NO1-CN-25515, Henry Ford Health System NO1-CN-25512, University of Minnesota, NO1-CN-25513, Washington University NO1-CN-25516, University of Pittsburgh NO1-CN-25511, University of Utah NO1-CN-25524 Marshfield Clinic Research Foundation NO1-CN-25518, University of Alabama at Birmingham NO1-CN-75022, Westat, Inc. NO1-CN-25476, University of California, Los Angeles NO1-CN-25404]. The PLCO Study is sponsored by National Cancer Institute's Division of Cancer Prevention, in collaboration with the Division of Cancer Epidemiology and Genetics.; The Shanghai Men's and Women's Health Studies were supported by the National Cancer Institute extramural research grants [R01CA82729, R01CA70867, R01CA124908] and by the Intramural Research Program of National Cancer Institute (Division of Cancer Epidemiology and Genetics). The Women's Health Initiative is funded by the National Heart, Lung, and Blood Institute through contracts [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221]. Role of the Sponsors: This project has been funded with federal funds from the National Cancer Institute, National Institutes of Health. The funding agency had no role in the conduct of the study, the interpretation of the data, or the decision to submit the manuscript for publication. NR 51 TC 47 Z9 48 U1 1 U2 14 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 13 EP 25 DI 10.1007/s10552-012-0078-8 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000002 PM 23112111 ER PT J AU Freedman, DM Curtis, RE Daugherty, SE Goedert, JJ Kuncl, RW Tucker, MA AF Freedman, D. Michal Curtis, Rochelle E. Daugherty, Sarah E. Goedert, James J. Kuncl, Ralph W. Tucker, Margaret A. TI The association between cancer and amyotrophic lateral sclerosis SO CANCER CAUSES & CONTROL LA English DT Article DE Amyotrophic lateral sclerosis; Neoplasms; Melanoma; Tongue neoplasms; Prostatic neoplasms ID MOTOR-NEURON DISEASE; PARKINSONS-DISEASE; PROSTATE-CANCER; GROWTH-FACTOR; MELANOMA; ALS; EXPRESSION; MORTALITY; SKIN; EPIDEMIOLOGY AB Increasing evidence suggests that some neurodegenerative disorders, such as Parkinson's disease, are inversely related to cancer. Few epidemiologic studies have examined the relationship between cancer and amyotrophic lateral sclerosis (ALS), another major neurodegenerative disease. This study addresses that gap. Using data from 16 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) Program of the U.S. National Cancer Institute and death certificates, we followed 2.7 million cancer survivors who were diagnosed between 1973 and 2007, and who survived at least 1 year following cancer diagnosis. The standardized mortality ratio (SMR) of observed to expected ALS deaths in cancer survivors was calculated. A total of 1,216 ALS deaths were reported among 1 year survivors of cancer over 16.6 million person-years of follow-up. ALS mortality was not significantly associated with the incidence of total cancers [SMR = 1.00 (95 % confidence interval (CI), 0.95-1.06)]. There was, however, a significantly elevated risk of ALS death among survivors of melanoma [SMR = 1.49 (95 % (CI), 1.17-1.85)] and of tongue cancer [SMR = 2.57 (95 % CI, 1.41-4.32)], and a significantly reduced ALS death risk among prostate cancer survivors [SMR = 0.86 (95 % CI, 0.76-0.96)]. Cancer at certain sites may be related to risk of ALS death. Possible biologic factors linking ALS to these cancers are discussed. Future studies should attempt to confirm these associations using incident ALS outcomes. Establishing relationships between cancer and neurodegenerative diseases, such as ALS, opens new opportunities for understanding related pathophysiologic and therapeutic possibilities for these diseases. C1 [Freedman, D. Michal; Curtis, Rochelle E.; Daugherty, Sarah E.; Goedert, James J.; Tucker, Margaret A.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. [Kuncl, Ralph W.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS Room 7036,6120 Exec Blvd, Bethesda, MD 20892 USA. EM freedmam@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; U.S. Public Health Service of the Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the U.S. Public Health Service of the Department of Health and Human Services. We thank Jeremy Miller of Information Management Services, Inc. for biomedical computer assistance and Dr. Robert J. Biggar of Queensland University of Technology for his helpful comments. NR 44 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 55 EP 60 DI 10.1007/s10552-012-0089-5 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000006 PM 23090035 ER PT J AU Eichholzer, M Platz, EA Bienstock, JL Monsegue, D Akereyeni, F Hollis, BW Horst, R Rifai, N Pollak, MN Barbir, A Agurs-Collins, T Rohrmann, S AF Eichholzer, Monika Platz, Elizabeth A. Bienstock, Jessica L. Monsegue, Deborah Akereyeni, Folasade Hollis, Bruce W. Horst, Ronald Rifai, Nader Pollak, Michael N. Barbir, Aline Agurs-Collins, Tanya Rohrmann, Sabine TI Racial variation in vitamin D cord blood concentration in white and black male neonates SO CANCER CAUSES & CONTROL LA English DT Article DE Vitamin D; Umbilical cord blood; Black and white Americans ID SERUM 25-HYDROXYVITAMIN D; FOR-GESTATIONAL-AGE; D DEFICIENCY; UNITED-STATES; PROSTATE-CANCER; HIGH PREVALENCE; PREGNANT-WOMEN; HUMAN PLACENTA; D METABOLITES; 1,25-DIHYDROXYVITAMIN-D AB The aim of this study is to evaluate racial variation in umbilical cord blood concentration of vitamin D and to explore its correlation with markers of the insulin-like growth factor axis (IGFs) and sex steroid hormones in white and black male neonates. In 2004-2005, venous umbilical cord blood samples were collected from 75 black and 38 white male neonates, along with maternal and birth characteristics from two hospitals in Maryland, United States. 25-Hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were measured by radioimmunoassay and testosterone, estradiol, and sex hormone-binding globulin (SHBG) by immunoassay and IGF-1, IGF-2, and IGF-binding protein-3 by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed. Mean 25(OH)D levels were lower in black than in white neonates (11.44; 95 % CI 10.10-12.95 ng/mL vs. 18.24; 95 % CI 15.32-21.72 ng/mL; p < 0.0001). Black neonates were at higher risk of suboptimal vitamin D levels [25(OH)D < 20 ng/mL] than whites (84 vs. 63 %). 25(OH)D concentrations varied by season in whites but not in blacks and were significantly inversely correlated with mother's parity (number of live births) in blacks but not in whites. Mean concentration of 1,25(OH)(2)D did not differ by race. 25(OH)D and 1,25(OH)(2)D did not correlate with IGFs, sex steroid hormones, and SHBG. Suboptimal vitamin D levels were prevalent especially in blacks and influenced by mother's parity and by season. The observed vitamin D differences between black and white neonates warrant further evaluation of the etiology of the disparity in chronic diseases in adulthood. C1 [Eichholzer, Monika; Barbir, Aline; Rohrmann, Sabine] Univ Zurich, Inst Social & Prevent Med, Div Canc Epidemiol & Prevent, CH-8001 Zurich, Switzerland. [Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Platz, Elizabeth A.] Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. [Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. [Bienstock, Jessica L.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. [Monsegue, Deborah] Howard Univ, Div Allied Hlth Sci, Dept Nutr Sci, Coll Nursing & Allied Hlth Sci, Washington, DC 20059 USA. [Akereyeni, Folasade] Howard Univ, Ctr Human Genome, Washington, DC 20059 USA. [Hollis, Bruce W.] Med Univ S Carolina, Div Pediat, Charleston, SC 29425 USA. [Horst, Ronald] Heartland Assays LLC, Ames, IA USA. [Rifai, Nader] Harvard Univ, Sch Med, Dept Lab Med, Boston, MA USA. [Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA. [Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael N.] McGill Univ, Montreal, PQ, Canada. [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Eichholzer, M (reprint author), Univ Zurich, Inst Social & Prevent Med, Div Canc Epidemiol & Prevent, Hirschengraben 84, CH-8001 Zurich, Switzerland. EM monika.eichholzer@ifspm.uzh.ch FU ISFE (Internationale Stiftung zur Forderung der Ernahrungsforschung und Ernahrungsaufklarung); National Cancer Institute [Hopkins CA091409, Howard CA091431] FX We thank Stacey Meyerer, laboratory manager, at the Johns Hopkins Bloomberg School of Public Health, for her assistance in the conduct of this study. The study has been supported by ISFE (Internationale Stiftung zur Forderung der Ernahrungsforschung und Ernahrungsaufklarung). This study was also supported by a National Cancer Institute U54 grant (Hopkins CA091409) and U54 (Howard CA091431). The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health. NR 49 TC 8 Z9 9 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 91 EP 98 DI 10.1007/s10552-012-0093-9 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000010 PM 23139102 ER PT J AU Gibson, TM Smedby, KE Skibola, CF Hein, DW Slager, SL de Sanjose, S Vajdic, CM Zhang, YW Chiu, BCH Wang, SS Hjalgrim, H Nieters, A Bracci, PM Kricker, A Zheng, TZ Kolar, C Cerhan, JR Darabi, H Becker, N Conde, L Holford, TR Weisenburger, DD De Roos, AJ Butterbach, K Riby, J Cozen, W Benavente, Y Palmers, C Holly, EA Sampson, JN Rothman, N Armstrong, BK Morton, LM AF Gibson, Todd M. Smedby, Karin E. Skibola, Christine F. Hein, David W. Slager, Susan L. de Sanjose, Silvia Vajdic, Claire M. Zhang, Yawei Chiu, Brian C-H. Wang, Sophia S. Hjalgrim, Henrik Nieters, Alexandra Bracci, Paige M. Kricker, Anne Zheng, Tongzhang Kolar, Carol Cerhan, James R. Darabi, Hatef Becker, Nikolaus Conde, Lucia Holford, Theodore R. Weisenburger, Dennis D. De Roos, Anneclaire J. Butterbach, Katja Riby, Jacques Cozen, Wendy Benavente, Yolanda Palmers, Casey Holly, Elizabeth A. Sampson, Joshua N. Rothman, Nathaniel Armstrong, Bruce K. Morton, Lindsay M. TI Smoking, variation in N-acetyltransferase 1 (NAT1) and 2 (NAT2), and risk of non-Hodgkin lymphoma: a pooled analysis within the InterLymph consortium SO CANCER CAUSES & CONTROL LA English DT Article DE Non-Hodgkin lymphoma; Gene environment interaction; Cigarette smoking; N-acetyltransferase; Follicular lymphoma ID CONTROL-STUDY EPILYMPH; CIGARETTE-SMOKING; GENETIC POLYMORPHISMS; BIOTRANSFORMATION ENZYMES; MOLECULAR-GENETICS; TOBACCO SMOKING; ASSOCIATION; ALCOHOL; CANCER; WOMEN AB Studies of smoking and risk of non-Hodgkin lymphoma (NHL) have yielded inconsistent results, possibly due to subtype heterogeneity and/or genetic variation impacting the metabolism of tobacco-derived carcinogens, including substrates of the N-acetyltransferase enzymes NAT1 and NAT2. We conducted a pooled analysis of 5,026 NHL cases and 4,630 controls from seven case-control studies in the international lymphoma epidemiology consortium to examine associations between smoking, variation in the N-acetyltransferase genes NAT1 and NAT2, and risk of NHL subtypes. Smoking data were harmonized across studies, and genetic variants in NAT1 and NAT2 were used to infer acetylation phenotype of the NAT1 and NAT2 enzymes, respectively. Pooled odds ratios (ORs) and 95 % confidence intervals (95 % CIs) for risk of NHL and subtypes were calculated using joint fixed effects unconditional logistic regression models. Current smoking was associated with a significant 30 % increased risk of follicular lymphoma (n = 1,176) but not NHL overall or other NHL subtypes. The association was similar among NAT2 slow (OR 1.36; 95 % CI 1.07-1.75) and intermediate/rapid (OR 1.27; 95 % CI 0.95-1.69) acetylators (p (interaction) = 0.82) and also did not differ by NAT1*10 allelotype. Neither NAT2 phenotype nor NAT1*10 allelotype was associated with risk of NHL overall or NHL subtypes. The current findings provide further evidence for a modest association between current smoking and follicular lymphoma risk and suggest that this association may not be influenced by variation in the N-acetyltransferase enzymes. C1 [Gibson, Todd M.; Sampson, Joshua N.; Rothman, Nathaniel; Morton, Lindsay M.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Gibson, Todd M.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA. [Smedby, Karin E.] Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden. [Skibola, Christine F.; Conde, Lucia; Riby, Jacques; Palmers, Casey] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. [Hein, David W.] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Hein, David W.] Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. [Slager, Susan L.; Cerhan, James R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [de Sanjose, Silvia; Benavente, Yolanda] IDIBELL, Inst Catala Oncol, Canc Epidemiol Res Programme, Unit Infect & Canc, Barcelona, Spain. [de Sanjose, Silvia] CIBER Epidemiol & Salud Publ, Madrid, Spain. [Vajdic, Claire M.] Univ New S Wales, Adult Canc Program, Sydney, NSW, Australia. [Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Lowy Canc Res Ctr, Sydney, NSW, Australia. [Zhang, Yawei; Zheng, Tongzhang; Holford, Theodore R.] Yale Univ, Yale Sch Publ Hlth, New Haven, CT USA. [Chiu, Brian C-H.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA. [Wang, Sophia S.] City Hope Natl Med Ctr, Duarte, CA USA. [Hjalgrim, Henrik] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. [Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Germany. [Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. [Kricker, Anne; Armstrong, Bruce K.] Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. [Kolar, Carol] Univ Nebraska Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE USA. [Darabi, Hatef] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Becker, Nikolaus; Butterbach, Katja] German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. [Weisenburger, Dennis D.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. [De Roos, Anneclaire J.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [De Roos, Anneclaire J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. [Cozen, Wendy] Univ So Calif, Keck Sch Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Gibson, TM (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7090, Bethesda, MD 20892 USA. EM gibsontm@mail.nih.gov RI Hein, David/A-9707-2008; de Sanjose Llongueras, Silvia/H-6339-2014; Morton, Lindsay/B-5234-2015; Armstrong, Bruce/K-9464-2015; Benavente, Yolanda/H-9810-2014; OI Morton, Lindsay/0000-0001-9767-2310; Armstrong, Bruce/0000-0001-8940-7525; Vajdic, Claire/0000-0002-3612-8298; Cerhan, James/0000-0002-7482-178X FU Spanish Ministry of Health FISS grant [PI11/01810, AGAUR_SGR01465, CIBERESP 06/06/0073]; Swedish Cancer Society [090659]; Danish Medical Research Council [FSS 09-63424]; National Cancer Institute [CA069269-01, CA92153-01]; National Health and Medical Research Council, Australia [990920] FX Intramural Research Program of the National Cancer Institute; Spanish Ministry of Health FISS grant PI11/01810, AGAUR_SGR01465, and CIBERESP 06/06/0073 (EpiLymph-Spain); Swedish Cancer Society (090659); Danish Medical Research Council (FSS 09-63424); National Cancer Institute (CA069269-01 and CA92153-01); National Health and Medical Research Council, Australia, grant 990920. NR 38 TC 9 Z9 12 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 125 EP 134 DI 10.1007/s10552-012-0098-4 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000014 PM 23160945 ER PT J AU Hofmann, JN Schwartz, K Chow, WH Ruterbusch, JJ Shuch, BM Karami, S Rothman, N Wacholder, S Graubard, BI Colt, JS Purdue, MP AF Hofmann, Jonathan N. Schwartz, Kendra Chow, Wong-Ho Ruterbusch, Julie J. Shuch, Brian M. Karami, Sara Rothman, Nathaniel Wacholder, Sholom Graubard, Barry I. Colt, Joanne S. Purdue, Mark P. TI The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans SO CANCER CAUSES & CONTROL LA English DT Article DE Renal cell carcinoma; Kidney cancer; Chronic renal failure; End-stage renal disease; Racial disparities ID ORGAN TRANSPLANT RECIPIENTS; AFRICAN-AMERICANS; APOL1 VARIANTS; KIDNEY-DISEASE; UNITED-STATES; RISK-FACTORS; CANCER; DIALYSIS; EPIDEMIOLOGY; HYPERTENSION AB In the United States, renal cell carcinoma (RCC) incidence is higher among blacks than among whites. Risk of RCC is elevated among end-stage renal disease patients, although no studies have looked at differences by race in the relationship between chronic renal failure and RCC. We investigated RCC risk in relation to chronic renal failure in a population-based case-control study of blacks and whites in Chicago and Detroit. Data, including information on kidney disease, were collected from interviews with 1,217 RCC cases (361 blacks, 856 whites) and 1,235 controls (523 blacks, 712 whites). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression. Risk of RCC was increased in relation to chronic renal failure (OR 4.7, 95 % CI 2.2-10.1) and dialysis (OR 18.0, 95 % CI 3.6-91). The association remained after defining exposure as those who had chronic renal failure a parts per thousand yen10 years prior to RCC diagnosis. Chronic renal failure was more strongly associated with RCC among blacks than among whites (OR 8.7, 95 % CI 3.3-22.9 and 2.0, 0.7-5.6, respectively; p (interaction) = 0.03) and among those without a history of diabetes relative to diabetic subjects (OR 8.3, 95 % CI 3.1-22.7 and 1.9, 0.6-5.9, respectively; p (interaction) = 0.03). These results suggest that chronic renal failure is a strong risk factor for RCC, particularly among black and non-diabetic subjects. Our findings of differences in risk estimates by race, to our knowledge the first such report, require replication. C1 [Hofmann, Jonathan N.; Karami, Sara; Rothman, Nathaniel; Colt, Joanne S.; Purdue, Mark P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schwartz, Kendra; Ruterbusch, Julie J.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA. [Schwartz, Kendra; Ruterbusch, Julie J.] Wayne State Univ, Sch Med, Dept Family Med, Detroit, MI USA. [Schwartz, Kendra; Ruterbusch, Julie J.] Karmanos Canc Inst, Detroit, MI USA. [Chow, Wong-Ho] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Shuch, Brian M.] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Wacholder, Sholom; Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hofmann, JN (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM hofmannjn@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The authors thank Faith Davis and other staff in the Division of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago for their contributions to data collection, as well as Kate Torres, Marsha Dunn, and other staff at Westat, Inc. and Stella Munuo and other staff at Information Management Services, Inc. for their efforts on this project. Finally, the authors express their gratitude to the participants in this study for their involvement. NR 22 TC 11 Z9 11 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD JAN PY 2013 VL 24 IS 1 BP 167 EP 174 DI 10.1007/s10552-012-0102-z PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 060KZ UT WOS:000312778000017 PM 23179659 ER PT J AU Parise, RA Anyang, BN Eiseman, JL Egorin, MJ Covey, JM Beumer, JH AF Parise, Robert A. Anyang, Bean N. Eiseman, Julie L. Egorin, Merrill J. Covey, Joseph M. Beumer, Jan H. TI Formation of active products of benzaldehyde dimethane sulfonate (NSC 281612, DMS612) in human blood and plasma and their activity against renal cell carcinoma lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE BEN metabolism; Alkylators; Degradation; Renal cell carcinoma; HPLC; Mass spectrometry; Metabolism; Aldehyde dehydrogenase; Stability; Cell lines; Cancer ID PHARMACOKINETICS; DEGRADATION; METABOLISM; AGENTS AB Benzaldehyde dimethane sulfonate (BEN, DMS612, NSC281612) is an alkylating agent with activity against renal cell carcinoma and is being evaluated clinically. To support clinical trials, we developed an LC-MS/MS assay to detect and quantitate BEN and its metabolites/decomposition products. We tested the stability and products of BEN and benzoic acid dimethane sulfonate (BA) in plasma, blood and five renal carcinoma cell lines in vitro. Further, we determined the IC50 of BEN, BA and four of their products in these cell lines. Low temperature and pH stabilized the analytes, and utilizing this resulted in an accurate, precise and reproducible assay. The half-lives of BEN and BA added to plasma in vitro were 220 and 5 min, while the half-life of BEN in whole blood was 18 min. The generation and degradation of up to 12 analytes were monitored, and structures confirmed with available authentic standards. The IC50 for BEN was 5- to 500-fold lower than that of any of its products, while the cellular metabolic activity toward BEN correlated with ALDH activity and IC50 values. We detected six of the in vitro products and their respective glucuronides in murine plasma after dosing BEN. The information gained from these experiments will be instrumental in the evaluation of the pharmacology of BEN in ongoing human trials. C1 [Parise, Robert A.; Beumer, Jan H.] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15213 USA. [Parise, Robert A.; Anyang, Bean N.; Eiseman, Julie L.; Egorin, Merrill J.; Beumer, Jan H.] Univ Pittsburgh, Mol Therapeut Drug Discovery Program, Inst Canc, Pittsburgh, PA 15213 USA. [Eiseman, Julie L.; Egorin, Merrill J.] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Sch Med, Pittsburgh, PA 15213 USA. [Egorin, Merrill J.] Univ Pittsburgh, Div Hematol Oncol, Dept Med, Sch Med, Pittsburgh, PA 15213 USA. [Covey, Joseph M.] NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD 20852 USA. [Beumer, Jan H.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Pittsburgh, PA 15213 USA. RP Beumer, JH (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Room G27E,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM beumerj@gmail.com OI Beumer, Jan/0000-0002-8978-9401 FU National Cancer Institute [N01-CM-52202, U01-CA099168]; National Institutes of Health, National Cancer Institute; [P30-CA47904] FX This work was supported by National Cancer Institute contract N01-CM-52202 and grant U01-CA099168. This project used the UPCI Clinical Pharmacology Analytical Facility (CPAF) and was supported in part by award P30-CA47904. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute. We thank Diane Mazzei and her colleagues at the University of Pittsburgh Animal Facility for their expert assistance, and the University of Pittsburgh Cancer Institute Hematology/Oncology Writing Group for constructive suggestions regarding the manuscript. We would like to acknowledge the late Dr Merrill Egorin for his help and guidance on conducting the experimentation that was required for this manuscript. He was a great mentor, colleague and friend, and he will not be forgotten. NR 20 TC 4 Z9 4 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2013 VL 71 IS 1 BP 73 EP 83 DI 10.1007/s00280-012-1980-1 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 063MW UT WOS:000313004900009 PM 23053264 ER PT J AU Shimizu, K Mizuno, T Shinga, J Asakura, M Kakimi, K Ishii, Y Masuda, K Maeda, T Sugahara, H Sato, Y Matsushita, H Nishida, K Hanada, K Dorrie, J Schaft, N Bickham, K Koike, H Ando, T Nagai, R Fujii, S AF Shimizu, Kanako Mizuno, Takuya Shinga, Jun Asakura, Miki Kakimi, Kazuhiro Ishii, Yasuyuki Masuda, Kenichi Maeda, Tomoji Sugahara, Hidetoshi Sato, Yusuke Matsushita, Hirokazu Nishida, Keigo Hanada, Kenichi Dorrie, Jan Schaft, Niels Bickham, Kara Koike, Hisashi Ando, Tsuyoshi Nagai, Ryozo Fujii, Shin-ichiro TI Vaccination with Antigen-Transfected, NKT Cell Ligand-Loaded, Human Cells Elicits Robust In Situ Immune Responses by Dendritic Cells SO CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; ALPHA-GALACTOSYLCERAMIDE; MESSENGER-RNA; PROTECTIVE IMMUNITY; CANCER-PATIENTS; PROSTATE-CANCER; INFLUENZA-VIRUS; MELANOMA-CELLS; TUMOR-IMMUNITY; CTL RESPONSES AB Both innate and adaptive immunity are crucial for cancer immunosurveillance, but precise therapeutic equations to restore immunosurveillance in patients with cancer patients have yet to be developed. In murine models, alpha-galactosylceramide (alpha-GalCer)-loaded, tumor antigen-expressing syngeneic or allogeneic cells can act as cellular adjuvants, linking the innate and adaptive immune systems. In the current study, we established human artificial adjuvant vector cells (aAVC) consisting of human HEK293 embryonic kidney cells stably transfected with the natural killer T (NKT) immune cell receptor CD1d, loaded with the CD1d ligand alpha-GalCer and then transfected with antigen-encoding mRNA. When administered to mice or dogs, these aAVC-activated invariant NKT (iNKT) cells elicited antigen-specific T-cell responses with no adverse events. In parallel experiments, using NOD/SCID/IL-2r gamma c(null)-immunodeficient (hDC-NOG) mouse model, we also showed that the human melanoma antigen, MART-1, expressed by mRNA transfected aAVCs can be cross-presented to antigen-specific T cells by human dendritic cells. Antigen-specific T-cell responses elicited and expanded by aAVCs were verified as functional in tumor immunity. Our results support the clinical development of aAVCs to harness innate and adaptive immunity for effective cancer immunotherapy. Cancer Res; 73(1); 62-73. (C) 2012 AACR. C1 [Shimizu, Kanako; Shinga, Jun; Asakura, Miki; Sugahara, Hidetoshi; Sato, Yusuke; Fujii, Shin-ichiro] RCAI, Inst Phys & Chem Res RIKEN, Res Unit Cellular Immunotherapy, Yokohama, Kanagawa, Japan. [Shimizu, Kanako] RCAI, Inst Phys & Chem Res RIKEN, Res Unit Therapeut Model, Yokohama, Kanagawa, Japan. [Ishii, Yasuyuki] RCAI, Inst Phys & Chem Res RIKEN, Lab Vaccine Design, Yokohama, Kanagawa, Japan. [Nishida, Keigo] RCAI, Inst Phys & Chem Res RIKEN, Lab Cytokine Signaling, Yokohama, Kanagawa, Japan. [Mizuno, Takuya] Yamaguchi Univ, Fac Agr, Dept Vet Med, Lab Vet Internal Med, Yamaguchi 753, Japan. [Kakimi, Kazuhiro; Matsushita, Hirokazu] Tokyo Univ Hosp, Dept Immunotherapeut, Tokyo 113, Japan. [Koike, Hisashi; Ando, Tsuyoshi; Nagai, Ryozo] Tokyo Univ Hosp, Translat Res Ctr, Tokyo 113, Japan. [Nagai, Ryozo] Univ Tokyo, Grad Sch Med, Dept Cardiovasc Med, Tokyo, Japan. [Koike, Hisashi] PMDA, Off Biol, Tokyo, Japan. [Masuda, Kenichi] Anim Allergy Clin Labs Inc, Sagamihara, Kanagawa, Japan. [Maeda, Tomoji] Iwate Med Univ, Sch Pharm, Dept Neurosci, Morioka, Iwate 020, Japan. [Hanada, Kenichi] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Dorrie, Jan; Schaft, Niels] Univ Hosp Erlangen, Dept Dermatol, Erlangen, Germany. [Bickham, Kara] Columbia Univ Coll Phys & Surg, Columbia Ctr Translat Immunol, New York, NY 10032 USA. RP Fujii, S (reprint author), RIKEN, RCAI, Res Unit Cellular Immunotherapy, Yokohama, Kanagawa 2300045, Japan. EM fujiis@rcai.riken.jp RI Dorrie, Jan/H-3678-2011; Hanada, Ken-ichi/L-2481-2013; Fujii, Shin-ichiro/O-6218-2015 OI Dorrie, Jan/0000-0002-3478-0741; Hanada, Ken-ichi/0000-0003-2959-1257; FU Ministry of Education, Culture, Sports, Science and Technology of Japan [23380186]; coordination, support and training program for translational research of Japan FX This work is supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan to K. Shimizu [Grants-in-Aid for Scientific Research (B) 23380186] and S. Fujii [Grants-in-Aid for Scientific Research (C)] and by a grant of coordination, support and training program for translational research of Japan. NR 50 TC 11 Z9 11 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 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2013 VL 73 IS 1 BP 62 EP 73 DI 10.1158/0008-5472.CAN-12-0759 PG 12 WC Oncology SC Oncology GA 063SF UT WOS:000313019800008 PM 23108144 ER PT J AU Hasina, R Mollberg, N Kawada, I Mutreja, K Kanade, G Yala, S Surati, M Liu, R Li, XQ Zhou, Y Ferguson, BD Nallasura, V Cohen, KS Hyjek, E Mueller, J Kanteti, R El Hashani, E Kane, D Shimada, Y Lingen, MW Husain, AN Posner, MC Waxman, I Villaflor, VM Ferguson, MK Varticovski, L Vokes, EE Gill, P Salgia, R AF Hasina, Rifat Mollberg, Nathan Kawada, Ichiro Mutreja, Karun Kanade, Geetanjali Yala, Soheil Surati, Mosmi Liu, Ren Li, Xiuqing Zhou, Yue Ferguson, Benjamin D. Nallasura, Vidya Cohen, Kenneth S. Hyjek, Elizabeth Mueller, Jeffery Kanteti, Rajani El Hashani, Essam Kane, Dorothy Shimada, Yutaka Lingen, Mark W. Husain, Aliya N. Posner, Mitchell C. Waxman, Irving Villaflor, Victoria M. Ferguson, Mark K. Varticovski, Lyuba Vokes, Everett E. Gill, Parkash Salgia, Ravi TI Critical Role for the Receptor Tyrosine Kinase EPHB4 in Esophageal Cancers SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL-CELL MIGRATION; NONMELANOMA SKIN-CANCER; HUMAN-PAPILLOMAVIRUS; ORAL CARCINOGENESIS; MELANOMA-CELLS; HPV DNA; EXPRESSION; GROWTH; HEAD; REORGANIZATION AB Esophageal cancer incidence is increasing and has few treatment options. In studying receptor tyrosine kinases associated with esophageal cancers, we have identified EPHB4 to be robustly overexpressed in cell lines and primary tumor tissues. In total, 94 squamous cell carcinoma, 82 adenocarcinoma, 25 dysplasia, 13 Barrett esophagus, and 25 adjacent or unrelated normal esophageal tissues were evaluated by immunohistochemistry. EPHB4 expression was significantly higher in all the different histologic categories than in adjacent normal tissues. In 13 esophageal cancer cell lines, 3 of the 9 SCC cell lines and 2 of the 4 adenocarcinomas expressed very high levels of EPHB4. An increased gene copy number ranging from 4 to 20 copies was identified in a subset of the overexpressing patient samples and cell lines. We have developed a novel 4-nitroquinoline 1-oxide (4-NQO)-induced mouse model of esophageal cancer that recapitulates the EPHB4 expression in humans. A specific small-molecule inhibitor of EPHB4 decreased cell viability in a time- and dose-dependent manner in 3 of the 4 cell lines tested. The small-molecule inhibitor and an EPHB4 siRNA also decreased cell migration (12%-40% closure in treated vs. 60%-80% in untreated), with decreased phosphorylation of various tyrosyl-containing proteins, EphB4, and its downstream target p125FAK. Finally, in a xenograft tumor model, an EPHB4 inhibitor abrogated tumor growth by approximately 60% compared with untreated control. EphB4 is robustly expressed and potentially serves as a novel biomarker for targeted therapy in esophageal cancers. Cancer Res; 73(1); 184-94. (C) 2012 AACR. C1 [Salgia, Ravi] Univ Chicago, Chest Oncol & Thorac Oncol Res Program, Dept Med, Sect Hematol Oncol, Chicago, IL 60637 USA. [Hyjek, Elizabeth; Mueller, Jeffery; Kane, Dorothy; Lingen, Mark W.; Husain, Aliya N.] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. [Liu, Ren; Li, Xiuqing; Zhou, Yue; Gill, Parkash] Univ So Calif, Div Hematol & Pathol, Dept Med, Los Angeles, CA USA. [Posner, Mitchell C.; Waxman, Irving; Ferguson, Mark K.] Univ Chicago, Dept Surg, Chicago, IL 60637 USA. [Shimada, Yutaka] Toyama Univ, Dept Surg & Sci, Toyama 930, Japan. [Varticovski, Lyuba] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Salgia, R (reprint author), Univ Chicago, Chest Oncol & Thorac Oncol Res Program, Dept Med, Sect Hematol Oncol, 5841 S Maryland Ave,MC2115, Chicago, IL 60637 USA. EM rsalgia@medicine.bsd.uchicago.edu FU NIH/NCI [5R01CA100750-08, 5R01CA129501-04]; Lederer Family Foundation; ASCO; National Cancer Institute, Bethesda, MD FX The study was supported by NIH/NCI 5R01CA100750-08 and 5R01CA129501-04 (R. Salgia), Lederer Family Foundation and ASCO Translational Award (E. E. Vokes), and Intramural program of the National Cancer Institute, Bethesda, MD (L. Varticovski). NR 43 TC 17 Z9 18 U1 0 U2 14 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2013 VL 73 IS 1 BP 184 EP 194 DI 10.1158/0008-5472.CAN-12-0915 PG 11 WC Oncology SC Oncology GA 063SF UT WOS:000313019800019 PM 23100466 ER PT J AU Tam, WF Hahnel, PS Schuler, A Lee, BH Okabe, R Zhu, N Pante, SV Raffel, G Mercher, T Wernig, G Bockamp, E Sasca, D Kreft, A Robinson, GW Hennighausen, L Gilliland, DG Kindler, T AF Tam, Winnie F. Haehnel, Patricia S. Schueler, Andrea Lee, Benjamin H. Okabe, Rachel Zhu, Nan Pante, Saskia V. Raffel, Glen Mercher, Thomas Wernig, Gerlinde Bockamp, Ernesto Sasca, Daniel Kreft, Andreas Robinson, Gertraud W. Hennighausen, Lothar Gilliland, D. Gary Kindler, Thomas TI STAT5 Is Crucial to Maintain Leukemic Stem Cells in Acute Myelogenous Leukemias Induced by MOZ-TIF2 SO CANCER RESEARCH LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; SELF-RENEWAL; CONSTITUTIVE ACTIVATION; MYELOPROLIFERATIVE DISEASE; CONFERS PROPERTIES; FLT3 MUTATIONS; MIXED-LINEAGE; MOUSE MODEL; FUSION AB MOZ-TIF2 is a leukemogenic fusion oncoprotein that confers self-renewal capability to hematopoietic progenitor cells and induces acute myelogenous leukemia (AML) with long latency in bone marrow transplantation assays. Here, we report that FLT3-ITD transforms hematopoietic cells in cooperation with MOZ-TIF2 in vitro and in vivo. Coexpression of FLT3-ITD confers growth factor independent survival/proliferation, shortens disease latency, and results in an increase in the number of leukemic stem cells (LSC). We show that STAT5, a major effector of aberrant FLT3-ITD signal transduction, is both necessary and sufficient for this cooperative effect. In addition, STAT5 signaling is essential for MOZ-TIF2-induced leukemic transformation itself. Lack of STAT5 in fetal liver cells caused rapid differentiation and loss of replating capacity of MOZ-TIF2-transduced cells enriched for LSCs. Furthermore, mice serially transplanted with Stat5(-/-) MOZ-TIF2 leukemic cells develop AML with longer disease latency and finally incomplete penetrance when compared with mice transplanted with Stat5(+/+) MOZ-TIF2 leukemic cells. These data suggest that STAT5AB is required for the self-renewal of LSCs and represents a combined signaling node of FLT3-ITD and MOZ-TIF2 driven leukemogenesis. Therefore, targeting aberrantly activated STAT5 or rewired downstream signaling pathways may be a promising therapeutic option. Cancer Res; 73(1); 373-84. (C)2012 AACR. C1 [Tam, Winnie F.; Lee, Benjamin H.; Okabe, Rachel; Zhu, Nan; Raffel, Glen; Mercher, Thomas; Wernig, Gerlinde; Gilliland, D. Gary; Kindler, Thomas] Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. [Haehnel, Patricia S.; Schueler, Andrea; Pante, Saskia V.; Bockamp, Ernesto; Sasca, Daniel; Kindler, Thomas] Univ Med Ctr, Dept Med 3, Div Hematol Oncol Pneumol, D-55131 Mainz, Germany. [Kreft, Andreas] Univ Med Ctr, Inst Pathol, D-55131 Mainz, Germany. Johannes Gutenberg Univ Mainz, Mainz, Germany. [Robinson, Gertraud W.; Hennighausen, Lothar] NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Kindler, T (reprint author), Univ Med Ctr, Dept Med 3, Div Hematol Oncol Pneumol, Genbeckstr 1, D-55131 Mainz, Germany. EM wtam@zalicus.com; thomas.kindler@ukmainz.de RI Kindler, Thomas/K-5995-2013; Mercher, Thomas/J-2446-2014; OI Mercher, Thomas/0000-0003-1552-087X; Bockamp, Ernesto/0000-0002-6181-1734 FU Howard Hughes Medical Institute (Boston, MA); National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK)/NIH; DFG FX D.G. Gilliland received funding support from the Howard Hughes Medical Institute (Boston, MA), L. Hennighausen and G. W. Robinson received funding support from the intramural program of the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK)/NIH and the DFG Mercator Visiting Professor program. NR 44 TC 9 Z9 11 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 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2013 VL 73 IS 1 BP 373 EP 384 DI 10.1158/0008-5472.CAN-12-0255 PG 12 WC Oncology SC Oncology GA 063SF UT WOS:000313019800037 PM 23149921 ER PT J AU Alberg, AJ Jorgensen, TJ Ruczinski, I Wheless, L Shugart, YY Berthier-Schaad, Y Kessing, B Hoffman-Bolton, J Helzlsouer, KJ Kao, WHL Francis, L Alani, RM Smith, MW Strickland, PT AF Alberg, Anthony J. Jorgensen, Timothy J. Ruczinski, Ingo Wheless, Lee Shugart, Yin Yao Berthier-Schaad, Yvette Kessing, Bailey Hoffman-Bolton, Judith Helzlsouer, Kathy J. Kao, W. H. Linda Francis, Lesley Alani, Rhoda M. Smith, Michael W. Strickland, Paul T. TI DNA repair gene variants in relation to overall cancer risk: a population-based study SO CARCINOGENESIS LA English DT Article ID O-6-METHYLGUANINE-DNA METHYLTRANSFERASE MGMT; NONMELANOMA SKIN-CANCER; PROMOTER METHYLATION; SUSCEPTIBILITY; METAANALYSIS; HYPERMETHYLATION; POLYMORPHISMS; ASSOCIATION; NONSMOKERS; COHORT AB The hypothesis that germ-line polymorphisms in DNA repair genes influence cancer risk has previously been tested primarily on a cancer site-specific basis. The purpose of this study was to test the hypothesis that DNA repair gene allelic variants contribute to globally elevated cancer risk by measuring associations with risk of all cancers that occurred within a population-based cohort. In the CLUE II cohort study established in 1989 in Washington County, MD, this study was comprised of all 3619 cancer cases ascertained through 2007 compared with a sample of 2296 with no cancer. Associations were measured between 759 DNA repair gene single nucleotide polymorphisms (SNPs) and risk of all cancers. A SNP in O-6-methylguanine-DNA methyltransferase, MGMT, (rs2296675) was significantly associated with overall cancer risk [per minor allele odds ratio (OR) 1.30, 95% confidence interval (CI) 1.191.43 and P-value: 4.1 10(8)]. The association between rs2296675 and cancer risk was stronger among those aged 54 years old than those who were epsilon 55 years at baseline (P-for-(interaction) 0.021). OR were in the direction of increased risk for all 15 categories of malignancies studied (P < 0.0001), ranging from 1.22 (P 0.42) for ovarian cancer to 2.01 (P 0.008) for urinary tract cancers; the smallest P-value was for breast cancer (OR 1.45, P 0.0002). The results indicate that the minor allele of MGMT SNP rs2296675, a common genetic marker with 37% carriers, was significantly associated with increased risk of cancer across multiple tissues. Replication is needed to more definitively determine the scientific and public health significance of this observed association. C1 [Alberg, Anthony J.; Wheless, Lee; Francis, Lesley] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Alberg, Anthony J.; Wheless, Lee; Francis, Lesley] Med Univ S Carolina, Div Epidemiol & Biostat, Dept Med, Charleston, SC 29425 USA. [Jorgensen, Timothy J.] Georgetown Univ, Sch Med, Dept Radiat Med, Washington, DC USA. [Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Shugart, Yin Yao] NIMH, Div Intramural Res Program, Rockville, MD 20857 USA. [Berthier-Schaad, Yvette; Hoffman-Bolton, Judith; Kao, W. H. Linda; Strickland, Paul T.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Berthier-Schaad, Yvette; Kessing, Bailey] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Frederick, MD USA. [Hoffman-Bolton, Judith] George W Comstock Ctr Publ Hlth Res & Prevent, Washington Cty, DC USA. [Helzlsouer, Kathy J.] Mercy Med Ctr, Prevent Res Ctr, Baltimore, MD USA. [Alani, Rhoda M.] Boston Univ, Sch Med, Dept Dermatol, Boston, MA 02118 USA. [Smith, Michael W.] SAIC Frederick Inc, NCI Frederick, Adv Technol Program, Genet & Genom Grp, Frederick, MD USA. [Strickland, Paul T.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. EM alberg@musc.edu OI Alani, Rhoda/0000-0003-2741-2665 FU US National Cancer Institute [R01 CA105069, HHSN26120080001E]; Intramural Research Program of the NCI, Center for Cancer Research; State of Maryland; Maryland Cigarette Restitution Fund; National Program of Cancer Registries of the Centers for Disease Control and Prevention FX US National Cancer Institute (R01 CA105069, HHSN26120080001E) and the Intramural Research Program of the NCI, Center for Cancer Research. This publication does not necessarily reflect the views or policies of the National Cancer Institute, National Institute of Mental Health, National Institutes of Health, US Department of Health and Human Services, the US government, or the Maryland Cancer Registry, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government.; Cancer incidence data were provided by the Maryland Cancer Registry, Center for Cancer Surveillance and Control, Department of Health and Mental Hygiene, which is funded by the State of Maryland, the Maryland Cigarette Restitution Fund, and the National Program of Cancer Registries of the Centers for Disease Control and Prevention. NR 37 TC 8 Z9 8 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2013 VL 34 IS 1 BP 86 EP 92 DI 10.1093/carcin/bgs304 PG 7 WC Oncology SC Oncology GA 065DQ UT WOS:000313128600011 PM 23027618 ER PT J AU Liao, LM Weinstein, SJ Pollak, M Li, Z Virtamo, J Albanes, D Chow, WH Purdue, MP AF Liao, Linda M. Weinstein, Stephanie J. Pollak, Michael Li, Zhen Virtamo, Jarmo Albanes, Demetrius Chow, Wong-Ho Purdue, Mark P. TI Prediagnostic circulating adipokine concentrations and risk of renal cell carcinoma in male smokers SO CARCINOGENESIS LA English DT Article ID BODY-MASS INDEX; PLASMA ADIPONECTIN LEVELS; BREAST-CANCER RISK; ACTIVATED PROTEIN-KINASE; ENDOMETRIAL CANCER; ADIPOSE-TISSUE; UNITED-STATES; LEPTIN CONCENTRATIONS; POSTMENOPAUSAL WOMEN; COLORECTAL-CANCER AB Despite a well-established link between obesity and renal cell carcinoma (RCC), the mechanism through which obesity acts to increase cancer risk is unclear. Adiponectin, leptin and resistin are adipocyte-secreted peptide hormones that may influence RCC development through their demonstrated effects on inflammation, insulin resistance and cell growth and proliferation. We conducted a nested casecontrol study to evaluate whether prediagnostic serum adiponectin, leptin and resistin levels are associated with RCC risk. This casecontrol study (273 cases and 273 controls) was nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of Finnish male smokers. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression models, with analyte levels modeled continuously and categorically (defined using quartiles among controls). High adiponectin levels were significantly associated with reduced RCC risk (Quartile 4 versus Quartile 1: OR 0.52, 95% CI 0.300.88; P trend 0.01). This association remained upon additional adjustment for body mass index at blood collection and exclusion of cases diagnosed within the first 2 years of follow-up. In addition, model adjustment for adiponectin resulted in a substantial attenuation of the association between BMI and RCC (OR per 5kg/m(2) changed from 1.19 to 1.05). No clear associations with RCC were observed for leptin or resistin. Our results suggest that elevated levels of circulating adiponectin are associated with decreased subsequent risk of RCC. These findings provide the strongest evidence to date, suggesting that the association between obesity and RCC is mediated at least in part through the effects of low adiponectin. C1 [Liao, Linda M.; Weinstein, Stephanie J.; Albanes, Demetrius; Chow, Wong-Ho; Purdue, Mark P.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Pollak, Michael; Li, Zhen] McGill Univ, Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ H3T 1E2, Canada. [Pollak, Michael; Li, Zhen] McGill Univ, Montreal, PQ, Canada. [Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. RP Liao, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM liaolm@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Liao, Linda/0000-0002-1923-5294 FU Intramural Research Program of the National Institutes of Health; National Cancer Institute; U.S. Public Health Service [N01-CN-45165, N01-RC-45035, N01-RC-37004]; National Cancer Institute, Department of Health and Human Services [HHSN261201000006C] FX Intramural Research Program of the National Institutes of Health and the National Cancer Institute; U.S. Public Health Service (N01-CN-45165, N01-RC-45035, N01-RC-37004); National Cancer Institute, Department of Health and Human Services (HHSN261201000006C). NR 49 TC 10 Z9 12 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2013 VL 34 IS 1 BP 109 EP 112 DI 10.1093/carcin/bgs322 PG 4 WC Oncology SC Oncology GA 065DQ UT WOS:000313128600014 PM 23042303 ER PT J AU La Maestra, S Micale, RT De Flora, S D'Agostini, F Ganchev, G Iltcheva, M Petkov, N Steele, VE Balansky, R AF La Maestra, Sebastiano Micale, Rosanna T. De Flora, Silvio D'Agostini, Francesco Ganchev, Gancho Iltcheva, Marietta Petkov, Nikolay Steele, Vernon E. Balansky, Roumen TI DNA damage in exfoliated cells and histopathological alterations in the urinary tract of mice exposed to cigarette smoke and treated with chemopreventive agents SO CARCINOGENESIS LA English DT Article ID ACTIVATED-RECEPTOR-GAMMA; INDUCED MAMMARY CANCERS; INDUCED LUNG-TUMORS; BLADDER-CANCER; UROTHELIAL CELLS; COMET ASSAY; PPAR AGONISTS; PIOGLITAZONE; CARCINOGENESIS; LIVER AB Cigarette smoke (CS) is convincingly carcinogenic in mice when exposure starts at birth. We investigated the induction and modulation of alterations in the kidney and urinary bladder of CS-exposed mice. A total of 484 strain H Swiss mice were either sham-exposed or exposed since birth to mainstream CS (MCS) for 4 months. Dietary agents, including myo-inositol, suberoylanilide hydroxamic acid, bexarotene, pioglitazone and a combination of bexarotene and pioglitazone, were administered after weaning. Comet analyses showed that, after 2 and 4 months, MCS causes DNA damage in exfoliated urothelial cells, which can be prevented by myo-inositol and the peroxisome proliferator-activated receptor- ligand pioglitazone. After 7 months, the 17.6% of MCS-exposed male mice exhibited lesions of the urinary tract versus the 6.1% of sham-exposed mice, which emphasizes the role of sex hormones in urinary tract carcinogenesis. Myo-inositol and the RXR-specific retinoid bexarotene did not affect these alterations. The histone deacetylase inhibitor suberoylanilide hydroxamic acid (Vorinostat) increased the incidence of kidney epithelium hyperplasia. Pioglitazone significantly enhanced the incidence of kidney lesions as compared with mice exposed to MCS only, indicating possible adverse effects of this antidiabetic drug, which were lost upon combination with bexarotene according to a combined chemoprevention strategy. RXR is a heterodymeric partner for peroxisome proliferator-activated receptor-, thereby modulating the expression of multiple target genes. In conclusion, there is contrast between the ability of pioglitazone to inhibit DNA damage in exfoliated cells and the alterations induced in the urinary tract of MCS-exposed mice, suggesting the occurrence of non-genotoxic mechanisms for this drug. C1 [La Maestra, Sebastiano; Micale, Rosanna T.; De Flora, Silvio; D'Agostini, Francesco; Balansky, Roumen] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy. [Ganchev, Gancho; Iltcheva, Marietta; Petkov, Nikolay; Balansky, Roumen] Natl Oncol Ctr, Sofia 1756, Bulgaria. [Steele, Vernon E.] NCI, Rockville, MD 20892 USA. RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy. EM sdf@unige.it FU US National Cancer Institute [N01-CN53301]; Bulgarian Ministry of Youth and Science (National Science Fund); Hasumi International Foundation FX US National Cancer Institute (contract N01-CN53301); Bulgarian Ministry of Youth and Science (National Science Fund); Hasumi International Foundation. NR 63 TC 9 Z9 9 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2013 VL 34 IS 1 BP 183 EP 189 DI 10.1093/carcin/bgs314 PG 7 WC Oncology SC Oncology GA 065DQ UT WOS:000313128600024 PM 23042096 ER PT J AU Yang, RL Liu, Y Kelk, P Qu, CY Akiyama, K Chen, C Atsuta, I Chen, WJ Zhou, YH Shi, ST AF Yang, Ruili Liu, Yi Kelk, Peyman Qu, Cunye Akiyama, Kentaro Chen, Chider Atsuta, Ikiru Chen, WanJun Zhou, Yanheng Shi, Songtao TI A subset of IL-17(+) mesenchymal stem cells possesses anti-Candida albicans effect SO CELL RESEARCH LA English DT Article DE stem cell biology; development; immunity; molecular pathogenesis ID INTERLEUKIN-17 FAMILY-MEMBERS; VERSUS-HOST-DISEASE; REGULATORY T-CELLS; STROMAL CELLS; IMMUNOSUPPRESSIVE PROPERTIES; RESPONSES; T(H)17; BETA; DIFFERENTIATION; MICE AB Bone marrow mesenchymal stem cells (MSCs) comprise a heterogeneous population of postnatal progenitor cells with profound immunomodulatory properties, such as upregulation of Foxp3(+) regulatory T cells (Tregs) and downregulation of Th17 cells. However, it is unknown whether different MSC subpopulations possess the same range of immunomodulatory function. Here, we show that a subset of single colony-derived MSCs producing IL-17 is different from bulk MSC population in that it cannot upregulate Tregs, downregulate Th17 cells, or ameliorate disease phenotypes in a colitis mouse model. Mechanistically, we reveal that IL-17, produced by these MSCs, activates the NF kappa B pathway to downregulate TGF-beta production in MSCs, resulting in abolishment of MSC-based immunomodulation. Furthermore, we show that NF kappa B is able to directly bind to TGF-beta promoter region to regulate TGF-beta expression in MSCs. Moreover, these IL-17(+) MSCs possess anti-Candida albicans growth effects in vitro and therapeutic effect in C. albicans-infected mice. In summary, this study shows that MSCs contain an IL-17(+) subset capable of inhibiting C. albicans growth, but attenuating MSC-based immunosuppression via NF kappa B-mediated downregulation of TGF-beta. C1 [Yang, Ruili; Zhou, Yanheng] Peking Univ, Sch & Hosp Stomatol, Dept Orthodont, Beijing 100081, Peoples R China. [Yang, Ruili; Liu, Yi; Kelk, Peyman; Qu, Cunye; Akiyama, Kentaro; Chen, Chider; Atsuta, Ikiru; Shi, Songtao] Univ So Calif, Ostrow Sch Dent, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. [Chen, WanJun] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Shi, ST (reprint author), Univ So Calif, Ostrow Sch Dent, Ctr Craniofacial Mol Biol, 2250 Alcazar St,CSA 103, Los Angeles, CA 90033 USA. EM yanhengzhou@gmail.com; songtaos@usc.edu RI Chen, Chider/L-9880-2016; OI Chen, Chider/0000-0003-2899-1208; Kelk, Peyman/0000-0003-1594-1738 FU National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Department of Health and Human Services [R01DE017449, R01 DE019932, R01 DE019413]; Ministry of Science and Technology of China [2010DFB32980]; NIDCR, NIH FX This work was supported by grants from the National Institute of Dental and Craniofacial Research (NIDCR), National Institutes of Health (NIH), Department of Health and Human Services (R01DE017449, R01 DE019932, and R01 DE019413 to S S), the Ministry of Science and Technology of China (2010DFB32980 to Y Z), and the Intramural Research Program of NIDCR, NIH (to W J C). NR 46 TC 17 Z9 19 U1 0 U2 16 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2013 VL 23 IS 1 SI SI BP 107 EP 121 DI 10.1038/cr.2012.179 PG 15 WC Cell Biology SC Cell Biology GA 066BL UT WOS:000313194700014 PM 23266891 ER PT J AU Nagaoka, T Karasawa, H Turbyville, T Rangel, MC Castro, NP Gonzales, M Baker, A Seno, M Lockett, S Greer, YE Rubin, JS Salomon, DS Bianco, C AF Nagaoka, Tadahiro Karasawa, Hideaki Turbyville, Thomas Rangel, Maria-Cristina Castro, Nadia P. Gonzales, Monica Baker, Alyson Seno, Masaharu Lockett, Stephen Greer, Yoshimi E. Rubin, Jeffrey S. Salomon, David S. Bianco, Caterina TI Cripto-1 enhances the canonical Wnt/beta-catenin signaling pathway by binding to LRP5 and LRP6 co-receptors SO CELLULAR SIGNALLING LA English DT Article DE Cripto-1; Wnt signaling; beta-Catenin; LRP5; LRP6 ID MAMMARY EPITHELIAL-CELLS; BETA-CATENIN; MESENCHYMAL TRANSITION; TERATOCARCINOMA CELLS; EXPRESSION; GENE; CANCER; GLYCOSYLPHOSPHATIDYLINOSITOL; INTERNALIZATION; PROTEIN AB Cripto-1 is implicated in multiple cellular events, including cell proliferation, motility and angiogenesis, through the activation of an intricate network of signaling pathways. A crosstalk between Cripto-1 and the canonical Wnt/beta-catenin signaling pathway has been previously described. In fact, Cripto-1 is a downstream target gene of the canonical Wnt/beta-catenin signaling pathway in the embryo and in colon cancer cells and T-cell factor (Tcf)/lymphoid enhancer factor binding sites have been identified in the promoter and the first intronic region of the mouse and human Cripto-1 genes. We now demonstrate that Cripto-1 modulates signaling through the canonical Wnt/beta-catenin/Tcf pathway by binding to the Wnt co-receptors low-density lipoprotein receptor-related protein (LRP) 5 and LRP6, which facilitates Wnt3a binding to LRP5 and LRP6. Cripto-1 functionally enhances Wnt3a signaling through cytoplasmic stabilization of beta-catenin and elevated beta-catenin/Tcf transcriptional activation. Conversely, Wnt3a further increases Cripto-1 stimulation of migration, invasion and colony formation in soft agar of HC11 mouse mammary epithelial cells, indicating that Cripto-1 and the canonical Wnt/beta-catenin signaling co-operate in regulating motility and in vitro transformation of mammary epithelial cells. Published by Elsevier Inc. C1 [Nagaoka, Tadahiro; Karasawa, Hideaki; Rangel, Maria-Cristina; Castro, Nadia P.; Gonzales, Monica; Baker, Alyson; Salomon, David S.; Bianco, Caterina] Frederick Natl Lab Canc Res, Lab Canc Prevent, Tumor Growth Factor Sect, Frederick, MD 21702 USA. [Turbyville, Thomas; Lockett, Stephen] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Opt Microscopy & Anal Lab, Frederick, MD 21702 USA. [Seno, Masaharu] Okayama Univ, Grad Sch Nat Sci & Technol, Lab Nanobiotechnol, Okayama 7008530, Japan. [Greer, Yoshimi E.; Rubin, Jeffrey S.] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Salomon, DS (reprint author), Frederick Natl Lab Canc Res, Lab Canc Prevent, Tumor Growth Factor Sect, 1050 Boyles St,Bldg 560,Room 12-46, Frederick, MD 21702 USA. EM salomond@mail.nih.gov; biancoc@mailnih.gov RI Rangel, Maria Cristina/P-7216-2014; SENO, Masaharu /B-2092-2011 OI Rangel, Maria Cristina/0000-0002-8002-9617; SENO, Masaharu /0000-0001-8547-6259 FU National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX We thank Drs. Michele Sanicola, Xi He, Matthew Warman, Roel Nusse and Akira Kikuchi for providing the materials. This work was supported by the National Institutes of Health intramural funding. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 47 TC 17 Z9 19 U1 0 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2013 VL 25 IS 1 BP 178 EP 189 DI 10.1016/j.cellsig.2012.09.024 PG 12 WC Cell Biology SC Cell Biology GA 058EM UT WOS:000312616900021 PM 23022962 ER PT J AU Venkatesan, B Valente, AJ Das, NA Carpenter, AJ Yoshida, T Delafontaine, JL Siebenlist, U Chandrasekar, B AF Venkatesan, Balachandar Valente, Anthony J. Das, Nitin A. Carpenter, Andrea J. Yoshida, Tadashi Delafontaine, Jean-Luc Siebenlist, Ulrich Chandrasekar, Bysani TI CIKS (Act1 or TRAF3IP2) mediates high glucose-induced endothelial dysfunction SO CELLULAR SIGNALLING LA English DT Article DE Hyperglycemia; Oxidative stress; TRAF3IP2; Act1; Endothelial dysfunction ID NF-KAPPA-B; OXIDATION PROTEIN PRODUCTS; GLYCATION END-PRODUCTS; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; AIRWAY INFLAMMATION; ADHESION MOLECULE-1; DIABETES-MELLITUS; ICAM-1 EXPRESSION; MONOCYTE ADHESION AB Hyperglycemia-induced endothelial dysfunction is characterized by enhanced inflammatory cytokine and adhesion molecule expression, and endothelial-monocyte adhesion. The adapter molecule CIKS (connection to IKK and SAPK/JNK; also known as Act1 or TRAF3IP2) is an upstream regulator of NF-kappa B and AP-1, and plays a role in inflammation and injury. Here we show that high glucose (FIG; 25 mM vs. 5 mM n-glucose)-induced endothelial-monocyte adhesion and inhibition of endothelial cell (EC) migration were both reversed by CIKS knockdown. In EC, HG induced CIKS mRNA and protein expression via DPI-inhibitable Nox4-dependent ROS generation. Further, HG induced CIKS transcription and enhanced CIKS promoter-dependent reporter gene activation via Nox4, ROS, AP-1 and C/EBP. Coimmunoprecipitation and immunoblotting revealed CIKS/IKK beta/JNK physical association under basal conditions that was enhanced by HG treatment. Importantly. CIKS knockdown inhibited HG-induced (i) IKK beta and JNK phosphorylation, (ii) p65 and c-Jun nuclear translocation, and (iii) NF-kappa B- and AP-1-dependent proinflammatory cytokine, chemokine, and adhesion molecule expression. Similar to HG, the deleterious metabolic products of chronic hyperglycemia, AGE-HSA, AOPPs-HSA and oxLDL, also induced CIKS-dependent endothelial dysfunction. Notably, aortas from streptozotocin-induced and the autoimmune type 1 diabetic NOD and Akita mice showed enhanced DPI-inhibitable ROS generation and CIKS expression. Since CIKS mediates high glucose-induced NF-kappa B and AP-1-dependent inflammatory signaling and endothelial dysfunction, targeting CIKS may delay progression of vascular diseases during diabetes mellitus and atherosclerosis. (C) 2012 Elsevier Inc. All rights reserved. C1 [Venkatesan, Balachandar; Yoshida, Tadashi; Delafontaine, Jean-Luc; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA. [Venkatesan, Balachandar; Chandrasekar, Bysani] SE Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA. [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Das, Nitin A.; Carpenter, Andrea J.] Univ Texas Hlth Sci Ctr San Antonio, Dept Cardiothorac Surg, San Antonio, TX 78229 USA. [Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave,SL 48, New Orleans, LA 70112 USA. EM bchandra@tulane.edu OI Yoshida, Tadashi/0000-0002-4544-1497 FU VA Office of Research and Development Biomedical Laboratory Research and Development Service [1IO1BX000246]; NIH/NHLBI [HL-86787]; Department of Veterans Affairs FX BC is a recipient of the Department of Veterans Affairs Research Career Scientist award, and is supported by VA Office of Research and Development Biomedical Laboratory Research and Development Service Award 1IO1BX000246 and the NIH/NHLBI grant HL-86787. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government. NR 45 TC 17 Z9 23 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2013 VL 25 IS 1 BP 359 EP 371 DI 10.1016/j.cellsig.2012.10.009 PG 13 WC Cell Biology SC Cell Biology GA 058EM UT WOS:000312616900040 PM 23085260 ER PT J AU Guerard, F Lee, YS Tripier, R Szajek, LP Deschamps, JR Brechbiel, MW AF Guerard, Francois Lee, Yong-Sok Tripier, Raphael Szajek, Lawrence P. Deschamps, Jeffrey R. Brechbiel, Martin W. TI Investigation of Zr(IV) and Zr-89(IV) complexation with hydroxamates: progress towards designing a better chelator than desferrioxamine B for immuno-PET imaging SO CHEMICAL COMMUNICATIONS LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; MONOCLONAL-ANTIBODIES; CHEMISTRY; ACID; ZIRCONIUM(IV); IRON(III); CANCER AB Single crystal X-ray diffraction shows that Zr(IV) forms an octa-coordinated complex with 4 bidentate hydroxamates whose solution structures were investigated by utilizing density functional theory at the level of B3LYP/DGDZVP. Stability constants obtained by potentiometry were in accordance with the tendency observed when radiolabeling with Zr-89. C1 [Guerard, Francois; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Lee, Yong-Sok] NIH, Ctr Mol Modeling, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Tripier, Raphael] Univ Brest, CNRS, UMR 6521, Lab Chim Electrochim Mol & Chim Analyt, F-29200 Brest, France. [Szajek, Lawrence P.] NIH, Positron Emiss Tomog Dept, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. [Deschamps, Jeffrey R.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov OI Deschamps, Jeffrey/0000-0001-5845-0010; Guerard, Francois/0000-0001-9795-2785 FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research; Center for Information Technology; NIDA [Y1-DA1101]; Naval Research Laboratory (NRL) [Y1-DA1101] FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research and the Center for Information Technology. The quantum chemical study utilized PC/LINUX clusters at the Center for Molecular Modeling of the NIH (http://cit.nih.gov). X-ray crystallographic studies were supported by NIDA through Interagency Agreement #Y1-DA1101 with the Naval Research Laboratory (NRL). NR 18 TC 38 Z9 38 U1 3 U2 53 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1359-7345 J9 CHEM COMMUN JI Chem. Commun. PY 2013 VL 49 IS 10 BP 1002 EP 1004 DI 10.1039/c2cc37549d PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 064FW UT WOS:000313059300015 PM 23250287 ER PT J AU Khan, AM Lubitz, SA Sullivan, LM Sun, JX Levy, D Vasan, RS Magnani, JW Ellinor, PT Benjamin, EJ Wang, TJ AF Khan, Abigail May Lubitz, Steven A. Sullivan, Lisa M. Sun, Jenny X. Levy, Daniel Vasan, Ramachandran S. Magnani, Jared W. Ellinor, Patrick T. Benjamin, Emelia J. Wang, Thomas J. TI Low Serum Magnesium and the Development of Atrial Fibrillation in the Community The Framingham Heart Study SO CIRCULATION LA English DT Article DE arrhythmias, cardiac; epidemiology; atrial fibrillation; magnesium ID ARTERY-BYPASS SURGERY; INTRAVENOUS MAGNESIUM; CORONARY-ARTERY; CARDIAC-SURGERY; METAANALYSIS; ARRHYTHMIAS; POTASSIUM; HYPOMAGNESEMIA; DISEASE; ASSOCIATION AB Background-Low serum magnesium has been linked to increased risk of atrial fibrillation (AF) after cardiac surgery. It is unknown whether hypomagnesemia predisposes to AF in the community. Methods and Results-We studied 3530 participants (mean age, 44 years; 52% women) from the Framingham Offspring Study who attended a routine examination and were free of AF and cardiovascular disease. We used Cox proportional hazard regression analysis to examine the association between serum magnesium at baseline and risk of incident AF. Analyses were adjusted for conventional AF risk factors, use of antihypertensive medications, and serum potassium. During up to 20 years of follow-up, 228 participants developed AF. Mean serum magnesium was 1.88 mg/dL. The age- and sex-adjusted incidence rate of AF was 9.4 per 1000 person-years (95% confidence interval, 6.7-11.9) in the lowest quartile of serum magnesium (<= 1.77 mg/dL) compared with 6.3 per 1000 person-years (95% confidence interval, 4.1-8.4) in the highest quartile (>= 1.99 mg/dL). In multivariable-adjusted models, individuals in the lowest quartile of serum magnesium were similar to 50% more likely to develop AF (adjusted hazard ratio, 1.52; 95% confidence interval, 1.00-2.31; P=0.05) compared with those in the upper quartiles. Results were similar after the exclusion of individuals on diuretics. Conclusions-Low serum magnesium is moderately associated with the development of AF in individuals without cardiovascular disease. Because hypomagnesemia is common in the general population, a link with AF may have potential clinical implications. Further studies are warranted to confirm our findings and to elucidate the underlying mechanisms. (Circulation. 2013;127:33-38.) C1 [Sullivan, Lisa M.; Levy, Daniel; Vasan, Ramachandran S.; Benjamin, Emelia J.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Khan, Abigail May] Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Lubitz, Steven A.; Ellinor, Patrick T.; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. [Sullivan, Lisa M.; Sun, Jenny X.] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.; Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA. RP Benjamin, EJ (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. EM Emelia@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute's Framingham Heart Study [N01-HC-25195]; National Institutes of Health [N01-HC-25195, 6R01-NS17950, 1R01HL092577, 1RC1HL101056, 1R01HL102214]; Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University FX This work was supported in part by the National Heart, Lung and Blood Institute's Framingham Heart Study (contract No. N01-HC-25195); National Institutes of Health grants and contracts N01-HC-25195, 6R01-NS17950, 1R01HL092577, 1RC1HL101056, and 1R01HL102214; and the Evans Center for Interdisciplinary Biomedical Research ARC on Atrial Fibrillation at Boston University (http://www.bumc.bu.edu/evanscenteribr/). NR 37 TC 38 Z9 39 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 JAN 1 PY 2013 VL 127 IS 1 BP 33 EP 38 DI 10.1161/CIRCULATIONAHA.111.082511 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 064EA UT WOS:000313052900020 PM 23172839 ER PT J AU Liu, NW Sanford, T Srinivasan, R Liu, JL Khurana, K Aprelikova, O Valero, V Bechert, C Worrell, R Pinto, PA Yang, YF Merino, M Linehan, WM Bratslavsky, G AF Liu, Nick W. Sanford, Thomas Srinivasan, Ramaprasad Liu, Jack L. Khurana, Kiranpreet Aprelikova, Olga Valero, Vladimir Bechert, Charles Worrell, Robert Pinto, Peter A. Yang, Youfeng Merino, Maria Linehan, W. Marston Bratslavsky, Gennady TI Impact of Ischemia and Procurement Conditions on Gene Expression in Renal Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PREDICT SURVIVAL; BREAST-CANCER; C-FOS; TISSUE; MICROARRAY; TUMOR; TIME; RNA; PROGNOSIS; SPECIMENS AB Purpose: Previous studies have shown that ischemia alters gene expression in normal and malignant tissues. There are no studies that evaluated effects of ischemia in renal tumors. This study examines the impact of ischemia and tissue procurement conditions on RNA integrity and gene expression in renal cell carcinoma. Experimental Design: Ten renal tumors were resected without renal hilar clamping from 10 patients with renal clear cell carcinoma. Immediately after tumor resection, a piece of tumor was snap frozen. Remaining tumor samples were stored at 4 degrees C, 22 degrees C, and 37 degrees C and frozen at 5, 30, 60, 120, and 240 minutes. Histopathologic evaluation was conducted on all tissue samples, and only those with greater than 80% tumor were selected for further analysis. RNA integrity was confirmed by electropherograms and quantitated using RNA integrity number index. Altered gene expression was assessed by paired, two-sample t test between the zero time point and aliquots from various conditions obtained from the same tumor. Results: One hundred and forty microarrays were conducted. Some RNA degradation was observed 240 minutes after resection at 37 degrees C. The expression of more than 4,000 genes was significantly altered by ischemia times or storage conditions. The greatest gene expression changes were observed with longer ischemia time and warmer tissue procurement conditions. Conclusion: RNA from kidney cancer remains intact for up to 4 hours post surgical resection regardless of storage conditions. Despite excellent RNA preservation, time after resection and procurement conditions significantly influence gene expression profiles. Meticulous attention to preacquisition variables is of paramount importance for accurate tumor profiling. Clin Cancer Res; 19(1); 42-49. (C) 2012 AACR. C1 [Bratslavsky, Gennady] SUNY Syracuse, Upstate Med Univ, Dept Urol, Syracuse, NY 13210 USA. [Liu, Nick W.; Sanford, Thomas; Srinivasan, Ramaprasad; Liu, Jack L.; Khurana, Kiranpreet; Valero, Vladimir; Worrell, Robert; Pinto, Peter A.; Yang, Youfeng; Linehan, W. Marston; Bratslavsky, Gennady] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Aprelikova, Olga] NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. [Bechert, Charles; Merino, Maria] NCI, Surg Pathol Branch, NIH, Bethesda, MD 20892 USA. RP Bratslavsky, G (reprint author), SUNY Syracuse, Upstate Med Univ, Dept Urol, 750 E Adams St, Syracuse, NY 13210 USA. EM bratslag@upstate.edu OI Khurana, Kiranpreet/0000-0002-2750-4909 FU NIH FX This study was supported entirely by the NIH Intramural Research Grant. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 34 TC 16 Z9 16 U1 0 U2 5 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 JAN 1 PY 2013 VL 19 IS 1 BP 42 EP 49 DI 10.1158/1078-0432.CCR-12-2606 PG 8 WC Oncology SC Oncology GA 064DM UT WOS:000313051100007 PM 23136194 ER PT J AU Rogal, SS Pinsky, PF Schoen, RE AF Rogal, Shari S. Pinsky, Paul F. Schoen, Robert E. TI Relationship Between Detection of Adenomas by Flexible Sigmoidoscopy and Interval Distal Colorectal Cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Sigmoidoscopy Quality; Adenoma Detection Rate; Colorectal Cancer Prevention; Epidemiology ID SCREENING TRIAL; QUALITY INDICATORS; COLONOSCOPY; PERFORMANCE AB BACKGROUND & AIMS: Low rates of adenoma detection by colonoscopy have been associated with increased rates of interval colorectal cancer. We evaluated the relationship between the rate of adenoma detection by flexible sigmoidoscopy and interval distal colorectal cancer. METHODS: We analyzed data from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer screening trial, which used flexible sigmoidoscopy as a colorectal cancer screening modality (46,835 subjects; 66,711 examinations by 93 examiners). An adenoma detection rate was defined for each examiner as the number of examinations that identified adenomas (confirmed by pathology analysis) divided by the total number of screening examinations. Interval cancers were defined as cancers presumed detectable but not detected, which was based on the stage at diagnosis and the elapsed time from screening to diagnosis. RESULTS: The Prostate, Lung, Colorectal, and Ovarian Cancer study identified 32 interval distal cancers. The incidence of interval cancer for individuals screened by examiners in the lowest quartile of distal adenoma detection (2.0%-7.2%) was 9.0/10,000 examinations, whereas the incidence of interval cancers was lower among individuals whose examiners were in higher quartiles of adenoma detection, ranging from 3.0 to 5.4/10,000 examinations. The odds of interval distal cancer were significantly increased for patients of examiners in the lowest quartile of distal adenoma detection (<7.2%), with an adjusted odds ratio of 2.4 (95% confidence interval, 1.1 5.0; P = .02). CONCLUSIONS: Lower levels of adenoma detection by flexible sigmoidoscopy increase the risk for interval distal cancer. Detection of distal adenomas is a marker of the performance quality of flexible sigmoidoscopy. The parent study is registered under ClinicalTrials.gov, number NCT00002540. C1 [Rogal, Shari S.; Schoen, Robert E.] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA. [Pinsky, Paul F.] NCI, Canc Prevent Div, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Schoen, RE (reprint author), C Wing PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM rschoen@pitt.edu FU NIH [T-32]; National Cancer Institute [NO1-CN255] FX Shari Rogal was supported by an NIH T-32 grant and Dr Robert E. Schoen by contract NO1-CN255 from the National Cancer Institute. NR 17 TC 17 Z9 17 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2013 VL 11 IS 1 BP 73 EP 78 DI 10.1016/j.cgh.2012.08.002 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 064YU UT WOS:000313112900017 PM 22902761 ER PT J AU Berger, VW AF Berger, Vance W. TI Efficacy and Degree of Bias in Knee Injury Prevention Studies: A Systematic Review of RCTs SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Letter C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Berger, Vance W.] UMBC, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vance917@gmail.com NR 5 TC 1 Z9 1 U1 0 U2 4 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 JAN PY 2013 VL 471 IS 1 BP 338 EP 339 DI 10.1007/s11999-012-2675-y PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 059PB UT WOS:000312716400051 PM 23129470 ER PT J AU Berger, VW AF Berger, Vance W. TI Efficacy and Degree of Bias in Knee Injury Prevention Studies: A Systematic Review of RCTs SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Letter ID TRIALS C1 [Berger, Vance W.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA. [Berger, Vance W.] UMBC, Bethesda, MD 20892 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vance917@gmail.com NR 8 TC 0 Z9 0 U1 0 U2 2 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 JAN PY 2013 VL 471 IS 1 BP 341 EP 342 DI 10.1007/s11999-012-2688-6 PG 2 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 059PB UT WOS:000312716400053 PM 23129476 ER PT J AU Colvis, CM Devaney, S Brady, LS Hudson, KL AF Colvis, C. M. Devaney, S. Brady, L. S. Hudson, K. L. TI Partnering for Therapeutics Discovery SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB The Discovering New Therapeutic Uses for Existing Molecules pilot program, led by the National Center for Advancing Translational Sciences (NCATS), uses innovative strategies such as crowdsourcing and template agreements to match researchers with a selection of molecular compounds from industry in order to test ideas for new therapeutic uses. Awardees will have the opportunity to validate and de-risk the targets of already well-developed compounds with the ultimate goal of identifying promising new treatments for patients. C1 [Colvis, C. M.; Devaney, S.; Brady, L. S.; Hudson, K. L.] NIH, Bethesda, MD 20892 USA. RP Colvis, CM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM ccolvis@mail.nih.gov NR 4 TC 3 Z9 3 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2013 VL 93 IS 1 BP 24 EP 25 DI 10.1038/clpt.2012.188 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 058EZ UT WOS:000312618200019 PM 23187876 ER PT J AU Wormser, GP Schriefer, M Aguero-Rosenfeld, ME Levin, A Steere, AC Nadelman, RB Nowakowski, J Marques, A Johnson, BJB Dumler, JS AF Wormser, Gary P. Schriefer, Martin Aguero-Rosenfeld, Maria E. Levin, Andrew Steere, Allen C. Nadelman, Robert B. Nowakowski, John Marques, Adriana Johnson, Barbara J. B. Dumler, J. Stephen TI Single-tier testing with the C6 peptide ELISA kit compared with two-tier testing for Lyme disease SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Lyme disease; Borrelia burgdorferi; Serology; C6 ELISA ID LINKED-IMMUNOSORBENT-ASSAY; IMMUNODOMINANT CONSERVED REGION; BORRELIA-BURGDORFERI; ANTIBODY-RESPONSES; SERODIAGNOSIS; RECOMBINANT; VLSE; ANTIGENS; DIAGNOSIS; PROTEIN AB For the diagnosis of Lyme disease, the 2-tier serologic testing protocol for Lyme disease has a number of shortcomings including low sensitivity in early disease; increased cost, time, and labor; and subjectivity in the interpretation of immunoblots. In this study, the diagnostic accuracy of a single-tier commercial C6 ELISA kit was compared with 2-tier testing. The results showed that the C6 ELISA was significantly more sensitive than 2-tier testing with sensitivities of 66.5% (95% confidence interval [CI] 61.7-71.1) and 35.2% (95% CI 30.6-40.1), respectively (P < 0.001) in 403 sera from patients with erythema migrans. The C6 ELISA had sensitivity statistically comparable to 2-tier testing in sera from Lyme disease patients with early neurologic manifestations (88.6% versus 77.3%, P = 0.13) or arthritis (98.3% versus 95.6%, P = 0.38). The specificities of C6 ELISA and 2-tier testing in over 2200 blood donors, patients with other conditions, and Lyme disease vaccine recipients were found to be 98.9% and 99.5%, respectively (P < 0.05, 95% CI surrounding the 0.6 percentage point difference of 0.04 to 1.15). In conclusion, using a reference standard of 2-tier testing, the C6 ELISA as a single-step serodiagnostic test provided increased sensitivity in early Lyme disease with comparable sensitivity in later manifestations of Lyme disease. The C6 ELISA had slightly decreased specificity. Future studies should evaluate the performance of the C6 ELISA compared with 2-tier testing in routine clinical practice. (C) 2013 Elsevier Inc. All rights reserved. C1 [Wormser, Gary P.; Nadelman, Robert B.; Nowakowski, John] New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. [Schriefer, Martin; Johnson, Barbara J. B.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Ft Collins, CO 80521 USA. [Aguero-Rosenfeld, Maria E.] New York Univ Langone Med Ctr, Dept Pathol, New York, NY 10016 USA. [Levin, Andrew] Immunetics Inc, Boston, MA 02210 USA. [Steere, Allen C.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. [Marques, Adriana] NIAID, NIH, Bethesda, MD 20892 USA. [Dumler, J. Stephen] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. RP Wormser, GP (reprint author), New York Med Coll, Div Infect Dis, Valhalla, NY 10595 USA. EM gary_wormser@nymc.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [R43 AI051926]; Intramural Research Program of the National Institute of Health (NIH) FX This work was supported by Public Health Service Grant R43 AI051926 from the National Institute of Allergy and Infectious Diseases (NIAID). It was also supported in part by the Intramural Research Program of the National Institute of Health (NIH). NR 45 TC 39 Z9 39 U1 1 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD JAN PY 2013 VL 75 IS 1 BP 9 EP 15 DI 10.1016/j.diagmicrobio.2012.09.003 PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 059CY UT WOS:000312683200003 PM 23062467 ER PT J AU Kim, WG Zhu, XG Kim, DW Zhang, LS Kebebew, E Cheng, SY AF Kim, Won Gu Zhu, Xuguang Kim, Dong Wook Zhang, Lisa Kebebew, Electron Cheng, Sheue-yann TI Reactivation of the Silenced Thyroid Hormone Receptor beta Gene Expression Delays Thyroid Tumor Progression SO ENDOCRINOLOGY LA English DT Article ID CARCINOMA CELL-LINES; BREAST-CANCER; NUCLEAR RECEPTORS; RETINOIC ACID; MOUSE MODEL; TR-BETA; GROWTH; MUTATION; 5-AZA-2'-DEOXYCYTIDINE; HYPERMETHYLATION AB That a knock-in mouse harboring a dominant-negative thyroid hormone receptor (TR)-beta (Thrb) mutation develops metastatic thyroid cancer strongly suggests the involvement of TR beta in carcinogenesis. Epigenetic silencing of the THRB gene is common in human cancers. The aim of the present study was to determine how DNA methylation affected the expression of the THRB gene in differentiated thyroid cancer (DTC) and how reexpression of the THRB gene attenuated the cancer phenotypes. We used methylation-specific PCR to examine the expression and promoter methylation of the THRB gene in DTC tissues. Thyroid cancer cells with hypermethylated THRB were treated with the demethylating agents 5'-aza-2'-deoxycytidine (5'-aza-CdR) and zebularine to evaluate their impact on the cancer cell phenotypes. THRB mRNA expression in DTC was 90% lower than in normal controls, and this decrease was associated with a higher tumor/lymph node staging. The promoter methylation level of the THRB gene had a significant negative correlation with the expression level of the THRB gene. Treatment of FTC-236 cells with 5'-aza-CdR or zebularine induced reexpression of the THRB gene and inhibited cell proliferation and migration. FTC-236 cells stably expressing TR beta exhibited lower cell proliferation and migration through inhibition of beta-catenin signaling pathways compared with FTC-236 without TR beta. 5'-Aza-CdR also led to suppression of tumor growth in an in vivo xenograft model using FTC-236 cells consistent with the cell-based studies. These finding indicate that TR beta is a tumor suppressor and could be tested as a potential therapeutic target. (Endocrinology 154: 25-35, 2013) C1 [Kim, Won Gu; Zhu, Xuguang; Kim, Dong Wook; Cheng, Sheue-yann] NCI, Mol Biol Lab, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Surg Branch, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov OI Kim, Won Gu/0000-0002-8404-7759 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX This work was supported by the Intramural Research Program at the Center for Cancer Research, National Cancer Institute, National Institutes of Health. NR 36 TC 16 Z9 17 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 25 EP 35 DI 10.1210/en.2012-1728 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500005 PM 23183175 ER PT J AU Stroth, N Kuri, BA Mustafa, T Chan, SA Smith, CB Eiden, LE AF Stroth, N. Kuri, B. A. Mustafa, T. Chan, S. -A. Smith, C. B. Eiden, L. E. TI PACAP Controls Adrenomedullary Catecholamine Secretion and Expression of Catecholamine Biosynthetic Enzymes at High Splanchnic Nerve Firing Rates Characteristic of Stress Transduction in Male Mice SO ENDOCRINOLOGY LA English DT Article ID CYCLASE-ACTIVATING POLYPEPTIDE; ADRENAL CHROMAFFIN CELLS; MESSENGER-RNA LEVELS; RECEPTOR ANTAGONIST; MEDULLA; STIMULATION; GALANIN; ENKEPHALIN; DISORDERS; RESPONSES AB The neuropeptide PACAP (pituitary adenylate cyclase-activating polypeptide) is a cotransmitter of acetylcholine at the adrenomedullary synapse, where autonomic regulation of hormone secretion occurs. We have previously reported that survival of prolonged metabolic stress in mice requires PACAP-dependent biosynthesis and secretion of adrenomedullary catecholamines (CAs). In the present experiments, we show that CA secretion evoked by direct high-frequency stimulation of the splanchnic nerve is abolished in native adrenal slices from male PACAP-deficient mice. Further, we demonstrate that PACAP is both necessary and sufficient for CA secretion ex vivo during stimulation protocols designed to mimic stress. In vivo, up-regulation of transcripts encoding adrenomedullary CA-synthesizing enzymes (tyrosine hydroxylase, phenylethanolamine N-methyltransferase) in response to both psychogenic and metabolic stressors (restraint and hypoglycemia) is PACAP-dependent. Stressor-induced alteration of the adrenomedullary secretory cocktail also appears to require PACAP, because up-regulation of galanin mRNA is abrogated in male PACAP-deficient mice. Wefurther show that hypoglycemia-induced corticosterone secretion is not PACAP-dependent, ruling out the possibility that glucocorticoids are the main mediators of the aforementioned effects. Instead, experiments with bovine chromaffin cells suggest that PACAP acts directly at the level of the adrenal medulla. By integrating prolonged CA secretion, expression of biosynthetic enzymes and production of modulatory neuropeptides such as galanin, PACAP is crucial for adrenomedullary function. Importantly, our results show that PACAP is the dominant adrenomedullary neurotransmitter during conditions of enhanced secretory demand. (Endocrinology 154: 330-339, 2013) C1 [Kuri, B. A.; Chan, S. -A.; Smith, C. B.] Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. [Stroth, N.; Mustafa, T.; Eiden, L. E.] NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Smith, CB (reprint author), Case Western Reserve Univ, Dept Physiol & Biophys, 10900 Euclid Ave, Cleveland, OH 44106 USA. EM cbs16@case.edu; eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X FU National Institute of Mental Health Intramural Research Project [1Z01MH002386]; National Institutes of Health Grant [TS HL07653] FX Work in L.E.E.'s laboratory was supported by National Institute of Mental Health Intramural Research Project 1Z01MH002386. B.A.K. was supported by National Institutes of Health Grant TS HL07653. NR 26 TC 15 Z9 15 U1 0 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 330 EP 339 DI 10.1210/en.2012-1829 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500033 PM 23221599 ER PT J AU Zemkova, H Kucka, M Bjelobaba, I Tomic, M Stojilkovic, SS AF Zemkova, Hana Kucka, Marek Bjelobaba, Ivana Tomic, Melanija Stojilkovic, Stanko S. TI Multiple Cholinergic Signaling Pathways in Pituitary Gonadotrophs SO ENDOCRINOLOGY LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; LUTEINIZING-HORMONE SECRETION; INDUCED CA2+ OSCILLATIONS; MUSCARINIC RECEPTOR; ANTERIOR-PITUITARY; RAT PITUITARY; CHOLINOMIMETIC CARBACHOL; INTERNATIONAL-UNION; POTASSIUM CHANNELS; HAIR-CELLS AB Acetylcholine (ACh) has been established as a paracrine factor in the anterior pituitary gland, but the receptors mediating ACh action and the cell types bearing these receptors have not been identified. Our results showed that the expression of the nicotinic subunits mRNAs followed the order beta 2 > beta 1 = alpha 9 > alpha 4 in cultured rat pituitary cells. The expression of the subunits in immortalized L beta T2 mouse gonadotrophs followed the order beta 2 > alpha 4 = alpha 1. M4 > M3 muscarinic receptor mRNA were also identified in pituitary and L beta T2 cells. The treatment of cultured pituitary cells with GnRH down-regulated the expression of alpha 9 and alpha 4 mRNAs, without affecting the expression of M3 and M4 receptor mRNAs, and ACh did not alter the expression of GnRH receptor mRNA. We also performed double immunostaining to show the expression of beta 2-subunit and M4 receptor proteins in gonadotrophs. Functional nicotinic channels capable of generating an inward current, facilitation of electrical activity, and Ca2+ influx were identified in single gonadotrophs and L beta T2 cells. In both cell types, the M3 receptor-mediated, phospholipase C-dependent Ca2+ mobilization activated an outward apamin-sensitive K+ current and caused hyperpolarization. The activation of M4 receptors by ACh inhibited cAMP production and GnRH-induced LH release in a pertussis toxin-sensitive manner. We concluded that multiple cholinergic receptors are expressed in gonadotrophs and that the main secretory action of ACh is inhibitory through M4 receptor-mediated down-regulation of cAMP production. The expression of nicotinic receptors in vitro compensates for the lack of regular GnRH stimulation of gonadotrophs. (Endocrinology 154: 421-433, 2013) C1 [Zemkova, Hana] Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, CR-14220 Prague 4, Czech Republic. [Zemkova, Hana; Kucka, Marek; Bjelobaba, Ivana; Tomic, Melanija; Stojilkovic, Stanko S.] Eunice Kennedy Shiver Natl Inst Child Hlth & Huma, Sect Cellular Signaling, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Bjelobaba, Ivana] Inst Biol Res Dr Sinisa Stankovic, Dept Neurobiol, Belgrade 11060, Serbia. RP Zemkova, H (reprint author), Acad Sci Czech Republic, Inst Physiol, Dept Cellular & Mol Neuroendocrinol, Videnska 1083, CR-14220 Prague 4, Czech Republic. EM zemkova@biomed.cas.cz; stojilks@mail.nih.gov RI Zemkova, Hana/C-1844-2012; Tomic, Melanija/C-3371-2016 FU Intramural Research Program of the National Institute of Child Health and Human Development; Internal Grant Agency of Academy of Sciences [IAA500110910, P304/12/G069]; Serbian Ministry of Education, Science, and Technological Development [41014] FX This work was supported by the Intramural Research Program of the National Institute of Child Health and Human Development (to M. K., M. T., and S. S. S.), the Internal Grant Agency of Academy of Sciences IAA500110910 and Project Excellence P304/12/G069 (to H.Z.), and the Serbian Ministry of Education, Science, and Technological Development Project 41014 (to I.B.). NR 64 TC 2 Z9 2 U1 3 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 421 EP 433 DI 10.1210/en.2012-1554 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500041 PM 23161872 ER PT J AU Whirledge, S Cidlowski, JA AF Whirledge, Shannon Cidlowski, John A. TI Estradiol Antagonism of Glucocorticoid-Induced GILZ Expression in Human Uterine Epithelial Cells and Murine Uterus SO ENDOCRINOLOGY LA English DT Article ID LEUCINE-ZIPPER GILZ; ESTROGEN-RECEPTOR; RAT UTERUS; EMBRYO IMPLANTATION; GENE-EXPRESSION; IN-VITRO; DEXAMETHASONE; PROLIFERATION; PREGNANCY; RESPONSES AB Sex hormone signaling regulates a variety of functions in the uterine endometrium essential for embryo implantation and immunity. Epithelial cells of the uterine endometrium are the target of the coordinated actions of estradiol (E-2) and progesterone. However, little information exists regarding the interplay of estrogens with glucocorticoids in this tissue. Using the human uterine epithelial cell line ECC1, E-2 was found to antagonize induction of the glucocorticoid-induced leucine zipper (GILZ) gene expression, which is associated with several of the immune-related functions of glucocorticoids. Interestingly, E-2 antagonizes glucocorticoid regulated nascent RNA GILZ expression within 1 h of hormone treatment. Repression of glucocorticoid-induced GILZ expression requires the estrogen receptor (ER), because both treatment with the ER-antagonist ICI 182,780 and small interfering RNA knockdown of ER alpha block E-2's ability to repress GILZ gene expression. Antagonism of glucocorticoid-induced GILZ expression may not be unique to ER alpha, as the ER beta agonist Liquiritigenin is also able to antagonize glucocorticoid signaling. Transcriptional regulation appears to be at the level of promoter binding. Both the glucocorticoid receptor and ER alpha are recruited to regions of the GILZ promoter containing glucocorticoid response elements and the transcriptional start site. Glucocorticoid receptor binding to these regions in the presence of dexamethasone decreases with E-2 treatment. GILZ gene expression was also found to be repressed in the whole mouse uterus treated with a combination of dexamethasone and E-2. Regulation of the antiinflammatory gene GILZ by glucocorticoids and E-2 suggests cross talk between the immune modulating functions of glucocorticoids and the reproductive actions of estradiol signaling. (Endocrinology 154: 499-510, 2013) C1 [Whirledge, Shannon; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, MD F3-07,POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences FX This research was supported by the Intramural Research Program of the National Institutes of Health National Institute of Environmental Health Sciences. NR 45 TC 11 Z9 11 U1 0 U2 12 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 499 EP 510 DI 10.1210/en.2012-1748 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500047 PM 23183181 ER PT J AU Peeters, RP Hernandez, A Ng, L Ma, M Sharlin, DS Pandey, M Simonds, WF St Germain, DL Forrest, D AF Peeters, Robin P. Hernandez, Arturo Ng, Lily Ma, Michelle Sharlin, David S. Pandey, Mritunjay Simonds, William F. St Germain, Donald L. Forrest, Douglas TI Cerebellar Abnormalities in Mice Lacking Type 3 Deiodinase and Partial Reversal of Phenotype by Deletion of Thyroid Hormone Receptor alpha 1 SO ENDOCRINOLOGY LA English DT Article ID DEVELOPING RAT CEREBELLUM; IODOTHYRONINE DEIODINASE; MOUSE CEREBELLUM; SEVERE IMPAIRMENT; NERVOUS-SYSTEM; TARGET GENES; BRAIN; EXPRESSION; HYPOTHYROIDISM; DIFFERENTIATION AB Thyroid hormone serves many functions throughout brain development, but the mechanisms that control the timing of its actions in specific brain regions are poorly understood. In the cerebellum, thyroid hormone controls formation of the transient external germinal layer, which contains proliferative granule cell precursors, subsequent granule cell migration, and cerebellar foliation. We report that the thyroid hormone-inactivating type 3 deiodinase (encoded by Dio3) is expressed in the mouse cerebellum at embryonic and neonatal stages, suggesting a need to protect cerebellar tissues from premature stimulation by thyroid hormone. Dio3(-/-) mice displayed reduced foliation, accelerated disappearance of the external germinal layer, and premature expansion of the molecular layer at juvenile ages. Furthermore, Dio3(-/-) mice exhibited locomotor behavioral abnormalities and impaired ability in descending a vertical pole. To ascertain that these phenotypes resulted from inappropriate exposure to thyroid hormone, thyroid hormone receptor alpha 1 (TR alpha 1) was removed from Dio3(-/-) mice, which substantially corrected the cerebellar and behavioral phenotypes. Deletion of TR alpha 1 did not correct the previously reported small thyroid gland or deafness in Dio3(-/-) mice, indicating that Dio3 controls the activation of specific receptor isoforms in different tissues. These findings suggest that type 3 deiodinase constrains the timing of thyroid hormone action during cerebellar development. (Endocrinology 154: 550-561, 2013) C1 [Peeters, Robin P.] Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Peeters, Robin P.; Ng, Lily; Ma, Michelle; Sharlin, David S.; Forrest, Douglas] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA. [Pandey, Mritunjay; Simonds, William F.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Hernandez, Arturo; St Germain, Donald L.] Dartmouth Med Sch, Dept Med, Lebanon, NH 03756 USA. [Sharlin, David S.] Minnesota State Univ, Dept Biol Sci, Mankato, MN 56001 USA. RP Peeters, RP (reprint author), Erasmus Univ, Med Ctr, Dept Internal Med, Dr Molewaterpl 50,Room Ee502, NL-3015 GE Rotterdam, Netherlands. EM r.peeters@erasmusmc.nl RI Peeters, Robin/P-3603-2014 FU ZonMw VENI Grant [91696017]; Erasmus Medical Center Fellowship; National Institutes of Health (NIH) [5R01DK079946, MH83220]; intramural research program at the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH FX This work was supported by ZonMw VENI Grant 91696017 and an Erasmus Medical Center Fellowship (to R. P. P.), National Institutes of Health (NIH) Grants 5R01DK079946 and MH83220 (to A. H. and D. G.) and by the intramural research program at the National Institute of Diabetes and Digestive and Kidney Diseases at the NIH. NR 56 TC 19 Z9 19 U1 2 U2 10 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2013 VL 154 IS 1 BP 550 EP 561 DI 10.1210/en.2012-1738 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 061SO UT WOS:000312868500052 PM 23161871 ER PT J AU Hu, W Bassig, BA Xu, J Zheng, TZ Zhang, YW Berndt, SI Holford, TR Hosgood, HD Leaderer, B Yeager, M Menashe, I Boyle, P Zou, KY Zhu, Y Chanock, S Lan, Q Rothman, N AF Hu, Wei Bassig, Bryan A. Xu, Jun Zheng, Tongzhang Zhang, Yawei Berndt, Sonja I. Holford, Theodore R. Hosgood, H. Dean, III Leaderer, Brian Yeager, Meredith Menashe, Idan Boyle, Peter Zou, Kaiyong Zhu, Yong Chanock, Stephen Lan, Qing Rothman, Nathaniel TI Polymorphisms in pattern-recognition genes in the innate immunity system and risk of non-Hodgkin lymphoma SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE pattern recognition; NHL; MBP; MASP2; innate immunity ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MANNOSE-BINDING LECTIN; ADAPTIVE IMMUNITY; COMMON VARIATION; GOLLI PROTEIN; T-CELLS; SUSCEPTIBILITY; ASSOCIATION; MALIGNANCIES; CONSORTIUM AB The pattern-recognition pathway plays an important role in infection recognition and immune responses, and previous studies have suggested an association between genetic variation in innate immunity genes and non-Hodgkin lymphoma (NHL). We evaluated NHL risk associated with genetic variation in pattern-recognition genes using data from a casecontrol study of NHL conducted in Connecticut women. Single nucleotide polymorphisms (SNPs) in 27 pattern-recognition genes were genotyped in 432 Caucasian incident NHL cases and 494 frequency-matched controls. Unconditional logistic regression was used to compute odds ratios (ORs) for NHL and common NHL subtypes in relation to individual SNPs and haplotypes. A gene-based analysis that adjusted for the number of tagSNPs genotyped in each gene showed a significant association with overall NHL for the MBP gene (P = 0.028), with the diffuse large B-cell lymphoma (DLBCL) subtype for the MASP2 gene (P = 0.011), and with the follicular lymphoma (FL) subtype for DEFB126 (P = 0.041). A SNP-based analysis showed that MBP rs8094402 was associated with decreased risks of overall NHL (allele risk OR = 0.72, P-trend = 0.0018), DLBCL (allele risk OR = 0.72, P-trend = 0.036), and FL (allele risk OR = 0.67, P-trend = 0.021), while MASP2 rs12711521 was associated with a decreased risk of DLBCL (allele risk OR = 0.57, P-trend = 0.0042). We also observed an increased risk of FL for DEFB126 rs6054706 (allele risk OR = 1.39, P-trend = 0.033). Our results suggest that genetic variation in pattern-recognition genes is associated with the risk of NHL or specific NHL subtypes, but these preliminary findings require replication in larger studies. Mol. Mutagen. 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Hu, Wei] NCI, Div Canc Epidemiol & Genet, Environm & Occupat Epidemiol Branch, NIH,DHHS, Bethesda, MD 20892 USA. [Zheng, Tongzhang; Zhang, Yawei; Holford, Theodore R.; Leaderer, Brian; Zhu, Yong] Yale Univ, Sch Publ Hlth, Div Environm Hlth Sci, New Haven, CT USA. [Boyle, Peter] Int Agcy Res Canc, F-69372 Lyon, France. [Zou, Kaiyong] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. RP Hu, W (reprint author), NCI, Div Canc Epidemiol & Genet, Environm & Occupat Epidemiol Branch, NIH,DHHS, 6120 Execut Blvd,EPS 5103, Bethesda, MD 20892 USA. EM wei.hu@nih.gov RI Hu, Wei/M-3524-2013; Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 NR 38 TC 7 Z9 7 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JAN PY 2013 VL 54 IS 1 BP 72 EP 77 DI 10.1002/em.21739 PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 063IX UT WOS:000312991300008 PM 23055202 ER PT J AU Hofland, J de Herder, WW Derks, L Hofland, LJ van Koetsveld, PM de Krijger, RR van Nederveen, FH Horvath, A Stratakis, CA de Jong, FH Feelders, RA AF Hofland, Johannes de Herder, Wouter W. Derks, Lieke Hofland, Leo J. van Koetsveld, Peter M. de Krijger, Ronald R. van Nederveen, Francien H. Horvath, Anelia Stratakis, Constantine A. de Jong, Frank H. Feelders, Richard A. TI Regulation of steroidogenesis in a primary pigmented nodular adrenocortical disease-associated adenoma leading to virilization and subclinical Cushing's syndrome SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MACRONODULAR ADRENAL-HYPERPLASIA; CARNEY COMPLEX; BETA-CATENIN; GLUCOCORTICOID-RECEPTOR; GENETIC-HETEROGENEITY; CORTISOL SECRETION; HORMONE-RECEPTORS; PRKAR1A GENE; MUTATIONS; TUMORS AB Context: Primary pigmented nodular adrenocortical disease (PPNAD) can lead to steroid hormone overproduction. Mutations in the cAMP protein kinase A regulatory subunit type 1A (PRKAR1A) are causative of PPNAD. Steroidogenesis in PPNAD can be modified through a local glucocorticoid feed-forward loop. Objective: Investigation of regulation of steroidogenesis in a case of PPNAD with virilization. Materials and methods: A 33-year-old woman presented with primary infertility due to hyperandrogenism. Elevated levels of testosterone and subclinical ACTH-independent Cushing's syndrome led to the discovery of an adrenal tumor, which was diagnosed as PPNAD. In vivo evaluation of aberrantly expressed hormone receptors showed no steroid response to known stimuli. Genetic analysis revealed a PRKAR1A protein-truncating Q28X mutation. After adrenalectomy, steroid levels normalized. Tumor cells were cultured and steroidogenic responses to ACTH and dexamethasone were measured and compared with those in normal adrenal and adrenocortical carcinoma cells. Expression levels of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) types 3 and 5 and steroid receptors were quantified in PPNAD, normal adrenal, and adrenal adenoma tissues. Results: Isolated PPNAD cells, analogous to normal adrenal cells, showed both increased steroidogenic enzyme expression and steroid secretion in response to ACTH. Dexamethasone did not affect steroid production in the investigated types of adrenal cells. 17 beta-HSD type 5 was expressed at a higher level in the PPNAD-associated adenoma compared with control adrenal tissue. Conclusion: PPNAD-associated adenomas can cause virilization and infertility by adrenal androgen overproduction. This may be due to steroidogenic control mechanisms that differ from those described for PPNAD without large adenomas. European Journal of Endocrinology 168 67-74 C1 [Hofland, Johannes; de Herder, Wouter W.; Derks, Lieke; Hofland, Leo J.; van Koetsveld, Peter M.; de Jong, Frank H.; Feelders, Richard A.] Erasmus MC, Endocrinol Sect, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [de Krijger, Ronald R.; van Nederveen, Francien H.] Erasmus MC, Dept Pathol, NL-3000 CA Rotterdam, Netherlands. [Horvath, Anelia; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA. RP Hofland, J (reprint author), Erasmus MC, Endocrinol Sect, Dept Internal Med, Room Ee 532,POB 2040, NL-3000 CA Rotterdam, Netherlands. EM j.hofland@erasmusmc.nl RI Hofland, Johannes/I-6379-2013; Hofland, Jan/Q-3542-2016 OI Hofland, Jan/0000-0001-8241-7069 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA FX This work was in part supported by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. NR 30 TC 5 Z9 5 U1 0 U2 3 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JAN PY 2013 VL 168 IS 1 BP 67 EP 74 DI 10.1530/EJE-12-0594 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 063GW UT WOS:000312985200014 PM 23065993 ER PT J AU Saranjam, H Chopra, SS Levy, H Stubblefield, BK Maniwang, E Cohen, IJ Baris, H Sidransky, E Tayebi, N AF Saranjam, Hamid Chopra, Sameer S. Levy, Harvey Stubblefield, Barbara K. Maniwang, Emerson Cohen, Ian J. Baris, Hagit Sidransky, Ellen Tayebi, Nahid TI A germline or de novo mutation in two families with Gaucher disease: implications for recessive disorders SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE acute neuronopathic Gaucher disease; glucocerebrosidase; germline mutation; DNA mutational analysis; molecular diagnostic ID GLUCOCEREBROSIDASE GENE; GBA; COMPLEXITY; ALLELES; L444P AB Gaucher disease (GD) is an autosomal recessive storage disorder that most commonly results from the inheritance of one identifiable mutant glucocerebrosidase (GBA1) allele from each parent. Here, we report two cases of type 2 GD resulting from the inheritance of one identifiable paternal mutant allele and one allele that likely resulted from a maternal germline mutation. Germline mutations or mosiacism are not generally associated with autosomal recessive disorders. The probands from the two unrelated families had the same maternal mutation, leu444pro, that we propose resulted from a de novo maternal germline mutation occurring at this known 'hotspot' for mutation. This first report of a germline mutation for a common point mutation leu444pro (c. 1448 T>C; p. leu483pro) in GD has significant implications for molecular diagnostics and genetic counseling in recessive disorders. European Journal of Human Genetics (2013) 21, 115-117; doi: 10.1038/ejhg.2012.105; published online 20 June 2012 C1 [Saranjam, Hamid; Stubblefield, Barbara K.; Maniwang, Emerson; Sidransky, Ellen; Tayebi, Nahid] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Chopra, Sameer S.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MD USA. [Chopra, Sameer S.; Levy, Harvey] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Genet, Boston, MD USA. [Cohen, Ian J.; Baris, Hagit] Rabin Med Ctr, Rapheal Recanti Genet Inst, Schneider Gaucher Clin, Petah Tiqwa, Israel. [Cohen, Ian J.; Baris, Hagit] Tel Aviv Univ, Sackler Fac Med, Ramat Aviv, Israel. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov RI Cohen, Ian/H-3358-2013 FU National Human Genome Research Institute; National Institutes of Health FX This work was supported by the Intramural Research Programs of the National Human Genome Research Institute and National Institutes of Health. We thank Dr Suzanne Hart for her helpful suggestions. NR 23 TC 4 Z9 5 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD JAN PY 2013 VL 21 IS 1 BP 115 EP 117 DI 10.1038/ejhg.2012.105 PG 3 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 056LX UT WOS:000312492500023 PM 22713811 ER PT J AU Zanotti-Fregonara, P Barth, VN Liow, JS Zoghbi, SS Clark, DT Rhoads, E Siuda, E Heinz, BA Nisenbaum, E Dressman, B Joshi, E Luffer-Atlas, D Fisher, MJ Masters, JJ Goebl, N Kuklish, SL Morse, C Tauscher, J Pike, VW Innis, RB AF Zanotti-Fregonara, Paolo Barth, Vanessa N. Liow, Jeih-San Zoghbi, Sami S. Clark, David T. Rhoads, Emily Siuda, Edward Heinz, Beverly A. Nisenbaum, Eric Dressman, Bruce Joshi, Elizabeth Luffer-Atlas, Debra Fisher, Matthew J. Masters, John J. Goebl, Nancy Kuklish, Steven L. Morse, Cheryl Tauscher, Johannes Pike, Victor W. Innis, Robert B. TI Evaluation in vitro and in animals of a new C-11-labeled PET radioligand for metabotropic glutamate receptors 1 in brain SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE mGlu1 receptors; PET; Brain ID POSITRON-EMISSION-TOMOGRAPHY; PRECLINICAL EVALUATION; RADIOSYNTHESIS; SUBTYPE-5; EXPOSURE; BINDING; MGLUR1; RAT AB Two allosteric modulators of the group I metabotropic glutamate receptors (mGluR1 and mGluR5) were evaluated as positron emission tomography (PET) radioligands for mGluR1. LY2428703, a full mGluR1 antagonist (IC50 8.9 nM) and partial mGluR5 antagonist (IC50 118 nM), and LSN2606428, a full mGluR1 and mGluR5 antagonist (IC50 35.3 nM and 10.2 nM, respectively) were successfully labeled with C-11 and evaluated as radioligands for mGluR1. The pharmacology of LY2428703 was comprehensively assessed in vitro and in vivo, and its biodistribution was investigated by liquid chromatography-mass spectrometry/mass spectrometry, and by PET imaging in the rat. In contrast, LSN2606428 was only evaluated in vitro; further evaluation was stopped due to its unfavorable pharmacological properties and binding affinity. C-11-LY2428703 showed promising characteristics, including: (1) high potency for binding to human mGluR1 (IC50 8.9 nM) with no significant affinity for other human mGlu receptors (mGluR2 through mGluR8); (2) binding to brain displaceable by administration of an mGluR1 antagonist; (3) only one major radiometabolite in both plasma and brain, with a negligible brain concentration (with 3.5 % of the total radioactivity in cerebellum) and no receptor affinity; (4) a large specific and displaceable signal in the mGluR1-rich cerebellum with no significant in vivo affinity for mGluR5, as shown by PET studies in rats; and (5) lack of substrate behavior for efflux transporters at the blood-brain barrier, as shown by PET studies conducted in wild-type and knockout mice. C-11-LY2428703, a new PET radioligand for mGluR1 quantification, displayed promising characteristics both in vitro and in vivo in rodents. C1 [Zanotti-Fregonara, Paolo; Liow, Jeih-San; Zoghbi, Sami S.; Clark, David T.; Morse, Cheryl; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Barth, Vanessa N.; Rhoads, Emily; Siuda, Edward; Heinz, Beverly A.; Nisenbaum, Eric; Dressman, Bruce; Joshi, Elizabeth; Luffer-Atlas, Debra; Fisher, Matthew J.; Masters, John J.; Goebl, Nancy; Kuklish, Steven L.; Tauscher, Johannes] Eli Lilly & Co, Indianapolis, IN 46225 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm B1D43,10 Ctr Dr,MSC 1026, Bethesda, MD 20892 USA. EM robert.innis@nih.gov RI Tauscher, Johannes/M-5976-2016 FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH) FX This work was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). NR 20 TC 10 Z9 10 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JAN PY 2013 VL 40 IS 2 BP 245 EP 253 DI 10.1007/s00259-012-2269-7 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 064GO UT WOS:000313061700011 PM 23135321 ER PT J AU Dieterich, LC Schiller, P Huang, H Wawrousek, EF Loskog, A Wanders, A Moons, L Dimberg, A AF Dieterich, Lothar C. Schiller, Petter Huang, Hua Wawrousek, Eric F. Loskog, Angelica Wanders, Alkwin Moons, Lieve Dimberg, Anna TI alpha B-Crystallin regulates expansion of CD11b(+)Gr-1(+) immature myeloid cells during tumor progression SO FASEB JOURNAL LA English DT Article DE heat-shock protein B5; inflammation; cancer; myelopoiesis ID HEAT-SHOCK PROTEINS; SUPPRESSOR-CELLS; MYOCARDIAL-INFARCTION; MULTIPLE-SCLEROSIS; ENDOTHELIAL-CELLS; IMMUNE-RESPONSES; KNOCKOUT MICE; BREAST-CANCER; INFLAMMATION; ANGIOGENESIS AB The molecular chaperone alpha B-crystallin has emerged as a target for cancer therapy due to its expression in human tumors and its role in regulating tumor angiogenesis. alpha B-crystallin also reduces neuroinflammation, but its role in other inflammatory conditions has not been investigated. Here, we examined whether alpha B-crystallin regulates inflammation associated with tumors and ischemia. We found that CD45(+) leukocyte infiltration is 3-fold increased in tumors and ischemic myocardium in alpha B-crystallin-deficient mice. Notably, alpha B-crystallin is prominently expressed in CD11b(+) Gr-1(+) immature myeloid cells (IMCs), known as regulators of angiogenesis and immune responses, while lymphocytes and mature granulocytes show low alpha B-crystallin expression. alpha B-Crystallin deficiency results in a 3-fold higher accumulation of CD11b(+) Gr-1(+) IMCs in tumors and a significant rise in CD11b(+) Gr-1(+) IMCs in spleen and bone marrow. Similarly, we noted a 2-fold increase in CD11b(+) Gr-1(+) IMCs in chronically inflamed livers in alpha B-crystallin-deficient mice. The effect of alpha B-crystallin on IMC accumulation is limited to pathological conditions, as CD11b(+) Gr-1(+) IMCs are not elevated in naive mice. Through ex vivo differentiation of CD11b(+) Gr-1(+) cells, we provide evidence that alpha B-crystallin regulates systemic expansion of IMCs through a cell-intrinsic mechanism. Our study suggests a key role of alpha B-crystallin in limiting expansion of CD11b(+) Gr-1(+) IMCs in diverse pathological conditions.-Dieterich, L. C., Schiller, P., Huang, H., Wawrousek, E. F., Loskog, A., Wanders, A., Moons, L., Dimberg, A. alpha B-Crystallin regulates expansion of CD11b(+) Gr-1(+) immature myeloid cells during tumor progression. FASEB J. 27, 151-162 (2013). www.fasebj.org C1 [Dieterich, Lothar C.; Schiller, Petter; Huang, Hua; Loskog, Angelica; Wanders, Alkwin; Dimberg, Anna] Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden. [Wawrousek, Eric F.] NEI, NIH, Bethesda, MD 20892 USA. [Moons, Lieve] Katholieke Univ Leuven, Dept Biol, Anim Physiol & Neurobiol Sect, Louvain, Belgium. RP Dimberg, A (reprint author), Uppsala Univ, Rudbeck Lab, Dept Immunol Genet & Pathol, SE-75185 Uppsala, Sweden. EM anna.dimberg@igp.uu.se NR 50 TC 2 Z9 2 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 JAN PY 2013 VL 27 IS 1 BP 151 EP 162 DI 10.1096/fj.12-213017 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 064VJ UT WOS:000313103200015 PM 23033322 ER PT J AU Shukla, V Zheng, YL Mishra, SK Amin, ND Steiner, J Grant, P Kesavapany, S Pant, HC AF Shukla, Varsha Zheng, Ya-Li Mishra, Santosh K. Amin, Niranjana D. Steiner, Joseph Grant, Philip Kesavapany, Sashi Pant, Harish C. TI A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice SO FASEB JOURNAL LA English DT Article DE Cdk5 hyperphosphorylation; neurodegeneration; therapeutics ID AMYLOID-PRECURSOR-PROTEIN; CYCLIN-DEPENDENT KINASE-5; INTERMEDIATE-FILAMENT PROTEINS; PAIRED HELICAL FILAMENTS; IN-VIVO; NEUROFIBRILLARY TANGLES; SYNAPTIC PLASTICITY; TRANSGENIC MICE; TAU HYPERPHOSPHORYLATION; PRESENILIN-1 TRANSGENES AB Alzheimer's disease (AD), one of the leading neurodegenerative disorders of older adults, which causes major socioeconomic burdens globally, lacks effective therapeutics without significant side effects. Besides the hallmark pathology of amyloid plaques and neurofibrillary tangles (NFTs), it has been reported that cyclin-dependent kinase 5 (Cdk5), a critical neuronal kinase, is hyperactivated in AD brains and is, in part, responsible for the above pathology. Here we show that a modified truncated 24-aa peptide (TFP5), derived from the Cdk5 activator p35, penetrates the blood-brain barrier after intraperitoneal injections, inhibits abnormal Cdk5 hyperactivity, and significantly rescues AD pathology (up to 70-80%) in 5XFAD AD model mice. The mutant mice, injected with TFP5 exhibit behavioral rescue, whereas no rescue was observed in mutant mice injected with either saline or scrambled peptide. However, TFP5 does not inhibit cell cycle Cdks or normal Cdk5/p35 activity, and thereby has no toxic side effects (even at 200 mg/kg), a common problem in most current therapeutics for AD. In addition, treated mice displayed decreased inflammation, amyloid plaques, NFTs, cell death, and an extended life by 2 mo. These results suggest TFP5 as a potential therapeutic, toxicity-free candidate for AD.-Shukla, V., Zheng, Y.-L., Mishra, S. K., Amin, N. D., Steiner, J., Grant, P., Kesavapany, S., Pant, H. C. A truncated peptide from p35, a Cdk5 activator, prevents Alzheimer's disease phenotypes in model mice. FASEB J. 27, 174-186 (2013). www.fasebj.org C1 [Pant, Harish C.] Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. [Steiner, Joseph] Natl Inst Neurol Disorders & Stroke, Neurotherapeut Dev Unit, Bethesda, MD 20892 USA. [Mishra, Santosh K.] Natl Inst Dent & Craniofacial Res, Mol Genet Unit, Lab Sensory Biol, NIH, Bethesda, MD USA. [Zheng, Ya-Li] Ningxia Peoples Hosp, Dept Nephrol, Yinchuan, Peoples R China. [Kesavapany, Sashi] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Neurobiol Program, Singapore 117595, Singapore. RP Pant, HC (reprint author), Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, 49 Convent Dr,MSC 4479,Bldg 49,Rm 2A28, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov FU U.S. National Institutes of Health (NIH), NINDS FX The authors thank Dr. Peter Davies (Albert Einstein College of Medicine, Bronx, NY, USA) for the generous gift of Alz-50 antibody. Help from Daniel Abebe (National Institute of Child Health and Human Development, Bethesda, MD, USA) in performing behavior assays is acknowledged. For cell culture studies, rat embryo cortices were provided by Dr. Yanmin Chen [National Institute of Neurological Disorders and Stroke (NINDS), Bethesda, MD, USA]. This work was supported by the intramural research program of the U.S. National Institutes of Health (NIH), NINDS. A patent application has been filed on behalf of NIH (patent application no. 13/249,003) regarding TFP5 as a potential therapeutic for AD. The authors declare no conflicts of interest. V. S. designed the study, performed the experiments, analyzed the data, and drafted the manuscript; S. K. M. participated in study design and analyzed behavior data; N. D. A. performed the in vitro activity analyses and provided the reagents; P. G. and J. S. contributed to experimental design and reviewed the manuscript; Y. Z. and S. K. performed initial in vitro studies; H. C. P. designed the study, analyzed data, and revised the manuscript. NR 71 TC 40 Z9 42 U1 1 U2 16 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 JAN PY 2013 VL 27 IS 1 BP 174 EP 186 DI 10.1096/fj.12-217497 PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 064VJ UT WOS:000313103200017 PM 23038754 ER PT J AU Arroyo, DS Soria, JA Gaviglio, EA Garcia-Keller, C Cancela, LM Rodriguez-Galan, MC Wang, JM Iribarren, P AF Arroyo, Daniela S. Soria, Javier A. Gaviglio, Emilia A. Garcia-Keller, Constanza Cancela, Liliana M. Rodriguez-Galan, Maria C. Wang, Ji Ming Iribarren, Pablo TI Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy SO FASEB JOURNAL LA English DT Article DE inflammation; peptidoglycan; CNS ID ADAPTIVE IMMUNE-RESPONSES; REACTIVE MICROGLIOSIS; POPULATION-CONTROL; DENDRITIC CELLS; ACTIVATION; APOPTOSIS; TLR2; NEUROTOXICITY; ASTROCYTES; PATHWAY AB Microglial cells are phagocytes in the central nervous system (CNS) and become activated in pathological conditions, resulting in microgliosis, manifested by increased cell numbers and inflammation in the affected regions. Thus, controlling microgliosis is important to prevent pathological damage to the brain. Here, we evaluated the contribution of Toll-like receptor 2 (TLR2) to microglial survival. We observed that activation of microglial cells with peptidoglycan (PGN) from Staphylococcus aureus and other TLR2 ligands results in cell activation followed by the induction of autophagy and autophagy-dependent cell death. In C57BL/6J mice, intracerebral injection of PGN increased the autophagy of microglial cells and reduced the microglial/macrophage cell number in brain parenchyma. Our results demonstrate a novel role of TLRs in the regulation of microglial cell activation and survival, which are important for the control of microgliosis and associated inflammatory responses in the CNS.-Arroyo, D. S., Soria, J. A., Gaviglio, E. A., Garcia-Keller, C., Cancela, L. M., Rodriguez-Galan, M. C., Wang, J. M., Iribarren, P. Toll-like receptor 2 ligands promote microglial cell death by inducing autophagy. FASEB J. 27, 299-312 (2013). www.fasebj.org C1 [Arroyo, Daniela S.; Soria, Javier A.; Gaviglio, Emilia A.; Rodriguez-Galan, Maria C.; Iribarren, Pablo] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, CIBICI,CONICET, RA-5000 Cordoba, Argentina. [Garcia-Keller, Constanza; Cancela, Liliana M.] Univ Nacl Cordoba, Fac Ciencias Quim, Dept Farmacol, IFEC,CONICET, RA-5000 Cordoba, Argentina. [Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Iribarren, P (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, CIBICI,CONICET, Ciudad Univ,X5000HUA, RA-5000 Cordoba, Argentina. EM piribarr@fcq.unc.edu.ar FU Fogarty International Center, U.S. National Institutes of Health (HIH) [1R01TW007621]; Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina; Secretaria de Ciencia y Tecnologia, Universidad Nacional de Cordoba (SECyT-UNC), Argentina FX The authors thank biochemist Paula Icely for technical support and secretarial assistance. This work was supported by the Fogarty International Center, U.S. National Institutes of Health (HIH; grant 1R01TW007621); Consejo Nacional de Investigaciones Cientificas y Tecnicas, Argentina; and Secretaria de Ciencia y Tecnologia, Universidad Nacional de Cordoba (SECyT-UNC), Argentina. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the Fogarty International Center, NIH. The authors declare no conflicts of interest. NR 55 TC 14 Z9 17 U1 2 U2 21 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 JAN PY 2013 VL 27 IS 1 BP 299 EP 312 DI 10.1096/fj.12-214312 PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 064VJ UT WOS:000313103200028 PM 23073832 ER PT J AU Taub, DD Hesdorffer, CS Ferrucci, L Madara, K Schwartz, JB Goetzl, EJ AF Taub, Dennis D. Hesdorffer, Charles S. Ferrucci, Luigi Madara, Karen Schwartz, Janice B. Goetzl, Edward J. TI Distinct energy requirements for human memory CD4 T-cell homeostatic functions SO FASEB JOURNAL LA English DT Article DE adherence; chemotaxis; apoptosis; glycolysis; fatty acid oxidation; immunosenescence ID ACTIVATED PROTEIN-KINASE; LIPID-METABOLISM; GLUCOSE-UPTAKE; LYMPHOCYTES; CHEMOTAXIS; EXPRESSION; GENERATION; PATHWAYS; EFFECTOR; FATE AB Differentiation and activation of CD4 memory T cells (T-mem cells) require energy from different sources, but little is known about energy sources for maintenance and surveillance activities of unactivated T-mem cells. Mitochondrial fatty acid oxidation (FAO) in human unactivated CD4 T-mem cells was significantly enhanced by inhibition of glycolysis, with respective means of 1.7- and 4.5-fold for subjects <45 yr and >65 yr, and by stimulation of AMP-activated protein kinase, with respective means of 1.3- and 5.2-fold. However, CCL19 and sphingosine 1-phosphate (S1P), which control homeostatic lymphoid trafficking of unactivated T-mem cells, altered FAO and glycolysis only minimally or not at all. Inhibition of CD4 T-mem-cell basal FAO, but not basal glycolysis, significantly suppressed CCL19- and S1P-mediated adherence to collagen by >50 and 20%, respectively, and chemotaxis by >20 and 50%. Apoptosis of unactivated T-mem cells induced by IL-2 deprivation or CCL19 was increased significantly by >150 and 70%, respectively, with inhibition of FAO and by >110 and 30% with inhibition of glycolysis. Anti-TCR antibody activation of T-mem cells increased their chemotaxis to CCL5, which was dependent predominantly on glycolysis rather than FAO. The sources supplying energy for diverse functions of unactivated T-mem cells differ from that required for function after immune activation.-Taub, D. D., Hesdorffer, C. S., Ferrucci, L., Madara, K., Schwartz, J. B., Goetzl, E. J. Distinct energy requirements for human memory CD4 T-cell homeostatic functions. FASEB J. 27, 342-349 (2013). www.fasebj.org C1 [Schwartz, Janice B.; Goetzl, Edward J.] Jewish Home San Francisco, Geriatr Res Labs, San Francisco, CA 94112 USA. [Taub, Dennis D.; Hesdorffer, Charles S.; Ferrucci, Luigi; Madara, Karen; Goetzl, Edward J.] NIA, NIH, Baltimore, MD 21224 USA. [Schwartz, Janice B.; Goetzl, Edward J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. RP Goetzl, EJ (reprint author), Jewish Home San Francisco, UCSF Geriatr Res Labs, 302 Silver Ave, San Francisco, CA 94112 USA. EM edward.goetzl@ucsf.edu FU endowment funds of the Jewish Home of San Francisco; U.S. National Institute on Aging FX This research was supported by endowment funds of the Jewish Home of San Francisco and the intramural research program of the U.S. National Institute on Aging. The authors are grateful to Judith H. Goetzl for preparation of the figures and table. The authors declare no conflicts of interest. NR 26 TC 5 Z9 5 U1 1 U2 9 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 JAN PY 2013 VL 27 IS 1 BP 342 EP 349 DI 10.1096/fj.12-217620 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 064VJ UT WOS:000313103200032 PM 22972918 ER PT J AU Milne, JLS Borgnia, MJ Bartesaghi, A Tran, EEH Earl, LA Schauder, DM Lengyel, J Pierson, J Patwardhan, A Subramaniam, S AF Milne, Jacqueline L. S. Borgnia, Mario J. Bartesaghi, Alberto Tran, Erin E. H. Earl, Lesley A. Schauder, David M. Lengyel, Jeffrey Pierson, Jason Patwardhan, Ardan Subramaniam, Sriram TI Cryo-electron microscopy - a primer for the non-microscopist SO FEBS JOURNAL LA English DT Review DE automated workflows; cellular architecture; cryo-electron microscopy; 3D imaging; electron crystallography; integrated structural biology; molecular reconstructions; single particle analysis; tomography; viral structures ID ELECTRON CRYO-TOMOGRAPHY; ESCHERICHIA-COLI; RADIATION-DAMAGE; 3-DIMENSIONAL RECONSTRUCTION; DIRECT VISUALIZATION; BIOLOGICAL MACROMOLECULES; MOLECULAR ARCHITECTURE; CONFORMATIONAL STATES; VITREOUS SECTIONS; MEMBRANE-PROTEINS AB Cryo-electron microscopy (cryo-EM) is increasingly becoming a mainstream technology for studying the architecture of cells, viruses and protein assemblies at molecular resolution. Recent developments in microscope design and imaging hardware, paired with enhanced image processing and automation capabilities, are poised to further advance the effectiveness of cryo-EM methods. These developments promise to increase the speed and extent of automation, and to improve the resolutions that may be achieved, making this technology useful to determine a wide variety of biological structures. Additionally, established modalities for structure determination, such as X-ray crystallography and nuclear magnetic resonance spectroscopy, are being routinely integrated with cryo-EM density maps to achieve atomic-resolution models of complex, dynamic molecular assemblies. In this review, which is directed towards readers who are not experts in cryo-EM methodology, we provide an overview of emerging themes in the application of this technology to investigate diverse questions in biology and medicine. We discuss the ways in which these methods are being used to study structures of macromolecular assemblies that range in size from whole cells to small proteins. Finally, we include a description of how the structural information obtained by cryo-EM is deposited and archived in a publicly accessible database. C1 [Milne, Jacqueline L. S.; Borgnia, Mario J.; Bartesaghi, Alberto; Tran, Erin E. H.; Earl, Lesley A.; Schauder, David M.; Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Lengyel, Jeffrey; Pierson, Jason] FEI Co, Hillsboro, OR USA. [Patwardhan, Ardan] European Bioinformat Inst, European Mol Biol Lab, Prot Data Bank Europe, Cambridge, England. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ss1@nih.gov OI Patwardhan, Ardan/0000-0001-7663-9028 FU Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD FX Work in our laboratory at the National Institutes of Health is supported by the Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. We thank Hong Zhou (Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, USA) for permission to use the images presented in Fig. 7. More information on our research program is available at http://electron.nci.nih.gov and http://livinglab.nih.gov. NR 113 TC 48 Z9 49 U1 13 U2 149 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X J9 FEBS J JI FEBS J. PD JAN PY 2013 VL 280 IS 1 BP 28 EP 45 DI 10.1111/febs.12078 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 063KA UT WOS:000312995400003 PM 23181775 ER PT J AU Chattopadhyay, MK Chen, WP Tabor, H AF Chattopadhyay, Manas K. Chen, Weiping Tabor, Herbert TI Escherichia coli glutathionylspermidine synthetase/amidase: phylogeny and effect on regulation of gene expression SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE bacteria; Enterobacteria; microarray; polyamines; spermidine ID TRYPANOTHIONE; GLUTATHIONE; METABOLISM; BIOSYNTHESIS; POLYAMINES; REDUCTASE; K-12; TRYPANOSOMATIDS; DEHYDROGENASE; INVOLVEMENT AB Glutathionylspermidine synthetase/amidase (Gss) and the encoding gene (gss) have only been studied in Escherichia coli and several members of the Kinetoplastida phyla. In the present article, we have studied the phylogenetic distribution of Gss and have found that Gss sequences are largely limited to certain bacteria and Kinetoplastids and are absent in a variety of invertebrate and vertebrate species, Archea, plants, and some Eubacteria. It is striking that almost all of the 75 Enterobacteria species that have been sequenced contain sequences with very high degree of homology to the E. coli Gss protein. To find out the physiological significance of glutathionylspermidine in E. coli, we have performed global transcriptome analyses. The microarray studies comparing gss+ and ?gss strains of E. coli show that a large number of genes are either up-regulated (76 genes more than threefold) or down-regulated (35 genes more than threefold) by the loss of the gss gene. Most significant categories of up-regulated genes include sulfur utilization, glutamine and succinate metabolism, polyamine and arginine metabolism, and purine and pyrimidine metabolism. C1 [Chattopadhyay, Manas K.; Tabor, Herbert] NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. [Chen, Weiping] NIDDKD, Microarray Core Facil, NIH, Bethesda, MD 20892 USA. RP Chattopadhyay, MK (reprint author), NIDDK, NIH, 8 Ctr Dr,Bldg 8,Room 223, Bethesda, MD 20892 USA. EM manasc@intra.niddk.nih.gov FU Intramural NIH HHS [Z99 DK999999] NR 37 TC 4 Z9 4 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0378-1097 EI 1574-6968 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD JAN PY 2013 VL 338 IS 2 BP 132 EP 140 DI 10.1111/1574-6968.12035 PG 9 WC Microbiology SC Microbiology GA 062SK UT WOS:000312942100004 PM 23106382 ER PT J AU Scaife, M Pacienza, N Au, BCY Wang, JCM Devine, S Scheid, E Lee, CJ Lopez-Perez, O Neschadim, A Fowler, DH Foley, R Medin, JA AF Scaife, M. Pacienza, N. Au, B. C. Y. Wang, J. C. M. Devine, S. Scheid, E. Lee, C-J Lopez-Perez, O. Neschadim, A. Fowler, D. H. Foley, R. Medin, J. A. TI Engineered human Tmpk fused with truncated cell-surface markers: versatile cell-fate control safety cassettes SO GENE THERAPY LA English DT Article DE lentivirus; cell-fate control; TMPK; AZT ID HUMAN THYMIDYLATE KINASE; SUICIDE GENE-THERAPY; DONOR T-CELLS; IN-VIVO; PHASE-I; INSERTIONAL ONCOGENESIS; ALPHA-GALACTOSIDASE; ADVERSE EVENT; FABRY-DISEASE; ZIDOVUDINE AB Cell-fate control gene therapy (CFCGT)-based strategies can augment existing gene therapy and cell transplantation approaches by providing a safety element in the event of deleterious outcomes. Previously, we described a novel enzyme/prodrug combination for CFCGT. Here, we present results employing novel lentiviral constructs harboring sequences for truncated surface molecules (CD19 or low-affinity nerve growth factor receptor) directly fused to that CFCGT cDNA (TmpkF105Y). This confers an enforced one-to-one correlation between cell marking and eradication functions. In-vitro analysis demonstrated the full functionality of the fusion product. Next, low-dose 3'-azido-3'-deoxythymidine (AZT) administration to non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice injected with transduced clonal K562 cells suppressed tumor growth; furthermore, one integrated vector on average was sufficient to mediate cytotoxicity. Further, in a murine xenogeneic leukemia-lymphoma model we also demonstrated in-vivo control over transduced Raji cells. Finally, in a proof-of-principle study to examine the utility of this cassette in combination with a therapeutic cDNA, we integrated this novel CFCGT fusion construct into a lentivector designed for treatment of Fabry disease. Transduction with this vector restored enzyme activity in Fabry cells and retained AZT sensitivity. In addition, human Fabry patient CD34(+) cells showed high transduction efficiencies and retained normal colony-generating capacity when compared with the non-transduced controls. These collective results demonstrated that this novel and broadly applicable fusion system may enhance general safety in gene-and cell-based therapies. Gene Therapy (2013) 20, 24-34; doi:10.1038/gt.2011.210; published online 12 January 2012 C1 [Pacienza, N.; Au, B. C. Y.; Wang, J. C. M.; Lee, C-J; Lopez-Perez, O.; Medin, J. A.] Univ Hlth Network, Ontario Canc Inst, Toronto, ON M5G 2M1, Canada. [Scaife, M.; Devine, S.; Neschadim, A.; Medin, J. A.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. [Wang, J. C. M.; Medin, J. A.] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. [Scheid, E.; Foley, R.] McMaster Univ, Ctr Gene Therapeut, Dept Pathol & Mol Med, Hamilton, ON, Canada. [Fowler, D. H.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Medin, JA (reprint author), Univ Hlth Network, Ontario Canc Inst, Canadian Blood Serv Bldg,67 Coll St,Room 406, Toronto, ON M5G 2M1, Canada. EM jmedin@uhnres.utoronto.ca OI Neschadim, Anton/0000-0003-1750-9703 FU Canadian Institutes of Health Research; CIHR Training Program in Regenerative Medicine (TPRM) FX We would like to especially thank the Fabry patients who donated bone marrow to facilitate these studies. This research was funded by a research operating grant from the Canadian Institutes of Health Research to Dr JA Medin. Funding for AN was provided by the CIHR Training Program in Regenerative Medicine (TPRM). NR 36 TC 7 Z9 8 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD JAN PY 2013 VL 20 IS 1 BP 24 EP 34 DI 10.1038/gt.2011.210 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 064EG UT WOS:000313053900004 PM 22241175 ER PT J AU Yu, CH Bonaduce, MJ Klar, AJS AF Yu, Chuanhe Bonaduce, Michael J. Klar, Amar J. S. TI Defining the Epigenetic Mechanism of Asymmetric Cell Division of Schizosaccharomyces japonicus Yeast SO GENETICS LA English DT Article ID MATING-TYPE INTERCONVERSION; FISSION YEAST; DNA STRANDS; S-POMBE; IMPRINT; REGION; DIRECTIONALITY; REPLICATION; SEGREGATION; BOUNDARIES AB A key question in developmental biology addresses the mechanism of asymmetric cell division. Asymmetry is crucial for generating cellular diversity required for development in multicellular organisms. As one of the potential mechanisms, chromosomally borne epigenetic difference between sister cells that changes mating/cell type has been demonstrated only in the Schizosaccharomyces pombe fission yeast. For technical reasons, it is nearly impossible to determine the existence of such a mechanism operating during embryonic development of multicellular organisms. Our work addresses whether such an epigenetic mechanism causes asymmetric cell division in the recently sequenced fission yeast, S. japonicus (with 36% GC content), which is highly diverged from the well-studied S. pombe species (with 44% GC content). We find that the genomic location and DNA sequences of the mating-type loci of S. japonicus differ vastly from those of the S. pombe species. Remarkably however, similar to S. pombe, the S. japonicus cells switch cell/mating type after undergoing two consecutive cycles of asymmetric cell divisions: only one among four "granddaughter" cells switches. The DNA-strand-specific epigenetic imprint at the mating-type locus1 initiates the recombination event, which is required for cellular differentiation. Therefore the S. pombe and S. japonicus mating systems provide the first two examples in which the intrinsic chirality of double helical structure of DNA forms the primary determinant of asymmetric cell division. Our results show that this unique strand-specific imprinting/segregation epigenetic mechanism for asymmetric cell division is evolutionary conserved. Motivated by these findings, we speculate that DNA-strand-specific epigenetic mechanisms might have evolved to dictate asymmetric cell division in diploid, higher eukaryotes as well. C1 [Yu, Chuanhe; Bonaduce, Michael J.; Klar, Amar J. S.] NIH, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NIH, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res, POB B, Frederick, MD 21702 USA. EM klara@mail.nih.gov FU National Institutes of Health, Frederick National Laboratory for Cancer Research FX We thank Jeremy Hyams for providing the Sj1 stock to us. The Intramural Research Program of the National Institutes of Health, Frederick National Laboratory for Cancer Research supports this research. NR 48 TC 10 Z9 11 U1 0 U2 8 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD JAN PY 2013 VL 193 IS 1 BP 85 EP 94 DI 10.1534/genetics.112.146233 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 062BS UT WOS:000312894700005 PM 23150598 ER PT J AU Giannuzzi, G Siswara, P Malig, M Marques-Bonet, T Mullikin, JC Ventura, M Eichler, EE AF Giannuzzi, Giuliana Siswara, Priscillia Malig, Maika Marques-Bonet, Tomas Mullikin, James C. Ventura, Mario Eichler, Evan E. CA NISC Comparative Sequencing Progra TI Evolutionary dynamism of the primate LRRC37 gene family SO GENOME RESEARCH LA English DT Article ID RECENT SEGMENTAL DUPLICATIONS; PROLINE-RICH POLYPEPTIDES; COPY NUMBER VARIATION; RAT VENTRAL PROSTATE; HUMAN GENOME; MAXIMUM-LIKELIHOOD; HUMAN LINEAGE; PROTEIN; EXPRESSION; REGION AB Core duplicons in the human genome represent ancestral duplication modules shared by the majority of intrachromosomal duplication blocks within a given chromosome. These cores are associated with the emergence of novel gene families in the hominoid lineage, but their genomic organization and gene characterization among other primates are largely unknown. Here, we investigate the genomic organization and expression of the core duplicon on chromosome 17 that led to the expansion of LRRC37 during primate evolution. A comparison of the LRRC37 gene family organization in human, orangutan, macaque, marmoset, and lemur genomes shows the presence of both orthologous and species-specific gene copies in all primate lineages. Expression profiling in mouse, macaque, and human tissues reveals that the ancestral expression of LRRC37 was restricted to the testis. In the hominid lineage, the pattern of LRRC37 became increasingly ubiquitous, with significantly higher levels of expression in the cerebellum and thymus, and showed a remarkable diversity of alternative splice forms. Transfection studies in HeLa cells indicate that the human FLAG-tagged recombinant LRRC37 protein is secreted after cleavage of a transmembrane precursor and its overexpression can induce filipodia formation. C1 [Giannuzzi, Giuliana; Ventura, Mario] Univ Bari Aldo Moro, Dipartimento Biol, I-70126 Bari, Italy. [Siswara, Priscillia; Malig, Maika; Ventura, Mario; Eichler, Evan E.] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. [Marques-Bonet, Tomas] Univ Pompeu Fabra, PRBB, Inst Biol Evolut UPF CSIC, IBE, Barcelona 08003, Catalonia, Spain. [Mullikin, James C.] NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. [Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NISC, Bethesda, MD 20892 USA. [Eichler, Evan E.] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Eichler, EE (reprint author), Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA. EM eee@gs.washington.edu RI Ventura, Mario/E-6420-2011; Marques-Bonet, Tomas/I-4618-2014 OI Ventura, Mario/0000-0001-7762-8777; Marques-Bonet, Tomas/0000-0002-5597-3075 FU National Institutes of Health (NIH) [HG002385, GM058815]; Intramural Research Program of the National Human Genome Research Institute, NIH FX We thank NIH Intramural Sequencing Center (NISC) for BAC clone sequence data generation and T. Brown for manuscript editing. This work was supported by National Institutes of Health (NIH) grants HG002385 and GM058815 to E.E.E. and in part by the Intramural Research Program of the National Human Genome Research Institute, NIH. E.E.E. is an investigator of the Howard Hughes Medical Institute. NR 57 TC 7 Z9 7 U1 1 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JAN PY 2013 VL 23 IS 1 BP 46 EP 59 DI 10.1101/gr.138842.112 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 062ZJ UT WOS:000312963400005 PM 23064749 ER PT J AU Schug, TT Abagyan, R Blumberg, B Collins, TJ Crews, D DeFur, PL Dickerson, SM Edwards, TM Gore, AC Guillette, LJ Hayes, T Heindel, JJ Moores, A Patisaul, HB Tal, TL Thayer, KA Vandenberg, LN Warner, JC Watson, CS vom Saal, FS Zoeller, RT O'Brien, KP Myers, JP AF Schug, T. T. Abagyan, R. Blumberg, B. Collins, T. J. Crews, D. DeFur, P. L. Dickerson, S. M. Edwards, T. M. Gore, A. C. Guillette, L. J. Hayes, T. Heindel, J. J. Moores, A. Patisaul, H. B. Tal, T. L. Thayer, K. A. Vandenberg, L. N. Warner, J. C. Watson, C. S. vom Saal, F. S. Zoeller, R. T. O'Brien, K. P. Myers, J. P. TI Designing endocrine disruption out of the next generation of chemicals SO GREEN CHEMISTRY LA English DT Article ID POLYBROMINATED DIPHENYL ETHERS; ORYZIAS-LATIPES EMBRYOS; FROGS XENOPUS-LAEVIS; DEVELOPMENTAL EXPOSURE; ESTROGENIC ACTIVITY; SCORING SYSTEM; TOXICITY; ZEBRAFISH; DOCKING; ACTIVATION AB A central goal of green chemistry is to avoid hazard in the design of new chemicals. This objective is best achieved when information about a chemical's potential hazardous effects is obtained as early in the design process as feasible. Endocrine disruption is a type of hazard that to date has been inadequately addressed by both industrial and regulatory science. To aid chemists in avoiding this hazard, we propose an endocrine disruption testing protocol for use by chemists in the design of new chemicals. The Tiered Protocol for Endocrine Disruption (TiPED) has been created under the oversight of a scientific advisory committee composed of leading representatives from both green chemistry and the environmental health sciences. TiPED is conceived as a tool for new chemical design, thus it starts with a chemist theoretically at "the drawing board." It consists of five testing tiers ranging from broad in silico evaluation up through specific cell- and whole organism-based assays. To be effective at detecting endocrine disruption, a testing protocol must be able to measure potential hormone-like or hormone-inhibiting effects of chemicals, as well as the many possible interactions and signaling sequellae such chemicals may have with cell-based receptors. Accordingly, we have designed this protocol to broadly interrogate the endocrine system. The proposed protocol will not detect all possible mechanisms of endocrine disruption, because scientific understanding of these phenomena is advancing rapidly. To ensure that the protocol remains current, we have established a plan for incorporating new assays into the protocol as the science advances. In this paper we present the principles that should guide the science of testing new chemicals for endocrine disruption, as well as principles by which to evaluate individual assays for applicability, and laboratories for reliability. In a 'proof-of-principle' test, we ran 6 endocrine disrupting chemicals (EDCs) that act via different endocrinological mechanisms through the protocol using published literature. Each was identified as endocrine active by one or more tiers. We believe that this voluntary testing protocol will be a dynamic tool to facilitate efficient and early identification of potentially problematic chemicals, while ultimately reducing the risks to public health. C1 [Schug, T. T.; Heindel, J. J.] NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, Res Triangle Pk, NC 27709 USA. [Abagyan, R.] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA. [Blumberg, B.] Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92717 USA. [Collins, T. J.] Carnegie Mellon Univ, Dept Chem, Pittsburgh, PA 15213 USA. [Crews, D.] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA. [DeFur, P. L.] Virginia Commonwealth Univ, Ctr Environm Studies, Richmond, VA USA. [Dickerson, S. M.; O'Brien, K. P.] Adv Green Chem, Charlottesville, VA USA. [Edwards, T. M.] Louisiana Tech Univ, Sch Biol Sci, Ruston, LA 71270 USA. [Gore, A. C.] Univ Texas Austin, Inst Neurosci, Austin, TX 78712 USA. [Guillette, L. J.] Med Univ S Carolina, Dept Obstet & Gynaecol, Charleston, SC 29425 USA. [Hayes, T.] Univ Calif Berkeley, Museum Vertebrate Zool, Lab Integrat Studies Amphibian Biol, Grp Endocrinol,Energy & Resources Grp, Berkeley, CA 94720 USA. [Hayes, T.] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. [Moores, A.] McGill Univ, Dept Chem, Ctr Green Chem & Catalysis, Montreal, PQ, Canada. [Patisaul, H. B.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Tal, T. L.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Thayer, K. A.] NIEHS, Off Hlth Assessment & Translat, Res Triangle Pk, NC 27709 USA. [Vandenberg, L. N.] Tufts Univ, Dept Biol, Medford, MA 02155 USA. [Vandenberg, L. N.] Tufts Univ, Ctr Regenerat & Dev Biol, Medford, MA 02155 USA. [Warner, J. C.] Warner Babcock Inst Green Chem, Wilmington, MA USA. [Watson, C. S.] Univ Texas Med Branch, Ctr Addict Res, Galveston, TX USA. [vom Saal, F. S.] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. [Zoeller, R. T.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. [Myers, J. P.] Environm Hlth Sci, Charlottesville, VA USA. RP Schug, TT (reprint author), NIEHS, Div Extramural Res & Training, Cellular Organ & Syst Pathobiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM schugt2@niehs.nih.gov; kpobrien@advancing-greenchemistry.org; jpmyers@ehsciences.org RI Moores, Audrey/C-9997-2011; Collins, Terrence/A-9807-2017; OI Moores, Audrey/0000-0003-1259-913X; Collins, Terrence/0000-0003-2611-9184; Gore, Andrea/0000-0001-5549-6793; Tal, Tamara/0000-0001-8365-9385 FU NIEHS [1R13ES016981-01]; Cedar Tree Foundation; Johnson Family Foundation; Kendeda Fund; Marisla Foundation; John Merck Fund; Passport Foundation FX We are grateful to the following scientists who participated in a two day retreat at Cavallo Point, California to help us develop and refine our thinking on this investigation: Paul Anastas, Evan Beach, Amy Cannon, Chad Ellis, Julie Haack, Andreas Kortenkamp, C.J. Li, Nicolas Olea, Sarah Vogel and Adelina Voutchkova. The work was supported by grants from NIEHS (grant no. 1R13ES016981-01), the Cedar Tree Foundation, the Johnson Family Foundation, the Kendeda Fund, the Marisla Foundation, the John Merck Fund, and the Passport Foundation. We thank Julie Jones for outstanding logistical and organizing efforts without which this collaboration would not have been possible. Raymond Tice (NIEHS/DNTP) provided constructive comments on the manuscript. NR 57 TC 38 Z9 38 U1 7 U2 80 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1463-9262 J9 GREEN CHEM JI Green Chem. PY 2013 VL 15 IS 1 BP 181 EP 198 DI 10.1039/c2gc35055f PG 18 WC Chemistry, Multidisciplinary; GREEN & SUSTAINABLE SCIENCE & TECHNOLOGY SC Chemistry; Science & Technology - Other Topics GA 057EN UT WOS:000312545400022 PM 25110461 ER PT J AU Xu, JF Lange, EM Lu, LY Zheng, SQL Wang, Z Thibodeau, SN Cannon-Albright, LA Teerlink, CC Camp, NJ Johnson, AM Zuhlke, KA Stanford, JL Ostrander, EA Wiley, KE Isaacs, SD Walsh, PC Maier, C Luedeke, M Vogel, W Schleutker, J Wahlfors, T Tammela, T Schaid, D McDonnell, SK DeRycke, MS Cancel-Tassin, G Cussenot, O Wiklund, F Gronberg, H Eeles, R Easton, D Kote-Jarai, Z Whittemore, AS Hsieh, CL Giles, GG Hopper, JL Severi, G Catalona, WJ Mandal, D Ledet, E Foulkes, WD Hamel, N Mahle, L Moller, P Powell, I Bailey-Wilson, JE Carpten, JD Seminara, D Cooney, KA Isaacs, WB AF Xu, Jianfeng Lange, Ethan M. Lu, Lingyi Zheng, Siqun L. Wang, Zhong Thibodeau, Stephen N. Cannon-Albright, Lisa A. Teerlink, Craig C. Camp, Nicola J. Johnson, Anna M. Zuhlke, Kimberly A. Stanford, Janet L. Ostrander, Elaine A. Wiley, Kathleen E. Isaacs, Sarah D. Walsh, Patrick C. Maier, Christiane Luedeke, Manuel Vogel, Walther Schleutker, Johanna Wahlfors, Tiina Tammela, Teuvo Schaid, Daniel McDonnell, Shannon K. DeRycke, Melissa S. Cancel-Tassin, Geraldine Cussenot, Olivier Wiklund, Fredrik Gronberg, Henrik Eeles, Ros Easton, Doug Kote-Jarai, Zsofia Whittemore, Alice S. Hsieh, Chih-Lin Giles, Graham G. Hopper, John L. Severi, Gianluca Catalona, William J. Mandal, Diptasri Ledet, Elisa Foulkes, William D. Hamel, Nancy Mahle, Lovise Moller, Pal Powell, Isaac Bailey-Wilson, Joan E. Carpten, John D. Seminara, Daniela Cooney, Kathleen A. Isaacs, William B. CA Int Consortium Prostate Canc Genet TI HOXB13 is a susceptibility gene for prostate cancer: results from the International Consortium for Prostate Cancer Genetics (ICPCG) SO HUMAN GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; GERMLINE MUTATIONS; SEQUENCE VARIANTS; LINKAGE ANALYSIS; BRCA2 GENE; LOCI; RISK; SCAN; FAMILIES; COMMON AB Prostate cancer has a strong familial component but uncovering the molecular basis for inherited susceptibility for this disease has been challenging. Recently, a rare, recurrent mutation (G84E) in HOXB13 was reported to be associated with prostate cancer risk. Confirmation and characterization of this finding is necessary to potentially translate this information to the clinic. To examine this finding in a large international sample of prostate cancer families, we genotyped this mutation and 14 other SNPs in or flanking HOXB13 in 2,443 prostate cancer families recruited by the International Consortium for Prostate Cancer Genetics (ICPCG). At least one mutation carrier was found in 112 prostate cancer families (4.6 %), all of European descent. Within carrier families, the G84E mutation was more common in men with a diagnosis of prostate cancer (194 of 382, 51 %) than those without (42 of 137, 30 %), P = 9.9 x 10(-8) [odds ratio 4.42 (95 % confidence interval 2.56-7.64)]. A family-based association test found G84E to be significantly over-transmitted from parents to affected offspring (P = 6.5 x 10(-6)). Analysis of markers flanking the G84E mutation indicates that it resides in the same haplotype in 95 % of carriers, consistent with a founder effect. Clinical characteristics of cancers in mutation carriers included features of high-risk disease. These findings demonstrate that the HOXB13 G84E mutation is present in 5 % of prostate cancer families, predominantly of European descent, and confirm its association with prostate cancer risk. While future studies are needed to more fully define the clinical utility of this observation, this allele and others like it could form the basis for early, targeted screening of men at elevated risk for this common, clinically heterogeneous cancer. C1 [Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.] Johns Hopkins Univ Hosp, Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21287 USA. [Xu, Jianfeng; Lu, Lingyi; Zheng, Siqun L.; Wang, Zhong] Wake Forest Univ, Bowman Gray Sch Med, Data Coordinating Ctr ICPCG, Winston Salem, NC USA. [Xu, Jianfeng; Lu, Lingyi; Zheng, Siqun L.; Wang, Zhong] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Lange, Ethan M.; Johnson, Anna M.; Zuhlke, Kimberly A.; Cooney, Kathleen A.] Univ Michigan, Sch Med, ICPCG Grp, Ann Arbor, MI USA. [Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA. [Lange, Ethan M.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Thibodeau, Stephen N.; Schaid, Daniel; McDonnell, Shannon K.; DeRycke, Melissa S.] Mayo Clin, ICPGC Grp, Rochester, MN USA. [Thibodeau, Stephen N.; DeRycke, Melissa S.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Cannon-Albright, Lisa A.; Teerlink, Craig C.; Camp, Nicola J.] Univ Utah, Sch Med, ICPCG Grp, Salt Lake City, UT USA. [Cannon-Albright, Lisa A.; Teerlink, Craig C.; Camp, Nicola J.] Univ Utah, Sch Med, Dept Med, Salt Lake City, UT USA. [Johnson, Anna M.; Zuhlke, Kimberly A.; Cooney, Kathleen A.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Stanford, Janet L.; Ostrander, Elaine A.] Fred Hutchinson Canc Res Ctr, ICPCG Grp, Seattle, WA 98104 USA. [Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Wiley, Kathleen E.; Isaacs, Sarah D.; Walsh, Patrick C.; Isaacs, William B.] Johns Hopkins Univ, ICPCG Grp, Baltimore, MD USA. [Maier, Christiane; Luedeke, Manuel; Vogel, Walther] Univ Ulm, ICPCG Grp, Ulm, Germany. [Maier, Christiane; Luedeke, Manuel] Univ Ulm, Dept Urol, Ulm, Germany. [Vogel, Walther] Univ Ulm, Inst Human Genet, Ulm, Germany. [Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo] Univ Tampere, ICPCG Grp, FIN-33101 Tampere, Finland. [Schleutker, Johanna; Wahlfors, Tiina; Tammela, Teuvo] Fimlab Labs, Tampere, Finland. [Schleutker, Johanna; Wahlfors, Tiina] Univ Tampere, Inst Biomed Technol BioMediTech, FIN-33101 Tampere, Finland. [Schleutker, Johanna] Univ Turku, Dept Med Biochem & Genet, Turku, Finland. [Tammela, Teuvo] Tampere Univ Hosp, Dept Urol, Tampere, Finland. [Schaid, Daniel; McDonnell, Shannon K.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. [Cancel-Tassin, Geraldine; Cussenot, Olivier] CeRePP ICPCG Grp, Paris, France. [Cancel-Tassin, Geraldine] CeRePP UPMC Univ, Paris, France. [Cussenot, Olivier] Hosp Tenon, APHP, Dept Urol, Paris, France. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Karolinska ICPCG Grp, Stockholm, Sweden. [Wiklund, Fredrik; Gronberg, Henrik] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Eeles, Ros; Kote-Jarai, Zsofia] Inst Canc Res, Sutton, Surrey, England. [Eeles, Ros; Kote-Jarai, Zsofia] Royal Marsden NHS Fdn Trust, Sutton, Surrey, England. [Easton, Doug] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Strangeways Lab, Cambridge, England. [Whittemore, Alice S.; Hsieh, Chih-Lin] Stanford Sch Med, BC CA HI ICPCG Grp, Stanford, CA USA. [Whittemore, Alice S.] Stanford Sch Med, Dept Hlth Res & Policy, Stanford, CA USA. [Whittemore, Alice S.] Stanford Sch Med, Stanford Comprehens Canc Ctr, Stanford, CA USA. [Hsieh, Chih-Lin] Univ So Calif, Dept Urol, Los Angeles, CA USA. [Hsieh, Chih-Lin] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA. [Giles, Graham G.; Hopper, John L.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia. [Giles, Graham G.; Hopper, John L.; Severi, Gianluca] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia. [Catalona, William J.] Northwestern Univ, ICPCG Grp, Chicago, IL 60611 USA. [Catalona, William J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Mandal, Diptasri; Ledet, Elisa] Louisiana State Univ, ICPCG Grp, New Orleans, LA USA. [Mandal, Diptasri; Ledet, Elisa] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. [Foulkes, William D.; Hamel, Nancy] McGill Univ, Dept Oncol, Program Canc Genet, Montreal, PQ, Canada. [Foulkes, William D.; Hamel, Nancy] McGill Univ, Dept Human Genet, Program Canc Genet, Montreal, PQ, Canada. [Foulkes, William D.; Hamel, Nancy] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ, Canada. [Mahle, Lovise; Moller, Pal] Norwegian Radium Hosp, Oslo, Norway. [Powell, Isaac; Bailey-Wilson, Joan E.; Carpten, John D.] African Amer Hereditary Prostate Canc ICPCG Grp, Detroit, MI USA. [Powell, Isaac] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. [Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Carpten, John D.] Translat Genom Res Inst, Genet Basis Human Dis Res Div, Phoenix, AZ USA. [Seminara, Daniela] NCI, NIH, Bethesda, MD 20892 USA. RP Isaacs, WB (reprint author), Johns Hopkins Univ Hosp, Johns Hopkins Med Inst, Dept Urol, Marburg 115,600 N Wolfe St, Baltimore, MD 21287 USA. EM wisaacs@jhmi.edu RI Whittemore, Alice/F-9925-2014; OI Bailey-Wilson, Joan/0000-0002-9153-2920; Eeles, Rosalind/0000-0002-3698-6241; Teerlink, Craig/0000-0002-1992-2326; albright, lisa/0000-0003-2602-3668; Giles, Graham/0000-0003-4946-9099; Ostrander, Elaine/0000-0001-6075-9738; Cancel-Tassin, Geraldine/0000-0002-9583-6382 FU National Institutes of Health [U01 CA89600]; NIH [R01 CA79596, R01 CA079596-10-S1, R01 CA136621, P50 CA69568]; University of Utah Huntsman Cancer Institute; Fred Hutchinson Cancer Research Center; National Human Genome Research Institute; CR-UK grant [C5047/A7357]; NIHR; Royal Marsden NHS Foundation Trust and Prostate Action; Cancer Research UK; European Commission [223175]; Swedish Cancer Society; Umea University Hospital, Umea, Sweden; Pirkanmaa Hospital District [9M094]; Finnish Cancer Organisations; Sigrid Juselius Foundation; Academy of Finland [116437, 251074]; Cancer Council Victoria, Tattersalls; The Whitten Foundation; Robert H Lurie Comprehensive Cancer Center; Urological Research Foundation; NCI [CA119069, CA129684] FX We would like to express our gratitude to the many families who participated in the studies involved in the International Consortium for Prostate Cancer Genetics (ICPCG). The ICPCG is funded by a grant from the National Institutes of Health U01 CA89600 (to W. B. I.). Additional support to members within the ICPCG is as follows: University of Michigan Group acknowledges NIH grants R01 CA79596, R01 CA079596-10-S1 (ARRA), R01 CA136621, and P50 CA69568. University of Utah Group: The authors thank the support from the University of Utah Huntsman Cancer Institute (to Lisa A. Cannon-Albright). FHCRC/NHGRI Group: Partial support was provided by the Fred Hutchinson Cancer Research Center (to Janet L. Stanford) and National Human Genome Research Institute (to Elaine A. Ostrander). ACTANE Group: We acknowledge support from CR-UK grant C5047/A7357 and the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust and Prostate Action (to Ros Eeles), and Cancer Research UK (to Doug Easton). This work was also supported by the European Commission's Seventh Framework Programme grant agreement no 223175 (HEALTH-F2-2009-223175), University of Umea Group: Partial support was provided by Swedish Cancer Society and a Spear grant from the Umea University Hospital, Umea, Sweden (to Henrik Gronberg). University of Tampere Group: Partial support was provided from The Competitive Research Funding of the Pirkanmaa Hospital District (9M094), Finnish Cancer Organisations, Sigrid Juselius Foundation and Academy of Finland (116437 and 251074) (to Johanna Schleutker). Australian Group: Recruitment was funded by Cancer Council Victoria, Tattersalls and The Whitten Foundation; JLH is an Australia Fellow of the National Health and Medical Research Council. Northwestern University Group: Partial support was provided from Robert H Lurie Comprehensive Cancer Center and the Urological Research Foundation (to William J. Catalona). LSUHSC-NO Group: Louisiana Board of Regents, Centers for Disease Control and Prevention. Data Coordinating Center: Partial support was provided by NCI CA119069 and CA129684 (to Jianfeng Xu). We also thank other investigators who contributed to this work: ACTANE Group: Daniel Leongamornlert, Ed Saunders, Malgorzata Tymrakiewicz, Lynne O'Brien, Emma Sawyer, Rosemary Wilkinson, and Stephen Edwards from The Institute of Cancer Research, Sutton, Surrey; Jacques Simard, from the Human Molecular Endocrinology Research Center, CHUL Research Center, Laval University, Quebec City, Canada; Timothy Bishop from Cancer Research UK, Genetic Epidemiology Laboratory, St James' University Hospital, Leeds, UK; Michael Badzioch; Tokhir Dadaev, Lesley McGuffog, Koveela Govindasami, and Michelle Guy from the UKGPCS Team. University of Ulm Group: Antje Rinckleb and Mark Schrader from Department of Urology, University of Ulm, Germany; Josef Hoegel and Christian Kubisch from Institute of Human Genetics, University of Ulm, Germany; and Kathleen Herkommer from Department of Urology, Technical University of Munich, Germany. Fred Hutchinson Cancer Research Center Group: Laura McIntosh. We thank Liesel FitzGerald for helpful comments and review. William Foulkes thanks Celia Greenwood for advice. NR 32 TC 52 Z9 55 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2013 VL 132 IS 1 BP 5 EP 14 DI 10.1007/s00439-012-1229-4 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 063NE UT WOS:000313005800002 PM 23064873 ER PT J AU Chen, F Chen, GK Stram, DO Millikan, RC Ambrosone, CB John, EM Bernstein, L Zheng, W Palmer, JR Hu, JJ Rebbeck, TR Ziegler, RG Nyante, S Bandera, EV Ingles, SA Press, MF Ruiz-Narvaez, EA Deming, SL Rodriguez-Gil, JL DeMichele, A Chanock, SJ Blot, W Signorello, L Cai, QY Li, GL Long, JR Huo, DZ Zheng, YL Cox, NJ Olopade, OI Ogundiran, TO Adebamowo, C Nathanson, KL Domchek, SM Simon, MS Hennis, A Nemesure, B Wu, SY Leske, MC Ambs, S Hutter, CM Young, A Kooperberg, C Peters, U Rhie, SK Wan, P Sheng, X Pooler, LC Van Den Berg, DJ Le Marchand, L Kolonel, LN Henderson, BE Haiman, CA AF Chen, Fang Chen, Gary K. Stram, Daniel O. Millikan, Robert C. Ambrosone, Christine B. John, Esther M. Bernstein, Leslie Zheng, Wei Palmer, Julie R. Hu, Jennifer J. Rebbeck, Tim R. Ziegler, Regina G. Nyante, Sarah Bandera, Elisa V. Ingles, Sue A. Press, Michael F. Ruiz-Narvaez, Edward A. Deming, Sandra L. Rodriguez-Gil, Jorge L. DeMichele, Angela Chanock, Stephen J. Blot, William Signorello, Lisa Cai, Qiuyin Li, Guoliang Long, Jirong Huo, Dezheng Zheng, Yonglan Cox, Nancy J. Olopade, Olufunmilayo I. Ogundiran, Temidayo O. Adebamowo, Clement Nathanson, Katherine L. Domchek, Susan M. Simon, Michael S. Hennis, Anselm Nemesure, Barbara Wu, Suh-Yuh Leske, M. Cristina Ambs, Stefan Hutter, Carolyn M. Young, Alicia Kooperberg, Charles Peters, Ulrike Rhie, Suhn K. Wan, Peggy Sheng, Xin Pooler, Loreall C. Van Den Berg, David J. Le Marchand, Loic Kolonel, Laurence N. Henderson, Brian E. Haiman, Christopher A. TI A genome-wide association study of breast cancer in women of African ancestry SO HUMAN GENETICS LA English DT Article ID SUSCEPTIBILITY LOCI; CONFER SUSCEPTIBILITY; COMMON VARIANTS; AMERICAN WOMEN; RISK; POPULATION; DIVERSITY; ALLELES; ORIGINS AB Genome-wide association studies (GWAS) in diverse populations are needed to reveal variants that are more common and/or limited to defined populations. We conducted a GWAS of breast cancer in women of African ancestry, with genotyping of > 1,000,000 SNPs in 3,153 African American cases and 2,831 controls, and replication testing of the top 66 associations in an additional 3,607 breast cancer cases and 11,330 controls of African ancestry. Two of the 66 SNPs replicated (p < 0.05) in stage 2, which reached statistical significance levels of 10(-6) and 10(-5) in the stage 1 and 2 combined analysis (rs4322600 at chromosome 14q31: OR = 1.18, p = 4.3 x 10(-6); rs10510333 at chromosome 3p26: OR = 1.15, p = 1.5 x 10(-5)). These suggestive risk loci have not been identified in previous GWAS in other populations and will need to be examined in additional samples. Identification of novel risk variants for breast cancer in women of African ancestry will demand testing of a substantially larger set of markers from stage 1 in a larger replication sample. C1 [Haiman, Christopher A.] USC Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. [Chen, Fang; Chen, Gary K.; Stram, Daniel O.; Ingles, Sue A.; Rhie, Suhn K.; Wan, Peggy; Sheng, Xin; Pooler, Loreall C.; Van Den Berg, David J.; Henderson, Brian E.; Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Millikan, Robert C.; Nyante, Sarah] Univ N Carolina, Lineberger Comprehens Canc Ctr, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. [Ambrosone, Christine B.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA. [John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA. [John, Esther M.] Stanford Univ, Sch Med, Stanford Canc Inst, Stanford, CA 94305 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Dept Populat Sci, Div Canc Etiol, Duarte, CA USA. [Zheng, Wei; Deming, Sandra L.; Blot, William; Signorello, Lisa; Cai, Qiuyin; Li, Guoliang; Long, Jirong] Vanderbilt Univ, Dept Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Vanderbilt Epidemiol Ctr,Sch Med, Nashville, TN USA. [Palmer, Julie R.; Ruiz-Narvaez, Edward A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. [Hu, Jennifer J.; Rodriguez-Gil, Jorge L.] Univ Miami, Miller Sch Med, Sylvester Comprehens Canc Ctr, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Rebbeck, Tim R.; DeMichele, Angela; Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Ziegler, Regina G.; Chanock, Stephen J.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, DC USA. [Bandera, Elisa V.] Canc Inst New Jersey, New Brunswick, NJ USA. [Press, Michael F.] Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Zheng, Yonglan; Cox, Nancy J.; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Ogundiran, Temidayo O.] Univ Ibadan, Coll Med, Dept Surg, Ibadan, Nigeria. [Adebamowo, Clement] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Simon, Michael S.] Wayne State Univ, Karmanos Canc Inst, Dept Oncol, Detroit, MI USA. [Hennis, Anselm] Univ W Indies, Res Inst Trop Med, Chron Dis Res Ctr, Bridgetown, Barbados. [Hennis, Anselm; Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. [Hutter, Carolyn M.; Young, Alicia; Kooperberg, Charles; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Van Den Berg, David J.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Epigenome Ctr, Los Angeles, CA 90033 USA. [Le Marchand, Loic; Kolonel, Laurence N.] Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. RP Haiman, CA (reprint author), USC Norris Comprehens Canc Ctr, Harlyne Norris Res Tower,1450 Biggy St,Room 1504, Los Angeles, CA 90033 USA. EM fangchen@usc.edu; haiman@usc.edu RI Bandera, Elisa/M-4169-2014; LI, GUOLIANG/E-7359-2015; OI Bandera, Elisa/0000-0002-8789-2755; LI, GUOLIANG/0000-0001-8493-4684; Ruiz-Narvaez, Edward/0000-0002-0339-5824; Palmer, Julie/0000-0002-6534-335X; Nathanson, Katherine/0000-0002-6740-0901; Adebamowo, Clement/0000-0002-6571-2880 FU Department of Defense Breast Cancer Research Program Era of Hope Scholar Award [W81XWH-08-1-0383]; Norris Foundation; MEC (National Institutes of Health) [R01-CA63464, R37-CA54281]; CARE (National Institute for Child Health and Development) [NO1-HD-3-3175]; WCHS (U.S. Army Medical Research and Material Command (USAMRMC) [DAMD-17-01-0-0334]; National Institutes of Health [R01-CA100598]; Breast Cancer Research Foundation; SFBCS (National Institutes of Health) [R01-CA77305]; United States Army Medical Research Program [DAMD17-96-6071]; NC-BCFR (National Institutes of Health) [U01-CA69417]; CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer) [P50-CA58223]; Center for Environmental Health and Susceptibility National Institute of Environmental Health Sciences, National Institutes of Health [P30-ES10126]; PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health); NBHS (National Institutes of Health) [R01-CA100374]; SCCS (National Institutes of Health) [R01-CA092447]; WFBC (National Institutes of Health) [R01-CA73629]; BWHS (National Institutes of Health) [R01-CA58420, R01-CA98663]; WISE (National Institutes of Health) [P01-CA77596]; National Institutes of Health Specialized Program of Research Excellence in Breast Cancer [P50-CA125183]; National Cancer Institute [R01-CA141712]; NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, National Institutes of Health [RFA-CA-06-503]; National Heart, Lung, and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services [N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, 44221]; NHLBI [N02-HL-64278] FX This work was supported by a Department of Defense Breast Cancer Research Program Era of Hope Scholar Award to CAH [W81XWH-08-1-0383] and the Norris Foundation. Each of the participating studies was supported by the following grants: MEC (National Institutes of Health grants R01-CA63464 and R37-CA54281); CARE (National Institute for Child Health and Development grant NO1-HD-3-3175); WCHS (U.S. Army Medical Research and Material Command (USAMRMC) grant DAMD-17-01-0-0334, the National Institutes of Health grant R01-CA100598, and the Breast Cancer Research Foundation); SFBCS (National Institutes of Health grant R01-CA77305 and United States Army Medical Research Program grant DAMD17-96-6071); NC-BCFR (National Institutes of Health grant U01-CA69417); CBCS (National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA58223, and Center for Environmental Health and Susceptibility National Institute of Environmental Health Sciences, National Institutes of Health, grant number P30-ES10126); PLCO (Intramural Research Program, National Cancer Institute, National Institutes of Health); NBHS (National Institutes of Health grant R01-CA100374); SCCS (National Institutes of Health grant R01-CA092447), WFBC (National Institutes of Health grant R01-CA73629); BWHS (National Institutes of Health grants R01-CA58420 and R01-CA98663) and WISE (National Institutes of Health grant P01-CA77596). OI Olopade and DHuo were supported by National Institutes of Health Specialized Program of Research Excellence in Breast Cancer, grant number P50-CA125183 and National Cancer Institute R01-CA141712. BBCS is supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The Breast Cancer Family Registry (BCFR) was supported by the National Cancer Institute, National Institutes of Health under RFA-CA-06-503 and through cooperative agreements with members of the Breast Cancer Family Registry and Principal Investigators. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government or the BCFR. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institute of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119,32122, 42107-26, 42129-32, and 44221. Funding for WHI SHARe genotyping was provided by NHLBI Contract N02-HL-64278. We thank the women who volunteered to participate in each study. We also thank Madhavi Eranti, Andrea Holbrook, Paul Poznaik, David Wong and Lucy Xia from the University of Southern California for their technical support. We would also like to acknowledge co-investigators from the WCHS study: Dana H. Bovbjerg (University of Pittsburgh), Lina Jandorf (Mount Sinai School of Medicine) and Gregory Ciupak, Warren Davis, Gary Zirpoli, Song Yao and Michelle Roberts from Roswell Park Cancer Institute. NR 34 TC 26 Z9 26 U1 0 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2013 VL 132 IS 1 BP 39 EP 48 DI 10.1007/s00439-012-1214-y PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 063NE UT WOS:000313005800005 PM 22923054 ER PT J AU Hansel, NN Ruczinski, I Rafaels, N Sin, DD Daley, D Malinina, A Huang, LL Sandford, A Murray, T Kim, Y Vergara, C Heckbert, SR Psaty, BM Li, G Elliott, WM Aminuddin, F Dupuis, J O'Connor, GT Doheny, K Scott, AF Boezen, HM Postma, DS Smolonska, J Zanen, P Hoesein, FAM de Koning, HJ Crystal, RG Tanaka, T Ferrucci, L Silverman, E Wan, E Vestbo, J Lomas, DA Connett, J Wise, RA Neptune, ER Mathias, RA Pare, PD Beaty, TH Barnes, KC AF Hansel, Nadia N. Ruczinski, Ingo Rafaels, Nicholas Sin, Don D. Daley, Denise Malinina, Alla Huang, Lili Sandford, Andrew Murray, Tanda Kim, Yoonhee Vergara, Candelaria Heckbert, Susan R. Psaty, Bruce M. Li, Guo Elliott, W. Mark Aminuddin, Farzian Dupuis, Josee O'Connor, George T. Doheny, Kimberly Scott, Alan F. Boezen, H. Marike Postma, Dirkje S. Smolonska, Joanna Zanen, Pieter Hoesein, Firdaus A. Mohamed de Koning, Harry J. Crystal, Ronald G. Tanaka, Toshiko Ferrucci, Luigi Silverman, Edwin Wan, Emily Vestbo, Jorgen Lomas, David A. Connett, John Wise, Robert A. Neptune, Enid R. Mathias, Rasika A. Pare, Peter D. Beaty, Terri H. Barnes, Kathleen C. TI Genome-wide study identifies two loci associated with lung function decline in mild to moderate COPD SO HUMAN GENETICS LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; POPULATION-BASED COHORTS; GENERAL-POPULATION; EARLY INTERVENTION; RAPID DECLINE; POLYMORPHISMS; HEALTH; SMOKING; SMOKERS; BRONCHODILATOR AB Accelerated lung function decline is a key COPD phenotype; however, its genetic control remains largely unknown. We performed a genome-wide association study using the Illumina Human660W-Quad v.1_A BeadChip. Generalized estimation equations were used to assess genetic contributions to lung function decline over a 5-year period in 4,048 European American Lung Health Study participants with largely mild COPD. Genotype imputation was performed using reference HapMap II data. To validate regions meeting genome-wide significance, replication of top SNPs was attempted in independent cohorts. Three genes (TMEM26, ANK3 and FOXA1) within the regions of interest were selected for tissue expression studies using immunohistochemistry. Two intergenic SNPs (rs10761570, rs7911302) on chromosome 10 and one SNP on chromosome 14 (rs177852) met genome-wide significance after Bonferroni. Further support for the chromosome 10 region was obtained by imputation, the most significantly associated imputed SNPs (rs10761571, rs7896712) being flanked by observed markers rs10761570 and rs7911302. Results were not replicated in four general population cohorts or a smaller cohort of subjects with moderate to severe COPD; however, we show novel expression of genes near regions of significantly associated SNPS, including TMEM26 and FOXA1 in airway epithelium and lung parenchyma, and ANK3 in alveolar macrophages. Levels of expression were associated with lung function and COPD status. We identified two novel regions associated with lung function decline in mild COPD. Genes within these regions were expressed in relevant lung cells and their expression related to airflow limitation suggesting they may represent novel candidate genes for COPD susceptibility. C1 [Barnes, Kathleen C.] Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. [Hansel, Nadia N.; Rafaels, Nicholas; Malinina, Alla; Huang, Lili; Murray, Tanda; Vergara, Candelaria; Wise, Robert A.; Neptune, Enid R.; Mathias, Rasika A.; Barnes, Kathleen C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. [Hansel, Nadia N.] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Sin, Don D.; Daley, Denise; Sandford, Andrew; Aminuddin, Farzian; Pare, Peter D.] Univ British Columbia, Dept Med, St Pauls Hosp, Div Respirol,James Hogg Res Ctr, Vancouver, BC, Canada. [Kim, Yoonhee] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. [Heckbert, Susan R.; Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA. [Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Psaty, Bruce M.; Li, Guo] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. [Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Dupuis, Josee; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA. [O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA. [Doheny, Kimberly; Scott, Alan F.] Johns Hopkins Univ, CIDR, Baltimore, MD USA. [Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. [Boezen, H. Marike; Postma, Dirkje S.; Smolonska, Joanna] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Dept Genet, Groningen, Netherlands. [Postma, Dirkje S.] Univ Groningen, Univ Med Ctr Groningen, Dept Pulmonol, Groningen, Netherlands. [Zanen, Pieter; Hoesein, Firdaus A. Mohamed] Univ Med Ctr Utrecht, Div Heart & Lungs, Utrecht, Netherlands. [de Koning, Harry J.] Erasmus MC, Dept Publ Hlth, Rotterdam, Netherlands. [Crystal, Ronald G.] Weill Cornell Med Coll, Dept Med Genet, New York, NY USA. [Tanaka, Toshiko; Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Silverman, Edwin; Wan, Emily] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. [Silverman, Edwin; Wan, Emily] Harvard Univ, Sch Med, Boston, MA USA. [Vestbo, Jorgen] Univ Copenhagen, Hvidovre Hosp, DK-2650 Hvidovre, Denmark. [Lomas, David A.] Univ Cambridge, Dept Med, Cambridge Inst Med Res, Cambridge CB2 2QQ, England. [Connett, John] Univ Minnesota, Sch Publ Hlth, Div Biostat, St Paul, MN 55108 USA. [Beaty, Terri H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. [Elliott, W. Mark] Univ British Columbia, St Pauls Hosp, James Hogg Res Ctr, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. RP Barnes, KC (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle,Room 3A-62A, Baltimore, MD 21224 USA. EM kbarnes@jhmi.edu OI Vestbo, Jorgen/0000-0001-6355-6362; O'Connor, George/0000-0002-6476-3926; Wise, Robert/0000-0002-8353-2349; Dupuis, Josee/0000-0003-2871-3603 FU National Human Genome Research Institute (NHGRI); GENEVA [U01HG 004738]; NHL-BI [HL095406-01]; Mary Beryl Patch Turnbull Scholar Program; NHLBI [HHSN268201200036C, 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, HL087652, HL105756, N01 HC 25195]; NINDS; NIA [AG-023629, AG-15928, AG-20098, AG-027058]; National Center of Advancing Translational Technologies CTSI grant [UL 1TR000124]; National Institute of Diabetes and Digestive and Kidney Diseases [DK063491]; GlaxoSmithKline; NIH, National Institute on Aging; MedStar Research Institute; European Union [201379]; NIH GEI [U01 HG004438]; [NIH/N01-HR-46002] FX This project was part of the Gene, Environment Association Studies (GENEVA) Consortium funded by the National Human Genome Research Institute (NHGRI) to enhance communication and collaboration among researchers conducting genome-wide studies of complex diseases. Our group benefited greatly from the work and efforts of the entire consortium, especially the Coordinating Center (directed by B. Weir and C. Laurie of the University of Washington) in data cleaning and preparation for submission to the Database for Genotypes and Phenotypes (dbGaP). Special thanks also to David Levine for additional, technical support. We also acknowledge the leadership of T. Manolio of NHGRI. We would also like to thank Helen Voelker and Kathy Farnell of the LHS Data Coordinating Center, University of Minnesota for assistance with the LHS database. We would also like to thank Corinne Boehm and Jane Romm of the Center for Inherited Disease Research, Johns Hopkins University, for technical support. The principal investigators and senior staff of the clinical and coordinating centers, the NHLBI, and members of the Safety and Data Monitoring Board of the Lung Health Study are as follows: Case Western Reserve University, Cleveland, OH: M. D. Altose, M. D. (Principal Investigator), C. D. Deitz, Ph.D. (Project Coordinator); Henry Ford Hospital, Detroit, MI: M. S. Eichenhorn, M. D. (Principal Investigator), K.J. Braden, A. A. S. (Project Coordinator), R. L. Jentons, M. A. L. L. P. (Project Coordinator); Johns Hopkins University School of Medicine, Baltimore, MD: R. A. Wise, M. D. (Principal Investigator), C. S. Rand, Ph.D. (Co-Principal Investigator), K. A. Schiller (Project Coordinator); Mayo Clinic, Rochester, MN: P. D. Scanlon, M. D. (Principal Investigator), G. M. Caron (Project Coordinator), K. S. Mieras, L. C. Walters; Oregon Health Sciences University, Portland: A. S. Buist, M. D. (Principal Investigator), L. R. Johnson, Ph.D. (LHS Pulmonary Function Coordinator), V.J. Bortz (Project Coordinator); University of Alabama at Birmingham: W. C. Bailey, M. D. (Principal Investigator), L. B. Gerald, Ph.D., M. S. P. H. (Project Coordinator); University of California, Los Angeles: D. P. Tashkin, M. D. (Principal Investigator), I. P. Zuniga (Project Coordinator); University of Manitoba, Winnipeg: N.R. Anthonisen, M. D. (Principal Investigator, Steering Committee Chair), J. Manfreda, M. D. (Co-Principal Investigator), R. P. Murray, Ph.D. (Co-Principal Investigator), S. C. Rempel-Rossum (Project Coordinator); University of Minnesota Coordinating Center, Minneapolis: J.E. Connett, Ph.D. (Principal Investigator), P. L. Enright, M. D., P. G. Lindgren, M. S., P. O'Hara, Ph.D., (LHS Intervention Coordinator), M. A. Skeans, M. S., H. T. Voelker; University of Pittsburgh, Pittsburgh, PA: R. M. Rogers, M. D. (Principal Investigator), M. E. Pusateri (Project Coordinator); University of Utah, Salt Lake City: R. E. Kanner, M. D. (Principal Investigator), G. M. Villegas (Project Coordinator); Safety and Data Monitoring Board: M. Becklake, M. D., B. Burrows, M. D. (deceased), P. Cleary, Ph.D., P. Kimbel, M. D. (Chairperson; deceased), L. Nett, R.N., R. R. T. (former member), J.K. Ockene, Ph.D., R. M. Senior, M. D. (Chairperson), G. L. Snider, M. D., W. Spitzer, M. D. (former member), O.D. Williams, Ph.D.; Morbidity and Mortality Review Board: T. E. Cuddy, M. D., R. S. Fontana, M. D., R. E. Hyatt, M. D., C. T. Lambrew, M. D., B. A. Mason, M. D., D. M. Mintzer, M. D., R. B. Wray, M. D.; National Heart, Lung, and Blood Institute staff, Bethesda, MD: S. S. Hurd, Ph.D.; (Former Director, Division of Lung Diseases), J.P. Kiley, Ph.D. (Former Project Officer and Director, Division of Lung Diseases), G. Weinmann, M. D. (Former Project Officer and Director, Airway Biology and Disease Program, DLD), M. C. Wu, Ph.D. (Division of Epidemiology and Clinical Applications). Principal investigators and centers participating in ECLIPSE include: Bulgaria: Y. Ivanov, Pleven; K. Kostov, Sofia. Canada: J. Bourbeau, Montreal; M. Fitzgerald, Vancouver; P. Hernandez, Halifax; K. Killian, Hamilton; R. Levy, Vancouver; F. Maltais, Montreal;. D O'Donnell, Kingston. Czech Republic: J. Krepelka, Praha. Denmark: J. Vestbo, Hvidovre. The Netherlands: E. Wouters, Horn. New Zealand: D. Quinn, Wellington. Norway: P. Bakke, Bergen, Slovenia: M. Kosnik, Golnik. Spain: A. Agusti, Jaume Sauleda, Palma de Mallorca. Ukraine: Y. Feschenko, Kiev; V. Gavrisyuk, Kiev; L. Yashina, Kiev. UK: L. Yashina, W. MacNee, Edinburgh; D. Singh, Manchester; J. Wedzicha, London. USA: A. Anzueto, San Antonio, TX; S. Braman, Providence. RI; R. Casaburi, Torrance CA; B. Celli, Boston, MA; G. Giessel, Richmond, VA; M. Gotfried, Phoenix, AZ; G. Greenwald, Rancho Mirage, CA; N. Hanania, Houston, TX; D, Mahler, Lebanon, NH; B. Make, Denver, CO; S. Rennard, Omaha, NE; C. Rochester, New Haven, CT; P. Scanlon, Rochester, MN; D. Schuller, Omaha, NE; F. Sciurba, Pittsburg, PA; A. Sharafkhaneh, Houston, TX; T. Siler, St Charles, MO; E. Silverman, Boston, MA; A. Wanner, Miami, FL; R. Wise, Baltimore, MD; R. ZuWallack, Hartford, CT. Steering Committee: H. Coxson (Canada), C. Crim (GlaxoSmithKline, USA), L. Edwards (GlaxoSmithKline, USA), D. Lomas (UK), W. MacNee (UK), E. Silverman (USA), R. Tal-Singer (Co-chair, GlaxoSmithKline, USA), J. Vestbo (Co-chair, Denmark), J. Yates (GlaxoSmithKline, USA). ScientiWc Committee: A. Agusti (Spain), P. Calverley (UK), B. Celli (USA), C. Crim (GlaxoSmithKline, USA), B. Miller (GlaxoSmithKline, US), W. MacNee (Chair, UK), S. Rennard (USA), R. Tal-Singer (GlaxoSmithKline, USA), E. Wouters (The Netherlands), J. Yates (GlaxoSmithKline, USA). Data deposition: Data can be obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs 000335.v1.p1through dbGaP accession number phs0003 35.v1.pl. This research was supported by GENEVA (U01HG 004738). The Lung Health Study I was supported by contract NIH/N01-HR-46002. Lung tissue validation studies were supported by the NHL-BI HL095406-01. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program. This CHS research was supported by NHLBI contracts HHSN268201200036C, 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, HL087652, HL105756 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. DNA handling and genotyping was supported in part by National Center of Advancing Translational Technologies CTSI grant UL 1TR000124 and National Institute of Diabetes and Digestive and Kidney Diseases grant DK063491 to the Southern California Diabetes Endocrinology Research Center. FHS was funded by N01 HC 25195 from NHLBI. ECLIPSE was supported by GlaxoSmithKline. The BLSA was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. A portion of that support was through a R&D contract with MedStar Research Institute.; COPACETIC (acronym of COPD Pathology: Addressing Critical gaps, Early Treatment & diagnosis and Innovative Concepts) is funded by the European Union FP7 program, grant agreement number: 201379. GWAS genotyping was performed at the Center for Inhreited Disease Research under the support of NIH GEI grant U01 HG004438. NR 38 TC 14 Z9 15 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JAN PY 2013 VL 132 IS 1 BP 79 EP 90 DI 10.1007/s00439-012-1219-6 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 063NE UT WOS:000313005800009 PM 22986903 ER PT J AU Lim, PH Bagci, U Bai, L AF Lim, Poay Hoon Bagci, Ulas Bai, Li TI Introducing Willmore Flow Into Level Set Segmentation of Spinal Vertebrae SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Kernel density estimation (KDE); level set; vertebrae segmentation; Willmore flow ID ACTIVE CONTOURS; IMAGES; MODEL AB Segmentation of spinal vertebrae in 3-D space is a crucial step in the study of spinal related disease or disorders. However, the complexity of vertebrae shapes, with gaps in the cortical bone and boundaries, as well as noise, inhomogeneity, and incomplete information in images, has made spinal vertebrae segmentation a difficult task. In this paper, we introduce a new method for an accurate spinal vertebrae segmentation that is capable of dealing with noisy images with missing information. This is achieved by introducing an edge-mounted Willmore flow, as well as a prior shape kernel density estimator, to the level set segmentation framework. While the prior shape model provides much needed prior knowledge when information is missing from the image, and draws the level set function toward prior shapes, the edge-mounted Willmore flow helps to capture the local geometry and smoothes the evolving level set surface. Evaluation of the segmentation results with ground-truth validation demonstrates the effectiveness of the proposed approach: an overall accuracy of 89.32 +/- 1.70% and 14.03 +/- 1.40 mm are achieved based on the Dice similarity coefficient and Hausdorff distance, respectively, while the inter-and intraobserver variation agreements are 92.11 +/- 1.97%, 94.94 +/- 1.69%, 3.32 +/- 0.46, and 3.80 +/- 0.56 mm. C1 [Lim, Poay Hoon; Bai, Li] Univ Nottingham, Sch Comp Sci, Nottingham NG8 1BB, England. [Bagci, Ulas] NIH, Bethesda, MD 20892 USA. RP Lim, PH (reprint author), Univ Nottingham, Sch Comp Sci, Nottingham NG8 1BB, England. EM psxphl@nottingham.ac.uk; ulas.bagci@nih.gov; Bai.Li@nottingham.ac.uk OI Bagci, Ulas/0000-0001-7379-6829 FU University of Nottingham FX Manuscript received June 11, 2012; revised September 11, 2012; accepted October 15, 2012. Date of publication October 22, 2012; date of current version December 14, 2012. This work is supported in part by the University of Nottingham. Asterisk indicates corresponding author. NR 31 TC 11 Z9 11 U1 0 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JAN PY 2013 VL 60 IS 1 BP 115 EP 122 DI 10.1109/TBME.2012.2225833 PN 1 PG 8 WC Engineering, Biomedical SC Engineering GA 062CV UT WOS:000312897600015 PM 23144025 ER PT J AU Chen, XJ Summers, RM Yao, JH AF Chen, Xinjian Summers, Ronald M. Yao, Jianhua TI Kidney Tumor Growth Prediction by Coupling Reaction-Diffusion and Biomechanical Model SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Biomechanical model; finite-element method (FEM); kidney tumor; reaction-diffusion model; tumor growth prediction ID GLIOMA GROWTH; BRAIN-TUMORS; DEFORMATION; IMAGES AB It is desirable to predict the tumor growth rate so that appropriate treatment can be planned in the early stage. Previously, we proposed a finite-element-method (FEM)-based 3-D kidney tumor growth prediction system using longitudinal images. A reaction-diffusion model was applied as the tumor growth model. In this paper, we not only improve the tumor growth model by coupling the reaction-diffusion model with a biomechanical model, but also take the surrounding tissues into account. Different diffusion and biomechanical properties are applied for different tissue types. An FEM is employed to simulate the coupled tumor growth model. Model parameters are estimated by optimizing an objective function of overlap accuracy using a hybrid optimization parallel search package. The proposed method was tested with kidney CT images of eight tumors from five patients with seven time points. The experimental results showed that the performance of the proposed method improved greatly compared to our previous work. C1 [Chen, Xinjian] Soochow Univ, Sch Elect & Informat Engn, Suzhou 215006, Jiangsu, Peoples R China. [Summers, Ronald M.; Yao, Jianhua] NIH, Radiol & Imaging Sci Dept, Bethesda, MD 20892 USA. RP Chen, XJ (reprint author), Soochow Univ, Sch Elect & Informat Engn, Suzhou 215006, Jiangsu, Peoples R China. EM xjchen@suda.edu.cn; rsummers@mail.nih.gov; jyao@mail.nih.gov RI Chen, Xinjian/E-8592-2016 FU Intramural NIH HHS [Z99 CL999999] NR 16 TC 9 Z9 9 U1 1 U2 10 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JAN PY 2013 VL 60 IS 1 BP 169 EP 173 DI 10.1109/TBME.2012.2222027 PN 2 PG 5 WC Engineering, Biomedical SC Engineering GA 062CY UT WOS:000312897900007 PM 23047857 ER PT J AU Brubaker, L Richter, HE Barber, MD Hsu, Y Rahn, DD Menefee, S Visco, A Spino, C Martin, S Meikle, SF AF Brubaker, Linda Richter, Holly E. Barber, Matthew D. Hsu, Yvonne Rahn, David D. Menefee, Shawn Visco, Anthony Spino, Cathie Martin, Susan Meikle, Susan F. TI Pelvic floor disorders clinical trials: participant recruitment and retention SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article DE Research; Focus group; Web focus group; Pelvic floor disorders; Incentives ID ONLINE FOCUS GROUPS; SYSTEM; WOMEN AB We used a focus-group methodology to gather information about women's knowledge and attitudes regarding research participation. Two in-person focus groups at seven clinical sites were conducted in women with pelvic floor disorder (PFD): one of women with clinical trial study experience and the other without such experience. One Web-based focus group combining both groups was also conducted. One hundred and five women (average age 58.6 years) participated. Participants in both groups believed that their physicians were the best source of information about clinical trials yet felt that other sources of trial information were important. Financial compensation was not a primary motivating factor for PFD trial enrollment but was, however, cited as an important consideration. Internet collection of data was feasible and provided information comparable with in-person focus groups. This study identified central themes guiding successful recruitment to and retention in PFD-related trials and provided insight regarding strategies that may guide future trials. C1 [Brubaker, Linda] Loyola Univ Chicago, Stritch Sch Med, Maywood, IL 60153 USA. [Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL USA. [Barber, Matthew D.] Cleveland Clin, Cleveland, OH 44106 USA. [Hsu, Yvonne] Univ Utah, Salt Lake City, UT USA. [Rahn, David D.] Univ Texas SW, Dallas, TX USA. [Menefee, Shawn] Kaiser Permanente, San Diego, CA USA. [Visco, Anthony] Duke, Durham, NC USA. [Spino, Cathie] Univ Michigan, Ann Arbor, MI 48109 USA. [Martin, Susan] RTI Hlth Solut, Ann Arbor, MI USA. [Meikle, Susan F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Brubaker, L (reprint author), Loyola Univ Chicago, Stritch Sch Med, 2160 S 1st Ave,SSOM413, Maywood, IL 60153 USA. EM lbrubaker@lumc.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241]; NIH Office of Research on Women's Health FX The Eunice Kennedy Shriver National Institute of Child Health and Human Development, (2U01 HD41249, 2U10 HD41250, 2U10 HD41261, 2U10 HD41267, 1U10 HD54136, 1U10 HD54214, 1U10 HD54215, 1U10 HD54241) and the NIH Office of Research on Women's Health NR 9 TC 0 Z9 0 U1 0 U2 5 PU SPRINGER LONDON LTD PI LONDON PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD JAN PY 2013 VL 24 IS 1 BP 73 EP 79 DI 10.1007/s00192-012-1824-x PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 064JX UT WOS:000313072300010 PM 22669424 ER PT J AU Srivastava, S Baxa, U Niu, G Chen, XY Veech, RL AF Srivastava, Shireesh Baxa, Ulrich Niu, Gang Chen, Xiaoyuan Veech, Richard L. TI A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice SO IUBMB LIFE LA English DT Article DE adipose tissue; mitochondrial size; sympathetic activity; energy expenditure; obesity; blood ketones ID SYMPATHETIC-NERVOUS-SYSTEM; MEDIUM-CHAIN TRIGLYCERIDE; FED CAFETERIA DIETS; LOW-CARBOHYDRATE; HIGH-FAT; UNCOUPLING PROTEIN-1; ENERGY-BALANCE; ADULT HUMANS; THERMOGENESIS; LEPTIN AB We evaluated the effects of feeding a ketogenic diet (KD) for a month on general physiology with emphasis on brown adipose tissue (BAT) in mice. KD did not reduce the caloric intake, or weight or lipid content of BAT. Relative epididymal fat pads were 40% greater in the mice fed the KD (P = 0.06) while leptin was lower (P < 0.05). Blood glucose levels were 30% lower while D-beta-hydroxybutyrate levels were about 3.5-fold higher in the KD group. Plasma insulin and leptin levels in the KD group were about half of that of the mice fed NIH-31 pellets (chow group). Median mitochondrial size in the interscapular BAT (IBAT) of the KD group was about 60% greater, whereas the median lipid droplet size was about half of that in the chow group. Mitochondrial oxidative phosphorylation proteins were increased (1.53-fold) and the uncoupling protein 1 levels were increased by threefold in mice fed the KD. The levels of PPAR?, PGC-1a, and Sirt1 in KD group were 1.53-fold while level of Sirt3 was about half of that in the chow-fed group. IBAT cyclic AMP levels were 60% higher in the KD group and cAMP response element binding protein was 2.5-fold higher, suggesting increased sympathetic system activity. These results demonstrate that a KD can also increase BAT mitochondrial size and protein levels. (c) 2012 IUBMB Life, 65(1):5866, 2013 C1 [Srivastava, Shireesh; Veech, Richard L.] NIAAA, Lab Metab Control, NIH, Rockville, MD 20852 USA. [Baxa, Ulrich] NIH, Electron Microscopy Lab, Adv Technol Program, SAIC Frederick Inc,Frederick Natl Lab Canc Res, Frederick, MD USA. [Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD USA. RP Veech, RL (reprint author), 5625 Fishers Lane,Room 2S-28, Rockville, MD 20852 USA. EM rveech@mail.nih.gov FU Intramural NIH HHS [ZIA AA000110-15] NR 30 TC 7 Z9 8 U1 1 U2 33 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1521-6543 J9 IUBMB LIFE JI IUBMB Life PD JAN PY 2013 VL 65 IS 1 SI SI BP 58 EP 66 DI 10.1002/iub.1102 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 061YM UT WOS:000312886200009 PM 23233333 ER PT J AU Fleischer, DM Burks, AW Vickery, BP Scurlock, AM Wood, RA Jones, SM Sicherer, SH Liu, AH Stablein, D Henning, AK Mayer, L Lindblad, R Plaut, M Sampson, HA AF Fleischer, David M. Burks, A. Wesley Vickery, Brian P. Scurlock, Amy M. Wood, Robert A. Jones, Stacie M. Sicherer, Scott H. Liu, Andrew H. Stablein, Donald Henning, Alice K. Mayer, Lloyd Lindblad, Robert Plaut, Marshall Sampson, Hugh A. CA Consortium Food Allergy Res CoFAR TI Sublingual immunotherapy for peanut allergy: A randomized, double-blind, placebo-controlled multicenter trial SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Peanut allergy; sublingual immunotherapy; desensitization; food allergy ID QUALITY-OF-LIFE; ORAL TOLERANCE INDUCTION; HAZELNUT FOOD ALLERGY; COWS MILK ALLERGY; NATURAL-HISTORY; ANAPHYLACTIC REACTIONS; RESOURCE IMPLICATIONS; BUDGET IMPACT; KIWI FRUIT; CHILDREN AB Background: There are presently no available therapeutic options for patients with peanut allergy. Objective: We sought to investigate the safety, efficacy, and immunologic effects of peanut sublingual immunotherapy (SLIT). Methods: After a baseline oral food challenge (OFC) of up to 2 g of peanut powder (approximately 50% protein; median successfully consumed dose [SCD], 46 mg), 40 subjects, aged 12 to 37 years (median, 15 years), were randomized 1:1 across 5 sites to daily peanut or placebo SLIT. A 5-g OFC was performed after 44 weeks, followed by unblinding; placebo-treated subjects then crossed over to higher dose peanut SLIT, followed by a subsequent crossover Week 44 5-g OFC. Week 44 OFCs from both groups were compared with baseline OFCs; subjects successfully consuming 5 g or at least 10-fold more peanut powder than the baseline OFC threshold were considered responders. Results: After 44 weeks of SLIT, 14 (70%) of 20 subjects receiving peanut SLIT were responders compared with 3 (15%) of 20 subjects receiving placebo (P < .001). In peanut SLIT responders, median SCD increased from 3.5 to 496 mg. After 68 weeks of SLIT, median SCD significantly increased to 996 mg (compared with Week 44, P = .05). The median SCD at the Week 44 Crossover OFC was significantly higher than baseline (603 vs 71 mg, P = .02). Seven (44%) of 16 crossover subjects were responders; median SCD increased from 21 to 496 mg among responders. Of 10,855 peanut doses through the Week 44 OFCs, 63.1% were symptom free; excluding oral-pharyngeal symptoms, 95.2% were symptom free. Conclusions: Peanut SLIT safely induced a modest level of desensitization in a majority of subjects compared with placebo. Longer duration of therapy showed statistically significant increases in the SCD. (J Allergy Clin Immunol 2013;131:119-27.) C1 [Fleischer, David M.; Liu, Andrew H.] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA. [Burks, A. Wesley; Vickery, Brian P.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. [Scurlock, Amy M.; Jones, Stacie M.] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Scurlock, Amy M.; Jones, Stacie M.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. [Sicherer, Scott H.; Mayer, Lloyd; Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, New York, NY USA. [Stablein, Donald; Henning, Alice K.; Lindblad, Robert] EMMES Corp, Rockville, MD USA. [Plaut, Marshall] NIAID, NIH, Bethesda, MD 20892 USA. RP Fleischer, DM (reprint author), Natl Jewish Hlth, Dept Pediat, 1400 Jackson St,J321, Denver, CO 80206 USA. EM Fleischerd@njhealth.org FU National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) [U19AI066738, U01AI066560]; National Center for Research Resources (NCRR)/National Institutes of Health (NIH) [UL1 RR025780]; NIH/National Center for Advancing Translational Sciences (National Jewish) [UL1 TR000154]; NCRR [UL1 TR000067, UL1 TR000039, UL1 RR024128, UL1 RR 025005]; NIH; Department of Defense; Wallace Research Foundation; NIH/NIAID; American Lung Association, Cephalon; Foundation of the American College of Allergy, Asthma Immunology; Thrasher Research Fund; Food Allergy & Anaphylaxis Network; National Peanut Board; NIAID; UpToDate; Elsevier-Wiley FX Supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases (NIAID) grant U19AI066738 and U01AI066560. The project was also supported by grant no. UL1 RR025780 from the National Center for Research Resources (NCRR)/National Institutes of Health (NIH) and grant nos. UL1 TR000154 from the NIH/National Center for Advancing Translational Sciences (National Jewish) and grant nos. UL1 TR000067 (Mount Sinai), UL1 TR000039 (Arkansas), UL1 RR024128 (North Carolina), and UL1 RR 025005 (Johns Hopkins) from the NCRR. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH.; D. M. Fleischer has received grants from the National Institutes of Health (NIH)/National Institutes of Allergy and Infectious Diseases (NIAID), has consultant arrangements with Sanofi-Aventis, is employed by National Jewish Health, and receives royalties from UpToDate. A. W. Burks has board memberships with the American Academy of Allergy, Asthma & Immunology, the NIH Hypersensitivity, Autoimmune, and Immune-mediated Diseases study section, the US Food and Drug Administration, and the Journal of Allergy and Clinical Immunology; is on advisory boards for the Food Allergy & Anaphylaxis Network, ActoGeniX, and Exploramed Development; has consultant arrangements with Merck, Novartis Pharma AG, the Dannon Company, McNeill Nutritionals, and Schering-Plough; is employed by UNC Children's Hospital and Duke University; has received grants from the NIH; has grants pending from the Department of Defense and the Wallace Research Foundation; receives payment for lectures from Myland Specialty; receives royalties from UpToDate; receives payment for development of educational presentations from Current Views; has stock/stock options with Allertein, Mastcell Pharmaceuticals, and Dow AgroSciences; and has received travel expenses from the European Academy of Allergy and Clinical Immunology. B. P. Vickery has received grants and travel support from the NIH/NIAID and has received grants from the American Lung Association, Cephalon, the Foundation of the American College of Allergy, Asthma & Immunology, and the Thrasher Research Fund. A. M. Scurlock has received grants from the NIH. R. A. Wood has consultant arrangements with the Asthma and Allergy Foundation of America, is employed by Johns Hopkins University, has provided expert testimony for the NIH, and received royalties from UpToDate. S. M. Jones has received grants from the NIH, the Food Allergy & Anaphylaxis Network, and the National Peanut Board; is on the Medical Advisory Board for the Food Allergy & Anaphylaxis Network; has received payment for lectures from Abbot Nutrition International, the Kentucky Society for Allergy, Asthma, and Immunology, the New England Allergy Society, the American College of Allergy, Asthma & Immunology, Indiana University Medical School and Riley Children's Hospital, the Spanish Society of Allergy and Clinic Immunology, and Oregon Allergy, Asthma & Immunology; and serves on the National Institute of Allergy and Infectious Disease Safety Monitoring Committee, the Arkansas Medicaid Drug Review Committee, and the NIAID Study Section. S. H. Sicherer has received grants from the NIH/NIAID and has consultant arrangements with the Food Allergy Initiative. D. Stablein has received grants from the NIH. A. K. Henning has received grants from the NIH. R. Lindblad has received grants from the NIH/NIAID. H. A. Sampson has received grants and travel support from the NIAID, has received grants from the NIH, is on the Danone Scientific Advisory Board, has consultant arrangements with Allertein Therapeutics and the Food Allergy Initiative, is employed by Mount Sinai Medical School, and has received royalties from Elsevier-Wiley and UpToDate. The rest of the authors declare that they have no relevant conflicts of interest. NR 52 TC 104 Z9 104 U1 2 U2 32 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2013 VL 131 IS 1 BP 119 EP U184 DI 10.1016/j.jaci.2012.11.011 PG 16 WC Allergy; Immunology SC Allergy; Immunology GA 062YR UT WOS:000312961200015 PM 23265698 ER PT J AU Du Toit, G Roberts, G Sayre, PH Plaut, M Bahnson, HT Mitchell, H Radulovic, S Chan, S Fox, A Turcanu, V Lack, G AF Du Toit, George Roberts, Graham Sayre, Peter H. Plaut, Marshall Bahnson, Henry T. Mitchell, Herman Radulovic, Suzana Chan, Susan Fox, Adam Turcanu, Victor Lack, Gideon CA Learning Early Peanut Allergy LEAP TI Identifying infants at high risk of peanut allergy: The Learning Early About Peanut Allergy (LEAP) screening study SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Peanut sensitization; peanut allergy; allergy risk factors; eczema; egg allergy; patient recruitment; allergy prevention; LEAP study ID MEDIATED FOOD ALLERGY; SKIN PRICK; ANAPHYLACTIC REACTIONS; IGE CONCENTRATIONS; CHILDREN; PREVALENCE; CHILDHOOD; SENSITIZATION; ADOLESCENTS; CHALLENGES AB Background: Peanut allergy (PA) is rare in countries in which peanuts are introduced early into infants' diets. Learning Early About Peanut Allergy (LEAP) is an interventional study aiming to assess whether PA can be prevented by oral tolerance induction. Objective: We sought to characterize a population screened for the risk of PA. Methods: Subjects screened for the LEAP interventional trial comprise the LEAP screening study cohort. Infants were aged 4 to 10 months and passed a prescreening questionnaire. Results: This analysis includes 834 infants (mean age, 7.8 months). They were split into the following: group I, patients with mild eczema and no egg allergy (n = 118); group II, patients with severe eczema, egg allergy, or both but 0-mm peanut skin prick test (SPT) wheal responses (n = 542); group III, patients with severe eczema, egg allergy, or both and 1- to 4-mm peanut wheal responses (n = 98); and group IV, patients with greater than 4-mm peanut wheal responses (n = 76). Unexpectedly, many (17%) in group II had peanut-specific IgE sensitization (>= 0.35 kU/L); 56% of group III were similarly sensitized. In contrast, none of the patients in group I and 91% of those in group IV had peanut-specific IgE sensitization. Sensitization on skin testing to peanut (SPT response of 1- 4 mm vs 0 mm) was associated with egg allergy and severe eczema (odds ratio [OR], 2.31 [95% CI, 1.39-3.86] and 2.47 [95% CI, 1.14-5.34], respectively). Similar associations were observed with specific IgE sensitization. Black race was associated with a significantly higher risk of peanut-specific IgE sensitization (OR, 5.30 [95% CI, 2.85-9.86]). Paradoxically, for a given specific IgE level, black race was protective against cutaneous sensitization (OR, 0.15 [95% CI, 0.04-0.61]). Conclusion: Egg allergy, severe eczema, or both appear to be useful criteria for identifying high-risk infants with an intermediate level of peanut sensitization for entry into a PA prevention study. The relationship between specific IgE level and SPT sensitization needs to be considered within the context of race. (J Allergy Clin Immunol 2013;131:135-43.) C1 [Du Toit, George; Radulovic, Suzana; Chan, Susan; Fox, Adam; Turcanu, Victor; Lack, Gideon] Kings Coll London, Kings Hlth Partners, MRC & Asthma UK Ctr Allerg Mech Asthma, London WC2R 2LS, England. [Du Toit, George; Radulovic, Suzana; Chan, Susan; Fox, Adam; Turcanu, Victor; Lack, Gideon] Guys & St Thomas NHS Fdn Trust, Dept Paediat Allergy, London, England. [Roberts, Graham] Univ Southampton, Southampton SO9 5NH, Hants, England. [Sayre, Peter H.] Immune Tolerance Network, San Francisco, CA USA. [Sayre, Peter H.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Plaut, Marshall] NIAID, Bethesda, MD 20892 USA. [Bahnson, Henry T.; Mitchell, Herman] Rho Fed Syst, Chapel Hill, NC USA. RP Lack, G (reprint author), St Thomas Hosp, 2nd Floor,South Wing, London SE1 7EH, England. EM gideon.lack@kcl.ac.uk RI Fox, Adam/O-3547-2015 OI Fox, Adam/0000-0002-3533-9798 FU Immune Tolerance Network; National Institute of Allergy and Infectious Diseases; Food Allergy Initiative, New York, NY; Food Standards Agency, United Kingdom; Food Allergy and Anaphylaxis Network, Fairfax, Va; MRC & Asthma UK Centre; King's College London; King's College Hospital NHS Foundation Trust; National Peanut Board, Atlanta, Ga; Immune Tolerance Network (ITN); National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health; ITN/NIAID; Food Allergy Initiative; National Peanut Board; Food Standards Agency; Food Allergy & Anaphylaxis Network; Department of Health through the National Institute for Health Research Comprehensive Biomedical Research Centre award; ITN; Food Allergy and Anaphylaxis Network; Sodilac; Novartis; Nestle Nutrition; GlaxoSmithKline; Serono Symposia International Foundation FX This study was supported by the Immune Tolerance Network (funded by the National Institute of Allergy and Infectious Diseases); the Food Allergy Initiative, New York, NY; the Food Standards Agency, United Kingdom; the Food Allergy and Anaphylaxis Network, Fairfax, Va; the MRC & Asthma UK Centre; and the Department of Health through 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 and King's College Hospital NHS Foundation Trust. The clinical trials unit is supported by the National Peanut Board, Atlanta, Ga.; G. Roberts has received research support from the Immune Tolerance Network (ITN). P. H. Sayre has received travel support from the National Institute of Allergy and Infectious Diseases (NIAID). H. T. Bahnson and H. Mitchell have received research support from the National Institutes of Health. S. Radulovic has received research support from the ITN/NIAID, the Food Allergy Initiative, and the National Peanut Board and has received travel support from Stallergenes and the Allergy Academy. S. Chan has received research support from the ITN/NIAID, the Food Allergy Initiative, the National Peanut Board, the Food Standards Agency, the Food Allergy & Anaphylaxis Network, MRC & Asthma UK Centre, and the Department of Health through the National Institute for Health Research Comprehensive Biomedical Research Centre award to the Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. V. Turcanu has received research support from the ITN. G. Lack has received research support from the ITN/NIAID, the Food Allergy Initiative, the National Peanut Board, the Food Standards Agency, the Food Allergy and Anaphylaxis Network, MRC Asthma UK Centre, and the Department of Health through the National Institute for Health Research Comprehensive Biomedical Research Centre award to the Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust; is on the DBV Technologies advisory board; is a voluntary scientific advisor for the Anaphylaxis Campaign and the National Peanut Board; has received lecture fees from Sodilac, Novartis, Nestle Nutrition, GlaxoSmithKline, and the Serono Symposia International Foundation; and has stock/stock options in DBV Technologies. The rest of the authors declare that they have no relevant conflicts of interest. NR 35 TC 58 Z9 59 U1 2 U2 26 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JAN PY 2013 VL 131 IS 1 BP 135 EP U215 DI 10.1016/j.jaci.2012.09.015 PG 21 WC Allergy; Immunology SC Allergy; Immunology GA 062YR UT WOS:000312961200017 PM 23174658 ER PT J AU Hood, K Brevard, J Nguyen, AB Belgrave, F AF Hood, Kristina Brevard, Joshua Anh Bao Nguyen Belgrave, Faye TI Stress Among African American Emerging Adults: The Role of Family and Cultural Factors SO JOURNAL OF CHILD AND FAMILY STUDIES LA English DT Article DE Family cohesion; Parental monitoring; Racial identity; Stress; African Americans ID ADOLESCENT ALCOHOL-USE; HEALTH-RISK BEHAVIORS; ETHNIC-IDENTITY; PROTECTIVE FACTORS; SELF-ESTEEM; ACADEMIC-ACHIEVEMENT; PARENTAL AUTHORITY; RACIAL IDENTITY; SOCIAL SUPPORT; DRUG-USE AB The aim of this study was to examine the effects of family and cultural variables on stress among African American emerging adults. Data from this study was collected as part of a larger study that examined cultural, family, and contextual factors and smoking among African American youth in 5th, 8th, and 12th grades. Data were collected from high school seniors at the end of their 12th grade year and 6 months post high school. Multiple regression analyses were conducted to determine whether racial identity, family cohesion, and parental monitoring influence students' perceived frequency of stress. Higher levels of racial identity were associated with more perceived stress. There were no significant main effects for either parental monitoring or family cohesion on stress. There were significant interactions between racial identity and parental monitoring and between parental monitoring and family cohesion. Study implications are discussed regarding the importance of stress reduction programs for African American emerging adults and for parents of these adults. C1 [Hood, Kristina; Brevard, Joshua; Belgrave, Faye] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. [Anh Bao Nguyen] NCI, Bethesda, MD 20892 USA. RP Hood, K (reprint author), Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA. EM hoodkb@vcu.edu OI Hood, Kristina/0000-0003-4817-9882 NR 58 TC 2 Z9 2 U1 1 U2 19 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1062-1024 J9 J CHILD FAM STUD JI J. Child Fam. Stud. PD JAN PY 2013 VL 22 IS 1 BP 76 EP 84 DI 10.1007/s10826-012-9639-4 PG 9 WC Family Studies; Psychology, Developmental; Psychiatry SC Family Studies; Psychology; Psychiatry GA 060NB UT WOS:000312783900008 ER PT J AU Kovalchik, SA Ronckers, CM Veiga, LHS Sigurdson, AJ Inskip, PD de Vathaire, F Sklar, CA Donaldson, SS Anderson, H Bhatti, P Hammond, S Leisenring, WM Mertens, AC Smith, SA Stovall, M Tucker, MA Weathers, RE Robison, LL Pfeiffer, RM AF Kovalchik, Stephanie A. Ronckers, Cecile M. Veiga, Lene H. S. Sigurdson, Alice J. Inskip, Peter D. de Vathaire, Florent Sklar, Charles A. Donaldson, Sarah S. Anderson, Harald Bhatti, Parveen Hammond, Sue Leisenring, Wendy M. Mertens, Ann C. Smith, Susan A. Stovall, Marilyn Tucker, Margaret A. Weathers, Rita E. Robison, Leslie L. Pfeiffer, Ruth M. TI Absolute Risk Prediction of Second Primary Thyroid Cancer Among 5-Year Survivors of Childhood Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NORDIC COUNTRIES; POOLED ANALYSIS; LATE MORTALITY; BREAST-CANCER; RADIATION; COHORT; RADIOTHERAPY; NEOPLASMS; MODELS; IRRADIATION AB Purpose We developed three absolute risk models for second primary thyroid cancer to assist with long-term clinical monitoring of childhood cancer survivors. Patients and Methods We used data from the Childhood Cancer Survivor Study (CCSS) and two nested case-control studies (Nordic CCSS; Late Effects Study Group). Model M1 included self-reported risk factors, model M2 added basic radiation and chemotherapy treatment information abstracted from medical records, and model M3 refined M2 by incorporating reconstructed radiation absorbed dose to the thyroid. All models were validated in an independent cohort of French childhood cancer survivors. Results M1 included birth year, initial cancer type, age at diagnosis, sex, and past thyroid nodule diagnosis. M2 added radiation (yes/no), radiation to the neck (yes/no), and alkylating agent (yes/no). Past thyroid nodule was consistently the strongest risk factor (M1 relative risk [RR], 10.8; M2 RR, 6.8; M3 RR, 8.2). In the validation cohort, 20-year absolute risk predictions for second primary thyroid cancer ranged from 0.04% to 7.4% for M2. Expected events agreed well with observed events for each model, indicating good calibration. All models had good discriminatory ability (M1 area under the receiver operating characteristics curve [AUC], 0.71; 95% CI, 0.64 to 0.77; M2 AUC, 0.80; 95% CI, 0.73 to 0.86; M3 AUC, 0.75; 95% CI, 0.69 to 0.82). Conclusion We developed and validated three absolute risk models for second primary thyroid cancer. Model M2, with basic prior treatment information, could be useful for monitoring thyroid cancer risk in childhood cancer survivors. J Clin Oncol 31: 119-127. (c) 2012 by American Society of Clinical Oncology C1 [Pfeiffer, Ruth M.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. [Ronckers, Cecile M.] Late Effects Childhood Canc Treatment, Dutch Childhood Oncol Grp, The Hague, Netherlands. [Veiga, Lene H. S.] Brazilian Nucl Energy Commiss, Rio De Janeiro, Brazil. [de Vathaire, Florent] Natl Inst Hlth & Med Res, U1018, Villejuif, France. [Sklar, Charles A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Donaldson, Sarah S.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. [Anderson, Harald] Lund Univ, Lund, Sweden. [Bhatti, Parveen; Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Hammond, Sue] Nationwide Childrens Hosp, Columbus, OH USA. [Mertens, Ann C.] Emory Univ, Sch Med, Atlanta, GA USA. [Smith, Susan A.; Stovall, Marilyn; Weathers, Rita E.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8030, Rockville, MD 20852 USA. EM pfeiffer@mail.nih.gov RI Tucker, Margaret/B-4297-2015; de Vathaire, Florent/L-2983-2016 FU Intramural Research Program of the National Cancer Institute (NCI), National Institutes of Health; NCI [U24 CA55727] FX Supported by the Intramural Research Program of the National Cancer Institute (NCI), National Institutes of Health. The Childhood Cancer Survivor Study was supported by Grant No. U24 CA55727 from the NCI (L.L.R.). NR 44 TC 17 Z9 17 U1 1 U2 21 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 JAN 1 PY 2013 VL 31 IS 1 BP 119 EP 127 DI 10.1200/JCO.2012.41.8996 PG 9 WC Oncology SC Oncology GA 062IE UT WOS:000312911900025 PM 23169509 ER PT J AU Wiestner, A AF Wiestner, Adrian TI Targeting B-Cell Receptor Signaling for Anticancer Therapy: The Bruton's Tyrosine Kinase Inhibitor Ibrutinib Induces Impressive Responses in B-Cell Malignancies SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ANTIGEN RECEPTORS; LYMPHOMA; PCI-32765; ACTIVATION; REGRESSION; INDICATE; SURVIVAL; BIOLOGY; SETS C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Wiestner, A (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 30 TC 54 Z9 60 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 JAN 1 PY 2013 VL 31 IS 1 BP 128 EP 130 DI 10.1200/JCO.2012.44.4281 PG 3 WC Oncology SC Oncology GA 062IE UT WOS:000312911900026 PM 23045586 ER PT J AU Kiblawi, ZN Smith, LM LaGasse, LL Derauf, C Newman, E Shah, R Arria, A Huestis, M DellaGrotta, S Dansereau, LM Neal, C Lester, B AF Kiblawi, Zeina N. Smith, Lynne M. LaGasse, Linda L. Derauf, Chris Newman, Elana Shah, Rizwan Arria, Amelia Huestis, Marilyn DellaGrotta, Sheri Dansereau, Lynne M. Neal, Charles Lester, Barry TI The Effect of Prenatal Methamphetamine Exposure on Attention as Assessed by Continuous Performance Tests: Results from the Infant Development, Environment, and Lifestyle Study SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE methamphetamine; prenatal; neurodevelopment; attention-deficit hyperactivity disorder (ADHD) ID SUBSTANCE EXPOSURE; COCAINE EXPOSURE; DRUG EXPOSURE; CHILDREN; ALCOHOL; AMPHETAMINE; PREGNANCY; AGE AB Objective: To assess for the increased risk of attention-deficit hyperactivity disorder (ADHD) in young children with prenatal methamphetamine exposure from the multicenter, longitudinal Infant Development, Environment, and Lifestyle (IDEAL) study. Methods: The IDEAL study enrolled 412 mother-infant pairs at 4 sites (Tulsa, OK; Des Moines, IA; Los Angeles, CA; and Honolulu, HI). Methamphetamine-exposed subjects (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched subjects (n = 208) denied methamphetamine use and had a negative meconium screen. This analysis included a subsample of 301 subjects who were administered the Conners' Kiddie Continuous Performance Test (K-CPT) at 5.5 years of age (153 exposed and 148 comparison). Hierarchical linear models adjusted for covariates tested exposure effects on K-CPT measures. Using the same covariates, logistic regression was used to determine the effect of exposure on the incidence of a positive ADHD confidence index score, defined as greater than 50%. Results: There were no differences between the groups in omission or commission errors or reaction time for correct trials. However, methamphetamine exposure was associated with subtle differences in other outcomes predictive of ADHD, including increased slope of reaction time across blocks (p < .001), increased variability in reaction time with longer interstimulus intervals (p < .01), and increased likelihood of greater than 50% on the ADHD confidence index (odds ratio, 3.1; 95% confidence interval, 1.2-7.8; p = .02). Conclusion: Prenatal methamphetamine exposure was associated with subtle differences in K-CPT scores at 5.5 years of age. Even at this relatively young age, these children exhibit indicators of risk for ADHD and warrant monitoring. (J Dev Behav Pediatr 34:31-37, 2013) C1 [Kiblawi, Zeina N.; Smith, Lynne M.] Harbor UCLA Med Ctr, David Geffen Sch Med, LA BioMed Inst, Los Angeles, CA USA. [LaGasse, Linda L.; DellaGrotta, Sheri; Dansereau, Lynne M.; Lester, Barry] Brown Univ, Women & Infants Hosp, Warren Alpert Med Sch, Ctr Study Children Risk, Providence, RI USA. [Derauf, Chris; Neal, Charles] Univ Hawaii, John A Burns Sch Med, Dept Pediat, Honolulu, HI 96822 USA. [Newman, Elana] Univ Tulsa, Dept Psychol, Tulsa, OK 74104 USA. [Shah, Rizwan] Iowa Hlth, Blank Hosp Reg Child Protect Ctr, Des Moines, IA USA. [Arria, Amelia] Univ Maryland, Sch Publ Hlth, Ctr Young Adult Hlth & Dev, College Pk, MD 20742 USA. [Huestis, Marilyn] NIDA, Intramural Res Program, NIH, Baltimore, MD USA. RP Smith, LM (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Inst, 1124 W Carson St,Box 446, Torrance, CA 90502 USA. EM smith@labiomed.org OI Arria, Amelia/0000-0002-6360-9265 FU NIDA [1RO1DA014948]; National Center on Research Resources Grant [1UL1-TR000124, 5P20 RR11091] FX Supported by NIDA Grant 1RO1DA014948 and in part by the National Center on Research Resources Grant 1UL1-TR000124 and 5P20 RR11091. The authors report no conflicts of interest to disclose. NR 30 TC 9 Z9 9 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD JAN PY 2013 VL 34 IS 1 BP 31 EP 37 DI 10.1097/DBP.0b013e318277a1c5 PG 7 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 063QS UT WOS:000313015500005 PM 23275056 ER PT J AU Zhou, H Liao, JY Aloor, J Nie, H Wilson, BC Fessler, MB Gao, HM Hong, JS AF Zhou, Hui Liao, Jieying Aloor, Jim Nie, Hui Wilson, Belinda C. Fessler, Michael B. Gao, Hui-Ming Hong, Jau-Shyong TI CD11b/CD18 (Mac-1) Is a Novel Surface Receptor for Extracellular Double-Stranded RNA To Mediate Cellular Inflammatory Responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-3; COMPLEMENT RECEPTOR-3; ESCHERICHIA-COLI; EPITHELIAL-CELLS; VIRAL-INFECTION; CR3 CD11B/CD18; NADPH OXIDASE; KAPPA-B; MACROPHAGES; ACTIVATION AB During viral infection, extracellular dsRNA is a potent signaling molecule that activates many innate immune cells, including macrophages. TLR3 is a well-known receptor for extracellular dsRNA, and internalization of extracellular dsRNA is required for endosomal TLR3 activation. Preserved inflammatory responses of TLR3-deficient macrophages to extracellular dsRNA strongly support a TLR3-independent mechanism in dsRNA-mediated immune responses. The present study demonstrated that CD11b/CD18 (Mac-1 [macrophage-1 Ag]), a surface integrin receptor, recognized extracellular dsRNA and induced macrophage immune responses. CD11b deficiency reduced inflammatory cytokine induction elicited by polyinosinic: polycytidylic acid (poly I: C; a synthetic dsRNA) in mouse sera and livers, as well as in cultured peritoneal macrophages. dsRNA-binding assay and confocal immunofluorescence showed that Mac-1, especially the CD11b subunit, interacted and colocalized with poly I: C on the surface of macrophages. Further mechanistic studies revealed two distinct signaling events following dsRNA recognition by Mac-1. First, Mac-1 facilitated poly I: C internalization through the activation of PI3K signaling and enhanced TLR3-dependent activation of IRF3 in macrophages. Second, poly I: C induced activation of phagocyte NADPH oxidase in a TLR3-independent, but Mac-1-dependent, manner. Subsequently, phagocyte NADPH oxidase-derived intracellular reactive oxygen species activated MAPK and NF-kappa B pathways. Our results indicate that extracellular dsRNA activates Mac-1 to enhance TLR3-dependent signaling and to trigger TLR3-independent, but Mac-1-dependent, inflammatory oxidative signaling, identifying a novel mechanistic basis for macrophages to recognize extracellular dsRNA to regulate innate immune responses. This study identifies Mac-1 as a novel surface receptor for extracellular dsRNA and implicates it as a potential therapeutic target for virus-related inflammatory diseases. The Journal of Immunology, 2013, 190: 115-125. C1 [Zhou, Hui; Liao, Jieying; Nie, Hui; Wilson, Belinda C.; Gao, Hui-Ming; Hong, Jau-Shyong] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA. [Aloor, Jim; Fessler, Michael B.] NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. [Gao, Hui-Ming] Nanjing Univ, Lab Neuroimmunol & Neuropharmacol, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China. RP Gao, HM (reprint author), NIEHS, Lab Toxicol & Pharmacol, POB 12233,MD F1-01, Res Triangle Pk, NC 27709 USA. EM gao2@niehs.nih.gov FU National Institutes of Health; National Institute of Environmental Health Sciences FX This work was supported by the Intramural Research Program of the National Institutes of Health and the National Institute of Environmental Health Sciences. NR 54 TC 18 Z9 21 U1 0 U2 15 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2013 VL 190 IS 1 BP 115 EP 125 DI 10.4049/jimmunol.1202136 PG 11 WC Immunology SC Immunology GA 061FB UT WOS:000312832500014 PM 23209319 ER PT J AU Kortum, RL Rouquette-Jazdanian, AK Miyaji, M Merrill, RK Markegard, E Pinski, JM Wesselink, A Nath, NN Alexander, CP Li, WM Kedei, N Roose, JP Blumberg, PM Samelson, LE Sommers, CL AF Kortum, Robert L. Rouquette-Jazdanian, Alexandre K. Miyaji, Michihiko Merrill, Robert K. Markegard, Evan Pinski, John M. Wesselink, Amelia Nath, Nandan N. Alexander, Clayton P. Li, Wenmei Kedei, Noemi Roose, Jeroen P. Blumberg, Peter M. Samelson, Lawrence E. Sommers, Connie L. TI A Phospholipase C-gamma 1-Independent, RasGRP1-ERK-Dependent Pathway Drives Lymphoproliferative Disease in Linker for Activation of T Cells-Y136F Mutant Mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; AVIAN-SARCOMA VIRUS; CELL-ACTIVATION; ERK ACTIVATION; RAS ACTIVATION; PKC-THETA; TYROSINE PHOSPHORYLATION; TRANSFORMING GENE; POINT MUTATION; RECEPTOR AB Mice expressing a germline mutation in the phospholipase C-gamma 1-binding site of linker for activation of T cells (LAT) show progressive lymphoproliferation and ultimately die at 4-6 mo age. The hyperactivated T cells in these mice show defective TCR-induced calcium flux but enhanced Ras/ERK activation, which is critical for disease progression. Despite the loss of LAT-dependent phospholipase C-gamma 1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major Ras guanine exchange factor responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4(+) T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70-and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, protein kinase C-theta, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. The Journal of Immunology, 2013, 190: 147-158. C1 [Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Samelson, Lawrence E.; Sommers, Connie L.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Markegard, Evan; Roose, Jeroen P.] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. [Kedei, Noemi; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), NCI, Lab Cellular & Mol Biol, NIH, 37 Convent Dr,Bldg 37,Room 2064, Bethesda, MD 20892 USA. EM sommersc@helix.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; National Institute of General Medical Sciences, National Institutes of Health FX This work was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. R. L. K. received additional support from a Pharmacology Research and Training Fellowship, National Institute of General Medical Sciences, National Institutes of Health. NR 66 TC 9 Z9 9 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2013 VL 190 IS 1 BP 147 EP 158 DI 10.4049/jimmunol.1201458 PG 12 WC Immunology SC Immunology GA 061FB UT WOS:000312832500017 PM 23209318 ER PT J AU Han, KL Thomas, SVM Koontz, SM Changpriroa, CM Ha, SK Malech, HL Kang, EM AF Han, Kyu Lee Thomas, Stephenie V. M. Koontz, Sherry M. Changpriroa, Cattlena M. Ha, Seung-Kwon Malech, Harry L. Kang, Elizabeth M. TI Adenosine A(2A) Receptor Agonist-Mediated Increase in Donor-Derived Regulatory T Cells Suppresses Development of Graft-versus-Host Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PREVENT GVHD; CYCLIC-AMP; ACTIVATION; INFLAMMATION; METHOTREXATE; GENERATION; EXPRESSION; VIVO; INTERLEUKIN-2 AB Graft-versus-host disease (GVHD) remains a significant complication of allogeneic transplantation. We previously reported that the adenosine A(2A) receptor (A(2A)R) specific agonist, ATL146e, decreases the incidence and severity of GVHD in a mouse transplant model. There is increasing interest in treatments that increase CD4(+)CD25(high)Foxp3(+) regulatory T cells (Tregs) to suppress GVHD. Our current study found in vitro that A(2A)R selective agonists enhanced TGF-beta-induced generation of mouse Tregs 2.3- to 3-fold. We demonstrated in vivo suppression of GVHD with specific A(2A)R agonists in two different murine GVHD transplant models associated with profound increases in both circulating and target tissue Tregs of donor origin. Three different A(2A)R agonists of differing potency, ATL146e, ATL370, and ATL1223, all significantly inhibited GVHD-associated weight loss and mortality. At the same time, Tregs shown to be of donor origin increased 5.1- to 7.4-fold in spleen, 2.7- to 4.6-fold in peripheral blood, 2.3- to 4.7-fold in colon, and 3.8- to 4.6-fold in skin. We conclude that specific activation of A(2A)R inhibits acute GVHD through an increase of donor-derived Tregs. Furthermore, the increased presence of Tregs in target tissues (colon and skin) of A(2A)R-specific agonist-treated mice is likely the mechanistic basis for the anti-inflammatory effect preventing acute GVHD. The Journal of Immunology, 2013, 190: 458-468. C1 [Han, Kyu Lee; Thomas, Stephenie V. M.; Koontz, Sherry M.; Changpriroa, Cattlena M.; Malech, Harry L.; Kang, Elizabeth M.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Ha, Seung-Kwon] SK Chem Inc, Life Sci Res & Dev Ctr, Songnam 463410, Gyeonggi Do, South Korea. RP Kang, EM (reprint author), NIAID, Lab Host Def, NIH, Bldg 10,Room 6 3752,10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM ekang@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases FX This work was supported by intramural funds from the National Institute of Allergy and Infectious Diseases. NR 52 TC 14 Z9 14 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 1 PY 2013 VL 190 IS 1 BP 458 EP 468 DI 10.4049/jimmunol.1201325 PG 11 WC Immunology SC Immunology GA 061FB UT WOS:000312832500051 PM 23225892 ER PT J AU Cheng, XW Tan, Y He, ML Lam, TTY Lu, X Viboud, C He, JF Zhang, SX Lu, JH Wu, CL Fang, SS Wang, X Xie, X Ma, HW Nelson, MI Kung, HF Holmes, EC Cheng, JQ AF Cheng, Xiaowen Tan, Yi He, Mingliang Lam, Tommy Tsan-Yuk Lu, Xing Viboud, Cecile He, Jianfan Zhang, Shunxiang Lu, Jianhua Wu, Chunli Fang, Shishong Wang, Xin Xie, Xu Ma, Hanwu Nelson, Martha I. Kung, Hsiang-fu Holmes, Edward C. Cheng, Jinquan TI Epidemiological Dynamics and Phylogeography of Influenza Virus in Southern China SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE influenza; epidemiology; southern China; seasonality; phylogeography ID SEASONALITY; SURVEILLANCE; CIRCULATION; EVOLUTION; SHENZHEN AB Background. Understanding the epidemiological dynamics of influenza virus is central to surveillance and vaccine strain selection. It has been suggested that tropical and subtropical regions represent the global source of influenza epidemics. However, our understanding of the epidemiological dynamics of influenza virus in these regions is limited by a relative lack of long-term data. Methods. We analyzed epidemiological and virological data on influenza recorded over a period of 15 years from the metropolitan city of Shenzhen in subtropical southern China. We used wavelet analysis to determine the periodicity of influenza epidemics and molecular phylogeographic analysis to investigate the role of Shenzhen and southern China in the global evolution of influenza virus. Results. We show that southern China is unlikely to represent an epicenter of global influenza activity, because activity in Shenzhen is characterized by significant annual cycles, multiple viral introductions every year, limited persistence across epidemic seasons, and viruses that generally are not positioned on the trunk of the global influenza virus phylogeny. Conclusions. We propose that novel influenza viruses emerge and evolve in multiple geographic localities and that the global evolution of influenza virus is complex and does not simply originate from a southern Chinese epicenter. C1 [Cheng, Xiaowen; Lu, Xing; He, Jianfan; Zhang, Shunxiang; Lu, Jianhua; Wu, Chunli; Fang, Shishong; Wang, Xin; Xie, Xu; Ma, Hanwu; Cheng, Jinquan] Shenzhen Ctr Dis Control & Prevent, Shenzhen 518055, Guangdong, Peoples R China. [Tan, Yi; He, Mingliang; Kung, Hsiang-fu] Chinese Univ Hong Kong, Stanley Ho Ctr Emerging Infect Dis, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China. [Tan, Yi; He, Mingliang; Kung, Hsiang-fu] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Fac Med, Hong Kong, Hong Kong, Peoples R China. [Tan, Yi; Viboud, Cecile; Nelson, Martha I.; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Lam, Tommy Tsan-Yuk; Holmes, Edward C.] Penn State Univ, Dept Biol, University Pk, PA 16802 USA. RP Cheng, JQ (reprint author), Shenzhen Ctr Dis Control & Prevent, 8 Longyuan Rd, Shenzhen 518055, Guangdong, Peoples R China. EM jqchengcdc@gmail.com RI Lam, Tommy Tsan-Yuk/D-4837-2012; OI Holmes, Edward/0000-0001-9596-3552 FU Research Fund for the Control of Infectious Diseases Commissioned Study, Food and Health Bureau, Hong Kong SAR (RFCID) [CU-09-01-01]; Influenza Program, Fogarty International Center, National Institutes of Health; Office of Global Affairs' International Influenza Unit, US Department of Health and Human Services FX This work was supported by the Research Fund for the Control of Infectious Diseases Commissioned Study, Food and Health Bureau, Hong Kong SAR (RFCID, CU-09-01-01) and by the Influenza Program, Fogarty International Center, National Institutes of Health, which is funded by the Office of Global Affairs' International Influenza Unit, US Department of Health and Human Services. NR 34 TC 16 Z9 18 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2013 VL 207 IS 1 BP 106 EP 114 DI 10.1093/infdis/jis526 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057ZU UT WOS:000312604200014 PM 22930808 ER PT J AU Oakley, MS Gerald, N Anantharaman, V Gao, YM Majam, V Mahajan, B Pham, PT Lotspeich-Cole, L Myers, TG McCutchan, TF Morris, SL Aravind, L Kumar, S AF Oakley, Miranda S. Gerald, Noel Anantharaman, Vivek Gao, Yamei Majam, Victoria Mahajan, Babita Phuong Thao Pham Lotspeich-Cole, Leda Myers, Timothy G. McCutchan, Thomas F. Morris, Sheldon L. Aravind, L. Kumar, Sanjai TI Radiation-Induced Cellular and Molecular Alterations in Asexual Intraerythrocytic Plasmodium falciparum SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE NOD2; IL-17; Th17; T lymphocytes; ocular toxoplasmosis; Toxoplasma gondii ID MALARIA VACCINE; TOPOISOMERASE-II; EXPRESSION; DEATH; PARASITES; PATHWAYS; INVASION; IMMUNITY; BERGHEI; STRESS AB Background. gamma-irradiation is commonly used to create attenuation in Plasmodium parasites. However, there are no systematic studies on the survival, reversion of virulence, and molecular basis for gamma-radiation-induced cell death in malaria parasites. Methods. The effect of gamma-irradiation on the growth of asexual Plasmodium falciparum was studied in erythrocyte cultures. Cellular and ultrastructural changes within the parasite were studied by fluorescence and electron microscopy, and genome-wide transcriptional profiling was performed to identify parasite biomarkers of attenuation and cell death. Results. gamma-radiation induced the death of P. falciparum in a dose-dependent manner. These parasites had defective mitosis, sparse cytoplasm, fewer ribosomes, disorganized and clumped organelles, and large vacuoles-observations consistent with "distressed" or dying parasites. A total of 185 parasite genes were transcriptionally altered in response to gamma-irradiation (45.9% upregulated, 54.1% downregulated). Loss of parasite survival was correlated with the downregulation of genes encoding translation factors and with upregulation of genes associated with messenger RNA-sequestering stress granules. Genes pertaining to cell-surface interactions, host-cell remodeling, and secreted proteins were also altered. Conclusions. These studies provide a framework to assess the safety of gamma-irradiation attenuation and promising targets for genetic deletion to produce whole parasite-based attenuated vaccines. C1 [Oakley, Miranda S.; Lotspeich-Cole, Leda; Morris, Sheldon L.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gerald, Noel; Majam, Victoria; Mahajan, Babita; Phuong Thao Pham; Kumar, Sanjai] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Gao, Yamei] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Anantharaman, Vivek; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIH, Microarray Res Facil, Res & Technol Branch, Bethesda, MD 20892 USA. [McCutchan, Thomas F.] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), 5516 Nicholson Ln, Kensington, MD 20895 USA. EM sanjai.kumar@fda.hhs.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Food and Drug Administration; National Institutes of Health FX This work was supported by the intramural grants from the Food and Drug Administration and National Institutes of Health. NR 34 TC 6 Z9 6 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN 1 PY 2013 VL 207 IS 1 BP 164 EP 174 DI 10.1093/infdis/jis645 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 057ZU UT WOS:000312604200021 PM 23100570 ER PT J AU Switzer, CH Miller, TW Farmer, PJ Fukuto, JM AF Switzer, Christopher H. Miller, Thomas W. Farmer, Patrick J. Fukuto, Jon M. TI Synthesis and characterization of lithium oxonitrate (LiNO) SO JOURNAL OF INORGANIC BIOCHEMISTRY LA English DT Article DE Nitroxyl; HNO; Nitric oxide; Angeli's salt; Piloty's acid; Oxonitrate(1-) ID DETERRENT AGENT CYANAMIDE; NITROXYL HNO; NITRIC-OXIDE; ALDEHYDE DEHYDROGENASE; NO; SODIUM; TRIOXODINITRATE(II); BIOCHEMISTRY; INHIBITION; REDUCTION AB The oxonitrate(1-) anion (NO-), the one-electron reduction product of nitric oxide and conjugate base of HNO, has not been synthesized and isolated due to the inherent reactivity of this anion. The large scale synthesis and characterization of a stable NO- salt is described here. The lithium salt of oxonitrate (LINO) was formed by the deprotonation of N-hydroxybenzenesulfonamide with phenyllithium in aprotic, deoxygenated conditions. UNO exhibited antiferromagnetic paramagnetism as determined by SQUID magnetometry, consistent with a triplet ground state of NO-. UNO reacted with HCl to yield nitrous oxide consistent with HNO formation and dimerization. UNO consumed 02 in a pH-dependent manner to initially produce peroxynitrite and eventually nitrite. Consistent with the reduction potential of NO, UNO exhibited an oxidation potential of approximately +0.80 V as determined by reactions with a series of viologen electron acceptors. LINO also reacted with ferric tetraphenylporphyrin chloride (Fe(TPP)Cl), potassium tetracyanonickelate (K2Ni(CN)(4)) and nitrosobenzene in a manner that is identical to other HNO/NO- donors. We conclude that the physical and chemical characteristics of UNO are indistinguishable from the experimentally and theoretically derived data on oxonitrate (1-) anion. The bulk synthesis and isolation of a stable (NO-)-N-3 salt described here allow the chemical and physical properties of this elusive nitrogen oxide to be thoroughly studied as this once elusive nitrogen oxide is now attainable. Published by Elsevier Inc. C1 [Switzer, Christopher H.; Miller, Thomas W.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA. [Farmer, Patrick J.] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA. [Fukuto, Jon M.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. RP Switzer, CH (reprint author), NCI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM switzerc@mail.nih.gov RI Switzer, Christopher/D-9203-2013; Miller, Thomas/G-1215-2011; OI Miller, Thomas/0000-0001-8645-2785; Farmer, Patrick/0000-0001-9911-999X FU National Institutes of Health [T32GM008496-08, 1R21ES016441-01]; National Science Foundation [CHE-1057942] FX This work was supported by the National Institutes of Health (T32GM008496-08 to C.H.S. and 1R21ES016441-01 to P.J.F.) and the National Science Foundation (CHE-1057942 to P.J.F.) NR 31 TC 4 Z9 4 U1 1 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0162-0134 J9 J INORG BIOCHEM JI J. Inorg. Biochem. PD JAN PY 2013 VL 118 BP 128 EP 133 DI 10.1016/j.jinorgbio.2012.09.022 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 065JN UT WOS:000313144700017 PM 23107606 ER PT J AU Russell, B Nasiak, M Kramer, N Johnston, J Biesecker, L Graham, JM AF Russell, B. Nasiak, M. Kramer, N. Johnston, J. Biesecker, L. Graham, J. M. TI DIAGNOSIS AND MANAGEMENT OF BOHRING-OPITZ SYNDROME CAUSED BY DE NOVO ASXL1 MUTATIONS SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract CT Western Regional Meeting of the American-Federation-for-Medical-Research CY JAN 24-26, 2013 CL Carmel, CA SP Amer Federat Med Res, Western Reg C1 [Russell, B.] UC Irvine, Irvine, CA USA. [Nasiak, M.; Kramer, N.; Graham, J. M.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Johnston, J.; Biesecker, L.] NIH, Bethesda, MD 20892 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 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD JAN PY 2013 VL 61 IS 1 MA 190 BP 165 EP 165 PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 058TT UT WOS:000312657900198 ER PT J AU Sinnott-Armstrong, W Miller, FG AF Sinnott-Armstrong, Walter Miller, Franklin G. TI What makes killing wrong? SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID BRAIN-DEATH AB What makes an act of killing morally wrong is not that the act causes loss of life or consciousness but rather that the act causes loss of all remaining abilities. This account implies that it is not even pro tanto morally wrong to kill patients who are universally and irreversibly disabled, because they have no abilities to lose. Applied to vital organ transplantation, this account undermines the dead donor rule and shows how current practices are compatible with morality. C1 [Sinnott-Armstrong, Walter] Duke Univ, Kenan Inst Eth, Durham, NC 27708 USA. [Sinnott-Armstrong, Walter] Duke Univ, Dept Philosophy, Durham, NC 27708 USA. [Sinnott-Armstrong, Walter; Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Sinnott-Armstrong, W (reprint author), Duke Univ, Kenan Inst Eth, Box 90432, Durham, NC 27708 USA. EM ws66@duke.edu NR 16 TC 4 Z9 4 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN PY 2013 VL 39 IS 1 BP 3 EP 7 DI 10.1136/medethics-2011-100351 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 057SV UT WOS:000312585200001 PM 22267342 ER PT J AU Sinnott-Armstrong, W Miller, FG AF Sinnott-Armstrong, Walter Miller, Franklin G. TI Killing versus totally disabling: a reply to critics SO JOURNAL OF MEDICAL ETHICS LA English DT Editorial Material C1 [Sinnott-Armstrong, Walter] Duke Univ, Dept Philosophy, Durham, NC 27708 USA. [Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA. RP Sinnott-Armstrong, W (reprint author), Duke Univ, Dept Philosophy, Box 90432, Durham, NC 27708 USA. EM ws66@duke.edu NR 5 TC 0 Z9 0 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN PY 2013 VL 39 IS 1 BP 12 EP 14 DI 10.1136/medethics-2012-100948 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 057SV UT WOS:000312585200005 PM 23161616 ER PT J AU Resnik, DB Dinse, GE AF Resnik, David B. Dinse, Gregg E. TI Scientific retractions and corrections related to misconduct findings SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID JOURNALS; POLICIES AB We examined all 208 closed cases involving official findings of research misconduct published by the US Office of Research Integrity from 1992 to 2011 to determine how often scientists mention in a retraction or correction notice that there was an ethical problem with an associated article. 75 of these cases cited at least one published article affected by misconduct for a total of 174 articles. For 127 of these 174, we found both the article and a retraction or correction statement. Since eight of the 127 published statements consisted of simply the word 'retracted,' our analysis focused on the remaining 119 for which a more detailed retraction or correction was published. Of these 119 statements, only 41.2% mentioned ethics at all (and only 32.8% named a specific ethical problem such as fabrication, falsification or plagiarism), whereas the other 58.8% described the reason for retraction or correction as error, loss of data or replication failure when misconduct was actually at issue. Among the published statements in response to an official finding of misconduct (within the time frame studied), the proportion that mentioned ethics was significantly higher in recent years than in earlier years, as was the proportion that named a specific problem. To promote research integrity, scientific journals should consider adopting policies concerning retractions and corrections similar to the guidelines developed by the Committee on Publication Ethics. Funding agencies and institutions should take steps to ensure that articles affected by misconduct are retracted or corrected. C1 [Resnik, David B.; Dinse, Gregg E.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, BOX 12233,Mail Drop CU 108, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU Intramural NIH HHS [ZIA ES102646-04] NR 13 TC 10 Z9 10 U1 3 U2 51 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JAN PY 2013 VL 39 IS 1 BP 46 EP 50 DI 10.1136/medethics-2012-100766 PG 5 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 057SV UT WOS:000312585200013 PM 22942373 ER PT J AU Lou, H Park, JJ Phillips, A Loh, YP AF Lou, Hong Park, Joshua J. Phillips, Andre Loh, Y. Peng TI gamma-Adducin Promotes Process Outgrowth and Secretory Protein Exit from the Golgi Apparatus SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE gamma-Adducin; F-actins; Neurite outgrowth; Vesicle budding; TGN; POMC/ACTH ID CARBOXYPEPTIDASE-E; KINASE-C; ALPHA-ADDUCIN; BETA-ADDUCIN; SORTING RECEPTOR; F-ACTIN; COMPLEX; PHOSPHORYLATION; ANGIOGENESIS; LOCALIZATION AB alpha, beta, and gamma adducins mediate F-actin remodeling of plasma membrane structures as heterotetramers. Here, we present two new functions of gamma-adducin. (1) Overexpression of gamma-adducin promoted formation of neurite-like processes in non-neuronal fibroblast COS7 cells. Conversely, overexpression of the C-terminal 38 amino acids of gamma-adducin (gamma Add(C38)) acting as a dominant negative inhibited formation of neurites/processes in Neuro2A cells and anterior pituitary AtT20 cells. (2) gamma-Adducin appears to facilitate pro-opiomelanocortin (POMC) exit from the trans-Golgi network (TGN) by re-organizing the actin network around the Golgi complex. Filamentous actins (F-actins) which formed puncti around the Golgi complex in control cells were dispersed in AtT20 cells stably transfected with gamma Add(C38). Furthermore, gamma Add(C38)-transfectants showed significant accumulation of POMC/adrenocorticotropin (ACTH) in the Golgi complex and diminished POMC/ACTH vesicles in the cell processes. The C-terminal 38 amino acids of gamma-adducin interacted with F-actins around the Golgi complex, to facilitate F-actin-mediated budding of POMC/ACTH vesicles from the TGN. Thus, we propose that gamma-adducin, via its interaction with F-actins, plays a critical role in actin remodeling to facilitate process/neurite outgrowth, as well as budding of POMC/ACTH vesicles from the TGN via its interaction with peri-Golgi F-actins. C1 [Lou, Hong; Park, Joshua J.; Phillips, Andre; Loh, Y. Peng] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA. [Park, Joshua J.] Univ Toledo, Dept Neurosci, Coll Med, Toledo, OH 43614 USA. RP Loh, YP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cellular Neurobiol Sect, Program Dev Neurosci, NIH, Bldg 49,Rm 5A22,49 Convent Dr, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU NICHD, NIH; NICHD K22 grant; ARRA grant FX We thank Dr. Niamh Cawley for helpful discussions (SCN, NICHD). We thank Dr. Vincent Schram (NICHD Microscopy Imaging Core) for technical support. This research was supported by the Intramural Research Program of the NICHD, NIH. Joshua J. Park has been supported by NICHD K22 and ARRA grants. NR 27 TC 4 Z9 4 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD JAN PY 2013 VL 49 IS 1 BP 1 EP 10 DI 10.1007/s12031-012-9827-0 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 061WW UT WOS:000312881900001 PM 22706708 ER PT J AU Alexander, BM Wang, MH Yung, WKA Fine, HA Donahue, BA Tremont, IW Richards, RS Kerlin, KJ Hartford, AC Curran, WJ Mehta, MP AF Alexander, Brian M. Wang, Meihua Yung, W. K. Alfred Fine, Howard A. Donahue, Bernadine A. Tremont, Ivo W. Richards, Ray S. Kerlin, Kevin J. Hartford, Alan C. Curran, Walter J. Mehta, Minesh P. TI A phase II study of conventional radiation therapy and thalidomide for supratentorial, newly-diagnosed glioblastoma (RTOG 9806) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Clinical trial; Controlled; Radiation therapy; Thalidomide; Angiogenesis inhibitor ID ENDOTHELIAL GROWTH-FACTOR; HIGH-GRADE GLIOMAS; RECURRENT GLIOBLASTOMA; TRIAL DESIGN; MULTIFORME; TEMOZOLOMIDE; ANGIOGENESIS; ADULTS; IRINOTECAN; EXPRESSION AB The Radiation Therapy Oncology Group (RTOG) initiated the single-arm, phase II study 9806 to determine the safety and efficacy of daily thalidomide with radiation therapy in patients with newly diagnosed glioblastoma. Patients were treated with thalidomide (200 mg daily) from day one of radiation therapy, increasing by 100-200 to 1,200 mg every 1-2 weeks until tumor progression or unacceptable toxicity. The median survival time (MST) of all 89 evaluable patients was 10 months. When compared with the historical database stratified by recursive partitioning analysis (RPA) class, this end point was not different [hazard ratio (HR) = 1.18; 95 % CI: 0.95-1.46; P = 0.93]. The MST of RPA class III and IV patients was 13.9 versus 12.5 months in controls (HR = 0.99; 95 % CI: 0.73-1.36; P = 0.48), and 4.3 versus 8.6 months in RPA class V controls (HR = 1.63, 95 % CI: 1.17-2.27; P = 0.99). In all, 34 % of patients discontinued thalidomide because of adverse events or refusal. The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy. In conclusion, thalidomide given simultaneously with radiation therapy was safe, but did not improve survival in patients with newly diagnosed glioblastoma. C1 [Alexander, Brian M.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. [Wang, Meihua] RTOG Stat Ctr, Philadelphia, PA USA. [Yung, W. K. Alfred; Tremont, Ivo W.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Fine, Howard A.] NCI, Neurooncol Branch, Bethesda, MD 20892 USA. [Donahue, Bernadine A.] Maimonides Hosp, Brooklyn, NY 11219 USA. [Richards, Ray S.] Intermt Med Ctr, St George, UT USA. [Kerlin, Kevin J.] SE Canc Control Consortium Inc, CCOP, Winston Salem, NC USA. [Hartford, Alan C.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Curran, Walter J.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. [Mehta, Minesh P.] NW Mem Hosp, Chicago, IL 60611 USA. RP Alexander, BM (reprint author), Dana Farber Brigham & Womens Canc Ctr, 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM bmalexander@lroc.harvard.edu OI mehta, minesh/0000-0002-4812-5713 FU RTOG grant from the National Cancer Institute (NCI) [U10 CA21661]; CCOP grant from the National Cancer Institute (NCI) [U10 CA37422] FX This trial was conducted by the Radiation Therapy Oncology Group (RTOG), and was supported by RTOG grant U10 CA21661 and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). This manuscript's contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. NR 36 TC 8 Z9 8 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2013 VL 111 IS 1 BP 33 EP 39 DI 10.1007/s11060-012-0987-0 PG 7 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 059RS UT WOS:000312723500005 PM 23086432 ER PT J AU Kreisl, TN Smith, P Sul, J Salgado, C Iwamoto, FM Shih, JH Fine, HA AF Kreisl, Teri Nguyen Smith, Perry Sul, Joohee Salgado, Carlos Iwamoto, Fabio M. Shih, Joanna H. Fine, Howard A. TI Continuous daily sunitinib for recurrent glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE Glioblastoma; Sunitinib; Angiogenesis; Bevacizumab; FDG PET ID SINGLE-AGENT BEVACIZUMAB; PHASE-II TRIAL; PROGRESSION; GLIOMAS AB Bevacizumab ((BEV) has become a mainstay of treating recurrent glioblastoma, but eventual tumor resistance is expected. Targeting multiple growth-associated signaling pathways may result in more effective treatment than targeting VEGF alone. Patients with recurrent glioblastoma were stratified by prior BEV exposure and treated with sunitinib 37.5 mg daily in this phase II study. Response evaluations were performed at baseline and at the end of every 4 week cycle. Six-month progression-free survival (PFS6) was the primary endpoint for both arms of the study. Secondary endpoints included health related quality of life measures and FDG-PET correlatives with patient outcomes. Sixty-three patients were accrued to this study; thirty-two were BEV-na < ve, 31 were BEV-resistant. PFS6 was 10.4 % [95 % CI 3.2-33.8] in the BEV-na < ve cohort and 0 % in the BEV-resistant cohort. Median overall survival was 9.4 months [95 % CI 6.15-21.90] in the BEV-na < ve cohort and 4.37 months [95 % CI 3.02-6.21] in the BEV-resistant cohort. 3/29 patients (10 %) of the BEV-na < ve, and 0/27 BEV-resistant patients achieved radiographic response. Thrombocytopenia, leukopenia, and neutropenia were the most common drug-associated adverse events and occurred with higher frequency than expected. Sunitinib treatment in BEV-na < ve patients did not appear to affect outcomes with subsequent BEV therapy. Continuous daily sunitinib did not prolong progression-free survival in BEV-na < ve nor BEV-resistant patients with recurrent glioblastoma. C1 [Kreisl, Teri Nguyen; Smith, Perry; Sul, Joohee; Salgado, Carlos; Iwamoto, Fabio M.; Fine, Howard A.] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. [Shih, Joanna H.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Kreisl, TN (reprint author), NCI, Neurooncol Branch, NIH, 9030 Old Georgetown Rd,225, Bethesda, MD 20892 USA. EM kreislt@mail.nih.gov NR 15 TC 33 Z9 34 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JAN PY 2013 VL 111 IS 1 BP 41 EP 48 DI 10.1007/s11060-012-0988-z PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 059RS UT WOS:000312723500006 PM 23086433 ER PT J AU Landoure, G Mochel, F Meilleur, K Ly, M Sangare, M Bocoum, N Bagayoko, K Coulibaly, T Sarr, AM Ba, HO Coulibaly, S Guinto, CO Toure, M Traore, M Fischbeck, KH AF Landoure, Guida Mochel, Fanny Meilleur, Katherine Ly, Madani Sangare, Modibo Bocoum, Nouhoum Bagayoko, Koumba Coulibaly, Thomas Sarr, Amadou M. Ba, Hamidou O. Coulibaly, Souleymane Guinto, Cheick O. Toure, Mahamadou Traore, Moussa Fischbeck, Kenneth H. TI Novel mutation in the ATM gene in a Malian family with ataxia telangiectasia SO JOURNAL OF NEUROLOGY LA English DT Letter ID DISORDERS C1 [Landoure, Guida; Coulibaly, Thomas; Guinto, Cheick O.; Traore, Moussa] Ctr Hosp Univ Point G, Serv Neurol, Bamako, Mali. [Landoure, Guida; Meilleur, Katherine; Sangare, Modibo; Fischbeck, Kenneth H.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. [Mochel, Fanny] Hop La Pitie Salpetriere, INSERM UMR S975, Brain & Spine Inst, Paris, France. [Mochel, Fanny] Hop La Pitie Salpetriere, AP HP, Dept Genet, Paris, France. [Mochel, Fanny] Univ Paris 06, Paris, France. [Ly, Madani] Ctr Hosp Univ Point G, Serv Hematooncol, Bamako, Mali. [Bocoum, Nouhoum; Bagayoko, Koumba] Univ Bamako, Fac Med Pharm & Odontostomatol, Bamako, Mali. [Sarr, Amadou M.] Lab Anal Med BIOTECH, Bamako, Mali. [Ba, Hamidou O.] Ctr Hosp Univ Gabriel Toure, Serv Cardiol, Bamako, Mali. [Coulibaly, Souleymane] Ctr Hosp Univ Point G, Psychiat Serv, Bamako, Mali. [Toure, Mahamadou] Ctr Hosp Mere Enfant Luxembourg, Serv Radiol, Bamako, Mali. RP Landoure, G (reprint author), Ctr Hosp Univ Point G, Serv Neurol, BP 333, Bamako, Mali. EM glandoure@gmail.com FU Intramural NIH HHS [ZIA NS002974-12] NR 13 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JAN PY 2013 VL 260 IS 1 BP 324 EP 326 DI 10.1007/s00415-012-6738-5 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 063NV UT WOS:000313007600050 PM 23142947 ER PT J AU Korzeniewski, SJ Grigorescu, V Kleyn, M Young, WI Birbeck, G Todem, D Romero, R Paneth, N AF Korzeniewski, Steven J. Grigorescu, Violanda Kleyn, Mary Young, William I. Birbeck, Gretchen Todem, David Romero, Roberto Paneth, Nigel TI Transient Hypothyroidism at 3-Year Follow-Up among Cases of Congenital Hypothyroidism Detected by Newborn Screening SO JOURNAL OF PEDIATRICS LA English DT Article ID SERVICES ADVISORY-COMMITTEE; HERITABLE DISORDERS; BONE MATURATION; UNITED-STATES; US SECRETARY; CHILDREN; DIAGNOSIS; THERAPY; PROGRAMS; AGE AB Objective To investigate the rate of transient thyroid deficiency and treatment compliance among cases with congenital hypothyroidism diagnosed and followed-up after age 3 years by newborn screening (NBS). Study design Cases detected by Michigan NBS between October 1, 2003, and December 31, 2007, and followed-up after age 3 years were included. The chi(2) and Fisher exact tests were used to test differences among followed and lost cases. Logistic regression models were used to investigate predictors of treatment cessation. Results Roughly 45% of eligible cases were lost to follow-up, and disease state (transient or permanent congenital hypothyroidism) could not be determined for 12 cases (7.9%). Of the 72 followed cases, 34 (47%) were considered permanent congenital hypothyroidism based on thyroid imaging findings (n = 7) or an increase in medication dosage over time (n = 27). One-quarter of followed cases with congenital hypothyroidism were no longer being treated, and of these, just over 83% stopped treatment without medical supervision. Of 23 cases that underwent a medically supervised trial without thyroid hormone medication, treatment was reinstated in 20. Laboratory confirmation of euthyroidism was available for 6 of 18 cases clinically deemed transient. After adjustment, black race was the strongest predictor of treatment cessation (OR, 9.86; 95% CI, 1.82-53.31). Treatment cessation was also more common among low birth weight infants and those admitted to the neonatal intensive care unit at birth. Conclusion We recommend that NBS programs include long-term follow-up through at least age 3 years to determine treatment compliance and disease permanence. Further research is needed to determine ideal follow-up program operations and reassessment methods for congenital hypothyroidism disease permanence. Guidelines that provide evidence-based reassessment methods would be beneficial for the healthcare providers of children with congenital hypothyroidism. (J Pediatr 2013;162:177-82). C1 [Korzeniewski, Steven J.; Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Detroit, MI USA. [Korzeniewski, Steven J.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Grigorescu, Violanda; Kleyn, Mary; Young, William I.] Michigan Dept Community Hlth, Lansing, MI USA. [Birbeck, Gretchen; Todem, David; Paneth, Nigel] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. RP Korzeniewski, SJ (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Hutzel Womens Hosp, 3990 John R,4 Brush Off 4817, Detroit, MI 48201 USA. EM sKorzeni@med.wayne.edu FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Department of Health and Human Services FX Supported in part by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, and Department of Health and Human Services. The authors declare no conflicts of interest. NR 27 TC 14 Z9 14 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 J9 J PEDIATR-US JI J. Pediatr. PD JAN PY 2013 VL 162 IS 1 BP 177 EP 182 DI 10.1016/j.jpeds.2012.06.050 PG 6 WC Pediatrics SC Pediatrics GA 062JK UT WOS:000312915900039 PM 22878110 ER PT J AU Sviridov, DO Andrianov, AM Anishchenko, IV Stonik, JA Amar, MJA Turner, S Remaley, AT AF Sviridov, Denis O. Andrianov, Alexander M. Anishchenko, Ivan V. Stonik, John A. Amar, Marcelo J. A. Turner, Scott Remaley, Alan T. TI Hydrophobic Amino Acids in the Hinge Region of the 5A Apolipoprotein Mimetic Peptide are Essential for Promoting Cholesterol Efflux by the ABCA1 Transporter SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HIGH-DENSITY-LIPOPROTEINS; IN-VIVO; APOA-I; DIELECTRIC MEDIUM; LIPID AFFINITY; BINDING; HDL; ATHEROSCLEROSIS; PROTEINS; CHARGES AB The bihelical apolipoprotein mimetic peptide 5A effluxes cholesterol from cells and reduces inflammation and atherosclerosis in animal models. We investigated how hydrophobic residues in the hinge region between the two helices are important in the structure and function of this peptide. By simulated annealing analysis and molecular dynamics modeling, two hydrophobic amino acids, F-18 and W-21, in the hinge region were predicted to be relatively surface-exposed and to interact with the aqueous solvent. Using a series of 5A peptide analogs in which F-18 or W-21 was changed to either F, W, A, or E, only peptides with hydrophobic amino acids in these two positions were able to readily bind and solubilize phospholipid vesicles. Compared with active peptides containing F or W, peptides containing E in either of these two positions were more than 10-fold less effective in effluxing cholesterol by the ABCA1 transporter. Intravenous injection of 5A in C57BL/6 mice increased plasma-free cholesterol (5A: 89.9 +/- 13.6 mg/dl; control: 38.7 +/- 4.3 mg/dl (mean +/- S. D.); P < 0.05) and triglycerides (5A: 887.0 +/- 172.0 mg/dl; control: 108.9 +/- 9.9 mg/dl; P < 0.05), whereas the EE peptide containing E in both positions had no effect. Finally, 5A increased cholesterol efflux approximately 2.5-fold in vivo from radiolabeled macrophages, whereas the EE peptide was inactive. These results provide a rationale for future design of therapeutic apolipoprotein mimetic peptides and provide new insights into the interaction of hydrophobic residues on apolipoproteins with phospholipids in the lipid microdomain created by the ABCA1 transporter during the cholesterol efflux process. C1 [Sviridov, Denis O.; Stonik, John A.; Amar, Marcelo J. A.; Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA. [Andrianov, Alexander M.] Natl Acad Sci Belarus, Inst Bioorgan Chem, Minsk, Byelarus. [Anishchenko, Ivan V.] Natl Acad Sci Belarus, United Inst Informat Problems, Minsk, Byelarus. [Turner, Scott] KineMed Inc, Emeryville, CA USA. RP Remaley, AT (reprint author), 10 Ctr Dr,Bldg 10,Room 2C433, Bethesda, MD 20892 USA. EM aremaley1@cc.nih.gov FU National Institutes of Health [National Heart, Lung, and Blood Institute]; KineMed Inc. FX This work was supported by the Intramural Research Program of the National Institutes of Health [National Heart, Lung, and Blood Institute]; and Cooperative Research and Development Agreement funds from KineMed Inc. NR 32 TC 6 Z9 6 U1 0 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JAN PY 2013 VL 344 IS 1 BP 50 EP 58 DI 10.1124/jpet.112.198143 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060VE UT WOS:000312805500007 PM 23042953 ER PT J AU Borek, D Dauter, Z Otwinowski, Z AF Borek, Dominika Dauter, Zbigniew Otwinowski, Zbyszek TI Identification of patterns in diffraction intensities affected by radiation exposure SO JOURNAL OF SYNCHROTRON RADIATION LA English DT Article; Proceedings Paper CT 7th International Workshop on X-Ray Damage to Biological Crystalline Samples CY MAR 14-16, 2012 CL ENGLAND DE radiation damage; matrix singular value decomposition; experimental phasing; radiolysis ID SINGULAR-VALUE DECOMPOSITION; PROTEIN CRYSTALS; MACROMOLECULAR CRYSTALS; SYNCHROTRON-RADIATION; CRYSTALLOGRAPHIC DATA; STRUCTURAL-CHANGES; ELECTRON-TRANSFER; DATA REDUCTION; X-RAYS; DAMAGE AB In an X-ray diffraction experiment, the structure of molecules and the crystal lattice changes owing to chemical reactions and physical processes induced by the absorption of X-ray photons. These structural changes alter structure factors, affecting the scaling and merging of data collected at different absorbed doses. Many crystallographic procedures rely on the analysis of consistency between symmetry-equivalent reflections, so failure to account for the drift of their intensities hinders the structure solution and the interpretation of structural results. The building of a conceptual model of radiation-induced changes in macromolecular crystals is the first step in the process of correcting for radiation-induced inconsistencies in diffraction data. Here the complexity of radiation-induced changes in real and reciprocal space is analysed using matrix singular value decomposition applied to multiple complete datasets obtained from single crystals. The model consists of a resolution-dependent decay correction and a uniform-per-unique-reflection term modelling specific radiation-induced changes. This model is typically sufficient to explain radiation-induced effects observed in diffraction intensities. This analysis will guide the parameterization of the model, enabling its use in subsequent crystallographic calculations. C1 [Borek, Dominika; Otwinowski, Zbyszek] UT SW Med Ctr Dallas, Dept Biophys, Dallas, TX 75390 USA. [Borek, Dominika; Otwinowski, Zbyszek] UT SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. [Dauter, Zbigniew] NCI, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA. RP Otwinowski, Z (reprint author), UT SW Med Ctr Dallas, Dept Biophys, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM zbyszek@work.swmed.edu RI Borek, Dominika/D-2943-2011 OI Borek, Dominika/0000-0002-4321-6253 FU NIGMS NIH HHS [R01 GM053163, GM053163] NR 57 TC 8 Z9 8 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-0495 J9 J SYNCHROTRON RADIAT JI J. Synchrot. Radiat. PD JAN PY 2013 VL 20 BP 37 EP 48 DI 10.1107/S0909049512048807 PN 1 PG 12 WC Instruments & Instrumentation; Optics; Physics, Applied SC Instruments & Instrumentation; Optics; Physics GA 057KE UT WOS:000312561300005 PM 23254654 ER PT J AU Caporino, NE Brodman, DM Kendall, PC Albano, AM Sherrill, J Piacentini, J Sakolsky, D Birmaher, B Compton, SN Ginsburg, G Rynn, M McCracken, J Gosch, E Keeton, C March, J Walkup, JT AF Caporino, Nicole E. Brodman, Douglas M. Kendall, Philip C. Albano, Anne Marie Sherrill, Joel Piacentini, John Sakolsky, Dara Birmaher, Boris Compton, Scott N. Ginsburg, Golda Rynn, Moira McCracken, James Gosch, Elizabeth Keeton, Courtney March, John Walkup, John T. TI Defining Treatment Response and Remission in Child Anxiety: Signal Detection Analysis Using the Pediatric Anxiety Rating Scale SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; treatment; measurement ID OBSESSIVE-COMPULSIVE SCALE; DISORDERS INTERVIEW SCHEDULE; COGNITIVE-BEHAVIORAL THERAPY; PARENT VERSIONS; DSM-IV; ADOLESCENTS; TRIAL; YOUTH; PSYCHOTHERAPY; RELIABILITY AB Objective: To determine optimal Pediatric Anxiety Rating Scale (PARS) percent reduction and raw score cut-offs for predicting treatment response and remission among children and adolescents with anxiety disorders. Method: Data were from a subset of youth (N = 438; 7-17 years of age) who participated in the Child/Adolescent Anxiety Multimodal Study (CAMS), a multi-site, randomized controlled trial that examined the relative efficacy of cognitive-behavioral therapy (CBT; Coping Cat), medication (sertraline [SRTD, their combination, and pill placebo for the treatment of separation anxiety disorder, generalized anxiety disorder, and social phobia. The clinician-rated PARS was administered pre- and posttreatment (delivered over 12 weeks). Quality receiver operating characteristic methods assessed the performance of various PARS percent reductions and absolute cut-off scores in predicting treatment response and remission, as determined by posttreatment ratings on the Clinical Global Impression scales and the Anxiety Disorders Interview Schedule for DSM-IV. Corresponding change in impairment was evaluated using the Child Anxiety Impact Scale. Results: Reductions of 35% and 50% on the six-item PARS optimally predicted treatment response and remission, respectively. Post-treatment PARS raw scores of 8 to 10 optimally predicted remission. Anxiety improved as a function of PARS-defined treatment response and remission. Conclusions: Results serve as guidelines for operationalizing treatment response and remission in future research and in making cross-study comparisons. These guidelines can facilitate translation of research findings into clinical practice. J. Am. Acad. Child Adolesc. Psychiatry; 2012;52(1):57-67. Clinical trial registration information Child and Adolescent Anxiety Disorders (CAMS); http://clinicaltrials.gov/; NCT00052078. C1 [Caporino, Nicole E.] Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. [Albano, Anne Marie; Rynn, Moira] Columbia Univ, Med Ctr, New York, NY 10027 USA. [Sherrill, Joel] NIMH, Div Serv & Intervent Res, Rockville, MD USA. [Piacentini, John; McCracken, James] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA. [Sakolsky, Dara; Birmaher, Boris] Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA 15260 USA. [Compton, Scott N.; March, John] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Ginsburg, Golda; Keeton, Courtney] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. [Gosch, Elizabeth] Philadelphia Coll Osteopath Med, Philadelphia, PA USA. [Walkup, John T.] Weill Cornell Med Coll, New York, NY USA. RP Caporino, NE (reprint author), Temple Univ, Dept Psychol, Weiss Hall,1701 N 13h St, Philadelphia, PA 19122 USA. EM nicole.caporino@temple.edu FU NIMH [U01 MH064089, U01 MH64092, U01 MH64003, U01 MH63747, U01 MH64107, U01 MH64088]; NIMH; Tourette Syndrome Association; Otsuka Pharmaceuticals; National Alliance for Research on Schizophrenia and Depression (NARSAD); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Eli Lilly and Co.; Pfizer; Merck; Shire; Seaside Therapeutics; Roche; Otsuka; Johns Hopkins Urban Health Institute; National Institute on Drug Abuse (NIDA); NARSAD; Abbott for NIH FX This research was supported by NIMH grants U01 MH064089 (J.T.W.), U01 MH64092 (A.M.A.), U01 MH64003 (B.B., S.N.C.), U01 MH63747 (P.C.K.), U01 MH64107 (J.M.), and U01 MH64088 (J.P.).; Dr. Kendall has received research support from NIMH. He has received honoraria from professional societies for speaking at conventions. He has received royalties from Guilford Press, Ericsson, Workbook Publishing, and Oxford University Press. Dr. Albano has received research support from NIMH. She has received honoraria from the American Psychological Association. She has served as a consultant to Brackett Global. She has received royalties from Oxford University Press. Dr. Piacentini has received grant or research support from NIMH, the Tourette Syndrome Association, and Otsuka Pharmaceuticals. He has reviewed survey materials related to the 2010 World Contraception Day media report for Bayer Schering Pharma. He has received book royalties from Guilford Press and Oxford University Press. He is a co-author of assessment tools, none of which are commercially published and therefore no royalties have been received. He has received speaking honoraria / travel support from the Tourette Syndrome Association and the International Obsessive Compulsive Disorder Foundation. Dr. Sakolsky has received research support from NIMH and the National Alliance for Research on Schizophrenia and Depression (NARSAD). She has received honoraria from the American Academy of Child and Adolescent Psychiatry for participation in the 37th Annual Review Course in Child and Adolescent Psychiatry and Training for the Oral Exams. Dr. Birmaher has received research support from NIMH. He has received royalties from Random House. Dr. Compton has received research support from NIMH. He has served as a consultant to Shire Pharmaceuticals. He has provided expert forensic testimony for mental health needs of children in high-conflict families. Dr. Rynn has received research support from NIMH, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Eli Lilly and Co., Pfizer, Merck, and Shire. She has served as a consultant to Shire. She has received royalties from American Psychiatric Publishing. Dr. McCracken has received research support from Seaside Therapeutics, Roche, and Otsuka. He has served as a consultant to BioMarin, PharmaNet, Roche, and Novartis. He has received research study drug from Shire. Dr. Gosch has received royalties from Springer Publishing Company. Dr. Keeton has received research support from NIMH and the Johns Hopkins Urban Health Institute. Dr. March has received research support from NIMH, the National Institute on Drug Abuse (NIDA), NARSAD, and Pfizer. He has served as a consultant to Atentiv, Bristol-Myers Squibb, Eli Lilly and Co., Pfizer, and Widay Pharmaceuticals. He has served on scientific advisory boards of Eli Lilly and Co., Pfizer, and Shire. He has served on the Data Safely Monitoring Boards (DSMB) of Eli Lilly and Co., NIDA, and Pfizer. He has received royalties from Guilford Press, MultiHealth Systems, and Oxford University Press. He retains equity in MedAvante. He has provided expert forensic consultation to DLA Piper. Dr. Walkup has received grant or research support from the Tourette Syndrome Association. He has served as a consultant to Shire. He has received free medication and placebo from Eli Lilly and Co., Pfizer, and Abbott for NIH-funded studies. He has served on the advisory board and speakers' bureau of the Tourette Syndrome Association. He has received royalties from Guilford Press and Oxford University Press. He has received honorarium for an Educational Meeting from the Tourette Syndrome Association.; He also has received travel support and honoraria for paid and unpaid activities from the Tourette Syndrome Association including an unpaid position on the Medical Advisory Board. Drs. Caporino, Sherrill, and Ginsburg, and Mr. Bradman report no biomedical financial interests or potential conflicts of interest. NR 39 TC 16 Z9 16 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JAN PY 2013 VL 52 IS 1 BP 57 EP 67 DI 10.1016/j.jaac.2012.10.006 PG 11 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 065JA UT WOS:000313143400007 PM 23265634 ER PT J AU Uchida, M Ito, T Nakamura, T Igarashi, H Oono, T Fujimori, N Kawabe, K Suzuki, K Jensen, RT Takayanagi, R AF Uchida, Masahiko Ito, Tetsuhide Nakamura, Taichi Igarashi, Hisato Oono, Takamasa Fujimori, Nao Kawabe, Ken Suzuki, Koichi Jensen, Robert T. Takayanagi, Ryoichi TI ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells SO LABORATORY INVESTIGATION LA English DT Article DE chronic pancreatitis; CX3CL1; ethanol; ERK pathway; pancreatic stellate cells ID SMOOTH-MUSCLE-CELLS; FRACTALKINE EXPRESSION; RHEUMATOID-ARTHRITIS; ALCOHOLIC PANCREATITIS; NEUROPATHIC PAIN; RECEPTOR CX3CR1; SPINAL-CORD; CHEMOKINE; IDENTIFICATION; PROLIFERATION AB The clinical course of chronic pancreatitis (CP) worsens with drinking, and pancreatic stellate cells (PSCs) have an important role in the pathogenesis of alcoholic CP. Chemokines recruit inflammatory cells, resulting in chronic pancreatic inflammation. Although serum levels of fractalkine (CX3CL1) are significantly elevated in patients with alcoholic CP, the mechanism of this elevation remains unclear. This study aims to determine the effects of cytokines, pathogen-associated molecular patterns (PAMPs), and ethanol and its metabolites on CX3CL1 secretion by PSCs. Male Wistar/Bonn Kobori (WBN/Kob) rats aged 15 to 20 weeks were used as rodent models of CP in vivo. PSCs were isolated from 6-week-old male Wistar rats. The effects of cytokines, PAMPs, and ethanol and its metabolites on chemokine production and activation of signaling pathways in PSCs in vitro were examined by real-time reverse transcription-polymerase chain reaction (RT-PCR), western blotting, and enzyme-linked immunosorbent assay. Expression of CX3CL1 and matrix metalloprotease (MMP)-2 was increased in the pancreas of WBN/Kob rats. The rat PSCs expressed CX3CL1, MMP-2, and a disintegrin and metalloprotease domain (ADAM) 17. Cytokines and PAMPs induced CX3CL1 release and activated extracellular signal-regulated kinase (ERK), MMP-9, and ADAM17. CX3CL1 release was suppressed by specific inhibitors of ERK, MMP, and ADAM, and ERK was associated with CX3CL1 transcription. Ethanol and phorbol myristate acetate synergistically increased CX3CL1 release. Real-time PCR and western blotting confirmed the synergistic activation of ERK and ADAM17. Ethanol synergistically increased CX3CL1 release via ERK and ADAM17 activation in PSCs. In conclusion, we demonstrated for the first time that ethanol synergistically increased CX3CL1 release from PSCs at least in part through activation of ERK mitogen-activated protein kinase and ADAM17. This might be one of the mechanisms of serum CX3CL1 elevation and disease progression in patients with alcoholic CP. Laboratory Investigation (2013) 93, 41-53; doi:10.1038/labinvest.2012.156; published online 12 November 2012 C1 [Ito, Tetsuhide] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 8128582, Japan. [Kawabe, Ken] Natl Hosp Org, Dept Kyushu Med Ctr, Fukuoka, Japan. [Suzuki, Koichi] Natl Inst Infect Dis, Dept Leprosy Res Ctr, Tokyo, Japan. [Jensen, Robert T.] NIDDK, Dept Cell Biol Sect, NIH, Bethesda, MD USA. RP Ito, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM itopapa@intmed3.med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 FU Ministry of Education, Culture, Sports, Science, and Technology, Japan [20590808]; Research Committee by the Ministry of Health, Labor, and Welfare Japan [50253448] FX We appreciate for the technical supports from the Research Support Center, Graduate School of Medical Sciences, Kyushu University. This work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan (20590808, TI) and the Research Committee provided by the Ministry of Health, Labor, and Welfare Japan (50253448, TI). NR 51 TC 11 Z9 11 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0023-6837 EI 1530-0307 J9 LAB INVEST JI Lab. Invest. PD JAN PY 2013 VL 93 IS 1 BP 41 EP 53 DI 10.1038/labinvest.2012.156 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 062BD UT WOS:000312893200005 PM 23147224 ER PT J AU Dodd, LE Wilkinson, RJ AF Dodd, Lori Elizabeth Wilkinson, Robert John TI Diagnosis of paediatric tuberculosis: the culture conundrum SO LANCET INFECTIOUS DISEASES LA English DT Editorial Material ID XPERT MTB/RIF TEST; PULMONARY TUBERCULOSIS; CHILDHOOD TUBERCULOSIS; AFRICAN CHILDREN; RESISTANCE; ACCURACY C1 [Dodd, Lori Elizabeth] NIAID, Biostat Res Branch, Div Clin Res, Bethesda, MD 20892 USA. [Wilkinson, Robert John] Univ Cape Town, Inst Infect Dis & Mol Med, Clin Infect Dis Res Initiat, ZA-7925 Observatory, South Africa. [Wilkinson, Robert John] MRC Natl Inst Med Res, London NW7 1AA, England. [Wilkinson, Robert John] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W2 1PG, England. RP Dodd, LE (reprint author), NIAID, Biostat Res Branch, Div Clin Res, 6700B Rockledge Dr,MSC 7630, Bethesda, MD 20892 USA. OI Wilkinson, Robert/0000-0002-2753-1800 FU Medical Research Council [MC_U117588499]; Wellcome Trust [088316] NR 15 TC 6 Z9 6 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2013 VL 13 IS 1 BP 3 EP 4 DI 10.1016/S1473-3099(12)70290-6 PG 2 WC Infectious Diseases SC Infectious Diseases GA 060FO UT WOS:000312762100003 PM 23134696 ER PT J AU Chang, LW Serwadda, D Quinn, TC Wawer, MJ Gray, RH Reynolds, SJ AF Chang, Larry W. Serwadda, David Quinn, Thomas C. Wawer, Maria J. Gray, Ronald H. Reynolds, Steven J. TI Combination implementation for HIV prevention: moving from clinical trial evidence to population-level effects SO LANCET INFECTIOUS DISEASES LA English DT Review ID SUB-SAHARAN AFRICA; CLUSTER-RANDOMIZED-TRIAL; RESOURCE-LIMITED SETTINGS; TO-CHILD TRANSMISSION; RECEIVING ANTIRETROVIRAL THERAPY; SEXUALLY-TRANSMITTED INFECTIONS; NON-INFERIORITY TRIAL; LOW-INCOME COUNTRIES; PEER HEALTH-WORKERS; TREATMENT SCALE-UP AB The promise of combination HIV prevention-the application of multiple HIV prevention interventions to maximise population-level effects-has never been greater. However, to succeed in achieving significant reductions in HIV incidence, an additional concept needs to be considered: combination implementation. Combination implementation for HIV prevention is the pragmatic, localised application of evidence-based strategies to enable high sustained uptake and quality of interventions for prevention of HIV. In this Review, we explore diverse implementation strategies including HIV testing and counselling models, task shifting, linkage to and retention in care, antiretroviral therapy support, behaviour change, demand creation, and structural interventions, and discusses how they could be used to complement HIV prevention efforts such as medical male circumcision and treatment as prevention. HIV prevention and treatment have arrived at a pivotal moment when combination efforts might result in substantial enough population-level effects to reverse the epidemic and drive towards elimination of HIV. Only through careful consideration of how to implement and operationalise HIV prevention interventions will the HIV community be able to move from clinical trial evidence to population-level effects. C1 [Chang, Larry W.; Quinn, Thomas C.; Reynolds, Steven J.] Johns Hopkins Sch Med, Div Infect Dis, Dept Med, Baltimore, MD 21287 USA. [Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. [Chang, Larry W.; Serwadda, David; Quinn, Thomas C.; Wawer, Maria J.; Gray, Ronald H.; Reynolds, Steven J.] Rakai Hlth Sci Program, Entebbe, Uganda. [Wawer, Maria J.; Gray, Ronald H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Chang, Larry W.] Johns Hopkins Bloomberg Sch Publ Hlth, Social & Behav Intervent Program, Dept Int Hlth, Baltimore, MD USA. [Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Lab Immunoregulat, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Chang, LW (reprint author), Johns Hopkins Sch Med, Div Infect Dis, Dept Med, 1503 E Jefferson St,Room 116, Baltimore, MD 21287 USA. EM lchang8@jhmi.edu FU National Institute of Mental Health at the National Institutes of Health [5K23MH086338]; Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health; National Institutes of Health; President's Emergency Plan for AIDS Relief; Bill and Melinda Gates Foundation FX We thank Caitlin Kennedy (Johns Hopkins University, Baltimore, MD, USA) for editorial contributions and Sarah Wendel (National Institutes of Health, Bethesda, MD, USA) for her assistance with the literature search. LWC is supported by the National Institute of Mental Health at the National Institutes of Health (5K23MH086338). TCQ and SJR are supported by the Division of Intramural Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health. MJW and RHG have grants from the National Institutes of Health, the President's Emergency Plan for AIDS Relief, and the Bill and Melinda Gates Foundation, which supported studies of relevance to this Review. These funding sources had no involvement in the writing of the manuscript or the decision to submit it for publication. LWC had full access to all data in the study and final responsibility for the decision to submit for publication. NR 168 TC 44 Z9 47 U1 1 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1473-3099 EI 1474-4457 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD JAN PY 2013 VL 13 IS 1 BP 65 EP 76 DI 10.1016/S1473-3099(12)70273-6 PG 12 WC Infectious Diseases SC Infectious Diseases GA 060FO UT WOS:000312762100030 PM 23257232 ER PT J AU Gulvady, AA Murphy, EJ Ciolino, HP Cabrera, RM Jolly, CA AF Gulvady, Apeksha A. Murphy, Eric J. Ciolino, Henry P. Cabrera, Robert M. Jolly, Christopher A. TI Glycerol-3-Phosphate Acyltransferase-1 Gene Ablation Results in Altered Thymocyte Lipid Content and Reduces Thymic T Cell Production in Mice SO LIPIDS LA English DT Article DE Glycerol-3-phosphate acyltransferase-1; Thymus; T cell development ID METABOLISM; LYMPHOCYTES; RESTRICTION; EXPRESSION; INFECTION; MEMORY; AGE AB Glycerol 3-phosphate acyltransferase-1 (GPAT-1) catalyzes the initial and rate-limiting step in de novo glycerophospholipid and triacylglycerol (TAG) biosynthesis. We have previously shown that peripheral T cell proliferation and cytokine production is altered in GPAT-1 gene-ablated (KO) mice. This finding is important in light of the reduction in GPAT-1 activity associated with aged T cells. To determine if the mechanism for altered peripheral T cell function is linked to altered T cell development, we assessed thymic function in 3, 6 and 16-week old GPAT-1 KO compared to wild type (WT) mice. At 16 weeks of age, there was a significant reduction in thymic T cell production in KO compared to WT mice but not at 6 weeks of age. The reduced thymic T cell production was associated with altered thymic development as confirmed by increased numbers of double-negative (DN) thymocytes and a significant reduction in the double positive (DP) thymocytes suggesting a developmental block at the DN stage. This change was accompanied by an increase in the single positive CD4 subset. These changes were associated with reduced glycerophospholipid mass while thymic cortex and medulla architecture was not altered by GPAT-1 KO. Taken together, these data suggest that GPAT-1 deletion is capable of reducing the number of new T cells produced via alterations in membrane receptor function rather than by causing deleterious changes within the thymic microenvironment explaining in part the observed alterations in peripheral T cell function. C1 [Gulvady, Apeksha A.; Cabrera, Robert M.; Jolly, Christopher A.] Univ Texas Austin, Dept Nutr Sci, Dell Pediat Res Inst R1800, Austin, TX 78723 USA. [Murphy, Eric J.] Univ N Dakota, Dept Physiol & Pharmacol, Grand Forks, ND 58201 USA. [Ciolino, Henry P.] NCI, Off Canc Ctr, Rockville, MD 20852 USA. RP Jolly, CA (reprint author), Univ Texas Austin, Dept Nutr Sci, Dell Pediat Res Inst R1800, 1400 Barbara Jordan Blvd, Austin, TX 78723 USA. EM jolly@austin.utexas.edu NR 20 TC 3 Z9 4 U1 0 U2 5 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 J9 LIPIDS JI Lipids PD JAN PY 2013 VL 48 IS 1 BP 3 EP 12 DI 10.1007/s11745-012-3741-7 PG 10 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 063NZ UT WOS:000313008000002 PM 23179391 ER PT J AU Long, DJ Lee, C Tien, C Fisher, R Hoerner, MR Hintenlang, D Bolch, WE AF Long, Daniel J. Lee, Choonsik Tien, Christopher Fisher, Ryan Hoerner, Matthew R. Hintenlang, David Bolch, Wesley E. TI Monte Carlo simulations of adult and pediatric computed tomography exams: Validation studies of organ doses with physical phantoms SO MEDICAL PHYSICS LA English DT Article DE computed tomography; Monte Carlo; organ dose; anthropomorphic phantom ID HYBRID COMPUTATIONAL PHANTOMS; TUBE CURRENT MODULATION; MULTIDETECTOR CT; ANTHROPOMORPHIC PHANTOMS; DOSIMETRY; FEMALE; CONSTRUCTION; RADIOLOGY; MODELS; TOOL AB Purpose: To validate the accuracy of a Monte Carlo source model of the Siemens SOMATOM Sensation 16 CT scanner using organ doses measured in physical anthropomorphic phantoms. Methods: The x-ray output of the Siemens SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code, MCNPX version 2.6. The resulting source model was able to perform various simulated axial and helical computed tomographic ( CT) scans of varying scan parameters, including beam energy, filtration, pitch, and beam collimation. Two custom-built anthropomorphic phantoms were used to take dose measurements on the CT scanner: an adult male and a 9-month-old. The adult male is a physical replica of the University of Florida reference adult male hybrid computational phantom, while the 9-month-old is a replica of the University of Florida Series B 9-month-old voxel computational phantom. Each phantom underwent a series of axial and helical CT scans, during which organ doses were measured using fiber-optic coupled plastic scintillator dosimeters developed at the University of Florida. The physical setup was reproduced and simulated in MCNPX using the CT source model and the computational phantoms upon which the anthropomorphic phantoms were constructed. Average organ doses were then calculated based upon these MCNPX results. Results: For all CT scans, good agreement was seen between measured and simulated organ doses. For the adult male, the percent differences were within 16% for axial scans, and within 18% for helical scans. For the 9-month-old, the percent differences were all within 15% for both the axial and helical scans. These results are comparable to previously published validation studies using GE scanners and commercially available anthropomorphic phantoms. Conclusions: Overall results of this study show that the Monte Carlo source model can be used to accurately and reliably calculate organ doses for patients undergoing a variety of axial or helical CT examinations on the Siemens SOMATOM Sensation 16 scanner. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4771934] C1 [Long, Daniel J.; Tien, Christopher; Hoerner, Matthew R.; Hintenlang, David; Bolch, Wesley E.] Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA. [Lee, Choonsik] NCI, NIH, Bethesda, MD 20892 USA. [Fisher, Ryan] Univ Florida, Dept Radiol, Gainesville, FL 32610 USA. RP Bolch, WE (reprint author), Univ Florida, J Crayton Pruitt Family Dept Biomed Engn, Gainesville, FL 32611 USA. EM wbolch@ufl.edu RI Lee, Choonsik/C-9023-2015 OI Lee, Choonsik/0000-0003-4289-9870 FU Radiation Epidemiology Branch of the National Cancer Institute [HHS-N2612-0090-0098P, HHS-N2612-0100-0692P]; Biomedical Research and Education Foundation FX The authors are thankful to Ms. Ale Ham at the University of Florida for her help with anthropomorphic phantom dose measurements. This work was supported by Contract Nos. HHS-N2612-0090-0098P and HHS-N2612-0100-0692P with the Radiation Epidemiology Branch of the National Cancer Institute, and by a grant from the Biomedical Research and Education Foundation. NR 25 TC 14 Z9 16 U1 0 U2 14 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2013 VL 40 IS 1 AR 013901 DI 10.1118/1.4771934 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063WR UT WOS:000313033200058 PM 23298124 ER PT J AU Partanen, A Tillander, M Yarmolenko, PS Wood, BJ Dreher, MR Kohler, MO AF Partanen, Ari Tillander, Matti Yarmolenko, Pavel S. Wood, Bradford J. Dreher, Matthew R. Kohler, Max O. TI Reduction of peak acoustic pressure and shaping of heated region by use of multifoci sonications in MR-guided high-intensity focused ultrasound mediated mild hyperthermia SO MEDICAL PHYSICS LA English DT Article DE MR-HIFU; thermotherapy; multifoci; mild hyperthermia ID TEMPERATURE-SENSITIVE LIPOSOMES; PROTON CHEMICAL-SHIFT; PHASED-ARRAY; DRUG-DELIVERY; IN-VIVO; THERMAL THERAPY; MAGNETIC FLUIDS; HIFU ABLATION; CANCER; CAVITATION AB Purpose: Ablative hyperthermia (>55 degrees C) has been used as a definitive treatment for accessible solid tumors not amenable to surgery, whereas mild hyperthermia (40-45 degrees C) has been shown effective as an adjuvant for both radiotherapy and chemotherapy. An optimal mild hyperthermia treatment is spatially accurate, with precise and homogeneous heating limited to the target region while also limiting the likelihood of unwanted thermal or mechanical bioeffects (tissue damage, vascular shutoff). Magnetic resonance imaging-guided high-intensity focused ultrasound (MR-HIFU) can noninvasively heat solid tumors under image-guidance. In a mild hyperthermia setting, a sonication approach utilizing multiple concurrent foci may provide the benefit of reducing acoustic pressure in the focal region (leading to reduced or no mechanical effects), while providing better control over the heating. The objective of this study was to design, implement, and characterize a multifoci sonication approach in combination with a mild hyperthermia heating algorithm, and compare it to the more conventional method of electronically sweeping a single focus. Methods: Simulations (acoustic and thermal) and measurements (acoustic, with needle hydrophone) were performed. In addition, heating performance of multifoci and single focus sonications was compared using a clinical MR-HIFU platform in a phantom (target = 4-16 mm), in normal rabbit thigh muscle (target = 8 mm), and in a Vx2 tumor (target = 8 mm). A binary control algorithm was used for real-time mild hyperthermia feedback control (target range = 40.5-41 degrees C). Data were analyzed for peak acoustic pressure and intensity, heating energy efficiency, temperature accuracy (mean), homogeneity of heating (standard deviation [SD], T10 and T90), diameter and length of the heated region, and thermal dose (CEM43). Results: Compared to the single focus approach, multifoci sonications showed significantly lower (67% reduction) peak acoustic pressures in simulations and hydrophone measurements. In a rabbit Vx2 tumor, both single focus and multifoci heating approaches were accurate (mean = 40.82 +/- 0.12 degrees C [single] and 40.70 +/- 0.09 degrees C [multi]) and precise (standard deviation = 0.65 +/- 0.05 degrees C [single] and 0.64 +/- 0.04 degrees C [multi]), producing homogeneous heating (T10-90 = 1.62 degrees C [single] and 1.41 degrees C [multi]). Heated regions were significantly shorter in the beam path direction (35% reduction, p < 0.05, Tukey) for multifoci sonications, i.e., resulting in an aspect ratio closer to one. Energy efficiency was lower for the multifoci approach. Similar results were achieved in phantom and rabbit muscle heating experiments. Conclusions: A multifoci sonication approach was combined with a mild hyperthermia heating algorithm, and implemented on a clinical MR-HIFU platform. This approach resulted in accurate and precise heating within the targeted region with significantly lower acoustic pressures and spatially more confined heating in the beam path direction compared to the single focus sonication method. The reduction in acoustic pressure and improvement in spatial control suggest that multifoci heating is a useful tool in mild hyperthermia applications for clinical oncology. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4769116] C1 [Tillander, Matti; Kohler, Max O.] Philips Med Syst, Vantaa 01510, Uusimaa, Finland. [Partanen, Ari; Yarmolenko, Pavel S.; Wood, Bradford J.; Dreher, Matthew R.] NCI, Ctr Intervent Oncol, Ctr Clin, NIH, Bethesda, MD 20892 USA. [Partanen, Ari] Univ Helsinki, Dept Phys, Helsinki 00014, Finland. [Partanen, Ari] Philips Healthcare, Cleveland, OH 44143 USA. [Yarmolenko, Pavel S.] Duke Univ, Dept Biomed Engn, Durham, NC 27708 USA. RP Kohler, MO (reprint author), Philips Med Syst, Vantaa 01510, Uusimaa, Finland. EM max.kohler@philips.com OI Partanen, Ari/0000-0003-1985-149X FU Center for Interventional Oncology; National Institutes of Health (NIH); Cooperative Research and Development Agreement (CRADA); Philips Healthcare FX The authors thank Dr. Caitlin Burke, Dr. Ashish Ranjan, Dr. Carmen Gacchina, and David Woods for their support with animal studies. This research was supported by the Center for Interventional Oncology and Intramural Research Program of the National Institutes of Health (NIH), and through a Cooperative Research and Development Agreement (CRADA) with Philips Healthcare. Ari Partanen, Matti Tillander, and Dr. Max Kohler are paid employees of Philips Healthcare. The mention of commercial products, their source, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the National Institutes of Health. NR 64 TC 13 Z9 13 U1 3 U2 29 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2013 VL 40 IS 1 AR 013301 DI 10.1118/1.4769116 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063WR UT WOS:000313033200054 PM 23298120 ER PT J AU Tan, S Yao, JH Yao, L Ward, MM AF Tan, Sovira Yao, Jianhua Yao, Lawrence Ward, Michael M. TI High precision semiautomated computed tomography measurement of lumbar disk and vertebral heights SO MEDICAL PHYSICS LA English DT Article DE intervertebral disk height; vertebral height; semiautomated measurement; precision/repeatability; CT ID SPINE; SEGMENTATION; OSTEOPOROSIS; FRACTURES; WOMEN; CT; MORPHOMETRY; REPLACEMENT; DIMENSIONS; HORMONE AB Purpose: Evaluation of treatments of many spine disorders requires precise measurement of the heights of vertebral bodies and disk spaces. The authors present a semiautomated computer algorithm measuring those heights from spine computed tomography (CT) scans and evaluate its precision. Methods: Eight patients underwent two spine CT scans in the same day. In each scan, five thoracolumbar vertebral heights and four disk heights were estimated using the algorithm. To assess precision, the authors computed the differences between the height measurements in the two scans, coefficients of variation (CV), and 95% limits of agreement. Intraoperator and interoperator precisions were evaluated. For local vertebral and disk height measurement (anterior, middle, posterior) the algorithm was compared to a manual mid-sagittal plane method. Results: The mean (standard deviation) interscan difference was as low as 0.043 (0.031) mm for disk heights and 0.044 (0.043) mm for vertebral heights. The corresponding 95% limits of agreement were [-0.085, 0.11] and [-0.10, 0.12] mm, respectively. Intraoperator and interoperator precision was high, with a maximal CV of 0.30%. For local vertebral and disk heights, the algorithm improved upon the precision of the manual mid-sagittal plane measurement by as much as a factor of 6 and 4, respectively. Conclusions: The authors evaluated the precision of a novel computer algorithm for measuring vertebral body heights and disk heights using short term repeat CT scans of patients. The 95% limits of agreement indicate that the algorithm can detect small height changes of the order of 0.1 mm. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4769412] C1 [Tan, Sovira; Ward, Michael M.] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Tan, S (reprint author), NIAMSD, NIH, Bldg 10,CRC Room 4-1339, Bethesda, MD 20892 USA. EM tanso@mail.nih.gov FU NIAMS; CC (NIH) FX This research was supported by the Intramural Research Program of NIAMS and CC (NIH). NR 45 TC 3 Z9 3 U1 0 U2 9 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2013 VL 40 IS 1 AR 011905 DI 10.1118/1.4769412 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063WR UT WOS:000313033200030 PM 23298096 ER PT J AU Ying, ZG Ciesielski, KC Udupa, JK Miller, RW AF Ying Zhuge Ciesielski, Krzysztof C. Udupa, Jayaram K. Miller, Robert W. TI GPU-based relative fuzzy connectedness image segmentation SO MEDICAL PHYSICS LA English DT Article DE image segmentation; fuzzy connectedness; graph-based methods; GPU implementations ID OBJECT DEFINITION; RANDOM-WALKS; GRAPH CUTS; ALGORITHMS; MINIMIZATION; VALIDATION; SYSTEM; VOLUME AB Purpose: Recently, clinical radiological research and practice are becoming increasingly quantitative. Further, images continue to increase in size and volume. For quantitative radiology to become practical, it is crucial that image segmentation algorithms and their implementations are rapid and yield practical run time on very large data sets. The purpose of this paper is to present a parallel version of an algorithm that belongs to the family of fuzzy connectedness (FC) algorithms, to achieve an interactive speed for segmenting large medical image data sets. Methods: The most common FC segmentations, optimizing an l(infinity)-based energy, are known as relative fuzzy connectedness (RFC) and iterative relative fuzzy connectedness (IRFC). Both RFC and IRFC objects (of which IRFC contains RFC) can be found via linear time algorithms, linear with respect to the image size. The new algorithm, P-ORFC (for parallel optimal RFC), which is implemented by using NVIDIA's Compute Unified Device Architecture (CUDA) platform, considerably improves the computational speed of the above mentioned CPU based IRFC algorithm. Results: Experiments based on four data sets of small, medium, large, and super data size, achieved speedup factors of 32.8x, 22.9x, 20.9x, and 17.5x, correspondingly, on the NVIDIA Tesla C1060 platform. Although the output of P-ORFC need not precisely match that of IRFC output, it is very close to it and, as the authors prove, always lies between the RFC and IRFC objects. Conclusions: A parallel version of a top-of-the-line algorithm in the family of FC has been developed on the NVIDIA GPUs. An interactive speed of segmentation has been achieved, even for the largest medical image data set. Such GPU implementations may play a crucial role in automatic anatomy recognition in clinical radiology. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4769418] C1 [Ying Zhuge; Miller, Robert W.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Ciesielski, Krzysztof C.] W Virginia Univ, Dept Math, Morgantown, WV 26506 USA. [Ciesielski, Krzysztof C.; Udupa, Jayaram K.] Univ Penn, Dept Radiol, Med Image Proc Grp, Philadelphia, PA 19104 USA. RP Ying, ZG (reprint author), NCI, Radiat Oncol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhugey@mail.nih.gov; KCies@math.wvu.edu; jay@mail.med.upenn.edu; rwmiller@mail.nih.gov FU National Cancer Institute, NIH FX This research was supported by the Intramural Research Program of the National Cancer Institute, NIH. NR 41 TC 0 Z9 1 U1 1 U2 16 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JAN PY 2013 VL 40 IS 1 AR 011903 DI 10.1118/1.4769418 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 063WR UT WOS:000313033200028 ER PT J AU Shah, M Mamyrova, G Targoff, IN Huber, AM Malley, JD Rice, MM Miller, FW Rider, LG AF Shah, Mona Mamyrova, Gulnara Targoff, Ira N. Huber, Adam M. Malley, James D. Rice, Madeline Murguia Miller, Frederick W. Rider, Lisa G. CA Childhood Myositis Heterogeneity C TI The Clinical Phenotypes of the Juvenile Idiopathic Inflammatory Myopathies SO MEDICINE LA English DT Article ID SIGNAL RECOGNITION PARTICLE; MYOSITIS-SPECIFIC AUTOANTIBODIES; TRANSFER RNA-SYNTHETASES; ADULT DERMATOMYOSITIS; ENVIRONMENTAL-FACTORS; LABORATORY FEATURES; PROGNOSTIC-FACTORS; POLYMYOSITIS; ONSET; CHILDREN AB The juvenile idiopathic inflammatory myopathies (JIIM) are systemic autoimmune diseases characterized by skeletal muscle weakness, characteristic rashes, and other systemic features. Although juvenile dermatomyositis (JDM), the most common form of JIIM, has been well studied, the other major clinical subgroups of JIIM, including juvenile polymyositis (JPM) and juvenile myositis overlapping with another autoimmune or connective tissue disease (JCTM), have not been well characterized, and their similarity to the adult clinical subgroups is unknown. We enrolled 436 patients with JIIM, including 354 classified as JDM, 33 as JPM, and 49 as JCTM, in a nationwide registry study. The aim of the study was to compare demographics; clinical features; laboratory measures, including myositis auto-antibodies; and outcomes among these clinical subgroups, as well as with published data on adult patients with idiopathic inflammatory myopathies (IIM) enrolled in a separate natural history study. We used random forest classification and logistic regression modeling to compare clinical subgroups, following univariate analysis. JDM was characterized by typical rashes, including Gottron papules, heliotrope rash, malar rash, periungual capillary changes, and other photosensitive and vasculopathic skin rashes. JPM was characterized by more severe weakness, higher creatine kinase levels, falling episodes, and more frequent cardiac disease. JCTM had more frequent interstitial lung disease, Raynaud phenomenon, arthralgia, and malar rash. Differences in autoantibody frequency were also evident, with anti-p155/140, anti-MJ, and anti-Mi-2 seen more frequently in patients with JDM, anti-signal recognition particle and anti-Jo-1 in JPM, and anti-U1-RNP, PM-Scl, and other myositis-associated autoantibodies more commonly present in JCTM. Mortality was highest in patients with JCTM, whereas hospitalizations and wheelchair use were highest in JPM patients. Several demographic and clinical features were shared between juvenile and adult IIM subgroups. However, JDM and JPM patients had a lower frequency of interstitial lung disease, Raynaud phenomenon, "mechanic's hands'' and carpal tunnel syndrome, and lower mortality than their adult counterparts. We conclude that juvenile myositis is a heterogeneous group of illnesses with distinct clinical subgroups, defined by varying clinical and demographic characteristics, laboratory features, and outcomes. (Medicine 2013; 92: 25-41) C1 [Rider, Lisa G.] NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,DHHS, Bethesda, MD 20892 USA. [Malley, James D.] NIH, Ctr Informat Technol, DHHS, Bethesda, MD 20892 USA. [Shah, Mona; Rice, Madeline Murguia] George Washington Univ, Sch Med, Dept Epidemiol & Biostat, Washington, DC USA. [Mamyrova, Gulnara] George Washington Univ, Sch Med, Dept Med, Div Rheumatol, Washington, DC USA. [Huber, Adam M.] IWK Hlth Ctr, Halifax, NS, Canada. [Huber, Adam M.] Dalhousie Univ, Halifax, NS, Canada. [Targoff, Ira N.] Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Oklahoma City, OK USA. [Targoff, Ira N.] Oklahoma Med Res Fdn, Oklahoma City, OK USA. RP Rider, LG (reprint author), NIEHS, Environm Autoimmun Grp, Program Clin Res, NIH,DHHS, Clin Res Ctr Room 4-2352,10 Ctr Dr,MSC 1301, Bethesda, MD 20892 USA. EM riderl@mail.nih.gov OI Ilowite, Norman/0000-0002-8298-8563; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU NIEHS; NIH [ES101074]; NIAMS; NIH; CBER, Food and Drug Administration; Cure JM Foundation; Myositis Association FX This work was supported in part by the Intramural Research Programs of NIEHS, NIH (project number ES101074), NIAMS, NIH, and CBER, Food and Drug Administration. Gulnara Mamyrova was supported by the Cure JM Foundation and previously by The Myositis Association. Ira Targoff is a consultant to the Oklahoma Medical Research Foundation Clinical Immunology Laboratory. NR 59 TC 32 Z9 34 U1 0 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD JAN PY 2013 VL 92 IS 1 BP 25 EP 41 DI 10.1097/MD.0b013e31827f264d PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 062VY UT WOS:000312952900004 PM 23263716 ER PT J AU Mason, C Foster-Schubert, KE Imayama, I Xiao, LR Kong, A Campbell, KL Duggan, CR Wang, CY Alfano, CM Ulrich, CM Blackburn, GL McTiernan, A AF Mason, Caitlin Foster-Schubert, Karen E. Imayama, Ikuyo Xiao, Liren Kong, Angela Campbell, Kristin L. Duggan, Catherine R. Wang, Ching-Yun Alfano, Catherine M. Ulrich, Cornelia M. Blackburn, George L. McTiernan, Anne TI History of weight cycling does not impede future weight loss or metabolic improvements in postmenopausal women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article DE Lifestyle intervention; Insulin resistance; Inflammation; Adipokines; Exercise ID HOMEOSTASIS MODEL ASSESSMENT; OLDER WOMEN; INSULIN SENSITIVITY; PHYSICAL-ACTIVITIES; LOSS MAINTENANCE; HEALTH; RISK; MORTALITY; DISEASE; GLUCOSE AB Objective. Given that the repetitive loss and regain of body weight, termed weight cycling, is a prevalent phenomenon that has been associated with negative physiological and psychological outcomes, the purpose of this study was to investigate weight change and physiological outcomes in women with a lifetime history of weight cycling enrolled in a 12-month diet and/or exercise intervention. Methods. 439 overweight, inactive, postmenopausal women were randomized to: i) dietary weight loss with a 10% weight loss goal (N = 118); ii) moderate-to-vigorous intensity aerobic exercise for 45 min/day, 5 days/week (n = 117); ii) both dietary weight loss and exercise (n = 117); or iv) control (n = 87). Women were categorized as non-, moderate- (>= 3 losses of >= 4.5 kg), or severe-cyclers (>= 3 losses of >= 9.1 kg). Trend tests and linear regression were used to compare adherence and changes in weight, body composition, blood pressure, insulin, C-peptide, glucose, insulin resistance (HOMA-IR), C-reactive protein, leptin, adiponectin, and interleukin-6 between cyclers and non-cyclers. Results. Moderate (n = 103) and severe (n = 77) cyclers were heavier and had less favorable metabolic profiles than non-cyclers at baseline. There were, however, no significant differences in adherence to the lifestyle interventions. Weight-cyclers (combined) had a greater improvement in HOMA-IR compared to non-cyclers participating in the exercise only intervention (P=.03), but no differences were apparent in the other groups. Conclusion. A history of weight cycling does not impede successful participation in lifestyle interventions or alter the benefits of diet and/or exercise on body composition and metabolic outcomes. (C) 2013 Elsevier Inc. All rights reserved. C1 [Mason, Caitlin; Imayama, Ikuyo; Xiao, Liren; Duggan, Catherine R.; Wang, Ching-Yun; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Foster-Schubert, Karen E.] Univ Washington, Sch Med, Dept Endocrinol Metab & Nutr, Seattle, WA USA. [Kong, Angela] Univ Illinois, Chicago, IL USA. [Campbell, Kristin L.] Univ British Columbia, Sch Physiotherapy, Vancouver, BC V5Z 1M9, Canada. [Alfano, Catherine M.] NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. [Ulrich, Cornelia M.] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Ulrich, Cornelia M.] Natl Ctr Tumour Dis, Heidelberg, Germany. [Blackburn, George L.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Nutr, Boston, MA 02215 USA. RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, M4-B874,POB 19024, Seattle, WA 98109 USA. EM amctiern@fhcrc.org RI Duggan, Catherine/F-9414-2015 OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute at the National Institutes of Health [R01 CA102504, U54-CA116847, 5KL2RR025015-03, R25 CA94880, 2R25CA057699-16]; Canadian Institutes of Health Research FX This work was supported by the National Cancer Institute at the National Institutes of Health (grant number: R01 CA102504, U54-CA116847, 5KL2RR025015-03 to K.F.S, R25 CA94880 and 2R25CA057699-16 to A.K.); and the Canadian Institutes of Health Research (Fellowship to CM & K.L.C). None of the funding agencies were involved in the trial design or conduct. While working on the trial, Dr. Alfano was employed at The Ohio State University, and located to NCI following completion of her effort on the NEW trial. NR 44 TC 11 Z9 11 U1 1 U2 22 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2013 VL 62 IS 1 BP 127 EP 136 DI 10.1016/j.metabol.2012.06.012 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 056PX UT WOS:000312504500015 PM 22898251 ER PT J AU Lenfant, C AF Lenfant, Claude TI Prospects of personalized medicine in cardiovascular diseases SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CORONARY-ARTERY-DISEASE; GENOMIC MEDICINE; MYOCARDIAL-INFARCTION; EPIGENETICS; ASSOCIATION; RISK; 9P21; PHARMACOGENOMICS; CLOPIDOGREL; GENOMEWIDE AB Cardiovascular diseases remain the dominant cause of death worldwide. In the last decades, the remarkable advances in human genetic and genomic research, plus the now common use of genome-wide association studies, have led to the identification of numerous genetic variants associated with specific cardiovascular traits and diseases. Although the clinical applications are limited because the genetic risk of common cardiovascular disease is still unexplained, and the mechanisms of action of the genetic factor(s) are not known, these research advances have, in turn, widely opened the concept of personalized medicine. In this paper, the status and prospects of personalized medicine for cardiovascular disease will be presented. This will be followed by a discussion of issues regarding the implementation of personalized medicine. (C) 2013 Elsevier Inc. All rights reserved. C1 [Lenfant, Claude] NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), POB 65278, Vancouver, WA 98665 USA. EM lenfantc@prodigy.net FU College International de Recherche Servier (CIRS) FX Publication of this article was supported by the College International de Recherche Servier (CIRS). NR 45 TC 7 Z9 8 U1 0 U2 14 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JAN PY 2013 VL 62 IS 1 SU 1 BP S6 EP S10 DI 10.1016/j.metabol.2012.08.018 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 056PZ UT WOS:000312504700003 PM 22999711 ER PT J AU Marin, JC Gonzalez, BA Poulin, E Casey, CS Johnson, WE AF Marin, Juan C. Gonzalez, Benito A. Poulin, Elie Casey, Ciara S. Johnson, Warren E. TI The influence of the arid Andean high plateau on the phylogeography and population genetics of guanaco (Lama guanicoe) in South America SO MOLECULAR ECOLOGY LA English DT Review DE camelids; contact zone; d-loop; Holocene; microsatellites; Patagonia ID MULTILOCUS GENOTYPE DATA; VICUNAS VICUGNA-VICUGNA; TIERRA-DEL-FUEGO; ATACAMA DESERT; MITOCHONDRIAL-DNA; MICROSATELLITE MARKERS; CLIMATE-CHANGE; DEMOGRAPHIC PARAMETERS; MAXIMUM-LIKELIHOOD; PATAGONIA AB A comprehensive study of the phylogeography and population genetics of the largest wild artiodactyl in the arid and cold-temperate South American environments, the guanaco (Lama guanicoe) was conducted. Patterns of molecular genetic structure were described using 514bp of mtDNA sequence and 14 biparentally inherited microsatellite markers from 314 samples. These individuals originated from 17 localities throughout the current distribution across Peru, Bolivia, Argentina and Chile. This confirmed well-defined genetic differentiation and subspecies designation of populations geographically separated to the northwest (L.g.cacsilensis) and southeast (L.g.guanicoe) of the central Andes plateau. However, these populations are not completely isolated, as shown by admixture prevalent throughout a limited contact zone, and a strong signal of expansion from north to south in the beginning of the Holocene. Microsatellite analyses differentiated three northwestern and 45 southeastern populations, suggesting patterns of genetic contact among these populations. Possible genetic refuges were identified, as were source-sink patterns of gene flow at historical and recent time scales. Conservation and management of guanaco should be implemented with an understanding of these local population dynamics while also considering the preservation of broader adaptive variation and evolutionary processes. C1 [Marin, Juan C.] Univ Bio Bio, Fac Ciencias, Dept Ciencias Basicas, Lab Genom & Biodiversidad, Chillan, Chile. [Gonzalez, Benito A.] Univ Chile, Lab Ecol Vida Silvestre, Fac Ciencias Forestales & Conservac Nat, Santiago, Chile. [Poulin, Elie] Univ Chile, Fac Ciencias, Dept Ciencias Ecol, Lab Ecol Mol,Inst Ecol & Biodiversidad, Santiago, Chile. [Casey, Ciara S.] Lincoln Univ, Dept Biol Sci, Lincoln, NE USA. [Johnson, Warren E.] NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Marin, JC (reprint author), Univ Bio Bio, Fac Ciencias, Dept Ciencias Basicas, Lab Genom & Biodiversidad, Casilla 447, Chillan, Chile. EM jcmarin@ubiobio.cl RI Poulin, Elie/C-2654-2012; Gonzalez, Benito/I-9570-2014; Johnson, Warren/D-4149-2016 OI Poulin, Elie/0000-0001-7736-0969; Gonzalez, Benito/0000-0001-8201-8789; Johnson, Warren/0000-0002-5954-186X FU CONICYT, Chile (Beca de Apoyo a Tesis Doctoral); FONDECYT, Chile [101105, 3050046]; Darwin Initiative for the Survival of Species (UK); British Embassy (Lima); NERC (UK) [GST/02/828]; Darwin Initiative [12/022]; European Commission [INCO-DC ICA4-2000-10229]; MACS; Intramural Research Program of the National Institutes of Health (NIH); National Cancer Institute (NCI) (US); CONICYT FX Financial support from the following organizations is gratefully acknowledged: CONICYT, Chile (Beca de Apoyo a Tesis Doctoral); FONDECYT, Chile Grant 101105 and Postdoctoral Grant 3050046; Darwin Initiative for the Survival of Species (UK), The British Embassy (Lima), NERC (UK) grant GST/02/828, Darwin Initiative grant 12/022, European Commission INCO-DC ICA4-2000-10229, MACS. This research was supported in part by the Intramural Research Program of the National Institutes of Health (NIH) and the National Cancer Institute (NCI) (US). This work was written by Benito A. Gonzalez during his PhD studies in the Programa de Doctorado en Ciencias Silvoagropecuarias y Veterinarias of the Universidad de Chile supported by CONICYT scholarship. In Peru we thank Maria Luisa del Rio (MINAM), Carlos Loret de Mola (CONAM), Gustavo Suarez de Freitas and Antonio Morizaki (INRENA), Wilder Trejo, Daniel Rivera, Daniel Arestegui, Leonidas Rodriguez, Carlos Flores and Dirky Arias at CONACS, Carlos Ponce (Conservation International). In Chile, we thank the Servicio Agricola y Ganadero, SAG (Permit 447, 2002), the Corporacion Nacional Forestal, CONAF (permit 6/02, 2002), for granting other collection permits and helping in collecting samples. We especially thanks C. Bonacic (Pontificia Universidad Catolica de Chile), O. Skewes (Universidad de Concepcion), F. de Smet (Valchac Ltd.), F. Novoa (Centro de Ecologia Aplicada Ltda), and Minera Los Pelambres, R. Baldi and V. Burgi (CENPAT, Argentina), E. Cuellar (WCS-Bolivia), A. Duarte (Zoologico de Mendoza, Argentina) for sharing samples; Homero Pezoa, Nicolas Aravena, for support in the laboratory and Pablo Orozco-teWengel (Cardiff University), for support in the software analyses. Special thanks are due to Jane C. Wheeler (CONOPA) for facilitating samples and collaboration, and Michael Bruford (Cardiff University) and Angel Spotorno (Universidad de Chile) for useful information, discussions, advice and support. Samples were transported under CITES authorization numbers 6282, 4222, 6007, 5971, 5177, 5178, 23355, 22967 and 22920. NR 121 TC 5 Z9 5 U1 5 U2 88 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0962-1083 EI 1365-294X J9 MOL ECOL JI Mol. Ecol. PD JAN PY 2013 VL 22 IS 2 BP 463 EP 482 DI 10.1111/mec.12111 PG 20 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 063KI UT WOS:000312996600016 PM 23206254 ER PT J AU Emery, AC Eiden, MV Eiden, LE AF Emery, Andrew C. Eiden, Maribeth V. Eiden, Lee E. TI A New Site and Mechanism of Action for the Widely Used Adenylate Cyclase Inhibitor SQ22,536 SO MOLECULAR PHARMACOLOGY LA English DT Article ID NERVE GROWTH-FACTOR; INDEPENDENT SIGNALING PATHWAY; BETA-GAMMA-SUBUNITS; PROTEIN-KINASE; NEURITE OUTGROWTH; PC12 CELLS; CYCLIC-AMP; ADENOSINE-ANALOGS; GENE-EXPRESSION; CAMP AB We evaluated the efficacy, potency, and selectivity of the three most commonly used adenylate cyclase (AC) inhibitors in a battery of cell lines constructed to study signaling via three discrete cAMP sensors identified in neuroendocrine cells. SQ22,536 [9-(tetrahydrofuryl)-adenine] and 2',5'-dideoxyadenosine (ddAd) are effective and potent AC inhibitors in HEK293 cells expressing a cAMP response element (CRE) reporter gene, and MDL-12,330A [cis-N-(2-phenylcyclopentyl)azacy-clotridec-1-en-2-amine hydrochloride] is not. Neuroscreen-1 (NS-1) cells were used to assess the specificity of the most potent AC inhibitor, SQ22,536, to block downstream cAMP signaling to phosphorylate CREB (via PKA); to activate Rap1 (via Epac); and to activate ERK signaling leading to neuritogenesis (via the newly described neuritogenic cAMP sensor NCS). SQ22,536 failed to inhibit the effects of cAMP analogs 8-Br-cAMP and 8-CPT-29-O-Me-cAMP on PKA-mediated CREB activation/phosphorylation and Epac-mediated Rap1 activation, indicating that it does not inhibit these cAMP pathways beyond the level of AC. On the other hand, SQ22,536, but not ddAd, inhibited the effects of cAMP analogs 8-Br-cAMP and 8-CPT-cAMP on ERK phosphorylation and neuritogenesis, indicating that it acts not only as an AC blocker, but also as an inhibitor of the NCS. The observed off-target actions of SQ22,536 are specific to cAMP signaling: SQ22,536 does not block the actions of compounds not related to cAMP signaling, including ERK induction by PMA, and ERK activation and neuritogenesis induced by NGF. These data led us to indicate a second target for SQ22,536 that should be considered when interpreting its effects in whole cell and in vivo experiments. C1 [Emery, Andrew C.; Eiden, Lee E.] NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Eiden, Maribeth V.] NIMH, Sect Directed Gene Transfer, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, 49 Convent Dr,Bldg 49,Room 5A-38, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Emery, Andrew/0000-0002-6760-2570; Eiden, Lee/0000-0001-7524-944X FU National Institutes of Health [National Institute of Mental Health] [1ZIAMH002386, 1ZIAMH002592] FX This work was funded by the Intramural Research Program of the National Institutes of Health [National Institute of Mental Health] [Projects 1ZIAMH002386 and 1ZIAMH002592]. NR 46 TC 11 Z9 11 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2013 VL 83 IS 1 BP 95 EP 105 DI 10.1124/mol.112.081760 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060SR UT WOS:000312798900010 PM 23053667 ER PT J AU Krzysik-Walker, SM Gonzalez-Mariscal, I Scheibye-Knudsen, M Indig, FE Bernier, M AF Krzysik-Walker, Susan M. Gonzalez-Mariscal, Isabel Scheibye-Knudsen, Morten Indig, Fred E. Bernier, Michel TI The Biarylpyrazole Compound AM251 Alters Mitochondrial Physiology via Proteolytic Degradation of ERR alpha SO MOLECULAR PHARMACOLOGY LA English DT Article ID ESTROGEN-RELATED RECEPTORS; PHOSPHORYLATION-DEPENDENT SUMOYLATION; PROLIFERATOR-ACTIVATED RECEPTOR; TRANSCRIPTIONAL CONTROL; PROTEASOMAL DEGRADATION; ANTAGONIST RIMONABANT; ORPHAN; PROTEIN; MICE; GENE AB The orphan nuclear receptor estrogen-related receptor alpha (ERR alpha) directs the transcription of nuclear genes involved in energy homeostasis control and the regulation of mitochondrial mass and function. A crucial role for controlling ERR alpha-mediated target gene expression has been ascribed to the biarylpyrazole compound 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide (AM251) through direct binding to and destabilization of ERR alpha protein. Here, we provide evidence that structurally related AM251 analogs also have negative impacts on ERR alpha protein levels in a cell-type-dependent manner while having no deleterious actions on ERR gamma. We show that these off-target cellular effects of AM251 are mediated by proteasomal degradation of nuclear ERR alpha. Cell treatment with the nuclear export inhibitor leptomycin B did not prevent AM251-induced destabilization of ERR alpha protein, whereas proteasome inhibition with MG132 stabilized and maintained its DNA-binding function, indicative of ERR alpha being a target of nuclear proteasomal complexes. NativePAGE analysis revealed that ERR alpha formed a similar to 220-kDa multiprotein nuclear complex that was devoid of ERR gamma and the coregulator peroxisome proliferator-activated receptor gamma coactivator-1. AM251 induced SUMO-2,3 incorporation in ERR alpha in conjunction with increased protein kinase C activity, whose activation by phorbol ester also promoted ERR alpha protein loss. Down-regulation of ERR alpha by AM251 or small interfering RNA led to increased mitochondria biogenesis while negatively impacting mitochondrial membrane potential. These results reveal a novel molecular mechanism by which AM251 and related compounds alter mitochondrial physiology through destabilization of ERR alpha. C1 [Bernier, Michel] NIA, Clin Invest Lab, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. [Scheibye-Knudsen, Morten] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bernier, M (reprint author), NIA, Clin Invest Lab, NIH, Biomed Res Ctr, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM bernierm@mail.nih.gov OI Gonzalez Mariscal, Isabel/0000-0003-1186-1212; Bernier, Michel/0000-0002-5948-368X FU National Institutes of Health [National Institute on Aging] FX This research was supported entirely by the Intramural Research Program of the National Institutes of Health [National Institute on Aging]. NR 46 TC 3 Z9 3 U1 1 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2013 VL 83 IS 1 BP 157 EP 166 DI 10.1124/mol.112.082651 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060SR UT WOS:000312798900015 PM 23066093 ER PT J AU Lu, VB Puhl, HL Ikeda, SR AF Lu, Van B. Puhl, Henry L., III Ikeda, Stephen R. TI N-Arachidonyl Glycine Does Not Activate G Protein-Coupled Receptor 18 Signaling via Canonical Pathways SO MOLECULAR PHARMACOLOGY LA English DT Article ID RAT SYMPATHETIC NEURONS; METABOTROPIC GLUTAMATE RECEPTORS; BETA-GAMMA-SUBUNITS; CA2+ CHANNELS; CALCIUM-CHANNELS; AMINO-ACIDS; POTASSIUM CHANNELS; MAMMALIAN NEURONS; ION CHANNELS; GPR18 AB Recent studies propose that N-arachidonyl glycine (NAGly), a carboxylic analogue of anandamide, is an endogenous ligand of the G alpha(i/o) protein-coupled receptor 18 (GPR18). However, a high-throughput beta-arrestin-based screen failed to detect activation of GPR18 by NAGly (Yin et al., 2009; JBC, 18: 12328). To address this inconsistency, this study investigated GPR18 coupling in a native neuronal system with endogenous signaling pathways and effectors. GPR18 was heterologously expressed in rat sympathetic neurons, and the modulation of N-type (Ca(v)2.2) calcium channels was examined. Proper expression and trafficking of receptor were confirmed by the "rim-like" fluorescence of fluorescently tagged receptor and the positive staining of external hemagglutinin-tagged GPR18-expressing cells. Application of NAGly on GPR18-expressing neurons did not inhibit calcium currents but instead potentiated currents in a voltage-dependent manner, similar to what has previously been reported (Guo et al., 2008; J Neurophysiol, 100: 1147). Other proposed agonists of GPR18, including anandamide and abnormal cannabidiol, also failed to induce inhibition of calcium currents. Mutants of GPR18, designed to constitutively activate receptors, did not tonically inhibit calcium currents, indicating a lack of GPR18 activation or coupling to endogenous G proteins. Other downstream effectors of G alpha(i/o)-coupled receptors, G protein-coupled inwardly rectifying potassium channels and adenylate cyclase, were not modulated by GPR18 signaling. Furthermore, GPR18 did not couple to other G proteins tested: G alpha(s), G alpha(z), and G alpha(15). These results suggest NAGly is not an agonist for GPR18 or that GPR18 signaling involves noncanonical pathways not examined in these studies. C1 [Lu, Van B.; Puhl, Henry L., III; Ikeda, Stephen R.] NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Sect Transmitter Signaling, Lab Mol Physiol, NIH, 5625 Fishers Lane,Room TS-11,MSC 9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508; Lu, Van/0000-0002-4880-6455; Puhl, Henry/0000-0003-3095-7201 FU National Institutes of Health [National Institute on Alcohol Abuse and Alcoholism] FX This research was supported by the Intramural Research Program of the National Institutes of Health [National Institute on Alcohol Abuse and Alcoholism] NR 55 TC 19 Z9 19 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JAN PY 2013 VL 83 IS 1 BP 267 EP 282 DI 10.1124/mol.112.081182 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 060SR UT WOS:000312798900025 PM 23104136 ER PT J AU Jabbi, M Nash, T Kohn, P Ianni, A Rubinstein, D Holroyd, T Carver, FW Masdeu, JC Kippenhan, JS Robinson, SE Coppola, R Berman, KF AF Jabbi, M. Nash, T. Kohn, P. Ianni, A. Rubinstein, D. Holroyd, T. Carver, F. W. Masdeu, J. C. Kippenhan, J. Shane Robinson, S. E. Coppola, R. Berman, K. F. TI Midbrain presynaptic dopamine tone predicts sustained and transient neural response to emotional salience in humans: fMRI, MEG and FDOPA PET SO MOLECULAR PSYCHIATRY LA English DT Letter ID GAMMA-BAND SYNCHRONIZATION; SYSTEM; SCHIZOPHRENIA; PERCEPTION C1 [Jabbi, M.; Nash, T.; Kohn, P.; Ianni, A.; Rubinstein, D.; Masdeu, J. C.; Kippenhan, J. Shane; Berman, K. F.] Sect Integrat Neuroimaging, Bethesda, MD USA. [Jabbi, M.; Nash, T.; Kohn, P.; Ianni, A.; Rubinstein, D.; Masdeu, J. C.; Kippenhan, J. Shane; Coppola, R.; Berman, K. F.] Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD USA. [Rubinstein, D.; Holroyd, T.; Carver, F. W.; Robinson, S. E.; Coppola, R.] NIMH, Magnetoencephalog Core Facil, NIH, Intramural Res Program, Bethesda, MD 20892 USA. RP Jabbi, M (reprint author), Sect Integrat Neuroimaging, Bethesda, MD USA. EM jabbim@gmail.com FU Intramural NIH HHS [Z01 MH002717-14]; NIGMS NIH HHS [T32 GM007198] NR 14 TC 3 Z9 3 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JAN PY 2013 VL 18 IS 1 BP 4 EP 6 DI 10.1038/mp.2012.12 PG 4 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 060JA UT WOS:000312771600004 PM 22411228 ER PT J AU Peluso, M Srivatanakul, P Jedpiyawongse, A Sangrajrang, S Munnia, A Piro, S Ceppi, M Boffetta, P Godschalk, RWL van Schooten, FJ AF Peluso, Marco Srivatanakul, Petcharin Jedpiyawongse, Adisorn Sangrajrang, Suleeporn Munnia, Armelle Piro, Sara Ceppi, Marcello Boffetta, Paolo Godschalk, Roger W. L. van Schooten, Frederik J. TI Aromatic DNA adducts and number of lung cancer risk alleles in Map-Ta-Phut Industrial Estate workers and nearby residents SO MUTAGENESIS LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; GENETIC POLYMORPHISMS; SMOKERS; HYDROCARBONS; MODULATION; ACTIVATION; VARIANTS; ALCOHOL; SMOKING; COHORT AB The Map-Ta-Phut Industrial Estate (MIE) in Rayong, Thailand, is the location of one of the largest industrial complexes in southeastern Asia. The MIE complex produces a mixture of air pollutants, including polycyclic aromatic hydrocarbons, compounds capable to induce the generation of DNA adducts. DNA adducts are considered to be a biomarker of carcinogen exposure; however, its production can be modulated by genetic susceptibility. Thus, we analysed the influence of EPHX1 His139Arg (A > G, rs2234922) and NQO1 Pro187Ser (C > T, rs1800566) involved in the metabolism of polycyclic aromatic hydrocarbons; MnSOD2 Val16Ala (C > T, rs1799725) a gene that acts against the free radical generation; APE1/Ref-1 Asp148Glu (T > G, rs3136820) a gene involved in the repair of DNA, and in the control of cell-cycle and apoptosis on leucocyte DNA adducts in 77 MIE workers, 69 Map-Ta-Phut residents, and 50 rural controls, Rayong, Thailand. We searched for associations with the osum of at-risk alleles' by combining the variant alleles of EPHX1, NQO1 and MnSOD2 together with the wild-type allele of APE1, since they appeared to influence lung cancer risk. Although our findings revealed significant associations between DNA adducts and the EPHX1 His139Arg and NQO1 Pro187Ser polymorphisms, the combination of at-risk alleles was found to affect DNA damage much stronger. DNA adducts were significantly increased in the individuals bearing 4 and epsilon 5 at-risk alleles [mean ratio (MR) 1.55, 95% CI 1.102.18, P 0.012, and MR 2.11, 95% CI 1.273.51, P 0.004, respectively)]. After correction for residence/employment categorisation, a significant increment was present in the MIE workers with epsilon 5 alleles (MR 2.88, 95% CI 1.465.71, P 0.003). Our data indicate relationships between the generation of DNA adducts and the enzymatic activities of EPHX and NQO1. The combination of unfavourable genetic variants seems to determine the individuals' susceptibility, rather than a single polymorphism. C1 [Peluso, Marco; Munnia, Armelle; Piro, Sara] Canc Prevent & Res Inst, Canc Risk Factor Branch, Florence, Italy. [Srivatanakul, Petcharin; Jedpiyawongse, Adisorn; Sangrajrang, Suleeporn] Natl Canc Inst, Mol Epidemiol Unit, Bangkok, Thailand. [Ceppi, Marcello] Natl Canc Inst, Mol Epidemiol Unit, Genoa, Italy. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Boffetta, Paolo] Mt Sinai Sch Med, Inst Translat Epidemiol, New York, NY USA. [Boffetta, Paolo] Int Prevent Res Inst, Lyon, France. [Godschalk, Roger W. L.; van Schooten, Frederik J.] Maastricht Univ, Dept Toxicol, Maastricht, Netherlands. RP Peluso, M (reprint author), Canc Prevent & Res Inst, Canc Risk Factor Branch, Florence, Italy. EM m.peluso@ispo.toscana.it FU National Cancer Institute, Bangkok, Thailand; 'Associazione Italiana per la Ricerca sul Cancro', Milan, Italy FX This study was supported from the National Cancer Institute, Bangkok, Thailand, and, partially, from the 'Associazione Italiana per la Ricerca sul Cancro', Milan, Italy. We thank Drs Yuwadee Chompituk, Somyos Deerasamee, Kris Palasuth, Mrs Kasemsri Huamchuen and the staff of Rayong Provincial Health Office for their assistance. Mrs Giulia Daniele is thanked for secretarial assistance. NR 40 TC 7 Z9 7 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2013 VL 28 IS 1 BP 57 EP 63 DI 10.1093/mutage/ges053 PG 7 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 061ZM UT WOS:000312888900007 PM 22987024 ER PT J AU Miao, LY Zhang, K Qiao, CY Jin, XY Zheng, CY Yang, B Sun, HC AF Miao, Leiying Zhang, Kai Qiao, Chunyan Jin, Xiangyu Zheng, Changyu Yang, Bai Sun, Hongchen TI Antitumor effect of human TRAIL on adenoid cystic carcinoma using magnetic nanoparticle-mediated gene expression SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Magnetic nanoparticles; Transgene therapy; Adenoid cystic carcinoma; Polyethylenimine; Apoptosis ID IRON-OXIDE NANOPARTICLES; APOPTOSIS-INDUCING LIGAND; REVERSE-TRANSCRIPTASE PROMOTER; IN-VIVO; DRUG-DELIVERY; MULTIFUNCTIONAL NANOPARTICLES; HUMAN HEPATOCYTES; SALIVARY-GLANDS; TUMOR; CANCER AB To overcome treatment limitations of adenoid cystic carcinoma, we developed a novel treatment combining gene therapy and nanotechnology. In this study, we created a plasmid, pACTERT-TRAIL, which used the human telomerase reverse transcriptase promoter, a tumor-specific promoter, to drive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). A Fe3O4-PEI-plasmid complex (FPP) was generated, in which the iron oxide nanoparticles were modified by positively charged polyethylenimine (PEI) to enable them to carry the negatively charged plasmid. In vitro transfection assays showed that efficiency of magnetofection (i.e., FPP transfection) was sixfold higher compared to PEI alone or Lipofectamine 2000 (hereafter referred to as lipofectin) (P < 0.05). Importantly, apoptotic assays demonstrated that FPP-mediated TRAIL gene transfer could efficiently induce apoptosis of SACC-83 cells in vitro and in vivo. These results demonstrate that magnetofection of the plasmids driven by the tumor-specific promoter hTERT provides an effective way to deliver therapeutic genes for the treatment of adenoid cystic carcinoma in the future. From the Clinical Editor: In this novel study addressing adenoid cystic carcinoma, the authors created a plasmid to drive tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Following that, a Fe3O4-PEI-plasmid complex (FPP) was generated, in which the iron oxide nanoparticles were modified by positively charged polyethylenimine (PEI) enabling them to carry the negatively charged plasmid, giving rise to sixfold higher transfection rates compared to standard technology. (C) 2013 Elsevier Inc. All rights reserved. C1 [Miao, Leiying; Qiao, Chunyan; Jin, Xiangyu; Sun, Hongchen] Jilin Univ, Sch Stomatol, Changchun 130041, Peoples R China. [Miao, Leiying; Zhang, Kai; Qiao, Chunyan; Yang, Bai] Jilin Univ, State Key Lab Supramol Struct & Mat, Changchun 130041, Peoples R China. [Zheng, Changyu] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. RP Sun, HC (reprint author), Jilin Univ, Sch Stomatol, Changchun 130041, Peoples R China. EM hcsun@mail.jlu.edu.cn FU National Natural Science Foundation of China [30672338, 30740420551, 30830108]; Science and Technology Development Program of Jilin Province [200705350, 201101051]; Open Project of State Key Laboratory of Supermolecular Structure and Materials [SKLSSM200904] FX This work was supported by grants from the National Natural Science Foundation of China (No. 30672338, 30740420551, and 30830108), Science and Technology Development Program of Jilin Province (200705350, 201101051), and Open Project of State Key Laboratory of Supermolecular Structure and Materials (SKLSSM200904). NR 50 TC 12 Z9 12 U1 3 U2 40 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JAN PY 2013 VL 9 IS 1 BP 141 EP 150 DI 10.1016/j.nano.2012.04.006 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 064CA UT WOS:000313047300016 PM 22633896 ER PT J AU Deloukas, P Kanoni, S Willenborg, C Farrall, M Assimes, TL Thompson, JR Ingelsson, E Saleheen, D Erdmann, J Goldstein, BA Stirrups, K Konig, IR Cazier, JB Johansson, A Hall, AS Lee, JY Willer, CJ Chambers, JC Esko, T Folkersen, L Goel, A Grundberg, E Havulinna, AS Ho, WK Hopewell, JC Eriksson, N Kleber, ME Kristiansson, K Lundmark, P Lyytikainen, LP Rafelt, S Shungin, D Strawbridge, RJ Thorleifsson, G Tikkanen, E Van Zuydam, N Voight, BF Waite, LL Zhang, WH Ziegler, A Absher, D Altshuler, D Balmforth, AJ Barroso, I Braund, PS Burgdorf, C Claudi-Boehm, S Cox, D Dimitriou, M Do, R Doney, ASF El Mokhtari, N Eriksson, P Fischer, K Fontanillas, P Franco-Cereceda, A Gigante, B Groop, L Gustafsson, S Hager, J Hallmans, G Han, BG Hunt, SE Kang, HM Illig, T Kessler, T Knowles, JW Kolovou, G Kuusisto, J Langenberg, C Langford, C Leander, K Lokki, ML Lundmark, A McCarthy, MI Meisinger, C Melander, O Mihailov, E Maouche, S Morris, AD Muller-Nurasyid, M Nikus, K Peden, JF Rayner, NW Rasheed, A Rosinger, S Rubin, D Rumpf, MP Schafer, A Sivananthan, M Song, C Stewart, AFR Tan, ST Thorgeirsson, G van der Schoot, CE Wagner, PJ Wells, GA Wild, PS Yang, TP Amouyel, P Arveiler, D Basart, H Boehnke, M Boerwinkle, E Brambilla, P Cambien, F Cupples, AL de Faire, U Dehghan, A Diemert, P Epstein, SE Evans, A Ferrario, MM Ferrieres, J Gauguier, D Go, AS Goodall, AH Gudnason, V Hazen, SL Holm, H Iribarren, C Jang, Y Kahonen, M Kee, F Kim, HS Klopp, N Koenig, W Kratzer, W Kuulasmaa, K Laakso, M Laaksonen, R Lee, JY Lind, L Ouwehand, WH Parish, S Park, JE Pedersen, NL Peters, A Quertermous, T Rader, DJ Salomaa, V Schadt, E Shah, SH Sinisalo, J Stark, K Stefansson, K Tregouet, DA Virtamo, J Wallentin, L Wareham, N Zimmermann, ME Nieminen, MS Hengstenberg, C Sandhu, MS Pastinen, T Syvanen, AC Hovingh, GK Dedoussis, G Franks, PW Lehtimaki, T Metspalu, A Zalloua, PA Siegbahn, A Schreiber, S Ripatti, S Blankenberg, SS Perola, M Clarke, R Boehm, BO O'Donnell, C Reilly, MP Marz, W Collins, R Kathiresan, S Hamsten, A Kooner, JS Thorsteinsdottir, U Danesh, J Palmer, CNA Roberts, R Watkins, H Schunkert, H Samani, NJ AF Deloukas, Panos Kanoni, Stavroula Willenborg, Christina Farrall, Martin Assimes, Themistocles L. Thompson, John R. Ingelsson, Erik Saleheen, Danish Erdmann, Jeanette Goldstein, Benjamin A. Stirrups, Kathleen Koenig, Inke R. Cazier, Jean-Baptiste Johansson, Asa Hall, Alistair S. Lee, Jong-Young Willer, Cristen J. Chambers, John C. Esko, Tonu Folkersen, Lasse Goel, Anuj Grundberg, Elin Havulinna, Aki S. Ho, Weang K. Hopewell, Jemma C. Eriksson, Niclas Kleber, Marcus E. Kristiansson, Kati Lundmark, Per Lyytikainen, Leo-Pekka Rafelt, Suzanne Shungin, Dmitry Strawbridge, Rona J. Thorleifsson, Gudmar Tikkanen, Emmi Van Zuydam, Natalie Voight, Benjamin F. Waite, Lindsay L. Zhang, Weihua Ziegler, Andreas Absher, Devin Altshuler, David Balmforth, Anthony J. Barroso, Ines Braund, Peter S. Burgdorf, Christof Claudi-Boehm, Simone Cox, David Dimitriou, Maria Do, Ron Doney, Alex S. F. El Mokhtari, NourEddine Eriksson, Per Fischer, Krista Fontanillas, Pierre Franco-Cereceda, Anders Gigante, Bruna Groop, Leif Gustafsson, Stefan Hager, Joerg Hallmans, Goran Han, Bok-Ghee Hunt, Sarah E. Kang, Hyun M. Illig, Thomas Kessler, Thorsten Knowles, Joshua W. Kolovou, Genovefa Kuusisto, Johanna Langenberg, Claudia Langford, Cordelia Leander, Karin Lokki, Marja-Liisa Lundmark, Anders McCarthy, Mark I. Meisinger, Christa Melander, Olle Mihailov, Evelin Maouche, Seraya Morris, Andrew D. Mueller-Nurasyid, Martina Nikus, Kjell Peden, John F. Rayner, N. William Rasheed, Asif Rosinger, Silke Rubin, Diana Rumpf, Moritz P. Schaefer, Arne Sivananthan, Mohan Song, Ci Stewart, Alexandre F. R. Tan, Sian-Tsung Thorgeirsson, Gudmundur van der Schoot, C. Ellen Wagner, Peter J. Wells, George A. Wild, Philipp S. Yang, Tsun-Po Amouyel, Philippe Arveiler, Dominique Basart, Hanneke Boehnke, Michael Boerwinkle, Eric Brambilla, Paolo Cambien, Francois Cupples, Adrienne L. de Faire, Ulf Dehghan, Abbas Diemert, Patrick Epstein, Stephen E. Evans, Alun Ferrario, Marco M. Ferrieres, Jean Gauguier, Dominique Go, Alan S. Goodall, Alison H. Gudnason, Villi Hazen, Stanley L. Holm, Hilma Iribarren, Carlos Jang, Yangsoo Kahonen, Mika Kee, Frank Kim, Hyo-Soo Klopp, Norman Koenig, Wolfgang Kratzer, Wolfgang Kuulasmaa, Kari Laakso, Markku Laaksonen, Reijo Lee, Ji-Young Lind, Lars Ouwehand, Willem H. Parish, Sarah Park, Jeong E. Pedersen, Nancy L. Peters, Annette Quertermous, Thomas Rader, Daniel J. Salomaa, Veikko Schadt, Eric Shah, Svati H. Sinisalo, Juha Stark, Klaus Stefansson, Kari Tregouet, David-Alexandre Virtamo, Jarmo Wallentin, Lars Wareham, Nicholas Zimmermann, Martina E. Nieminen, Markku S. Hengstenberg, Christian Sandhu, Manjinder S. Pastinen, Tomi Syvanen, Ann-Christine Hovingh, G. Kees Dedoussis, George Franks, Paul W. Lehtimaki, Terho Metspalu, Andres Zalloua, Pierre A. Siegbahn, Agneta Schreiber, Stefan Ripatti, Samuli Blankenberg, Stefan S. Perola, Markus Clarke, Robert Boehm, Bernhard O. O'Donnell, Christopher Reilly, Muredach P. Maerz, Winfried Collins, Rory Kathiresan, Sekar Hamsten, Anders Kooner, Jaspal S. Thorsteinsdottir, Unnur Danesh, John Palmer, Colin N. A. Roberts, Robert Watkins, Hugh Schunkert, Heribert Samani, Nilesh J. CA CARDIoGRAMplusC4D Consortium DIAGRAM Consortium CARDIOGENENICS Consortium MuTHER Consortium Wellcome Trust Case Control TI Large-scale association analysis identifies new risk loci for coronary artery disease SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; GENETIC-VARIANTS; COMPLEX TRAITS; ATHEROSCLEROSIS; POPULATION; EXPRESSION AB Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways. C1 [Deloukas, Panos; Kanoni, Stavroula; Stirrups, Kathleen; Barroso, Ines; Hunt, Sarah E.; Langford, Cordelia; Yang, Tsun-Po; Ouwehand, Willem H.; Sandhu, Manjinder S.; Ripatti, Samuli] Wellcome Trust Sanger Inst, Cambridge, England. [Willenborg, Christina; Erdmann, Jeanette] Univ Lubeck, Inst Integrat & Expt, Lubeck, Germany. [Farrall, Martin; Goel, Anuj; McCarthy, Mark I.; Peden, John F.; Rayner, N. William; Gauguier, Dominique; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Farrall, Martin; Cazier, Jean-Baptiste; Goel, Anuj; Watkins, Hugh] Univ Oxford, Radcliffe Dept Med, Oxford, England. [Assimes, Themistocles L.; Goldstein, Benjamin A.; Knowles, Joshua W.; Quertermous, Thomas] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Thompson, John R.] Univ Leicester, Dept Hlth Sci, Leicester, Leics, England. [Ingelsson, Erik; Gustafsson, Stefan; Song, Ci; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan. [Saleheen, Danish; Rasheed, Asif; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England. [Saleheen, Danish; Ho, Weang K.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA. [Koenig, Inke R.; Ziegler, Andreas] Univ Lubeck, Inst Med Biometrie & Stat, Lubeck, Germany. [Saleheen, Danish; Johansson, Asa; Eriksson, Niclas; Wallentin, Lars; Siegbahn, Agneta] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Hall, Alistair S.] Univ Leeds, Div Cardiovasc & Neuronal Remodelling, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Lee, Jong-Young; Han, Bok-Ghee; Lee, Ji-Young] Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Genome Sci, Yeonje Ri, Chungwon Gun, South Korea. [Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA. [Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. [Chambers, John C.; Zhang, Weihua] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England. [Esko, Tonu; Fischer, Krista; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia. [Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia. [Folkersen, Lasse; Strawbridge, Rona J.; Eriksson, Per; Hamsten, Anders] Karolinska Inst, Atherosclerosis Res Ctr, Dept Med, Stockholm, Sweden. [Folkersen, Lasse; Strawbridge, Rona J.; Eriksson, Per; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden. [Grundberg, Elin] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England. [Havulinna, Aki S.; Kristiansson, Kati; Kuulasmaa, Kari; Salomaa, Veikko; Virtamo, Jarmo; Perola, Markus] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Clin Trial Serv Unit, Oxford, England. [Hopewell, Jemma C.; Parish, Sarah; Clarke, Robert; Collins, Rory] Univ Oxford, Epidemiol Studies Unit, Oxford, England. [Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Mannheim Inst Publ Hlth Social & Prevent Med, Med Fac Mannheim, D-6800 Mannheim, Germany. [Kleber, Marcus E.] Ludwigshafen Risk & Cardiovasc Hlth LURIC, Freiburg, Germany. [Lundmark, Per; Lundmark, Anders; Lind, Lars; Syvanen, Ann-Christine] Uppsala Univ, Dept Med Sci, Uppsala, Sweden. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland. [Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Dept Clin Sci, Sch Med, SF-33520 Tampere, Finland. [Rafelt, Suzanne; Braund, Peter S.; Goodall, Alison H.; Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. [Shungin, Dmitry; Franks, Paul W.] Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Skane Univ Hosp,Diabet Ctr, Malmo, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Genet Epidemiol & Clin Res Grp, Med Sect, Umea, Sweden. [Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Odontol, Umea, Sweden. [Thorleifsson, Gudmar; Holm, Hilma; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland. [Tikkanen, Emmi; Wagner, Peter J.] Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland. [Tikkanen, Emmi; Wagner, Peter J.; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland. [Van Zuydam, Natalie; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland. [Voight, Benjamin F.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA. [Waite, Lindsay L.; Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, AL USA. [Altshuler, David; Do, Ron; Fontanillas, Pierre; Kathiresan, Sekar] Broad Inst Harvard & MIT, Cambridge, MA USA. [Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Altshuler, David; Do, Ron] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Balmforth, Anthony J.] Univ Leeds, Div Cardiovasc & Diabet Res, Multidisciplinary Cardiovasc Res Ctr, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England. [Braund, Peter S.; Goodall, Alison H.; Samani, Nilesh J.] Glenfield Hosp, NIHR, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England. [Burgdorf, Christof; Kessler, Thorsten; Rumpf, Moritz P.; Schunkert, Heribert] Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany. [Claudi-Boehm, Simone] Univ Ulm, Med Ctr, Ulm, Germany. [Cox, David] Pfizer, Biotherapeut & Bioinnovat Ctr, San Francisco, CA USA. [Dimitriou, Maria; Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece. [El Mokhtari, NourEddine; Rubin, Diana] Kreiskrankenhaus Rendsburg, Innere Med Klin, Rendsburg, Germany. [Franco-Cereceda, Anders] Karolinska Inst, Dept Mol Med & Surg, Cardiothorac Surg Unit, Stockholm, Sweden. [Gigante, Bruna; Leander, Karin; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden. [Groop, Leif; Melander, Olle] Lund Univ, Dept Clin Sci Diabet & Endocrinol, Malmo Univ Hosp, Malmo, Sweden. [Hager, Joerg] CEA, Genom Inst, Natl Genotyping Ctr, Paris, France. [Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Sect Nutr Res, Umea, Sweden. [Kang, Hyun M.; Boehnke, Michael] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA. [Illig, Thomas; Klopp, Norman] Hannover Med Sch, Hannover Unified Biobank, D-3000 Hannover, Germany. [Kolovou, Genovefa] Onassis Cardiac Surg Ctr 356, Cardiol Dept 1, Athens, Greece. [Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland. [Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland. [Langenberg, Claudia; Wareham, Nicholas; Sandhu, Manjinder S.] Addenbrookes Hosp, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England. [Lokki, Marja-Liisa] Univ Helsinki, Transplantat Lab, Haartman Inst, Helsinki, Finland. [McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. [McCarthy, Mark I.] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England. [Meisinger, Christa; Peters, Annette] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany. [Maouche, Seraya; Cambien, Francois; Tregouet, David-Alexandre] Univ Paris 06, INSERM, Unite Mixte Rech UMR S937, ICAN, Paris, France. [Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany. [Mueller-Nurasyid, Martina] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany. [Nikus, Kjell] Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere, Finland. [Rosinger, Silke; Boehm, Bernhard O.] Univ Ulm, Dept Internal Med, Div Endocrinol & Diabet, Med Ctr, D-7900 Ulm, Germany. [Schaefer, Arne; Schreiber, Stefan] Univ Kiel, Inst Klin Mol Biol, Kiel, Germany. [Sivananthan, Mohan] Univ Leeds, Div Epidemiol, Multidisciplinary Cardiovascular Res Ctr MCRC, Leeds, W Yorkshire, England. [Sivananthan, Mohan] Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds, W Yorkshire, England. [Stewart, Alexandre F. R.; Wells, George A.; Roberts, Robert] Univ Ottawa, Inst Heart, Cardiovasc Res Methods Ctr Ontario, Ottawa, ON, Canada. [Stewart, Alexandre F. R.; Wells, George A.; Roberts, Robert] Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada. [Tan, Sian-Tsung; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, NHLI, Hammersmith Hosp, London, England. [Thorgeirsson, Gudmundur; Gudnason, Villi; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland. [Thorgeirsson, Gudmundur] Landspitali Univ Hosp, Dept Med, Reykjavik, Iceland. [van der Schoot, C. Ellen] Sanquin, Dept Expt Immunohematol, Amsterdam, Netherlands. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Ctr Thrombosis & Hemostasis, Univ Med Ctr Mainz, Mainz, Germany. [Wild, Philipp S.] Johannes Gutenberg Univ Mainz, Dept Med 2, Univ Med Ctr Mainz, Mainz, Germany. [Amouyel, Philippe] Univ Lille Nord France, Inst Pasteur Lille, INSERM U744, Lille, France. [Arveiler, Dominique] Univ Strasbourg, Dept Epidemiol & Publ Hlth, EA3430, Strasbourg, France. [Basart, Hanneke; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands. [Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Brambilla, Paolo] Univ Milano Bicocca, Dept Expt Med, Monza, Italy. [Cupples, Adrienne L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Cupples, Adrienne L.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Dehghan, Abbas; O'Donnell, Christopher] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands. [Diemert, Patrick; Blankenberg, Stefan S.] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany. [Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, Washington, DC 20010 USA. [Evans, Alun] Queens Univ Belfast, Ctr Publ Hlth, Belfast, Antrim, North Ireland. [Ferrario, Marco M.] Univ Insubria, Res Ctr Epidemiol & Prevent Med EPIMED, Dept Clin & Expt Med, Varese, Italy. [Ferrieres, Jean] Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France. [Gauguier, Dominique] INSERM, UMR S872, Cordeliers Res Ctr, Paris, France. [Go, Alan S.; Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Gudnason, Villi] Iceland Heart Assoc, Kopavogur, Iceland. [Hazen, Stanley L.] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA. [Jang, Yangsoo] Yonsei Univ, Div Cardiol, Dept Internal Med, Cardiovascu Genome Ctr, Seoul 120749, South Korea. [Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. [Kee, Frank] Queens Univ Belfast, UK Clin Res Collaborat UKCRC, Ctr Excellence Publ Hlth No Ireland, Belfast, Antrim, North Ireland. [Kim, Hyo-Soo] Seoul Natl Univ Hosp, Dept Internal Med, Ctr Cardiovasc, Seoul 110744, South Korea. [Koenig, Wolfgang] Univ Ulm, Med Ctr, Dept Internal Med 2, Ulm, Germany. [Kratzer, Wolfgang; Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge, England. [Ouwehand, Willem H.] Natl Hlth Serv NHS Blood & Transplant, Cambridge, England. [Park, Jeong E.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Cardiol, Seoul, South Korea. [Peters, Annette] Munich Heart Alliance, Munich, Germany. [Rader, Daniel J.] Univ Penn, Dept Med, Div Translat Med & Human Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. [Schadt, Eric] Mt Sinai Sch Med, Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY USA. [Shah, Svati H.] Duke Univ, Med Ctr, Dept Med, Ctr Human Genet, Durham, NC 27710 USA. [Shah, Svati H.] Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. [Sinisalo, Juha; Nieminen, Markku S.] Helsinki Univ Cent Hosp, Div Cardiol, Dept Med, Helsinki, Finland. [Stark, Klaus; Zimmermann, Martina E.; Hengstenberg, Christian] Klin & Poliklin Innere Med II, Regensburg, Germany. [Pastinen, Tomi] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Zalloua, Pierre A.] Lebanese Amer Univ, Beirut, Lebanon. [Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA. [Maerz, Winfried] Synlab Acad, Mannheim, Germany. [Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar; CARDIOGENENICS Consortium] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Deloukas, P (reprint author), Wellcome Trust Sanger Inst, Cambridge, England. EM panos@sanger.ac.uk; njs@leicester.ac.uk RI Strawbridge, Rona/H-5422-2012; Boehm, Bernhard/F-8750-2015; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Deloukas, Panos/B-2922-2013; Palmer, Colin/C-7053-2008; Knowles, Josh/C-9241-2013; Altshuler, David/A-4476-2009; Meisinger, Christine/B-5358-2014; Schreiber, Stefan/B-6748-2008; Laaksonen, Reijo/D-6323-2014; Willenborg, Christina/D-2668-2012; Johansson, Asa/G-5270-2011; Erdmann, Jeanette/P-7513-2014; Kessler, Thorsten/O-7426-2015; Peters, Annette/A-6117-2011; Lyytikainen, Leo-Pekka/C-8544-2016; Tregouet, David-Alexandre/E-3961-2016; Study, GoDARTS/K-9448-2016; Konig, Inke/A-4544-2009; Leander, Karin/C-7261-2017; OI Strawbridge, Rona/0000-0001-8506-3585; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Deloukas, Panos/0000-0001-9251-070X; Palmer, Colin/0000-0002-6415-6560; Altshuler, David/0000-0002-7250-4107; Schreiber, Stefan/0000-0003-2254-7771; Willenborg, Christina/0000-0001-5217-6882; Johansson, Asa/0000-0002-2915-4498; Ziegler, Andreas/0000-0002-8386-5397; Franks, Paul/0000-0002-0520-7604; Meisinger, Christa/0000-0002-9026-6544; zalloua, pierre/0000-0002-8494-5081; Kuulasmaa, Kari/0000-0003-2165-1411; Watkins, Hugh/0000-0002-5287-9016; Ouwehand, Willem/0000-0002-7744-1790; Sinisalo, Juha/0000-0002-0169-5137; Yang, Tsun-Po/0000-0002-9077-4434; Lee, Ji-Young/0000-0002-7784-1401; HO, WEANG KEE/0000-0002-8269-7344; Hunt, Sarah/0000-0002-8350-1235; Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231; Ferrario, Marco M/0000-0003-2741-7124; Gigante, Bruna/0000-0003-4508-7990; Folkersen, Lasse/0000-0003-0708-9530; Kleber, Marcus/0000-0003-0663-7275; Dehghan, Abbas/0000-0001-6403-016X; Maouche, Seraya/0000-0001-8186-1635; Lyytikainen, Leo-Pekka/0000-0002-7200-5455; Leander, Karin/0000-0002-1404-9222; Song, Ci/0000-0002-0947-9068; Shungin, Dmitry/0000-0001-7900-5856; Esko, Tonu/0000-0003-1982-6569; Kristiansson, Kati/0000-0003-4688-107X; Willer, Cristen/0000-0001-5645-4966 FU Merck; British Heart Foundation (BHF) Centre of Research Excellence FX The study was designed and conducted by the Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU) at the University of Oxford. Genotyping was supported by a grant to Oxford University and Centre National de Genotypage (CNG) from Merck. The funders had no role in the design of the study or in the data collection or analysis. We especially acknowledge the participants in the study, the Steering Committee and our collaborators. J.C.H. acknowledges support from the British Heart Foundation (BHF) Centre of Research Excellence. NR 34 TC 436 Z9 444 U1 16 U2 110 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JAN PY 2013 VL 45 IS 1 BP 25 EP U52 DI 10.1038/ng.2480 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 061HJ UT WOS:000312838800009 ER PT J AU Jiang, DK Sun, JL Cao, GW Liu, Y Lin, DX Gao, YZ Ren, WH Long, XD Zhang, HX Ma, XP Wang, Z Jiang, W Chen, TY Gao, Y Sun, LD Long, JR Huang, HX Wang, D Yu, HJ Zhang, PY Tang, LS Peng, B Cai, H Liu, TT Zhou, P Liu, F Lin, XL Tao, S Wan, B Sai-Yin, HXG Qin, LX Yin, JH Liu, L Wu, C Pei, Y Zhou, YF Zhai, Y Lu, PX Tan, AH Zuo, XB Fan, J Chang, J Gu, XL Wang, NJ Li, Y Liu, YK Zhai, K Zhang, HW Hu, ZB Liu, J Yi, Q Xiang, YB Shi, R Ding, Q Zheng, W Shu, XO Mo, ZN Shugart, YY Zhang, XJ Zhou, GQ Shen, HB Zheng, SL Xu, JF Yu, L AF Jiang, De-Ke Sun, Jielin Cao, Guangwen Liu, Yao Lin, Dongxin Gao, Yu-Zhen Ren, Wei-Hua Long, Xi-Dai Zhang, Hongxing Ma, Xiao-Pin Wang, Zhong Jiang, Wei Chen, Tao-Yang Gao, Yong Sun, Liang-Dan Long, Ji-Rong Huang, Hui-Xing Wang, Dan Yu, Hongjie Zhang, Pengyin Tang, Li-Sha Peng, Bo Cai, Hao Liu, Ting-Ting Zhou, Ping Liu, Fang Lin, Xiaoling Tao, Sha Wan, Bo Sai-Yin, He-Xi Ge Qin, Lun-Xiu Yin, Jianhua Liu, Li Wu, Chen Pei, Yan Zhou, Yuan-Feng Zhai, Yun Lu, Pei-Xin Tan, Aihua Zuo, Xian-Bo Fan, Jia Chang, Jiang Gu, Xiaoli Wang, Neng-Jin Li, Yang Liu, Yin-Kun Zhai, Kan Zhang, Hongwei Hu, Zhibin Liu, Jun Yi, Qing Xiang, Yongbing Shi, Rong Ding, Qiang Zheng, Wei Shu, Xiao-Ou Mo, Zengnan Shugart, Yin Yao Zhang, Xue-Jun Zhou, Gangqiao Shen, Hongbing Zheng, S. Lilly Xu, Jianfeng Yu, Long TI Genetic variants in STAT4 and HLA-DQ genes confer risk of hepatitis B virus-related hepatocellular carcinoma SO NATURE GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY BILIARY-CIRRHOSIS; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCUS; INTERFERON-GAMMA; VIRAL-INFECTION; POPULATION; ALLELES; CHINESE AB To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P-meta = 2.48 x 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P-meta = 2.72 x 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P-trend = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 x 10(-14)). C1 [Jiang, De-Ke; Ren, Wei-Hua; Ma, Xiao-Pin; Jiang, Wei; Huang, Hui-Xing; Wang, Dan; Tang, Li-Sha; Peng, Bo; Cai, Hao; Liu, Ting-Ting; Zhou, Ping; Wan, Bo; Sai-Yin, He-Xi Ge; Liu, Jun; Yi, Qing] Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. [Sun, Jielin; Wang, Zhong; Tao, Sha; Zheng, S. Lilly; Xu, Jianfeng] Wake Forest Univ, Bowman Gray Sch Med, Ctr Canc Genom, Winston Salem, NC USA. [Cao, Guangwen; Yin, Jianhua; Zhang, Hongwei] Second Mil Med Univ, Dept Epidemiol, Shanghai, Peoples R China. [Liu, Yao; Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Key Lab Modern Toxicol, Minist Educ, Nanjing, Peoples R China. [Liu, Yao; Hu, Zhibin; Shen, Hongbing] Nanjing Med Univ, Sch Publ Hlth, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China. [Liu, Yao; Hu, Zhibin] Nanjing Med Univ, State Key Lab Reprod Med, Sch Publ Hlth, Nanjing, Peoples R China. [Lin, Dongxin; Wu, Chen; Chang, Jiang; Zhai, Kan] Chinese Acad Med Sci, Dept Etiol & Carcinogenesis, Canc Inst & Hosp, Beijing 100730, Peoples R China. [Lin, Dongxin; Wu, Chen; Chang, Jiang; Zhai, Kan] Peking Union Med Coll, Beijing 100021, Peoples R China. [Gao, Yu-Zhen] Soochow Univ, Dept Forens Med, Coll Med, Suzhou, Peoples R China. [Ren, Wei-Hua; Pei, Yan] Henan Univ Sci & Technol, Dept Surg, Affiliated Hosp 1, Luoyang, Peoples R China. [Long, Xi-Dai; Zhou, Yuan-Feng] Youjiang Med Coll Nationalities, Dept Pathol, Baise, Peoples R China. [Zhang, Hongxing; Zhai, Yun; Gu, Xiaoli; Zhou, Gangqiao] Beijing Inst Radiat Med, Beijing Proteome Res Ctr, State Key Lab Prote, Beijing, Peoples R China. [Chen, Tao-Yang; Lu, Pei-Xin; Wang, Neng-Jin] Qidong Liver Canc Inst, Qidong, Peoples R China. [Gao, Yong; Tan, Aihua; Mo, Zengnan] Guangxi Med Univ, Inst Urol & Nephrol, Affiliated Hosp 1, Nanning, Peoples R China. [Gao, Yong; Tan, Aihua; Mo, Zengnan] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning, Peoples R China. [Gao, Yong; Yu, Hongjie; Zhang, Pengyin; Liu, Fang; Lin, Xiaoling; Xu, Jianfeng] Fudan Univ, Fudan VARI Ctr Genet Epidemiol, Shanghai 200433, Peoples R China. [Sun, Liang-Dan; Zuo, Xian-Bo; Li, Yang; Zhang, Xue-Jun] Anhui Med Univ, Inst Dermatol, Hefei, Peoples R China. [Sun, Liang-Dan; Zuo, Xian-Bo; Li, Yang; Zhang, Xue-Jun] Anhui Med Univ, Dept Dermatol, Hosp 1, Hefei, Peoples R China. [Sun, Liang-Dan; Zuo, Xian-Bo; Li, Yang; Zhang, Xue-Jun] Minist Natl Sci & Technol, State Key Lab Incubat Base Dermatol, Hefei, Peoples R China. [Long, Ji-Rong] Vanderbilt Univ, Sch Med, Dept Med, Vanderbilt Epidemiol Ctr,Vanderbilt Ingram Canc C, Nashville, TN 37212 USA. [Qin, Lun-Xiu; Fan, Jia; Liu, Yin-Kun] Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. [Qin, Lun-Xiu; Fan, Jia; Liu, Yin-Kun] Fudan Univ, Dept Liver Surg, Zhongshan Hosp, Shanghai 200433, Peoples R China. [Liu, Li] Nantong Tumor Hosp, Dept Hepatobiliary Surg, Nantong, Peoples R China. [Liu, Jun] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. [Yi, Qing] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma Myeloma, Houston, TX 77030 USA. [Yi, Qing] Univ Texas MD Anderson Canc Ctr, Div Canc Med, Houston, TX 77030 USA. [Yi, Qing] Univ Texas MD Anderson Canc Ctr, Ctr Canc Immunol Res, Houston, TX 77030 USA. [Xiang, Yongbing] Shanghai Canc Inst, Shanghai, Peoples R China. [Shi, Rong] Shanghai Jiao Tong Univ, Sch Publ Hlth, Shanghai 200030, Peoples R China. [Ding, Qiang] Fudan Univ, Fudan Inst Urol, Huashan Hosp, Shanghai 200433, Peoples R China. [Shugart, Yin Yao] NIMH, Unit Stat Genom, Div Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA. [Yu, Long] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. RP Yu, L (reprint author), Fudan Univ, State Key Lab Genet Engn, Inst Genet, Sch Life Sci, Shanghai 200433, Peoples R China. EM jxu@wfubmc.edu; longyu@fudan.edu.cn RI Jiang, Deke/M-6945-2013; Chen, Gang/G-2722-2010; Fan, Jia/C-6689-2017 FU National Natural Science Foundation of China for Creative Research Groups [30024001]; National Key Sci-Tech Special Project of China [2013ZX10002010, 2008ZX10002-020]; Shanghai Municipal Science and Technology Commission; National Natural Science Foundation of China [31071193, 31100895, 30800946]; Director Foundation of the State Key Laboratory of Genetic Engineering; Fund from X.-J. Qu and Chang-An Capital of Beijing; Fund from S.-J. Yan and Tianying S. T. Group of Jiangsu; MOE Foundation of Cheung Kong Scholars Program; Huashan Hospital, Fudan University; Fudan-VARI Center for Genetic Epidemiology, Fudan University; Foundation for the Author of National Excellent Doctoral Dissertation [201081]; Program for New Century Excellent Talents in University [NCET-10-0178]; Priority Academic Program Development of Jiangsu Higher Education Institutions FX We thank all the subjects who participated in this study. We also thank Y. Shi and L. He from Bio-X Institutes of Shanghai Jiao Tong University for helping with data analysis of typical Chinese population control subjects, and L. Jin, Y. Zhong, H.-H. Wang and W.-Y. Yan from the School of Life Sciences of Fudan University and H.-B. Shu from College of Life Sciences of Wuhan University for suggestions on this study. The study is supported by the National Natural Science Foundation of China for Creative Research Groups (30024001 to L. Y.), the National Key Sci-Tech Special Project of China (2013ZX10002010 and 2008ZX10002-020 to L. Y.), the Project of the Shanghai Municipal Science and Technology Commission (to L. Y.), the National Natural Science Foundation of China (31071193 to L. Y. and 31100895 to D.-K.J.), Director Foundation of the State Key Laboratory of Genetic Engineering (to L. Y.), the Fund from X.-J. Qu and Chang-An Capital of Beijing (to L. Y.), the Fund from S.-J. Yan and Tianying S. T. Group of Jiangsu (to L. Y.), MOE Foundation of Cheung Kong Scholars Program (to J.L. and Q. Y.), an intramural research grant from Huashan Hospital, Fudan University (to J.X.) and an intramural research grant from Fudan-VARI Center for Genetic Epidemiology, Fudan University (to J.X.). This work is partly funded by the National Natural Science Foundation of China (30800946 to H. S.), Foundation for the Author of National Excellent Doctoral Dissertation (201081 to H. S.), the Program for New Century Excellent Talents in University (NCET-10-0178 to H. S.), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (to H.S.). NR 45 TC 108 Z9 122 U1 12 U2 99 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 EI 1546-1718 J9 NAT GENET JI Nature Genet. PD JAN PY 2013 VL 45 IS 1 BP 72 EP U105 DI 10.1038/ng.2483 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 061HJ UT WOS:000312838800015 PM 23242368 ER PT J AU Abrahamsson, S Chen, JJ Hajj, B Stallinga, S Katsov, AY Wisniewski, J Mizuguchi, G Soule, P Mueller, F Darzacq, CD Darzacq, X Wu, C Bargmann, CI Agard, DA Dahan, M Gustafsson, MGL AF Abrahamsson, Sara Chen, Jiji Hajj, Bassam Stallinga, Sjoerd Katsov, Alexander Y. Wisniewski, Jan Mizuguchi, Gaku Soule, Pierre Mueller, Florian Darzacq, Claire Dugast Darzacq, Xavier Wu, Carl Bargmann, Cornelia I. Agard, David A. Dahan, Maxime Gustafsson, Mats G. L. TI Fast multicolor 3D imaging using aberration-corrected multifocus microscopy SO NATURE METHODS LA English DT Article ID POINT-SPREAD FUNCTION; QUANTUM-DOT; DYNAMICS; TRACKING; YEAST; TIME AB Conventional acquisition of three-dimensional (3D) microscopy data requires sequential z scanning and is often too slow to capture biological events. We report an aberration-corrected multifocus microscopy method capable of producing an instant focal stack of nine 2D images. Appended to an epifluorescence microscope, the multifocus system enables high-resolution 3D imaging in multiple colors with single-molecule sensitivity, at speeds limited by the camera readout time of a single image. C1 [Abrahamsson, Sara] Univ Calif San Francisco, Joint Grad Grp Bioengn, San Francisco, CA 94143 USA. [Abrahamsson, Sara] Univ Calif Berkeley, San Francisco, CA USA. [Chen, Jiji; Hajj, Bassam; Wisniewski, Jan; Mizuguchi, Gaku; Darzacq, Claire Dugast; Darzacq, Xavier; Wu, Carl; Dahan, Maxime] Howard Hughes Med Inst, Transcript Imaging Consortium, Ashburn, VA USA. [Abrahamsson, Sara; Katsov, Alexander Y.; Bargmann, Cornelia I.] Rockefeller Univ, Lab Neural Circuits & Behav, New York, NY 10021 USA. [Stallinga, Sjoerd; Wu, Carl] Delft Univ Technol, Dept Imaging Sci & Technol, Delft, Netherlands. [Wisniewski, Jan; Mizuguchi, Gaku] NCI, Lab Biochem & Mol Biol, Bethesda, MD 20892 USA. [Soule, Pierre; Mueller, Florian; Darzacq, Claire Dugast; Darzacq, Xavier] Ecole Normale Super, Inst Biol, CNRS, Unite Mixte Rech UMR 8197, F-75231 Paris, France. [Mueller, Florian] Inst Pasteur, Imaging & Modeling Grp, CNRS, Unite Rech Associee 2582, Paris, France. [Bargmann, Cornelia I.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. [Darzacq, Claire Dugast] Univ Paris Diderot, Paris, France. [Agard, David A.] Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA USA. [Agard, David A.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. [Dahan, Maxime] Ecole Normale Super, Inst Biol, CNRS UMR 8552, Lab Kastler Brossel, F-75231 Paris, France. [Dahan, Maxime] Ecole Normale Super, Dept Phys, F-75231 Paris, France. RP Abrahamsson, S (reprint author), Univ Calif San Francisco, Joint Grad Grp Bioengn, San Francisco, CA 94143 USA. EM sara.abrahamsson@gmail.com; maxime.dahan@curie.fr RI Mueller, Florian/C-9075-2012; Dahan, Maxime /F-1740-2010; OI Mueller, Florian/0000-0002-9622-4396; Bargmann, Cornelia/0000-0002-8484-0618 FU Jane Coffin Childs postdoctoral fellowship; Fulbright fellowship; Agence Nationale pour la Recherche [ANR-08-PCVI-0013]; US National Institutes of Health [GM31627]; HHMI; Center for Cancer Research, National Cancer Institute FX We dedicate this paper to the late Mats Gustafsson. We thank K. Wicker, R. Heinzmann, T. Wilson and D. Grunwald for valuable discussions about multifocus microscopy; C. Zimmer for his help with the 3D localization algorithm; F. Amat and A. Verma for assistance with data processing; L. Shao, L. Winoto, J. Sedat, R. Singer and E. Betzig for discussions on 3D microscopy; V. Iyer for discussions on hardware control; Z. Zhang and Y. Li (HHMI Janelia Farm) for sharing reagents; H. White and H. Rego for assistance in live-cell imaging; and V. Butler and R. Kerr (HHMI Janelia Farm) and W. Schafer (MRC Laboratory of Molecular Biology) for the C. elegans strain. S.A. would like to thank G. Rubin, K. Moses and R. Tijan for ensuring continued funding for this project during and after the difficult time of M.G.'s sickness. A.Y.K. is supported by a Jane Coffin Childs postdoctoral fellowship. M.D. acknowledges the support of a Fulbright fellowship. X.D. and M.D. are supported by grant ANR-08-PCVI-0013 from Agence Nationale pour la Recherche. D.A.A. is supported by US National Institutes of Health grant GM31627. S.A., C.I.B. and D.A.A. are supported by the HHMI. J.W., G.M. and C.W. are supported by the Center for Cancer Research, National Cancer Institute and HHMI. NR 19 TC 74 Z9 74 U1 4 U2 92 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD JAN PY 2013 VL 10 IS 1 BP 60 EP U80 DI 10.1038/NMETH.2277 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 060WW UT WOS:000312810100037 PM 23223154 ER PT J AU Lugli, E Gattinoni, L Roberto, A Mavilio, D Price, DA Restifo, NP Roederer, M AF Lugli, Enrico Gattinoni, Luca Roberto, Alessandra Mavilio, Domenico Price, David A. Restifo, Nicholas P. Roederer, Mario TI Identification, isolation and in vitro expansion of human and nonhuman primate T stem cell memory cells SO NATURE PROTOCOLS LA English DT Article ID POLYCHROMATIC FLOW-CYTOMETRY; HUMAN NAIVE; DIFFERENTIATION; PROLIFERATION; LYMPHOCYTES; HOMEOSTASIS; ACTIVATION; SUBSETS; ANTIGEN AB The T cell compartment is phenotypically and functionally heterogeneous; subsets of naive and memory cells have different functional properties, and also differ with respect to homeostatic potential and the ability to persist in vivo. Human stem cell memory T (T-SCM) cells, which possess superior immune reconstitution and antitumor response capabilities, can be identified by polychromatic flow cytometry on the basis of the simultaneous expression of several naive markers together with the memory marker CD95. We describe here a protocol based on the minimum set of markers required for optimal identification of human and nonhuman primate (NHP) T-SCM cells with commonly available flow cytometers. By using flow sorters, T-SCM cells can thereby be isolated efficiently at high yield and purity. With the use of the 5.5-h isolation procedure, depending on the number of cells needed, the sorting procedure can last for 2-15 h. We also indicate multiple strategies for their efficient expansion in vitro at consistent numbers for functional characterization or adoptive transfer experiments. C1 [Lugli, Enrico; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, US Natl Inst Hlth NIH, Bethesda, MD 20892 USA. [Lugli, Enrico; Roberto, Alessandra; Mavilio, Domenico] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy. [Gattinoni, Luca; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Mavilio, Domenico] Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy. [Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff, S Glam, Wales. [Restifo, Nicholas P.] NIH, NIH Ctr Regenerat Med, Bethesda, MD 20892 USA. RP Lugli, E (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, US Natl Inst Hlth NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM luglie@mail.nih.gov; roederer@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Price, David/C-7876-2013; OI Gattinoni, Luca/0000-0003-2239-3282; Price, David/0000-0001-9416-2737; Restifo, Nicholas P./0000-0003-4229-4580; Mavilio, Domenico/0000-0001-6147-0952 FU NIH Intramural Research Program; Associazione Italiana per la Ricerca sul Cancro FX We thank J. Yu and M. Beddall (ImmunoTechnology Section, VRC) for antibody conjugation; S.P. Perfetto, D. Ambrozak and R. Nguyen (Flow Cytometry Core, VRC) for assistance with cell sorting; M.F. Quigley (Immunology Laboratory, VRC) for providing the HLA-A*0201 + donor; and the other members of the ImmunoTechnology section for continuous discussion. This work was supported by the NIH Intramural Research Program and by the Associazione Italiana per la Ricerca sul Cancro to E.L. NR 22 TC 44 Z9 47 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PD JAN PY 2013 VL 8 IS 1 BP 33 EP 42 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 064DO UT WOS:000313051300003 PM 23222456 ER PT J AU Kapogiannis, D Reiter, DA Willette, AA Mattson, MP AF Kapogiannis, Dimitrios Reiter, David A. Willette, Auriel A. Mattson, Mark P. TI Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network SO NEUROIMAGE LA English DT Article DE Default mode network; Excitation; Inhibition; Microcircuit; Brain network; Connectivity; Precuneus ID RESOLVED NMR-SPECTROSCOPY; HUMAN BRAIN; ALZHEIMERS-DISEASE; RAT-BRAIN; IN-VIVO; FMRI; INHIBITION; RESPONSES; NEUROSTEROIDS; DEPOSITION AB The balance between excitatory glutamatergic projection neurons and inhibitory GABAergic interneurons determines the function of cortical microcircuits. How these neurotransmitters relate to the functional status of an entire macro-scale network remains unknown. The posteromedial cortex (PMC) is the default mode network (DMN) node with the greatest functional connectivity; therefore, we hypothesized that PMC glutamate and GABA predict intrinsic functional connectivity (iFC) across the entire DMN. In 20 healthy men, we combined J-resolved magnetic resonance spectroscopy to measure glutamate and GABA in the PMC and resting fMRI followed by group Independent Components Analysis to extract the entire DMN. We showed that, controlling for age and partial GM volume in the MRS voxel, PMC glutamate and GABA explained about half of the variance of DMN iFC (represented by the network's beta coefficient for rest). Glutamate correlated positively and GABA correlated negatively with DMN iFC; in an alternative statistical model which included the glutamate/GABA ratio, the ratio correlated positively with DMN iFC. Age had no independent association with DMN iFC. No other network was associated with PMC glutamate or GABA. We conclude that regional neurotransmitter concentrations in a network node strongly predict network but not global brain iFC. Published by Elsevier Inc. C1 [Kapogiannis, Dimitrios; Reiter, David A.; Willette, Auriel A.] Natl Inst Aging Intramural Res Program, Clin Res Branch, Baltimore, MD 21225 USA. [Willette, Auriel A.; Mattson, Mark P.] Natl Inst Aging Intramural Res Program, Neurosci Lab, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Kapogiannis, D (reprint author), Natl Inst Aging Intramural Res Program, Clin Res Branch, 3001 S Hanover St, Baltimore, MD 21225 USA. EM kapogiannisd@mail.nih.gov FU Intramural Research Program of the National Institute on Aging (NIA/NIH) FX This research was supported by the Intramural Research Program of the National Institute on Aging (NIA/NIH). The authors would like to thank Peter Boesiger, Anke Henning and Alexander Fuchs for their help with the JPRESS implementation and analysis. NR 64 TC 40 Z9 40 U1 3 U2 26 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 JAN 1 PY 2013 VL 64 BP 112 EP 119 DI 10.1016/j.neuroimage.2012.09.029 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200011 PM 23000786 ER PT J AU Avram, AV Ozarslan, E Sarlls, JE Basser, PJ AF Avram, Alexandru V. Oezarslan, Evren Sarlls, Joelle E. Basser, Peter J. TI In vivo detection of microscopic anisotropy using quadruple pulsed-field gradient (qPFG) diffusion MRI on a clinical scanner SO NEUROIMAGE LA English DT Article DE Multiple pulsed-field gradient; Diffusion MRI; Multiple-wave-vector; Diffusion-weighted image; Microscopic anisotropy; Axon diameter ID COMPARTMENT SHAPE ANISOTROPY; AXON DIAMETER DISTRIBUTION; HUMAN BRAIN; CORPUS-CALLOSUM; MULTIPLE CONCATENATIONS; WATER DIFFUSION; SIZE ESTIMATION; WHITE-MATTER; NMR; SYSTEM AB We report our design and implementation of a quadruple pulsed-field gradient (qPFG) diffusion MRI pulse sequence on a whole-body clinical scanner and demonstrate its ability to non-invasively detect restriction-induced microscopic anisotropy in human brain tissue. The microstructural information measured using qPFG diffusion MRI in white matter complements that provided by diffusion tensor imaging (DTI) and exclusively characterizes diffusion of water trapped in microscopic compartments with unique measures of average cell geometry. We describe the effect of white matter fiber orientation on the expected MR signal and highlight the importance of incorporating such information in the axon diameter measurement using a suitable mathematical framework. Integration of qPFG diffusion-weighted images (DWI) with fiber orientations measured using high-resolution DTI allows the estimation of average axon diameters in the corpus callosum of healthy human volunteers. Maps of inter-hemispheric average axon diameters reveal an anterior-posterior variation in good topographical agreement with anatomical measurements reported in previous post-mortem studies. With further technical refinements and additional clinical validation, qPFG diffusion MRI could provide a quantitative whole-brain histological assessment of white and gray matter, enabling a wide range of neuroimaging applications for improved diagnosis of neurodegenerative pathologies, monitoring neurodevelopmental processes, and mapping brain connectivity. Published by Elsevier Inc. C1 [Avram, Alexandru V.; Oezarslan, Evren; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA. [Oezarslan, Evren] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA. [Sarlls, Joelle E.] NINDS, NIH, Bethesda, MD 20892 USA. RP Avram, AV (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 13,Room 3W16,13 S Dr, Bethesda, MD 20814 USA. EM alexandru.avram@nih.gov RI Ozarslan, Evren/B-4858-2013; Basser, Peter/H-5477-2011 OI Ozarslan, Evren/0000-0003-0859-1311; FU Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Neurological Disorders and Stroke (NINDS); Center for Neuroscience and Regenerative Medicine (CNRM) within the Department of Defense (DoD); Henry Jackson Foundation (HJF) FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Neurological Disorders and Stroke (NINDS). EO was supported by the Center for Neuroscience and Regenerative Medicine (CNRM) within the Department of Defense (DoD) and the Henry Jackson Foundation (HJF). In vivo MRI experiments were performed at the NIH MRI Research Facility (NMRF). The authors would like to thank Carlo Pierpaoli and Michal E. Komlosh for helpful discussions. NR 46 TC 20 Z9 20 U1 1 U2 18 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 JAN 1 PY 2013 VL 64 BP 229 EP 239 DI 10.1016/j.neuroimage.2012.08.048 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200022 PM 22939872 ER PT J AU Volkow, ND Kim, SW Wang, GJ Alexoff, D Logan, J Muench, L Shea, C Telang, F Fowler, JS Wong, C Benveniste, H Tomasi, D AF Volkow, Nora D. Kim, Sung Won Wang, Gene-Jack Alexoff, David Logan, Jean Muench, Lisa Shea, Colleen Telang, Frank Fowler, Joanna S. Wong, Christopher Benveniste, Helene Tomasi, Dardo TI Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain SO NEUROIMAGE LA English DT Article DE Glia; PET; FDG; Alcoholism; Withdrawal; Acetate ID ETHANOL WITHDRAWAL SYNDROME; CEREBRAL-BLOOD-FLOW; RAT-BRAIN; IN-VIVO; ASTROCYTES; TRANSPORT; STIMULATION; MARKER; PET; CONSEQUENCES AB Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also the metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FOG) with the largest decrements in cerebellum and occipital cortex and the smallest in the thalamus. In contrast, alcohol intoxication caused a significant increase in [1-C-11]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in the cerebellum and the smallest in the thalamus. In heavy alcohol drinkers [1-C-11]acetate brain uptake during alcohol challenge tended to be higher than in occasional drinkers (p<0.06) and the increases in [1-C-11]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-C-11]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (i.e. ketogenic diets) may have in alcoholics undergoing alcohol detoxification. (C) 2012 Published by Elsevier Inc. C1 [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. [Volkow, Nora D.; Kim, Sung Won; Muench, Lisa; Telang, Frank; Wong, Christopher; Tomasi, Dardo] NIAAA, Bethesda, MD 20892 USA. [Wang, Gene-Jack; Alexoff, David; Logan, Jean; Shea, Colleen; Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. [Benveniste, Helene] SUNY Stony Brook, Dept Anesthesiol, Stony Brook, NY 11794 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd 6001,Room 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 FU NIH's Intramural Research Program (NIAAA); DOE [DE-AC01-76CH00016] FX We thank David Schlyer, Paul Vaska, Youwen Xu, Pauline Carter, Millard Jayne and Karen Apelskog for their contributions and Ruben Baler for editorial assistance. Research was supported by NIH's Intramural Research Program (NIAAA) and by DOE (DE-AC01-76CH00016). NR 52 TC 22 Z9 23 U1 0 U2 23 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JAN 1 PY 2013 VL 64 BP 277 EP 283 DI 10.1016/j.neuroimage.2012.08.057 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200026 PM 22947541 ER PT J AU Weise, CM Thiyyagura, P Reiman, EM Chen, KW Krakoff, J AF Weise, Christopher M. Thiyyagura, Pradeep Reiman, Eric M. Chen, Kewei Krakoff, Jonathan TI Fat-free body mass but not fat mass is associated with reduced gray matter volume of cortical brain regions implicated in autonomic and homeostatic regulation SO NEUROIMAGE LA English DT Article DE Fat-free mass; Fat mass; Obesity; VBM; MRI; Gray matter; Prefrontal cortex ID MEDIAL PREFRONTAL CORTEX; LEFT-VENTRICULAR MASS; POSITRON-EMISSION-TOMOGRAPHY; MACAQUE MONKEYS; BLOOD-BRAIN; ENERGY-EXPENDITURE; GASTRIC DISTENSION; CINGULATE CORTEX; INSULAR CORTEX; FOLLOW-UP AB Obesity has been associated with alterations of both functional and structural aspects of the human central nervous system. In obese individuals both fat mass (FM; primarily consisting of adipose tissue) and fat-free mass (FFM; all non-adipose tissues) are increased and it remains unknown whether these compartments have separate effects on human brain morphology. We used voxel-based morphometry to investigate the relationships between measures of body composition and regional gray matter volume (GMV) in 76 healthy adults with a wide range of adiposity (24 F/52 M: age 32.1 +/- 8.8 years; percentage of body fat [PFAT%]25.5 +/- 10.9%; BMI 29.8 +/- 8.9). Fat-free mass index (FFMI kg x m(-2)) showed negative associations in bilateral temporal regions, the bilateral medial and caudolateral OFC, and the left insula. Fat mass index (FMI kg x m(-2)) showed similar, but less extensive negative associations within temporal cortical regions and the left caudolateral orbitofrontal cortex (OFC). In addition, negative associations were seen for FM! with GMV of the cerebellum. Associations of FFMI with temporal and medial orbitofrontal GMV appeared to be independent of adiposity. No associations were seen between measures of adiposity (i.e. FM and PFAT) and GMV when adjusted for FFM. The majority of regions that we find associated with FFM have been implicated in the regulation of eating behavior and show extensive projections to central autonomic and homeostatic core structures. These data indicate that not adipose tissue or relative adiposity itself, but obesity related increases in absolute tissue mass and particularly FFM may have a more predominant effect on the human brain. This might be explained by the high metabolic demand of FM and related increases in total energy needs. Published by Elsevier Inc. C1 [Weise, Christopher M.] NIDDK, NIH, PECRB, Obes & Diabet Clin Res Sect,DHHS, Phoenix, AZ 85016 USA. [Thiyyagura, Pradeep; Reiman, Eric M.; Chen, Kewei] Banner Alzheimers Inst, Dept Psychiat, Phoenix, AZ USA. [Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA. RP Weise, CM (reprint author), NIDDK, NIH, PECRB, Obes & Diabet Clin Res Sect,DHHS, 4212 N 16th St, Phoenix, AZ 85016 USA. EM christopher.weise@nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU Intramural NIH HHS [Z99 DK999999] NR 87 TC 16 Z9 16 U1 1 U2 12 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 JAN 1 PY 2013 VL 64 BP 712 EP 721 DI 10.1016/j.neuroimage.2012.09.005 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 056PU UT WOS:000312504200067 PM 22974975 ER PT J AU Landman, BA Bogovic, JA Carass, A Chen, M Roy, S Shiee, N Yang, Z Kishore, B Pham, D Bazin, PL Resnick, SM Prince, JL AF Landman, Bennett A. Bogovic, John A. Carass, Aaron Chen, Min Roy, Snehashis Shiee, Navid Yang, Zhen Kishore, Bhaskar Dzung Pham Bazin, Pierre-Louis Resnick, Susan M. Prince, Jerry L. TI System for Integrated Neuroimaging Analysis and Processing of Structure SO NEUROINFORMATICS LA English DT Article DE Brain; MRI; Cortical surface; White matter parcellation; Fiber tracking; Sub-cortical segmentation ID MAGNETIC-RESONANCE IMAGES; DIFFUSION TENSOR IMAGES; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; WHITE-MATTER TRACTS; ECHO-PLANAR IMAGES; HUMAN BRAIN; TISSUE CLASSIFICATION; MR-IMAGES; SEGMENTATION AB Mapping brain structure in relation to neurological development, function, plasticity, and disease is widely considered to be one of the most essential challenges for opening new lines of neuro-scientific inquiry. Recent developments with MRI analysis of structural connectivity, anatomical brain segmentation, cortical surface parcellation, and functional imaging have yielded fantastic advances in our ability to probe the neurological structure-function relationship in vivo. To date, the image analysis efforts in each of these areas have typically focused on a single modality. Here, we extend the cortical reconstruction using implicit surface evolution (CRUISE) methodology to perform efficient, consistent, and topologically correct analyses in a natively multi-parametric manner. This effort combines and extends state-of-the-art techniques to simultaneously consider and analyze structural and diffusion information alongside quantitative and functional imaging data. Robust and consistent estimates of the cortical surface extraction, cortical labeling, diffusion-inferred contrasts, diffusion tractography, and subcortical parcellation are demonstrated in a scan-rescan paradigm. Accompanying this demonstration, we present a fully automated software system complete with validation data. C1 [Landman, Bennett A.] Vanderbilt Univ, Dept Elect Engn, Nashville, TN 37235 USA. [Landman, Bennett A.; Prince, Jerry L.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD USA. [Landman, Bennett A.] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN 37235 USA. [Bogovic, John A.; Carass, Aaron; Chen, Min; Roy, Snehashis; Shiee, Navid; Yang, Zhen; Dzung Pham; Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Kishore, Bhaskar; Dzung Pham; Prince, Jerry L.] Johns Hopkins Univ, Russell H Morgan Dept Radiol & Radiol Sci, Sch Med, Baltimore, MD USA. [Dzung Pham] Ctr Neurosci & Regenerat Med, Washington, DC USA. [Resnick, Susan M.] NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. [Bazin, Pierre-Louis] Max Plank Inst Human Cognit & Brain Sci, Dept Neurophys, Leipzig, Germany. RP Landman, BA (reprint author), Vanderbilt Univ, Dept Elect Engn, 2301 Vanderbilt Pl,Stn B,POB 351679, Nashville, TN 37235 USA. EM bennett.landman@vanderbilt.edu RI Prince, Jerry/A-3281-2010; OI Prince, Jerry/0000-0002-6553-0876; Bazin, Pierre-Louis/0000-0002-0141-5510; Roy, Snehashis/0000-0002-7997-3993; Carass, Aaron/0000-0003-4939-5085 FU NIH/NIA [N01-AG-4-0012]; NINDS [5R01NS070906, 1R03EB012461, 1R01NS056307]; [NIH/NIDAK25DA025356]; [NIH/NINDSR01NS054255] FX The authors are appreciative of the careful feedback from the anonymous reviewers and editor (Dr. David Kennedy). This research was supported by NIH/NIA N01-AG-4-0012, NINDS 5R01NS070906, 1R03EB012461, 1R01NS056307, NIH/NIDAK25DA025356 (Bazin), and NIH/NINDSR01NS054255 (Pham). NR 65 TC 6 Z9 6 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1539-2791 J9 NEUROINFORMATICS JI Neuroinformatics PD JAN PY 2013 VL 11 IS 1 BP 91 EP 103 DI 10.1007/s12021-012-9159-9 PG 13 WC Computer Science, Interdisciplinary Applications; Neurosciences SC Computer Science; Neurosciences & Neurology GA 064HO UT WOS:000313065000008 PM 22932976 ER PT J AU Myers, CS Taylor, RC Salmeron, BJ Waters, AJ Heishman, SJ AF Myers, Carol S. Taylor, Richard C. Salmeron, Betty J. Waters, Andrew J. Heishman, Stephen J. TI Nicotine Enhances Alerting, but not Executive, Attention in Smokers and Nonsmokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID NEVER-SMOKERS; NETWORKS; PERFORMANCE; BLINK AB Introduction: Difficulty concentrating is a symptom of nicotine withdrawal that can contribute to relapse in individuals trying to quit smoking. The purpose of this study was to determine the effects of nicotine on executive and alerting attention in smokers and nonsmokers. Methods: Thirty daily smokers who were not tobacco deprived and 30 nonsmokers participated in the study. Participants received a single dose of intranasal nicotine (0, 0.5, or 1.5 mg) at each of 3 experimental sessions on separate days. Participants completed subjective ratings and 3 attention tasks before and after nicotine administration. Results: Nicotine had no effect on executive attention as assessed by a Rapid Serial Visual Presentation (RSVP) task or the Attention Network Test in smokers and nonsmokers. In contrast, nicotine enhanced alerting attention by decreasing errors on a Continuous Performance Test (CPT) in nonsmokers and improving the correct identification of target words on the RSVP task in smokers. Nonsmokers were more sensitive than smokers to the subjective, but not the cardiovascular, effects of nicotine. Conclusions: The acute administration of intranasal nicotine improved alerting attention in nonsmokers as measured by the CPT, and in smokers as measured by the RSVP. Understanding the elements of attention enhanced by nicotine might guide the development of novel medications for tobacco dependence. C1 [Myers, Carol S.; Taylor, Richard C.; Salmeron, Betty J.; Heishman, Stephen J.] NIDA, Intramural Res Program, Baltimore, MD 21224 USA. [Waters, Andrew J.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. RP Myers, CS (reprint author), NIDA, Intramural Res Program, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM cmyers@intra.nida.nih.gov RI Salmeron, Betty Jo/M-1793-2016 OI Salmeron, Betty Jo/0000-0003-1699-9333 FU National Institutes of Health (NIH) Intramural Research Program, National Institute on Drug Abuse FX This research was funded by the National Institutes of Health (NIH) Intramural Research Program, National Institute on Drug Abuse. NR 16 TC 5 Z9 5 U1 3 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JAN PY 2013 VL 15 IS 1 BP 277 EP 281 DI 10.1093/ntr/nts108 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 061WM UT WOS:000312880900036 PM 22573728 ER PT J AU Salari, R Kimchi-Sarfaty, C Gottesman, MM Przytycka, TM AF Salari, Raheleh Kimchi-Sarfaty, Chava Gottesman, Michael M. Przytycka, Teresa M. TI Sensitive measurement of single-nucleotide polymorphism-induced changes of RNA conformation: application to disease studies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EUKARYOTIC MESSENGER-RNAS; IRON-RESPONSIVE ELEMENT; SECONDARY STRUCTURE; SYNONYMOUS MUTATIONS; PROTEIN EXPRESSION; ESCHERICHIA-COLI; L-FERRITIN; STABILITY; SEQUENCE; DATABASE AB Single-nucleotide polymorphisms (SNPs) are often linked to critical phenotypes such as diseases or responses to vaccines, medications and environmental factors. However, the specific molecular mechanisms by which a causal SNP acts is usually not obvious. Changes in RNA secondary structure emerge as a possible explanation necessitating the development of methods to measure the impact of single-nucleotide variation on RNA structure. Despite the recognition of the importance of considering the changes in Boltzmann ensemble of RNA conformers in this context, a formal method to perform directly such comparison was lacking. Here, we solved this problem and designed an efficient method to compute the relative entropy between the Boltzmann ensembles of the native and a mutant structure. On the basis of this theoretical progress, we developed a software tool, remuRNA, and investigated examples of its application. Comparing the impact of common SNPs naturally occurring in populations with the impact of random point mutations, we found that structural changes introduced by common SNPs are smaller than those introduced by random point mutations. This suggests a natural selection against mutations that significantly change RNA structure and demonstrates, surprisingly, that randomly inserted point mutations provide inadequate estimation of random mutations effects. Subsequently, we applied remuRNA to determine which of the disease-associated non-coding SNPs are potentially related to RNA structural changes. C1 [Salari, Raheleh; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Przytycka, TM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM przytyck@mail.nih.gov FU National Institutes of Health, National Library of Medicine and National Cancer Institute; Center for Biologics Evaluation and Research FDA; NSERC PDF; National Institutes of Health, National Library of Medicine FX The Intramural Research Program of the National Institutes of Health, National Library of Medicine and National Cancer Institute; the Research Participation program at the Center for Biologics Evaluation and Research FDA; NSERC PDF (in part, to R. S.). The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 36 TC 21 Z9 21 U1 1 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 44 EP 53 DI 10.1093/nar/gks1009 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900037 PM 23125360 ER PT J AU Rijal, K Maraia, RJ AF Rijal, Keshab Maraia, Richard J. TI RNA polymerase III mutants in TFIIF alpha-like C37 that cause terminator readthrough with no decrease in transcription output SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN LA ANTIGEN; IN-VITRO; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; ACCURATE TERMINATION; CLEAVAGE ACTIVITY; BINDING PROTEIN; SERINE 366; GENE; MAF1 AB How eukaryotic RNA polymerases switch from elongation to termination is unknown. Pol III subunits Rpc53 and Rpc37 (C53/37) form a heterodimer homologous to TFIIF beta/alpha. C53/37 promotes efficient termination and together with C11 also mediates pol III recycling in vitro. We previously developed Schizosaccharomyces pombe strains that report on two pol III termination activities: RNA oligo(U) 3'-end cleavage, and terminator readthrough. We randomly mutagenized C53 and C37 and isolated many C37 mutants with terminator readthrough but no comparable C53 mutants. The majority of C37 mutants have strong phenotypes with up to 40% readthrough and map to a C-terminal tract previously localized near Rpc2p in the pol III active center while a minority represent a distinct class with weaker phenotype, less readthrough and 3'-oligo(U) lengthening. Nascent pre-tRNAs released from a terminator by C37 mutants have shorter 3'-oligo(U) tracts than in cleavage-deficient C11 double mutants indicating RNA 3'-end cleavage during termination. We asked whether termination deficiency affects transcription output in the mutants in vivo both by monitoring intron-containing nascent transcript levels and C-14-uridine incorporation. Surprisingly, multiple termination mutants have no decrease in transcript output relative to controls. These data are discussed in context of current models of pol III transcription. C1 [Rijal, Keshab; Maraia, Richard J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA. [Maraia, Richard J.] US PHS, Rockville, MD USA. RP Maraia, RJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA. EM maraiar@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. Funding for open access charge: Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 64 TC 14 Z9 14 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 139 EP 155 DI 10.1093/nar/gks985 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900044 PM 23093604 ER PT J AU Cagliero, C Jin, DJ AF Cagliero, Cedric Jin, Ding Jun TI Dissociation and re-association of RNA polymerase with DNA during osmotic stress response in Escherichia coli SO NUCLEIC ACIDS RESEARCH LA English DT Article ID NUCLEOID-ASSOCIATED PROTEINS; LAMBDA-PR PROMOTER; GENE-EXPRESSION; BACTERIAL OSMOREGULATION; POTASSIUM GLUTAMATE; GROWTH-RATE; BINDING; ROLES; K-12; TRANSCRIPTION AB The thermodynamic association of RNA polymerase (RNAP) with DNA is sensitive to salt concentration in vitro. Paradoxically, previous studies of changes in osmolarity during steady-state cell growth found no dependence between the association of RNAP to DNA and K+ concentration in Escherichia coli. We reevaluated this issue by following the interaction of RNAP and genomic DNA in time-course experiments during the hyper-osmotic response. Our results show that the interaction is temporally controlled by the same physical chemistry principle in the cell as in vitro. RNAP rapidly dissociates from the genome during the initial response when the cytoplasmic K+ accumulates transiently, and concurrently the nucleoid becomes hyper-condensed. The freed RNAP re-associates with the genome during a subsequent osmoadaptation phase when organic osmoprotectants accumulate as K+ levels decrease. RNAP first surrounds the hyper-condensed nucleoid forming a sphere of RNAP before it progressively moves in to the center of the nucleoid. Our findings reinterpret the dynamic protein-DNA interactions during osmotic stress response. We discuss the implications of the dissociation/association of RNAP for osmotic protection and nucleoid structure. C1 [Cagliero, Cedric; Jin, Ding Jun] NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21701 USA. RP Jin, DJ (reprint author), NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21701 USA. EM jind@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX Funding for open access charge: The Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 67 TC 15 Z9 15 U1 4 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 315 EP 326 DI 10.1093/nar/gks988 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900058 PM 23093594 ER PT J AU Purzycka, KJ Legiewicz, M Matsuda, E Eizentstat, LD Lusvarghi, S Saha, A Le Grice, SFJ Garfinkel, DJ AF Purzycka, Katarzyna J. Legiewicz, Michal Matsuda, Emiko Eizentstat, Linda D. Lusvarghi, Sabrina Saha, Agniva Le Grice, Stuart F. J. Garfinkel, David J. TI Exploring Ty1 retrotransposon RNA structure within virus-like particles SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PRIMER BINDING-SITE; REVERSE TRANSCRIPTION; SECONDARY STRUCTURE; ELEMENT TRANSPOSITION; SACCHAROMYCES-CEREVISIAE; TERTIARY STRUCTURE; STRAND TRANSFER; GENOMIC RNA; TYPE-1 RNA; YEAST AB Ty1, a long terminal repeat retrotransposon of Saccharomyces, is structurally and functionally related to retroviruses. However, a differentiating aspect between these retroelements is the diversity of the replication strategies used by long terminal repeat retrotransposons. To understand the structural organization of cis-acting elements present on Ty1 genomic RNA from the GAG region that control reverse transcription, we applied chemoenzymatic probing to RNA/tRNA complexes assembled in vitro and to the RNA in virus-like particles. By comparing different RNA states, our analyses provide a comprehensive structure of the primer-binding site, a novel pseudoknot adjacent to the primer-binding sites, three regions containing palindromic sequences that may be involved in RNA dimerization or packaging and candidate protein interaction sites. In addition, we determined the impact of a novel form of transposon control based on Ty1 antisense transcripts that associate with virus-like particles. Our results support the idea that antisense RNAs inhibit retrotransposition by targeting Ty1 protein function rather than annealing with the RNA genome. C1 [Purzycka, Katarzyna J.; Legiewicz, Michal; Lusvarghi, Sabrina; Le Grice, Stuart F. J.] Frederick Natl Lab Canc Res, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. [Purzycka, Katarzyna J.] Polish Acad Sci, Inst Bioorgan Chem, Lab Struct Chem Nucle Acids, PL-61704 Poznan, Poland. [Matsuda, Emiko] Frederick Natl Lab Canc Res, Gene Regulat & Chromosomal Biol Lab, Frederick, MD 21702 USA. [Eizentstat, Linda D.; Saha, Agniva; Garfinkel, David J.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. RP Le Grice, SFJ (reprint author), Frederick Natl Lab Canc Res, RT Biochem Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM legrices@mail.nih.gov; djgarf@bmb.uga.edu FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; NIH [GM095622]; National Institutes of Health; University of Georgia Research Foundation FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, University of Georgia Research Foundation and NIH [GM095622 to D.J.G.]. Funding for open access charge: National Institutes of Health. NR 57 TC 11 Z9 11 U1 1 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 463 EP 473 DI 10.1093/nar/gks983 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900069 PM 23093595 ER PT J AU Rajan, R Prasad, R Taneja, B Wilson, SH Mondragon, A AF Rajan, Rakhi Prasad, Rajendra Taneja, Bhupesh Wilson, Samuel H. Mondragon, Alfonso TI Identification of one of the apurinic/apyrimidinic lyase active sites of topoisomerase V by structural and functional studies SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DNA-REPAIR ACTIVITIES; BASE EXCISION-REPAIR; CRYSTAL-STRUCTURE; DIFFRACTION DATA; POLYMERASE-BETA; MECHANISM; ENDONUCLEASE; RECOGNITION; BINDING; GLYCOSYLASE AB Topoisomerase V (Topo-V) is the only member of a novel topoisomerase subtype. Topo-V is unique because it is a bifunctional enzyme carrying both topoisomerase and DNA repair lyase activities within the same protein. Previous studies had shown that the topoisomerase domain spans the N-terminus of the protein and is followed by 12 tandem helix-hairpin-helix [(HhH)(2)] domains. There are at least two DNA repair lyase active sites for apurinic/apyrimidinic (AP) site processing, one within the N-terminal region and the second within the C-terminal domain of Topo-V, but their exact locations and characteristics are unknown. In the present study, the N-terminal 78-kDa fragment of Topo-V (Topo-78), containing the topoisomerase domain and one of the lyase DNA repair domains, was characterized by structural and biochemical studies. The results show that an N-terminal 69-kDa fragment is the minimal fragment with both topoisomerase and AP lyase activities. The lyase active site of Topo-78 is at the junction of the fifth and sixth (HhH)(2) domains. From the biochemical and structural data, it appears that Lys571 is the most probable nucleophile responsible for the lyase activity. Our experiments also suggest that Topo-V most likely acts as a Class I AP endonuclease in vivo. C1 [Rajan, Rakhi; Taneja, Bhupesh; Mondragon, Alfonso] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA. [Prasad, Rajendra; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Mondragon, A (reprint author), Northwestern Univ, Dept Mol Biosci, 2205 Tech Dr, Evanston, IL 60208 USA. EM a-mondragon@northwestern.edu RI Rajan, Rakhi/K-2477-2016 FU Michigan Economic Development Corporation; Michigan Technology Tri-Corridor; Department of Energy (DOE); R.H. Lurie Comprehensive Cancer Center of Northwestern University; American Heart Association [10POST2600325]; National Institutes of Health [R01GM51350]; NIH FX We acknowledge staff and instrumentation support from the Keck Biophysics Facility and the Center for Structural Biology at Northwestern University, and Life Science Collaborative Access Team station (LS-CAT) at the Advanced Photon Source (APS) at Argonne National Laboratory. LS-CAT was supported by the Michigan Economic Development Corporation and the Michigan Technology Tri-Corridor. Use of the APS is supported by the Department of Energy (DOE). Support from the R.H. Lurie Comprehensive Cancer Center of Northwestern University to the Structural Biology Facility is also acknowledged. We thank Alexei Slesarev for providing some of the Topoisomerase V plasmids.; American Heart Association postdoctoral fellow [10POST2600325 to R. R.]. National Institutes of Health [R01GM51350 to A. M.]. Funding for open access charge: NIH. NR 40 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 BP 657 EP 666 DI 10.1093/nar/gks1017 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900086 PM 23125368 ER PT J AU Acland, A Agarwala, R Barrett, T Beck, J Benson, DA Bollin, C Bolton, E Bryant, SH Canese, K Church, DM Clark, K DiCuccio, M Dondoshansky, I Federhen, S Feolo, M Geer, LY Gorelenkov, V Hoeppner, M Johnson, M Kelly, C Khotomlianski, V Kimchi, A Kimelman, M Kitts, P Krasnov, S Kuznetsov, A Landsman, D Lipman, DJ Lu, ZY Madden, TL Madej, T Maglott, DR Marchler-Bauer, A Karsch-Mizrachi, I Murphy, T Ostell, J O'Sullivan, C Panchenko, A Phan, L Pruitt, DPKD Rubinstein, W Sayers, EW Schneider, V Schuler, GD Sequeira, E Sherry, ST Shumway, M Sirotkin, K Siyan, K Slotta, D Soboleva, A Starchenko, G Tatusova, TA Trawick, B Vakatov, D Wang, YL Ward, M Wilbur, WJ Yaschenko, E Zbicz, K AF Acland, Abigail Agarwala, Richa Barrett, Tanya Beck, Jeff Benson, Dennis A. Bollin, Colleen Bolton, Evan Bryant, Stephen H. Canese, Kathi Church, Deanna M. Clark, Karen DiCuccio, Michael Dondoshansky, Ilya Federhen, Scott Feolo, Michael Geer, Lewis Y. Gorelenkov, Viatcheslav Hoeppner, Marilu Johnson, Mark Kelly, Christopher Khotomlianski, Viatcheslav Kimchi, Avi Kimelman, Michael Kitts, Paul Krasnov, Sergey Kuznetsov, Anatoliy Landsman, David Lipman, David J. Lu, Zhiyong Madden, Thomas L. Madej, Tom Maglott, Donna R. Marchler-Bauer, Aron Karsch-Mizrachi, Ilene Murphy, Terence Ostell, James O'Sullivan, Christopher Panchenko, Anna Phan, Lon Pruitt, Don Preussm Kim D. Rubinstein, Wendy Sayers, Eric W. Schneider, Valerie Schuler, Gregory D. Sequeira, Edwin Sherry, Stephen T. Shumway, Martin Sirotkin, Karl Siyan, Karanjit Slotta, Douglas Soboleva, Alexandra Starchenko, Grigory Tatusova, Tatiana A. Trawick, Bart Vakatov, Denis Wang, Yanli Ward, Minghong Wilbur, W. John Yaschenko, Eugene Zbicz, Kerry CA NCBI Resource Coordinators TI Database resources of the National Center for Biotechnology Information SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ONLINE MENDELIAN INHERITANCE; BIOLOGICAL PATHWAYS; GENE ONTOLOGY; NCBI; SEQUENCES; GENOMES; SEARCH; TOOL; ANNOTATION; ARCHIVE AB In addition to maintaining the GenBank (R) nucleic acid sequence database, the National Center for Biotechnology Information (NCBI, http://www.ncbi.nlm.nih.gov) provides analysis and retrieval resources for the data in GenBank and other biological data made available through the NCBI web site. NCBI resources include Entrez, the Entrez Programming Utilities, MyNCBI, PubMed, PubMed Central, Gene, the NCBI Taxonomy Browser, BLAST, BLAST Link (BLink), Primer-BLAST, COBALT, Splign, RefSeq, UniGene, HomoloGene, ProtEST, dbMHC, dbSNP, dbVar, Epigenomics, the Genetic Testing Registry, Genome and related tools, the Map Viewer, Model Maker, Evidence Viewer, Trace Archive, Sequence Read Archive, BioProject, BioSample, Retroviral Genotyping Tools, HIV-1/Human Protein Interaction Database, Gene Expression Omnibus, Probe, Online Mendelian Inheritance in Animals, the Molecular Modeling Database, the Conserved Domain Database, the Conserved Domain Architecture Retrieval Tool, Biosystems, Protein Clusters and the PubChem suite of small molecule databases. Augmenting many of the web applications are custom implementations of the BLAST program optimized to search specialized data sets. All of these resources can be accessed through the NCBI home page. C1 [Acland, Abigail; Agarwala, Richa; Barrett, Tanya; Beck, Jeff; Benson, Dennis A.; Bollin, Colleen; Bolton, Evan; Bryant, Stephen H.; Canese, Kathi; Church, Deanna M.; Clark, Karen; DiCuccio, Michael; Dondoshansky, Ilya; Federhen, Scott; Feolo, Michael; Geer, Lewis Y.; Gorelenkov, Viatcheslav; Hoeppner, Marilu; Johnson, Mark; Kelly, Christopher; Khotomlianski, Viatcheslav; Kimchi, Avi; Kimelman, Michael; Kitts, Paul; Krasnov, Sergey; Kuznetsov, Anatoliy; Landsman, David; Lipman, David J.; Lu, Zhiyong; Madden, Thomas L.; Madej, Tom; Maglott, Donna R.; Marchler-Bauer, Aron; Karsch-Mizrachi, Ilene; Murphy, Terence; Ostell, James; O'Sullivan, Christopher; Panchenko, Anna; Phan, Lon; Pruitt, Don Preussm Kim D.; Rubinstein, Wendy; Sayers, Eric W.; Schneider, Valerie; Schuler, Gregory D.; Sequeira, Edwin; Sherry, Stephen T.; Shumway, Martin; Sirotkin, Karl; Siyan, Karanjit; Slotta, Douglas; Soboleva, Alexandra; Starchenko, Grigory; Tatusova, Tatiana A.; Trawick, Bart; Vakatov, Denis; Wang, Yanli; Ward, Minghong; Wilbur, W. John; Yaschenko, Eugene; Zbicz, Kerry; NCBI Resource Coordinators] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov RI Geer, Lewis/H-2714-2014; OI Trawick, Bart/0000-0002-3635-3508; Marchler-Bauer, Aron/0000-0003-1516-0712; Landsman, David/0000-0002-9819-6675 FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 64 TC 127 Z9 129 U1 1 U2 72 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D8 EP D20 DI 10.1093/nar/gks1189 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300002 ER PT J AU Barrett, T Wilhite, SE Ledoux, P Evangelista, C Kim, IF Tomashevsky, M Marshall, KA Phillippy, KH Sherman, PM Holko, M Yefanov, A Lee, H Zhang, NG Robertson, CL Serova, N Davis, S Soboleva, A AF Barrett, Tanya Wilhite, Stephen E. Ledoux, Pierre Evangelista, Carlos Kim, Irene F. Tomashevsky, Maxim Marshall, Kimberly A. Phillippy, Katherine H. Sherman, Patti M. Holko, Michelle Yefanov, Andrey Lee, Hyeseung Zhang, Naigong Robertson, Cynthia L. Serova, Nadezhda Davis, Sean Soboleva, Alexandra TI NCBI GEO: archive for functional genomics data sets-update SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION AB The Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) is an international public repository for high-throughput microarray and next-generation sequence functional genomic data sets submitted by the research community. The resource supports archiving of raw data, processed data and metadata which are indexed, cross-linked and searchable. All data are freely available for download in a variety of formats. GEO also provides several web-based tools and strategies to assist users to query, analyse and visualize data. This article reports current status and recent database developments, including the release of GEO2R, an R-based web application that helps users analyse GEO data. C1 [Barrett, Tanya; Wilhite, Stephen E.; Ledoux, Pierre; Evangelista, Carlos; Kim, Irene F.; Tomashevsky, Maxim; Marshall, Kimberly A.; Phillippy, Katherine H.; Sherman, Patti M.; Holko, Michelle; Yefanov, Andrey; Lee, Hyeseung; Zhang, Naigong; Robertson, Cynthia L.; Serova, Nadezhda; Soboleva, Alexandra] NCI, Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. [Davis, Sean] NCI, Mol Genet Sect, Genet Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, T (reprint author), NCI, Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA. EM barrett@ncbi.nlm.nih.gov OI Davis, Sean/0000-0002-8991-6458 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 19 TC 863 Z9 874 U1 11 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D991 EP D995 DI 10.1093/nar/gks1193 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300141 PM 23193258 ER PT J AU Benson, DA Cavanaugh, M Clark, K Karsch-Mizrachi, I Lipman, DJ Ostell, J Sayers, EW AF Benson, Dennis A. Cavanaugh, Mark Clark, Karen Karsch-Mizrachi, Ilene Lipman, David J. Ostell, James Sayers, Eric W. TI GenBank SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; ARCHIVE AB GenBank (R) (http://www.ncbi.nlm.nih.gov) is a comprehensive database that contains publicly available nucleotide sequences for almost 260 000 formally described species. These sequences are obtained primarily through submissions from individual laboratories and batch submissions from large-scale sequencing projects, including whole-genome shotgun (WGS) and environmental sampling projects. Most submissions are made using the web-based BankIt or standalone Sequin programs, and GenBank staff assigns accession numbers upon data receipt. Daily data exchange with the European Nucleotide Archive (ENA) and the DNA Data Bank of Japan (DDBJ) ensures worldwide coverage. GenBank is accessible through the NCBI Entrez retrieval system, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping, protein structure and domain information, and the biomedical journal literature via PubMed. BLAST provides sequence similarity searches of GenBank and other sequence databases. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. To access GenBank and its related retrieval and analysis services, begin at the NCBI home page: www.ncbi.nlm.nih.gov. C1 [Benson, Dennis A.; Cavanaugh, Mark; Clark, Karen; Karsch-Mizrachi, Ilene; Lipman, David J.; Ostell, James; Sayers, Eric W.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Sayers, EW (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM sayers@ncbi.nlm.nih.gov FU National Institutes of Health; National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health; National Library of Medicine. NR 13 TC 572 Z9 584 U1 5 U2 113 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D36 EP D42 DI 10.1093/nar/gks1195 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300006 PM 23193287 ER PT J AU Cer, RZ Donohue, DE Mudunuri, US Temiz, NA Loss, MA Starner, NJ Halusa, GN Volfovsky, N Yi, M Luke, BT Bacolla, A Collins, JR Stephens, RM AF Cer, Regina Z. Donohue, Duncan E. Mudunuri, Uma S. Temiz, Nuri A. Loss, Michael A. Starner, Nathan J. Halusa, Goran N. Volfovsky, Natalia Yi, Ming Luke, Brian T. Bacolla, Albino Collins, Jack R. Stephens, Robert M. TI Non-B DB v2.0: a database of predicted non-B DNA-forming motifs and its associated tools SO NUCLEIC ACIDS RESEARCH LA English DT Article ID REARRANGEMENTS; DUPLICATIONS; PROMOTER; COMPLEX AB The non-B DB, available at http://nonb.abcc.ncifcrf.gov, catalogs predicted non-B DNA-forming sequence motifs, including Z-DNA, G-quadruplex, A-phased repeats, inverted repeats, mirror repeats, direct repeats and their corresponding subsets: cruciforms, triplexes and slipped structures, in several genomes. Version 2.0 of the database revises and re-implements the motif discovery algorithms to better align with accepted definitions and thresholds for motifs, expands the non-B DNA-forming motifs coverage by including short tandem repeats and adds key visualization tools to compare motif locations relative to other genomic annotations. Non-B DB v2.0 extends the ability for comparative genomics by including re-annotation of the five organisms reported in non-B DB v1.0, human, chimpanzee, dog, macaque and mouse, and adds seven additional organisms: orangutan, rat, cow, pig, horse, platypus and Arabidopsis thaliana. Additionally, the non-B DB v2.0 provides an overall improved graphical user interface and faster query performance. C1 [Cer, Regina Z.; Donohue, Duncan E.; Mudunuri, Uma S.; Temiz, Nuri A.; Loss, Michael A.; Starner, Nathan J.; Halusa, Goran N.; Volfovsky, Natalia; Yi, Ming; Luke, Brian T.; Bacolla, Albino; Collins, Jack R.; Stephens, Robert M.] SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. [Bacolla, Albino] Univ Texas Austin, Div Pharmacol & Toxicol, Dell Pediat Res Inst, Austin, TX 78723 USA. RP Stephens, RM (reprint author), SAIC Frederick Inc, Adv Biomed Comp Ctr, Informat Syst Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM stephensr@mail.nih.gov RI Bacolla, Albino/N-3877-2013 OI Bacolla, Albino/0000-0003-0206-8423 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; CBIIT/caBIG ISRCE yellow task [09-260] FX Funding for open access charge: This work was supported in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E and funding from CBIIT/caBIG ISRCE yellow task #09-260 to NCI-Frederick. NR 17 TC 25 Z9 26 U1 3 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D94 EP D100 DI 10.1093/nar/gks955 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300014 PM 23125372 ER PT J AU Fernandez-Suarez, XM Galperin, MY AF Fernandez-Suarez, Xose M. Galperin, Michael Y. TI The 2013 Nucleic Acids Research Database Issue and the online Molecular Biology Database Collection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MODEL ORGANISM DATABASE; BINDING SITES; GENOME; RESOURCE; UPDATE; PROJECT; SEQUENCES; INFORMATION; ASSOCIATION; PHENOTYPES AB The 20th annual Database Issue of Nucleic Acids Research includes 176 articles, half of which describe new online molecular biology databases and the other half provide updates on the databases previously featured in NAR and other journals. This year's highlights include two databases of DNA repeat elements; several databases of transcriptional factors and transcriptional factor-binding sites; databases on various aspects of protein structure and protein-protein interactions; databases for metagenomic and rRNA sequence analysis; and four databases specifically dedicated to Escherichia coli. The increased emphasis on using the genome data to improve human health is reflected in the development of the databases of genomic structural variation (NCBI's dbVar and EBI's DGVa), the NIH Genetic Testing Registry and several other databases centered on the genetic basis of human disease, potential drugs, their targets and the mechanisms of protein-ligand binding. Two new databases present genomic and RNAseq data for monkeys, providing wealth of data on our closest relatives for comparative genomics purposes. The NAR online Molecular Biology Database Collection, available at http://www.oxfordjournals.org/nar/database/a/, has been updated and currently lists 1512 online databases. The full content of the Database Issue is freely available online on the Nucleic Acids Research website (http://nar.oxfordjournals.org/). C1 [Galperin, Michael Y.] NIH, NCBI, Natl Lib Med, Bethesda, MD 20894 USA. EM xose.m.fernandez@gmail.com; nardatabase@gmail.com OI Galperin, Michael/0000-0002-2265-5572 FU U.S. National Institutes of Health at the National Library of Medicine FX Intramural Research Program of the U.S. National Institutes of Health at the National Library of Medicine [to M.Y.G.]. Funding for open access charge: Waived by Oxford University Press. NR 56 TC 38 Z9 40 U1 1 U2 34 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D1 EP D7 DI 10.1093/nar/gks1297 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300001 PM 23203983 ER PT J AU Fingerman, IM Zhang, X Ratzat, W Husain, N Cohen, RF Schuler, GD AF Fingerman, Ian M. Zhang, Xuan Ratzat, Walter Husain, Nora Cohen, Robert F. Schuler, Gregory D. TI NCBI Epigenomics: What's new for 2013 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID EPIGENETIC INHERITANCE; DNA ELEMENTS; CHROMATIN; CANCER; ENCYCLOPEDIA; GENOME; RNAS AB The Epigenomics resource at the National Center for Biotechnology Information (NCBI) has been created to serve as a comprehensive public repository for whole-genome epigenetic data sets (www.ncbi.nlm.nih.gov/epigenomics). We have constructed this resource by selecting the subset of epigenetics-specific data from the Gene Expression Omnibus (GEO) database and then subjecting them to further review and annotation. Associated data tracks can be viewed using popular genome browsers or downloaded for local analysis. We have performed extensive user testing throughout the development of this resource, and new features and improvements are continuously being implemented based on the results. We have made substantial usability improvements to user interfaces, enhanced functionality, made identification of data tracks of interest easier and created new tools for preliminary data analyses. Additionally, we have made efforts to enhance the integration between the Epigenomics resource and other NCBI databases, including the Gene database and PubMed. Data holdings have also increased dramatically since the initial publication describing the NCBI Epigenomics resource and currently consist of > 3700 viewable and downloadable data tracks from 955 biological sources encompassing five well-studied species. This updated manuscript highlights these changes and improvements. C1 [Fingerman, Ian M.; Zhang, Xuan; Ratzat, Walter; Husain, Nora; Cohen, Robert F.; Schuler, Gregory D.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Fingerman, IM (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA. EM fingerma@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 31 TC 11 Z9 11 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D221 EP D225 DI 10.1093/nar/gks1171 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300030 PM 23193265 ER PT J AU Hoeppner, MA AF Hoeppner, Marilu A. TI NCBI Bookshelf: books and documents in life sciences and health care SO NUCLEIC ACIDS RESEARCH LA English DT Article AB Bookshelf ( ext-link-type="uri" xlink:href="http://www.ncbi.nlm.nih.gov/books/" xmlns:xlink="http://www.w3.org/1999/xlink">http://www.ncbi.nlm.nih.gov/books/) is a full-text electronic literature resource of books and documents in life sciences and health care at the National Center for Biotechnology Information (NCBI). Created in 1999 with a single book as an encyclopedic reference for resources such as PubMed and GenBank, it has grown to its current size of > 1300 titles. Unlike other NCBI databases, such as GenBank and Gene, which have a strict data structure, books come in all forms; they are diverse in publication types, formats, sizes and authoring models. The Bookshelf data format is XML tagged in the NCBI Book DTD (Document Type Definition), modeled after the National Library of Medicine journal article DTDs. The book DTD has been used for systematically tagging the diverse data formats of books, a move that has set the foundation for the growth of this resource. Books at NCBI followed the route of journal articles in the PubMed Central project, using the PubMed Central architectural framework, workflows and processes. Through integration with other NCBI molecular databases, books at NCBI can be used to provide reference information for biological data and facilitate its discovery. This article describes Bookshelf at NCBI: its growth, data handling and retrieval and integration with molecular databases. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Hoeppner, MA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 45 Ctr Dr, Bethesda, MD 20892 USA. EM hoeppner@ncbi.nlm.nih.gov FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 10 TC 1 Z9 1 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D1251 EP D1260 DI 10.1093/nar/gks1279 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300177 PM 23203889 ER PT J AU Lappalainen, I Lopez, J Skipper, L Hefferon, T Spalding, JD Garner, J Chen, C Maguire, M Corbett, M Zhou, G Paschall, J Ananiev, V Flicek, P Church, DM AF Lappalainen, Ilkka Lopez, John Skipper, Lisa Hefferon, Timothy Spalding, J. Dylan Garner, John Chen, Chao Maguire, Michael Corbett, Matt Zhou, George Paschall, Justin Ananiev, Victor Flicek, Paul Church, Deanna M. TI dbVar and DGVa: public archives for genomic structural variation SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COPY NUMBER VARIATION; VARIANTS; ONTOLOGY; MAP AB Much has changed in the last two years at DGVa (http://www.ebi.ac.uk/dgva) and dbVar (http://www.ncbi.nlm.nih.gov/dbvar). We are now processing direct submissions rather than only curating data from the literature and our joint study catalog includes data from over 100 studies in 11 organisms. Studies from human dominate with data from control and case populations, tumor samples as well as three large curated studies derived from multiple sources. During the processing of these data, we have made improvements to our data model, submission process and data representation. Additionally, we have made significant improvements in providing access to these data via web and FTP interfaces. C1 [Lopez, John; Hefferon, Timothy; Garner, John; Chen, Chao; Zhou, George; Ananiev, Victor; Church, Deanna M.] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Lappalainen, Ilkka; Skipper, Lisa; Spalding, J. Dylan; Maguire, Michael; Corbett, Matt; Paschall, Justin; Flicek, Paul] European Bioinformat Inst, Hinxton CB10 1SD, Cambs, England. RP Church, DM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM flicek@ebi.ac.uk; church@ncbi.nlm.nih.gov RI chen, chao/D-2665-2014; OI Skipper, Lisa/0000-0002-1524-9787; Lappalainen, Ilkka/0000-0001-5762-893X; Spalding, John Dylan/0000-0002-4285-2493; Flicek, Paul/0000-0002-3897-7955 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine; Wellcome Trust [WT084107MA]; European Molecular Biology Laboratory; NCBI FX The Intramural Research Program of the National Institutes of Health, National Library of Medicine for the work on dbVar; the Wellcome Trust (grant number WT084107MA) and by the European Molecular Biology Laboratory for the DGVa. Funding for open access charge: NCBI. NR 20 TC 44 Z9 44 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D936 EP D941 DI 10.1093/nar/gks1213 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300132 PM 23193291 ER PT J AU Marchler-Bauer, A Zheng, CJ Chitsaz, F Derbyshire, MK Geer, LY Geer, RC Gonzales, NR Gwadz, M Hurwitz, DI Lanczycki, CJ Lu, F Lu, SN Marchler, GH Song, JS Thanki, N Yamashita, RA Zhang, DC Bryant, SH AF Marchler-Bauer, Aron Zheng, Chanjuan Chitsaz, Farideh Derbyshire, Myra K. Geer, Lewis Y. Geer, Renata C. Gonzales, Noreen R. Gwadz, Marc Hurwitz, David I. Lanczycki, Christopher J. Lu, Fu Lu, Shennan Marchler, Gabriele H. Song, James S. Thanki, Narmada Yamashita, Roxanne A. Zhang, Dachuan Bryant, Stephen H. TI CDD: conserved domains and protein three-dimensional structure SO NUCLEIC ACIDS RESEARCH LA English DT Article ID DATABASE; CLASSIFICATION; ASSIGNMENT; GENOMES; PFAM AB CDD, the Conserved Domain Database, is part of NCBI's Entrez query and retrieval system and is also accessible via http://www.ncbi.nlm.nih.gov/Structure/cdd/cdd.shtml. CDD provides annotation of protein sequences with the location of conserved domain footprints and functional sites inferred from these footprints. Pre-computed annotation is available via Entrez, and interactive search services accept single protein or nucleotide queries, as well as batch submissions of protein query sequences, utilizing RPS-BLAST to rapidly identify putative matches. CDD incorporates several protein domain and full-length protein model collections, and maintains an active curation effort that aims at providing fine grained classifications for major and well-characterized protein domain families, as supported by available protein three-dimensional (3D) structure and the published literature. To this date, the majority of protein 3D structures are represented by models tracked by CDD, and CDD curators are characterizing novel families that emerge from protein structure determination efforts. C1 [Marchler-Bauer, Aron; Zheng, Chanjuan; Chitsaz, Farideh; Derbyshire, Myra K.; Geer, Lewis Y.; Geer, Renata C.; Gonzales, Noreen R.; Gwadz, Marc; Hurwitz, David I.; Lanczycki, Christopher J.; Lu, Fu; Lu, Shennan; Marchler, Gabriele H.; Song, James S.; Thanki, Narmada; Yamashita, Roxanne A.; Zhang, Dachuan; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Marchler-Bauer, A (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38 A,Room 8N805,8600 Rockville Pike, Bethesda, MD 20894 USA. EM bauer@ncbi.nlm.nih.gov RI Geer, Lewis/H-2714-2014; OI Marchler-Bauer, Aron/0000-0003-1516-0712 FU Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS FX Funding for open access charge: Intramural Research Program of the National Library of Medicine at the National Institutes of Health/DHHS. NR 15 TC 400 Z9 409 U1 3 U2 95 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D348 EP D352 DI 10.1093/nar/gks1243 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300050 PM 23197659 ER PT J AU Nakamura, Y Cochrane, G Karsch-Mizrachi, I AF Nakamura, Yasukazu Cochrane, Guy Karsch-Mizrachi, Ilene CA Int Nucleotide Sequence Database TI The International Nucleotide Sequence Database Collaboration SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ARCHIVE AB The International Nucleotide Sequence Database Collaboration (INSDC; http://www.insdc.org), one of the longest-standing global alliances of biological data archives, captures, preserves and provides comprehensive public domain nucleotide sequence information. Three partners of the INSDC work in cooperation to establish formats for data and metadata and protocols that facilitate reliable data submission to their databases and support continual data exchange around the world. In this article, the INSDC current status and update for the year of 2012 are presented. Among discussed items of international collaboration meeting in 2012, BioSample database and changes in submission are described as topics. C1 [Nakamura, Yasukazu] Res Org Informat & Syst, Natl Inst Genet, DDBJ Ctr, Mishima, Shizuoka 4118510, Japan. [Cochrane, Guy] EMBL European Bioinformat Inst, Cambridge CB10 1SD, England. [Karsch-Mizrachi, Ilene] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Nakamura, Y (reprint author), Res Org Informat & Syst, Natl Inst Genet, DDBJ Ctr, Mishima, Shizuoka 4118510, Japan. EM yn@nig.ac.jp OI Cochrane, Guy/0000-0001-7954-7057; Nakamura, Yasukazu/0000-0002-6782-5715 FU Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); European Molecular Biology Laboratory; Wellcome Trust; European Commission; Biotechnology and Biological Sciences Research Council; National Institutes of Health; National Library of Medicine; MEXT, Japan FX DDBJ by the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT); European Nucleotide Archive by the European Molecular Biology Laboratory, the Wellcome Trust, the FP7 Programme of the European Commission and the Biotechnology and Biological Sciences Research Council; NCBI by the Intramural Research Program of the National Institutes of Health; National Library of Medicine. Funding for open access charge: DDBJ management expense grant from MEXT, Japan. NR 7 TC 67 Z9 68 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D21 EP D24 DI 10.1093/nar/gks1084 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300003 PM 23180798 ER PT J AU Pipes, L Li, S Bozinoski, M Palermo, R Peng, XX Blood, P Kelly, S Weiss, JM Thierry-Mieg, J Thierry-Mieg, D Zumbo, P Chen, RH Schroth, GP Mason, CE Katze, MG AF Pipes, Lenore Li, Sheng Bozinoski, Marjan Palermo, Robert Peng, Xinxia Blood, Phillip Kelly, Sara Weiss, Jeffrey M. Thierry-Mieg, Jean Thierry-Mieg, Danielle Zumbo, Paul Chen, Ronghua Schroth, Gary P. Mason, Christopher E. Katze, Michael G. TI The non-human primate reference transcriptome resource (NHPRTR) for comparative functional genomics SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RNA-SEQ DATA; EXPRESSION LEVELS; GENE; EVOLUTION; SEQUENCE; CHIMPANZEE; INSIGHTS AB RNA-based next-generation sequencing (RNA-Seq) provides a tremendous amount of new information regarding gene and transcript structure, expression and regulation. This is particularly true for non-coding RNAs where whole transcriptome analyses have revealed that the much of the genome is transcribed and that many non-coding transcripts have widespread functionality. However, uniform resources for raw, cleaned and processed RNA-Seq data are sparse for most organisms and this is especially true for non-human primates (NHPs). Here, we describe a large-scale RNA-Seq data and analysis infrastructure, the NHP reference transcriptome resource (http://nhprtr.org); it presently hosts data from12 species of primates, to be expanded to 15 species/subspecies spanning great apes, old world monkeys, new world monkeys and prosimians. Data are collected for each species using pools of RNA from comparable tissues. We provide data access in advance of its deposition at NCBI, as well as browsable tracks of alignments against the human genome using the UCSC genome browser. This resource will continue to host additional RNA-Seq data, alignments and assemblies as they are generated over the coming years and provide a key resource for the annotation of NHP genomes as well as informing primate studies on evolution, reproduction, infection, immunity and pharmacology. C1 [Schroth, Gary P.] Illumina Inc, Hayward, CA 94595 USA. [Pipes, Lenore; Li, Sheng; Bozinoski, Marjan; Zumbo, Paul; Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA. [Pipes, Lenore; Li, Sheng; Bozinoski, Marjan; Zumbo, Paul; Mason, Christopher E.] Weill Cornell Med Coll, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA. [Pipes, Lenore; Mason, Christopher E.] Weill Cornell Med Coll, Triinst Training Program Computat Biol & Med, New York, NY 10065 USA. [Bozinoski, Marjan] Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA. [Palermo, Robert; Peng, Xinxia; Kelly, Sara; Weiss, Jeffrey M.; Katze, Michael G.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Blood, Phillip] Pittsburgh Supercomp Ctr, Pittsburgh, PA 15213 USA. [Thierry-Mieg, Jean; Thierry-Mieg, Danielle] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. [Chen, Ronghua] Merck & Co Inc, Mol Informat, Informat IT, Boston, MA 02115 USA. RP Schroth, GP (reprint author), Illumina Inc, Hayward, CA 94595 USA. EM gschroth@illumina.com; chm2042@med.cornell.edu; honey@u.washington.edu RI Li, Sheng/A-1964-2014; THIERRY-MIEG, Jean/F-1975-2017 OI THIERRY-MIEG, Jean/0000-0002-0396-6789 FU National Institutes of Health Office of Research Infrastructure Programs [R24RR032341]; Washington National Primate Research Center [P51RR000166]; XSEDE super-computing cluster [MCB120116]; STRIDE Center for Systems and Translational Research for Infectious Diseases at the University of Washington; National Center for Biotechnology Information (NCBI); Intramural Research Program of the NIH, National Library of Medicine; NIH; NCRR; [1R01NS076465-02] FX National Institutes of Health Office of Research Infrastructure Programs [R24RR032341]; Washington National Primate Research Center [P51RR000166 to Katze Laboratory]; [1R01NS076465-02 to Mason Laboratory]; XSEDE super-computing cluster [MCB120116]; STRIDE Center for Systems and Translational Research for Infectious Diseases at the University of Washington; National Center for Biotechnology Information (NCBI) [to J.T.-M. and D.T.-M.]; Intramural Research Program of the NIH, National Library of Medicine [partial]. Funding for open access charge: NIH and NCRR grants. NR 26 TC 21 Z9 21 U1 0 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D906 EP D914 DI 10.1093/nar/gks1268 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300128 PM 23203872 ER PT J AU Rubinstein, WS Maglott, DR Lee, JM Kattman, BL Malheiro, AJ Ovetsky, M Hem, V Gorelenkov, V Song, GF Wallin, C Husain, N Chitipiralla, S Katz, KS Hoffman, D Jang, W Johnson, M Karmanov, F Ukrainchik, A Denisenko, M Fomous, C Hudson, K Ostell, JM AF Rubinstein, Wendy S. Maglott, Donna R. Lee, Jennifer M. Kattman, Brandi L. Malheiro, Adriana J. Ovetsky, Michael Hem, Vichet Gorelenkov, Viatcheslav Song, Guangfeng Wallin, Craig Husain, Nora Chitipiralla, Shanmuga Katz, Kenneth S. Hoffman, Douglas Jang, Wonhee Johnson, Mark Karmanov, Fedor Ukrainchik, Alexander Denisenko, Mikhail Fomous, Cathy Hudson, Kathy Ostell, James M. TI The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency SO NUCLEIC ACIDS RESEARCH LA English DT Article AB The National Institutes of Health Genetic Testing Registry (GTR; available online at http://www.ncbi.nlm.nih.gov/gtr/) maintains comprehensive information about testing offered worldwide for disorders with a genetic basis. Information is voluntarily submitted by test providers. The database provides details of each test (e.g. its purpose, target populations, methods, what it measures, analytical validity, clinical validity, clinical utility, ordering information) and laboratory (e.g. location, contact information, certifications and licenses). Each test is assigned a stable identifier of the format GTR000000000, which is versioned when the submitter updates information. Data submitted by test providers are integrated with basic information maintained in National Center for Biotechnology Information's databases and presented on the web and through FTP (ftp.ncbi.nih.gov/pub/GTR/_README.html). C1 [Rubinstein, Wendy S.; Maglott, Donna R.; Lee, Jennifer M.; Kattman, Brandi L.; Malheiro, Adriana J.; Ovetsky, Michael; Hem, Vichet; Gorelenkov, Viatcheslav; Song, Guangfeng; Wallin, Craig; Husain, Nora; Chitipiralla, Shanmuga; Katz, Kenneth S.; Hoffman, Douglas; Jang, Wonhee; Johnson, Mark; Karmanov, Fedor; Ukrainchik, Alexander; Denisenko, Mikhail; Ostell, James M.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Fomous, Cathy] NIH, Off Biotechnol Act, Bethesda, MD 20894 USA. [Hudson, Kathy] NIH, Off Director, Bethesda, MD 20894 USA. RP Rubinstein, WS (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM wendy.rubinstein@nih.gov FU Intramural Research Program of the NIH, National Library of Medicine; NIH Office of the Director FX Intramural Research Program of the NIH, National Library of Medicine and the NIH Office of the Director. Funding for open access charge: Intramural Research Program of the NIH, National Library of Medicine. NR 13 TC 29 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D925 EP D935 DI 10.1093/nar/gks1173 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300131 PM 23193275 ER PT J AU Schneider, VA Chen, HC Clausen, C Meric, PA Zhou, ZG Bouk, N Husain, N Maglott, DR Church, DM AF Schneider, Valerie A. Chen, Hsiu-Chuan Clausen, Cliff Meric, Peter A. Zhou, Zhigang Bouk, Nathan Husain, Nora Maglott, Donna R. Church, Deanna M. TI Clone DB: an integrated NCBI resource for clone-associated data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID KNOCKOUT MOUSE CONSORTIUM; EMBRYONIC STEM-CELLS; FUNCTIONAL GENOMICS; STRUCTURAL VARIATION; GENE-FUNCTION; SEQUENCE; EVOLUTION; TRAP; CHROMOSOMES; WINDOW AB The National Center for Biotechnology Information (NCBI) Clone DB (http://www.ncbi.nlm.nih.gov/clone/) is an integrated resource providing information about and facilitating access to clones, which serve as valuable research reagents in many fields, including genome sequencing and variation analysis. Clone DB represents an expansion and replacement of the former NCBI Clone Registry and has records for genomic and cell-based libraries and clones representing more than 100 different eukaryotic taxa. Records provide details of library construction, associated sequences, map positions and information about resource distribution. Clone DB is indexed in the NCBI Entrez system and can be queried by fields that include organism, clone name, gene name and sequence identifier. Whenever possible, genomic clones are mapped to reference assemblies and their map positions provided in clone records. Clones mapping to specific genomic regions can also be searched for using the NCBI Clone Finder tool, which accepts queries based on sequence coordinates or features such as gene or transcript names. Clone DB makes reports of library, clone and placement data on its FTP site available for download. With Clone DB, users now have available to them a centralized resource that provides them with the tools they will need to make use of these important research reagents. C1 [Schneider, Valerie A.; Chen, Hsiu-Chuan; Clausen, Cliff; Meric, Peter A.; Zhou, Zhigang; Bouk, Nathan; Husain, Nora; Maglott, Donna R.; Church, Deanna M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Schneider, VA (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. EM schneiva@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 26 TC 7 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D1070 EP D1078 DI 10.1093/nar/gks1164 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300152 PM 23193260 ER PT J AU Van Doorslaer, K Tan, QN Xirasagar, S Bandaru, S Gopalan, V Mohamoud, Y Huyen, Y McBride, AA AF Van Doorslaer, Koenraad Tan, Qina Xirasagar, Sandhya Bandaru, Sandya Gopalan, Vivek Mohamoud, Yasmin Huyen, Yentram McBride, Alison A. TI The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID CLASSIFICATION; TYPE-16; TOOL AB The goal of the Papillomavirus Episteme (PaVE) is to provide an integrated resource for the analysis of papillomavirus (PV) genome sequences and related information. The PaVE is a freely accessible, web-based tool (http://pave.niaid.nih.gov) created around a relational database, which enables storage, analysis and exchange of sequence information. From a design perspective, the PaVE adopts an Open Source software approach and stresses the integration and reuse of existing tools. Reference PV genome sequences have been extracted from publicly available databases and reannotated using a custom-created tool. To date, the PaVE contains 241 annotated PV genomes, 2245 genes and regions, 2004 protein sequences and 47 protein structures, which users can explore, analyze or download. The PaVE provides scientists with the data and tools needed to accelerate scientific progress for the study and treatment of diseases caused by PVs. C1 [Van Doorslaer, Koenraad; McBride, Alison A.] NIAID, DNA Tumor Virus Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Tan, Qina; Xirasagar, Sandhya; Bandaru, Sandya; Gopalan, Vivek; Mohamoud, Yasmin; Huyen, Yentram] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD USA. RP McBride, AA (reprint author), NIAID, DNA Tumor Virus Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI Van Doorslaer, Koenraad/0000-0002-2985-0733; McBride, Alison/0000-0001-5607-5157 FU Intramural Research Program [1ZIAAI001071]; Office of Science Management and Operations of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health; NIAID Intramural Research Program [1ZIAAI001071] FX The Intramural Research Program [1ZIAAI001071] and Office of Science Management and Operations of the National Institutes of Allergy and Infectious Diseases, National Institutes of Health. Funding for open access charge: NIAID Intramural Research Program [1ZIAAI001071]. NR 15 TC 53 Z9 53 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D571 EP D578 DI 10.1093/nar/gks984 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300081 PM 23093593 ER PT J AU Varshney, GK Huang, HG Zhang, SY Lu, J Gildea, DE Yang, ZA Wolfsberg, TG Lin, S Burgess, SM AF Varshney, Gaurav K. Huang, Haigen Zhang, Suiyuan Lu, Jing Gildea, Derek E. Yang, Zhongan Wolfsberg, Tyra G. Lin, Shuo Burgess, Shawn M. TI The Zebrafish Insertion Collection (ZInC): a web based, searchable collection of zebrafish mutations generated by DNA insertion SO NUCLEIC ACIDS RESEARCH LA English DT Article ID LARGE GENE LISTS; MUTAGENESIS; GENOME; CLONING; SCREEN AB ZInC (Zebrafish Insertional Collection, http://research.nhgri.nih.gov/ZInC/) is a web-searchable interface of insertional mutants in zebrafish. Over the last two decades, the zebrafish has become a popular model organism for studying vertebrate development as well as for modeling human diseases. To facilitate such studies, we are generating a genome-wide knockout resource that targets every zebrafish protein-coding gene. All mutant fish are freely available to the scientific community through the Zebrafish International Resource Center (ZIRC). To assist researchers in finding mutant and insertion information, we developed a comprehensive database with a web front-end, the ZInC. It can be queried using multiple types of input such as ZFIN (Zebrafish Information Network) IDs, UniGene accession numbers and gene symbols from zebrafish, human and mouse. In the future, ZInC may include data from other insertional mutation projects as well. ZInC cross-references all integration data with the ZFIN (http://zfin.org/). C1 [Varshney, Gaurav K.; Zhang, Suiyuan; Gildea, Derek E.; Wolfsberg, Tyra G.; Burgess, Shawn M.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Huang, Haigen; Lu, Jing; Yang, Zhongan; Lin, Shuo] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. RP Burgess, SM (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM shuolin@ucla.edu; burgess@mail.nih.gov RI Varshney, Gaurav/L-5261-2014; OI Burgess, Shawn/0000-0003-1147-0596; Varshney, Gaurav K./0000-0002-0429-1904 FU National Human Genome Research Institute, National Institutes of Health; NIH [DK084349] FX Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (to S. B. and T. W.) and R01 grant NIH DK084349 (to S. L.). Funding for open access charge: Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health (to S. B. and T. W.) and R01 grant NIH DK084349 (to S.L.). NR 18 TC 14 Z9 14 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 EI 1362-4962 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS D1 BP D861 EP D864 DI 10.1093/nar/gks946 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 062BE UT WOS:000312893300122 PM 23180778 ER PT J AU Girgis, HZ Sheetlin, SL AF Girgis, Hani Z. Sheetlin, Sergey L. TI MsDetector: toward a standard computational tool for DNA microsatellites detection SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TANDEM REPEATS; TRINUCLEOTIDE REPEATS; APPROXIMATE REPEATS; HUMAN-DISEASE; SEQUENCES; IDENTIFICATION; GENOMES; ELEMENT; SEARCH; FINDER AB Microsatellites (MSs) are DNA regions consisting of repeated short motif(s). MSs are linked to several diseases and have important biomedical applications. Thus, researchers have developed several computational tools to detect MSs. However, the currently available tools require adjusting many parameters, or depend on a list of motifs or on a library of known MSs. Therefore, two laboratories analyzing the same sequence with the same computational tool may obtain different results due to the user-adjustable parameters. Recent studies have indicated the need for a standard computational tool for detecting MSs. To this end, we applied machine-learning algorithms to develop a tool called MsDetector. The system is based on a hidden Markov model and a general linear model. The user is not obligated to optimize the parameters of MsDetector. Neither a list of motifs nor a library of known MSs is required. MsDetector is memory-and time-efficient. We applied MsDetector to several species. MsDetector located the majority of MSs found by other widely used tools. In addition, MsDetector identified novel MSs. Furthermore, the system has a very low false-positive rate resulting in a precision of up to 99%. MsDetector is expected to produce consistent results across studies analyzing the same sequence. C1 [Girgis, Hani Z.; Sheetlin, Sergey L.] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20896 USA. RP Sheetlin, SL (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, 9600 Rockville Pike, Bethesda, MD 20896 USA. EM sheetlin@ncbi.nlm.nih.gov FU National Institutes of Health, National Library of Medicine FX Funding for open access charge: The Intramural Research Program of the National Institutes of Health, National Library of Medicine. NR 36 TC 1 Z9 1 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2013 VL 41 IS 1 AR e22 DI 10.1093/nar/gks881 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 061ZW UT WOS:000312889900022 PM 23034809 ER PT J AU Partridge, EE Greenlee, RT Riley, TL Commins, J Ragard, L Xu, JL Buys, SS Prorok, PC Fouad, MN AF Partridge, Edward E. Greenlee, Robert T. Riley, Thomas L. Commins, John Ragard, Lawrence Xu, Jian-Lun Buys, Saundra S. Prorok, Philip C. Fouad, Mona N. TI Assessing the Risk of Ovarian Malignancy in Asymptomatic Women With Abnormal CA 125 and Transvaginal Ultrasound Scans in the Prostate, Lung, Colorectal, and Ovarian Screening Trial SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MULTIVARIATE INDEX ASSAY; PELVIC MASSES; INTERNATIONAL MULTICENTER; PREOPERATIVE DIAGNOSIS; POSTMENOPAUSAL WOMEN; MENOPAUSAL STATUS; RANDOMIZED-TRIAL; ADNEXAL MASS; CANCER; CA-125 AB OBJECTIVE: To estimate the risk of ovarian malignancy among asymptomatic women with abnormal transvaginal ultrasound scans or CA 125 and to provide guidance to physicians managing these women. METHODS: A cohort of women from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial with abnormal ovarian results at the initial (T0) and subsequent (T1+) screens were analyzed to estimate which findings were associated with high risk of ovarian cancer. Cancer risks more than 10% were designated as high and risks of 3% or less were designated as low. RESULTS: For the T0 screen, two high-risk categories were identified: CA 125 of 70 or more with negative transvaginal ultrasound scan (positive predictive value [PPV] 15.9%, CI 14.7-17.7%); and positive for both CA 125 and transvaginal ultrasound scan (PPV 25.0%, CI 23.3-27.3%). For T1+ screens, three high-risk categories were identified: negative transvaginal ultrasound scan with change in CA 125 of 45 or more (PPV 29.0%, CI 28.3-30.3%); increase in size of cyst 6 cm or more with negative CA 125 (PPV 13.3%, CI 10.5-18.0%); and positive for both tests (PPV 42.9%, CI 40.0-46.0%). High-risk criteria for T0 provide a sensitivity of 60%, specificity of 96.2%, PPV of 19.7%, and a negative predictive value (NPV) of 99.3%. T1+ criteria yielded a sensitivity of 85.3%, specificity of 95.6%, PPV of 29.6%, and NPV of 99.7%. CONCLUSIONS: High-risk categories for predicting risk of cancer in women with abnormal CA 125, transvaginal ultrasound scan, or both at initial and subsequent screens have been identified. The large number of women in this study, the 4-year complete follow-up, and small number of invasive cancers in the low-risk categories provide guidance for clinical decisions regarding need for surgery in these women. (Obstet Gynecol 2013;121:25-31) DOI: http://10.1097/AOG.0b013e3182755e14 C1 Univ Alabama Birmingham, Birmingham, AL USA. Marshfield Clin Res Fdn, Marshfield, WI USA. Westat Corp, Informat Management Serv, Rockville, MD USA. NCI, Rockville, MD USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. RP Partridge, EE (reprint author), UAB Comprehens Canc Ctr, 1802 6th Ave S, Birmingham, AL 35294 USA. EM eep3840@uab.edu FU National Cancer Institute; Division of Cancer Prevention of the National Cancer Institute; Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health, Department of Health and Human Services [NIH-NO1-CN-75022, NCI-NO1-CA-75022-70] FX The National Cancer Institute funded the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. This research also was supported by contracts from the Division of Cancer Prevention of the National Cancer Institute and by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics National Cancer Institute, National Institutes of Health, Department of Health and Human Services (NIH-NO1-CN-75022 and NCI-NO1-CA-75022-70). NR 24 TC 7 Z9 7 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2013 VL 121 IS 1 BP 25 EP 31 DI 10.1097/AOG.0b013e3182755e14 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 060LN UT WOS:000312779500005 PM 23262924 ER PT J AU Rossouw, JE Manson, JE Kaunitz, AM Anderson, GL AF Rossouw, Jacques E. Manson, JoAnn E. Kaunitz, Andrew M. Anderson, Garnet L. TI Lessons Learned From the Women's Health Initiative Trials of Menopausal Hormone Therapy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID ESTROGEN PLUS PROGESTIN; CORONARY-HEART-DISEASE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; EQUINE ESTROGEN; RISK; HYSTERECTOMY; BENEFITS AB We re-evaluate the Women's Health Initiative findings and their implications for clinical practice. Menopausal hormone therapy (HT) was effective for relief of vasomotor symptoms, and the risk of coronary heart disease (CHD) tended to be reduced in women close to menopause compared with the increased risk in women more distant from menopause. In recently menopausal women, short-term absolute risks of stroke and venous thromboembolism were small. Estrogen plus progestin therapy, but not estrogen therapy, increased the risk of breast cancer with a suggestion of greater risk when initiated close to the menopause. Menopausal HT increased the risk of CHD in women more than 20 years distant from menopause, particularly in women with vasomotor symptoms. It remains unknown whether the suggestive benefit for CHD in younger women will translate into benefits or harms if menopausal HT is continued into older ages. Based on Women's Health Initiative data, the use of menopausal HT for fewer than 5 years is a reasonable option for the relief of moderate to severe vasomotor symptoms. The risks seen with estrogen plus progestin therapy suggest careful periodic reassessment of the ongoing therapy needs for women taking estrogen plus progestin therapy. The more favorable profile of estrogen therapy allows for individualized management with respect to duration of use when symptoms persist. For both estrogen therapy and estrogen plus progestin therapy, the baseline risk profile of the individual woman needs to be taken into account. Menopausal HT is not suitable for long-term prevention of CHD given risks of stroke, venous thromboembolism, and breast cancer (for estrogen plus progestin therapy) found in both clinical trials and in observational studies. (Obstet Gynecol 2013;121:172-6) DOI: http://10.1097/AOG.0b013e31827a08c8 C1 [Rossouw, Jacques E.; Manson, JoAnn E.; Kaunitz, Andrew M.; Anderson, Garnet L.] NHLBI, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, 6701 Rockledge Dr,Room 9192, Bethesda, MD 20892 USA. EM rossouwj@nih.gov OI Anderson, Garnet/0000-0001-5087-7837 FU Intramural NIH HHS [Z99 HL999999] NR 14 TC 26 Z9 30 U1 0 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JAN PY 2013 VL 121 IS 1 BP 172 EP 176 DI 10.1097/AOG.0b013e31827a08c8 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 060LN UT WOS:000312779500025 PM 23262943 ER PT J AU Leuschen, JN Schuman, SG Winter, KP McCall, MN Wong, WT Chew, EY Hwang, T Srivastava, S Sarin, N Clemons, T Harrington, M Toth, CA AF Leuschen, Jessica N. Schuman, Stefanie G. Winter, Katrina P. McCall, Michelle N. Wong, Wai T. Chew, Emily Y. Hwang, Thomas Srivastava, Sunil Sarin, Neeru Clemons, Traci Harrington, Molly Toth, Cynthia A. TI Spectral-Domain Optical Coherence Tomography Characteristics of Intermediate Age-related Macular Degeneration SO OPHTHALMOLOGY LA English DT Article ID GEOGRAPHIC ATROPHY; VISUAL-ACUITY; CHOROIDAL NEOVASCULARIZATION; FUNDUS AUTOFLUORESCENCE; NATURAL-HISTORY; SEVERITY SCALE; RISK-FACTORS; EYE DISEASE; FOLLOW-UP; SD-OCT AB Purpose: Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. Design: Prospective cross-sectional study. Participants: We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. Methods: Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with >= 1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. Main Outcome Measures: We assessed SD-OCT characteristics at baseline. Results: In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. Conclusions: Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression. C1 [Leuschen, Jessica N.; Schuman, Stefanie G.; Winter, Katrina P.; McCall, Michelle N.; Sarin, Neeru; Toth, Cynthia A.] Duke Eye Ctr, Durham, NC 27710 USA. [Wong, Wai T.; Chew, Emily Y.] NEI, Bethesda, MD 20892 USA. [Hwang, Thomas] Devers Eye Inst, Portland, OR USA. [Srivastava, Sunil] Emory Eye Ctr, Atlanta, GA USA. [Clemons, Traci; Harrington, Molly] EMMES Corp, Rockville, MD USA. RP Toth, CA (reprint author), Duke Eye Ctr, Box 3802,Erwin Rd, Durham, NC 27710 USA. RI Wong, Wai/B-6118-2017 OI Wong, Wai/0000-0003-0681-4016 FU Genentech; Sirion Therapeutics; Bioptigen, Inc; Alcon Laboratories, Inc; Genentech [IST-4400S]; Alcon Laboratories FX The authors have made the following disclosures:; Cynthia A. Toth: Research support-Genentech, Sirion Therapeutics, Bioptigen, Inc, Alcon Laboratories, Inc; potential royalties-Bioptigen, Inc, Alcon Laboratories, Inc.; Duke University has an equity and intellectual property interest in Bioptigen.; This project (ClinicalTrials.gov identifier: NCT00734487, August 13, 2008) was funded in part by Genentech grant (IST-4400S), Bioptigen (equipment), and Alcon Laboratories (unrestricted startup grant). NR 45 TC 28 Z9 28 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2013 VL 120 IS 1 BP 140 EP 150 DI 10.1016/j.ophtha.2012.07.004 PG 11 WC Ophthalmology SC Ophthalmology GA 063PI UT WOS:000313011700021 PM 22968145 ER PT J AU Gregory, AC Kempen, JH Daniel, E Kacmaz, RO Foster, CS Jabs, DA Levy-Clarke, GA Nussenblatt, RB Rosenbaum, JT Suhler, EB Thorne, JE AF Gregory, Anthony C., II Kempen, John H. Daniel, Ebenezer Kacmaz, R. Oktay Foster, C. Stephen Jabs, Douglas A. Levy-Clarke, Grace A. Nussenblatt, Robert B. Rosenbaum, James T. Suhler, Eric B. Thorne, Jennifer E. CA Systemic Immunosuppressive Therapy TI Risk Factors for Loss of Visual Acuity among Patients with Uveitis Associated with Juvenile Idiopathic Arthritis: The Systemic Immunosuppressive Therapy for Eye Diseases Study SO OPHTHALMOLOGY LA English DT Article ID OCULAR INFLAMMATORY DISEASES; RHEUMATOID-ARTHRITIS; OPHTHALMOLOGIC EXAMINATIONS; PEDIATRIC UVEITIS; COMPLICATIONS; CHILDHOOD; OUTCOMES; PROGNOSTICATORS; EPIDEMIOLOGY; PREVALENCE AB Purpose: To describe the incidence of and risk factors for visual acuity (VA) loss and ocular complications in patients with juvenile idiopathic arthritis (JIA)-associated uveitis. Design: Multicenter retrospective cohort study. Participants: A total of 327 patients (596 affected eyes) with JIA-associated uveitis managed at 5 tertiary uveitis clinics in the United States. Methods: Participants were identified from the Systemic Immunosuppressive Therapy for Eye Diseases (SITE) cohort study. Demographic and clinical characteristics were obtained for every eye of every patient at every visit via medical record review by trained expert reviewers. Main Outcome Measures: Loss of VA to 20/50 or to 20/200 or worse thresholds and the development of ocular complications. Results: At presentation, 240 eyes (40.3%) had a VA of <= 20/50, 144 eyes (24.2%) had a VA of <= 20/200, and 359 eyes (60.2%) had at least 1 ocular complication. The incidences of VA loss to the <= 20/50 and <= 20/200 thresholds were 0.18 and 0.09 per eye-year (EY), respectively; the incidence of developing at least 1 new ocular complication over follow-up was 0.15/EY (95% confidence interval [CI], 0.13-0.17). However, among eyes with uveitis that had no complications at presentation, the rate of developing at least 1 ocular complication during follow-up was lower (0.04/EY; 95% CI, 0.02-0.06). Posterior synechiae, active uveitis, and prior intraocular surgery were statistically significantly associated with VA to the <= 20/50 and <= 20/200 thresholds both at presentation and during follow-up. Increasing (time-updated) anterior chamber cell grade was associated with increased rates of visual loss in a dose-dependent fashion. Use of immunosuppressive drugs was associated with a reduced risk of visual loss, particularly for the <= 20/50 outcome (hazard ratio, 0.40; 95% CI, 0.21-0.75; P < 0.01). Conclusions: Ocular complications and vision loss were common in our cohort. Increasing uveitis activity was associated with increased risk of vision loss, and use of immunosuppressive drugs was associated with reduced risk of vision loss, suggesting that control of inflammation and use of immunosuppression may be critical aspects in improving the outcomes of patients with JIA-related uveitis. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2013; 120:186-192 (C) 2013 by the American Academy of Ophthalmology. C1 [Gregory, Anthony C., II; Thorne, Jennifer E.] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, Baltimore, MD 21287 USA. [Kempen, John H.; Daniel, Ebenezer] Univ Penn, Sch Med, Dept Ophthalmol, Perelman Sch Med, Philadelphia, PA 19104 USA. [Kempen, John H.] Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Kacmaz, R. Oktay] Allergan Pharmaceut Inc, Irvine, CA 92715 USA. [Kacmaz, R. Oktay; Foster, C. Stephen] Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. [Foster, C. Stephen] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Jabs, Douglas A.; Thorne, Jennifer E.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Clin Trials, Dept Epidemiol, Baltimore, MD 21287 USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Ophthalmol, New York, NY USA. [Jabs, Douglas A.] Mt Sinai Sch Med, Dept Med, New York, NY USA. [Levy-Clarke, Grace A.; Nussenblatt, Robert B.] NEI, Immunol Lab, Bethesda, MD 20892 USA. [Rosenbaum, James T.; Suhler, Eric B.] Oregon Hlth & Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. [Rosenbaum, James T.] Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. [Suhler, Eric B.] Portland VA Med Ctr, Portland, OR USA. RP Thorne, JE (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Dept Ophthalmol, 600 N Wolfe St,Woods Bldg,Room 476, Baltimore, MD 21287 USA. EM jthorne@jhmi.edu OI Daniel, Ebenezer/0000-0002-2027-2316 FU National Eye Institute, National Institutes of Health, Bethesda, Maryland [ey014943]; Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania; Research to Prevent Blindness Inc, New York, New York; Research to Prevent Blindness; National Eye Institute FX Supported primarily by Grant ey014943 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland (Dr. Kempen). Additional support was provided by the Paul and Evanina Mackall Foundation, Philadelphia, Pennsylvania, and Research to Prevent Blindness Inc, New York, New York. Dr. Kempen is a Research to Prevent Blindness James S. Adams Special Scholar Award recipient. Dr. Thorne is a Research to Prevent Blindness Harrington Special Scholar Award recipient. Drs. Jabs and Rosenbaum are Research to Prevent Blindness Senior Scientific Investigator Award recipients. Dr. Levy-Clarke was previously and Dr. Nussenblatt continues to be supported by intramural funds of the National Eye Institute. NR 39 TC 51 Z9 53 U1 0 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD JAN PY 2013 VL 120 IS 1 BP 186 EP 192 DI 10.1016/j.ophtha.2012.07.052 PG 7 WC Ophthalmology SC Ophthalmology GA 063PI UT WOS:000313011700027 PM 23062650 ER PT J AU Lateef, T Cui, LH Heaton, L Nakamura, EF Ding, JH Ahmed, S Merikangas, KR AF Lateef, Tarannum Cui, Lihong Heaton, Leanne Nakamura, Erin F. Ding, Jinhui Ahmed, Sameer Merikangas, Kathleen R. TI Validation of a Migraine Interview for Children and Adolescents SO PEDIATRICS LA English DT Article DE headache; migraine; interview validation ID TENSION-TYPE HEADACHE; IHS CRITERIA; DIAGNOSTIC-CRITERIA; PEDIATRIC MIGRAINE; NATIONAL SAMPLE; YOUNG-ADULTS; AGREEMENT; PARENT; AGE; CHILDHOOD AB OBJECTIVE: To date there are no structured interviews to ascertain the diagnostic criteria for headache in children. The objective of this study was to assess the validity of the Diagnostic Interview of Headache Syndromes-Child Version (DIHS-C), which was developed at the National Institute of Mental Health for a community-based family study of headache syndromes and comorbid disorders. METHODS: The DIHS-C is a fully structured diagnostic interview composed of an open-ended clinical history, modules with key symptoms for each of the major headache subtypes, and associated impairment, duration, frequency, course, and treatment. This article presents the validation of the interview in a sample of 104 children evaluated as part of a community-based family study of migraine. RESULTS: The sensitivity of interview diagnosis compared with an expert neurologist's diagnosis of migraine was 98%, and the specificity was 61%. Similar levels of sensitivity and specificity were found by gender and age of the children. CONCLUSIONS: The DIHS-C provides a new tool that can enhance the reliability of pediatric diagnoses in both clinical and community settings. Pediatrics 2013;131:e96-e102 C1 [Lateef, Tarannum] Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. [Lateef, Tarannum; Cui, Lihong; Heaton, Leanne; Nakamura, Erin F.; Ahmed, Sameer; Merikangas, Kathleen R.] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA. [Ding, Jinhui] NIA, Div Intramural Res Programs, Bethesda, MD 20892 USA. RP Lateef, T (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave, Washington, DC 20010 USA. EM tlateef@childrensnational.org FU National Institutes of Health (NIH) FX Funded by the National Institutes of Health (NIH). NR 31 TC 3 Z9 3 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2013 VL 131 IS 1 BP E96 EP E102 DI 10.1542/peds.2012-1008 PG 7 WC Pediatrics SC Pediatrics GA 063PO UT WOS:000313012400012 PM 23266928 ER PT J AU White, JG Hess, RA Gahl, WA Introne, W AF White, James G. Hess, Richard A. Gahl, William A. Introne, Wendy TI Rapid ultrastructural detection of success or failure after bone marrow transplantation in the Chediak-Higashi Syndrome SO PLATELETS LA English DT Article DE Chediak-Higashi Syndrome; bone marrow transplantation; ultrastructural techniques ID PLATELETS AB The present study has used electron microscopic techniques to rapidly detect the success or failure of bone marrow transplantation in three patients with the Chediak-Higashi Syndrome (CHS). The most rapid procedure was the whole mount technique to determine the presence or absence of dense bodies, which are inherently electron-opaque, serotonin-containing storage organelles in platelets. Dense bodies were present in normal numbers in platelets from two patients with successful transplantation and absent in thrombocytes from another patient in whom the transplant had failed. C1 [White, James G.] Univ Minnesota, Dept Lab Med Pathol & Pediat, Sch Med, Minneapolis, MN 55455 USA. [Hess, Richard A.; Gahl, William A.] NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Gahl, William A.; Introne, Wendy] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP White, JG (reprint author), Univ Minnesota, Dept Lab Med Pathol & Pediat, Sch Med, MMC 490, Minneapolis, MN 55455 USA. EM White003@umn.edu FU Intramural NIH HHS [ZIA HG000215-10] NR 18 TC 1 Z9 1 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2013 VL 24 IS 1 BP 71 EP 74 DI 10.3109/09537104.2011.654293 PG 4 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 061SW UT WOS:000312869500009 PM 22738378 ER PT J AU Shehata, ML Harouni, AA Skrok, J Basha, TA Boyce, D Lechtzin, N Mathai, SC Girgis, R Osman, NF Lima, JAC Bluemke, DA Hassoun, PM Vogel-Claussen, J AF Shehata, Monda L. Harouni, Ahmed A. Skrok, Jan Basha, Tamer A. Boyce, Danielle Lechtzin, Noah Mathai, Stephen C. Girgis, Reda Osman, Nael F. Lima, Joao A. C. Bluemke, David A. Hassoun, Paul M. Vogel-Claussen, Jens TI Regional and Global Biventricular Function in Pulmonary Arterial Hypertension: A Cardiac MR Imaging Study SO RADIOLOGY LA English DT Article ID RIGHT-VENTRICULAR FUNCTION; MYOCARDIAL-FUNCTION; STRAIN; INDEX; ANATOMY; VOLUME; MASS AB Purpose: To determine whether chronic pulmonary arterial pressure (PAP) elevation affects regional biventricular function and whether regional myocardial function may be reduced in pulmonary arterial hypertension (PAH) patients with preserved global right ventricular (RV) function. Materials and Methods: After informed consent, 35 PAH patients were evaluated with right heart catheterization and cardiac magnetic resonance (MR) imaging and compared with 13 healthy control subjects. Biventricular segmental, section, and mean ventricular peak systolic longitudinal strain (E-LL), as well as left ventricular (LV) circumferential and RV tangential strains were compared between PAH patients and control subjects and correlated with global function and catheterization of the right heart indexes. Spearman rho correlation with Bonferroni correction was used. Multiple linear regression analysis was performed to determine predictors for regional myocardial function. Results: In the RV of PAH patients, longitudinal contractility was reduced at the basal, mid, and apical levels, and tangential contractility was reduced at the midventricular level. Mean RV E-LL positively correlated with mean PAP (r = 0.62, P < .0014) and pulmonary vascular resistance index (PVRI) (r = 0.77, P < .0014). Mean PAP was a predictor of mean RV E-LL (beta = .19, P = .005) in a multiple linear regression analysis. In the LV, reduced LV longitudinal and circumferential contractility were noted at the base. LV anteroseptal E-LL positively correlated with increased mean PAP (r = 0.5, P = .03) and septal eccentricity index (r = 0.5, P = .01). In a subgroup of PAH patients with normal global RV function, significantly reduced RV longitudinal contractility was noted at basal and mid anterior septal insertions, as well as the mid anterior RV wall (P < .05 for all). Conclusion: In PAH patients, reduced biventricular regional function is associated with increased RV afterload (mean PAP and PVRI). Cardiac MR imaging helps identify regional RV dysfunction in PAH patients with normal global RV function. (C) RSNA, 2012 C1 [Shehata, Monda L.; Harouni, Ahmed A.; Skrok, Jan; Basha, Tamer A.; Osman, Nael F.; Vogel-Claussen, Jens] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. [Boyce, Danielle; Lechtzin, Noah; Mathai, Stephen C.; Girgis, Reda; Hassoun, Paul M.] Johns Hopkins Univ, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21287 USA. [Lima, Joao A. C.] Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD 21287 USA. [Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Vogel-Claussen, Jens] Hannover Med Sch, Dept Radiol, D-3000 Hannover, Germany. RP Vogel-Claussen, J (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, 600 N Wolfe St,Nelson Basement MRI 110, Baltimore, MD 21287 USA. EM vogel-claussen.jens@mh-hannover.de OI Bluemke, David/0000-0002-8323-8086 FU National Institutes of Health [1P50 HL084946-01, 1P50HL08946]; National Heart, Lung, and Blood Institute [K23 HL092287]; Synapse; Cystic Fibrosis Foundation; Glead Sciences; Actelion; Bayer; United Therapeutics FX This research was supported by the National Institutes of Health (grants 1P50 HL084946-01 and 1P50HL08946) and by the National Heart, Lung, and Blood Institute (grant K23 HL092287). D. A. B. is an employee of the National Institutes of Health.; M.L.S. No relevant conflicts of interest to disclose. A. A. H. No relevant conflicts of interest to disclose. J.S. No relevant conflicts of interest to disclose. T. A. B. No relevant conflicts of interest to disclose. D. B. No relevant conflicts of interest to disclose. N.L. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received consultancy fee from Synapse, payment for expert testimony from University of Miami, institution received grants or has grants pending from Cystic Fibrosis Foundation, received payment for lectures including service on speakers bureaus from Respironics. Other relationships: none to disclose. S. C. M. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received consultancy fees from Glead Sciences, Actelion, Bayer, and United Therapeutics; institution received unrestricted educational grant from Glead Sciences. Other relationships: none to disclose. R. G. No relevant conflicts of interest to disclose. N.F.O. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: employed by, received royalties and stock or stock options from Diagnosoft. Other relationships: none to disclose. J.A.C.L. No relevant conflicts of interest to disclose. D. A. B. No relevant conflicts of interest to disclose. P. M. H. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received consultany fees from Pfizer and Glead Sciences, institution received grants or has grants pending for PAH database from Actelion and United Therapeutics. Other relationships: none to disclose. J.V. No relevant conflicts of interest to disclose. NR 24 TC 24 Z9 24 U1 0 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2013 VL 266 IS 1 BP 114 EP 122 DI 10.1148/radiol.12111599 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 061JQ UT WOS:000312844700016 PM 23151825 ER PT J AU Weisinger, B Greenstein, D Mattai, A Clasen, L Lalonde, F Feldman, S Miller, R Tossell, JW Vyas, NS Stidd, R David, C Gogtay, N AF Weisinger, Brian Greenstein, Deanna Mattai, Anand Clasen, Liv Lalonde, Francois Feldman, Sara Miller, Rachel Tossell, Julia W. Vyas, Nora S. Stidd, Reva David, Christopher Gogtay, Nitin TI Lack of Gender Influence on Cortical and Subcortical Gray Matter Development in Childhood-Onset Schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; adolescent; sex differences; cortical; subcortical; gray matter; gender; childhood-onset ID FIRST-EPISODE SCHIZOPHRENIA; SEX-DIFFERENCES; BRAIN-DEVELOPMENT; GEOMETRICALLY ACCURATE; HIPPOCAMPAL VOLUMES; AMYGDALA VOLUME; MRI DATA; ADOLESCENCE; 1ST-EPISODE; MORPHOLOGY AB Background: Progressive cortical gray matter (GM) abnormalities are an established feature of schizophrenia and are more pronounced in rare, severe, and treatment refractory childhood-onset schizophrenia (COS) cases. The effect of sex on brain development in schizophrenia is poorly understood and studies to date have produced inconsistent results. >Methods: Using the largest to date longitudinal sample of COS cases (n = 104, scans = 249, Male/Female [M/F] = 57/47), we compared COS sex differences with sex differences in a sample of matched typically developing children (n = 104, scans = 244, M/F = 57/47), to determine whether or not sex had differential effects on cortical and subcortical brain development in COS. Results: Our results showed no significant differential sex effects in COS for either GM cortical thickness or subcortical volume development (sex x diagnosis x age interaction; false discovery rate q = 0.05). Conclusion: Sex appears to play a similar role in cortical and subcortical GM development in COS as it does in normally developing children. C1 [Weisinger, Brian; Greenstein, Deanna; Mattai, Anand; Clasen, Liv; Lalonde, Francois; Feldman, Sara; Miller, Rachel; Tossell, Julia W.; Vyas, Nora S.; Stidd, Reva; David, Christopher; Gogtay, Nitin] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Weisinger, B (reprint author), NIMH, Child Psychiat Branch, 10-3N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM brian.weisinger@nih.gov FU National Institutes of Mental Health FX The intramural program of the National Institutes of Mental Health supported this work. NR 65 TC 5 Z9 5 U1 2 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD JAN PY 2013 VL 39 IS 1 BP 52 EP 58 DI 10.1093/schbul/sbr049 PG 7 WC Psychiatry SC Psychiatry GA 061WQ UT WOS:000312881300009 PM 21613381 ER PT J AU Checkley, MA Mitchell, JA Eizenstat, LD Lockett, SJ Garfinkel, DJ AF Checkley, Mary Ann Mitchell, Jessica A. Eizenstat, Linda D. Lockett, Stephen J. Garfinkel, David J. TI Ty1 Gag Enhances the Stability and Nuclear Export of Ty1 mRNA SO TRAFFIC LA English DT Article DE Gag; mRNA; nuclear export; retrotransposon; Saccharomyces; Ty1 ID ROUS-SARCOMA-VIRUS; SACCHAROMYCES-CEREVISIAE; LOCALIZATION SIGNAL; YEAST NUCLEUS; VIRAL-RNA; PROTEIN; RETROTRANSPOSITION; DOMAIN; TRANSPOSITION; PARTICLES AB Retrotransposon and retroviral RNA delivery to particle assembly sites is essential for their replication. mRNA and Gag from the Ty1 retrotransposon colocalize in cytoplasmic foci, which are required for transposition and may be the sites for virus-like particle (VLP) assembly. To determine which Ty1 components are required to form mRNA/Gag foci, localization studies were performed in a Ty1-less strain expressing galactose-inducible Ty1 plasmids (pGTy1) containing mutations in GAG or POL. Ty1 mRNA/Gag foci remained unaltered in mutants defective in Ty1 protease (PR) or deleted for POL. However, Ty1 mRNA containing a frameshift mutation (Ty1fs) that prevents the synthesis of all proteins accumulated in the nucleus. Ty1fs RNA showed a decrease in stability that was mediated by the cytoplasmic exosome, nonsense-mediated decay (NMD) and the processing body. Localization of Ty1fs RNA remained unchanged in an nmd2 Delta mutant. When Gag and Ty1fs mRNA were expressed independently, Gag provided in trans increased Ty1fs RNA level and restored localization of Ty1fs RNA in cytoplasmic foci. Endogenously expressed Gag also localized to the nuclear periphery independent of RNA export. These results suggest that Gag is required for Ty1 mRNA stability, efficient nuclear export and localization into cytoplasmic foci. C1 [Checkley, Mary Ann; Garfinkel, David J.] Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. [Mitchell, Jessica A.; Eizenstat, Linda D.; Garfinkel, David J.] Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. [Lockett, Stephen J.] SAIC Frederick Inc, Adv Technol Program, Frederick, MD 21702 USA. RP Garfinkel, DJ (reprint author), Frederick Natl Lab Canc Res, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. EM djgarf@bmb.uga.edu OI Garfinkel, David/0000-0001-6234-2426 FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; University of Georgia Research Foundation; NIH [GM095622]; National Cancer Institute, National Institutes of Health [HHSN2612008000001E]; National Science Foundation [1011RH25213] FX We thank Francisco Malagon and Agniva Saha for helpful discussions, Jeffrey Strathern for sharing laboratory resources, Benjamin Luttge for critical review of the manuscript and Kimberley Peifley, De Chen and the UGA Coverdell Microscopy Center for technical assistance with the confocal microscopes. This work is supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research, the University of Georgia Research Foundation, and NIH grant GM095622 awarded to D.J.G. This work is also funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract HHSN2612008000001E. J.A.M. is supported by the National Science Foundation Graduate Research Fellowship 1011RH25213. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products or organizations does not imply endorsement by the U. S. government. NR 72 TC 9 Z9 9 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-9219 J9 TRAFFIC JI Traffic PD JAN PY 2013 VL 14 IS 1 BP 57 EP 69 DI 10.1111/tra.12013 PG 13 WC Cell Biology SC Cell Biology GA 065DS UT WOS:000313128800007 PM 22998189 ER PT J AU Koonin, EV Csuros, M Rogozin, IB AF Koonin, Eugene V. Csuros, Miklos Rogozin, Igor B. TI Whence genes in pieces: reconstruction of the exon-intron gene structures of the last eukaryotic common ancestor and other ancestral eukaryotes SO WILEY INTERDISCIPLINARY REVIEWS-RNA LA English DT Review ID RIBOSOMAL-PROTEIN GENES; SPLICEOSOMAL INTRONS; EVOLUTIONARY DYNAMICS; MOLECULAR EVOLUTION; PLANT PARASITISM; U12-TYPE INTRONS; GIARDIA-LAMBLIA; SNRNP PROTEIN; RICH GENES; ORIGIN AB In eukaryotes, protein-coding sequences are interrupted by non-coding sequences known as introns. During mRNA maturation, introns are excised by the spliceosome and the coding regions, exons, are spliced to form the mature coding region. The intron densities widely differ between eukaryotic lineages, from 6 to 7 introns per kb of coding sequence in vertebrates, some invertebrates and green plants, to only a few introns across the entire genome in many unicellular eukaryotes. Evolutionary reconstructions using maximum likelihood methods suggest intron-rich ancestors for each major group of eukaryotes. For the last common ancestor of animals, the highest intron density of all extant and extinct eukaryotes was inferred, at 120130% of the human intron density. Furthermore, an intron density within 5374% of the human values was inferred for the last eukaryotic common ancestor. Accordingly, evolution of eukaryotic genes in all lines of descent involved primarily intron loss, with substantial gain only at the bases of several branches including plants and animals. These conclusions have substantial biological implications indicating that the common ancestor of all modern eukaryotes was a complex organism with a gene architecture resembling those in multicellular organisms. Alternative splicing most likely initially appeared as an inevitable result of splicing errors and only later was employed to generate structural and functional diversification of proteins. WIREs RNA 2013, 4:93105. doi: 10.1002/wrna.1143 For further resources related to this article, please visit the WIREs website. This article is a U.S. Government work, and as such, is in the public domain in the United States of America. C1 [Koonin, Eugene V.; Rogozin, Igor B.] NIH, Natl Ctr Biotechnol Informat, NLM, Bethesda, MD 20892 USA. [Csuros, Miklos] Univ Montreal, Dept Comp Sci & Operat Res, Montreal, PQ, Canada. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, NLM, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 102 TC 7 Z9 7 U1 0 U2 38 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1757-7004 J9 WIRES RNA JI Wiley Interdiscip. Rev.-RNA PD JAN-FEB PY 2013 VL 4 IS 1 BP 93 EP 105 DI 10.1002/wrna.1143 PG 13 WC Cell Biology SC Cell Biology GA 059WI UT WOS:000312735800007 PM 23139082 ER PT J AU Li, XL AF Li, Xiaoling TI SIRT1 and energy metabolism SO ACTA BIOCHIMICA ET BIOPHYSICA SINICA LA English DT Review DE SIRT1; energy metabolism; aging; nutrients; metabolic sensor ID PROTEIN DEACETYLASE ACTIVITY; PANCREATIC BETA-CELLS; DIET-INDUCED OBESITY; STIMULATED INSULIN-SECRETION; SMALL-MOLECULE ACTIVATORS; NAD(+) SALVAGE PATHWAY; CALORIE RESTRICTION; CIRCADIAN CLOCK; PPAR-GAMMA; NICOTINAMIDE PHOSPHORIBOSYLTRANSFERASE AB Sirtuin 1 (SIRT1) is the most conserved mammalian NAD-dependent protein deacetylase that has emerged as a key metabolic sensor in various metabolic tissues. In response to different environmental stimuli, SIRT1 directly links the cellular metabolic status to the chromatin structure and the regulation of gene expression, thereby modulating a variety of cellular processes such as energy metabolism and stress response. Recent studies have shown that SIRT1 controls both glucose and lipid metabolism in the liver, promotes fat mobilization and stimulates brown remodeling of the white fat in white adipose tissue, controls insulin secretion in the pancreas, senses nutrient availability in the hypothalamus, influences obesity-induced inflammation in macrophages, and modulates the activity of circadian clock in metabolic tissues. This review focuses on the role of SIRT1 in regulating energy metabolism at different metabolic tissues. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Li, XL (reprint author), NIEHS, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Lix3@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences [Z01 ES102205] FX The work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences to X.L. (Z01 ES102205). NR 136 TC 53 Z9 57 U1 1 U2 59 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1672-9145 EI 1745-7270 J9 ACTA BIOCH BIOPH SIN JI Acta Biochim. Biophys. Sin. PD JAN PY 2013 VL 45 IS 1 SI SI BP 51 EP 60 DI 10.1093/abbs/gms108 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 058NG UT WOS:000312640100008 PM 23257294 ER PT J AU Kristinsson, SY Eloranta, S Dickman, PW Andersson, TML Turesson, I Landgren, O Bjorkholm, M AF Kristinsson, Sigurdur Y. Eloranta, Sandra Dickman, Paul W. Andersson, Therese M-L. Turesson, Ingemar Landgren, Ola Bjorkholm, Magnus TI Patterns of survival in lymphoplasmacytic lymphoma/waldenstrom macroglobulinemia: A population-based study of 1,555 patients diagnosed in Sweden from 1980 to 2005 SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID STEM-CELL TRANSPLANTATION; WALDENSTROMS MACROGLOBULINEMIA; PROGNOSTIC-FACTORS; SCORING SYSTEM; PHASE-II; FLUDARABINE; BORTEZOMIB; RITUXIMAB; LYMPHOMA; RISK AB Clinical management of lymphoplasmacytic lymphoma (LPL)/Waldenstrom macroglobulinemia (WM) has changed considerably over recent years, reflected in the use of new therapeutic agents (purine analogs, monoclonal antibodies, thalidomide- and bortezomib-based therapies). No population-based studies and few randomized trials have been performed to assess survival in newly diagnosed LPL/WM. We performed a large population-based study in Sweden including 1,555 LPL/WM patients diagnosed from 1980 to 2005. Relative survival ratios (RSRs) and excess mortality rate ratios (EMRR) were computed as measures of survival. Survival of LPL/WM patients has improved significantly (P = 0.007) over time with 5-year RSR = 0.57 (95% confidence interval [CI] 0.460.68), 0.65 (0.570.73), 0.74 (0.680.80), 0.72 (0.660.77), and 0.78 (0.710.85) for patients diagnosed during the calendar periods 19801985, 19861990, 19911995, 19962000, and 20012005, respectively. Improvement in 1- and 5-year relative survival was found in all age groups and for LPL and WM separately. Patients with WM had lower excess mortality compared to LPL (EMRR = 0.38; 95% CI 0.300.48). Older age at diagnosis was associated with a poorer survival (P < 0.001). Taken together, we found a significant improvement in survival in LPL/WM over time. Despite this progress, new effective agents with a more favourable toxicity profile are needed to further improve survival in LPL/WM, especially in the elderly. Am. J. Hematol. 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Kristinsson, Sigurdur Y.; Landgren, Ola; Bjorkholm, Magnus] Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. [Kristinsson, Sigurdur Y.] Univ Iceland, Fac Med, Reykjavik, Iceland. [Kristinsson, Sigurdur Y.] Landspitali Natl Univ Hosp, Dept Hematol, Reykjavik, Iceland. [Eloranta, Sandra; Dickman, Paul W.; Andersson, Therese M-L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Turesson, Ingemar] Skane Univ Hosp, Dept Hematol, Malmo, Sweden. [Landgren, Ola] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kristinsson, SY (reprint author), Karolinska Univ Hosp Solna, Div Hematol, Dept Med, SE-17176 Stockholm, Sweden. EM sigurdur.kristinsson@ki.se RI Dickman, Paul/B-4572-2013; Kristinsson, Sigurdur /M-2910-2015; Andersson, Therese/E-7107-2016 OI Dickman, Paul/0000-0002-5788-3380; Kristinsson, Sigurdur /0000-0002-4964-7476; Andersson, Therese/0000-0001-8644-9041 FU Stockholm County Council; Karolinska Institutet; Cancer Society in Stockholm; Intramural Research Program of the NIH, NCI FX This research was supported by grants from the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institutet, the Cancer Society in Stockholm, and the Intramural Research Program of the NIH, NCI. The authors thank Ms. Shiva Ayobi, The National Board of Health and Welfare, Stockholm, Sweden; Ms. Susanne Dahllof, Statistics Sweden, Orebro, Sweden; and Ms. Emily Steplowski, Information Management Services, Silver Spring, MD, for important efforts in the development of this database. NR 38 TC 19 Z9 19 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2013 VL 88 IS 1 BP 60 EP 65 DI 10.1002/ajh.23351 PG 6 WC Hematology SC Hematology GA 057BJ UT WOS:000312536500011 PM 23165980 ER PT J AU Schrack, JA Simonsick, EM Ferrucci, L AF Schrack, Jennifer A. Simonsick, Eleanor M. Ferrucci, Luigi TI The Relationship of the Energetic Cost of Slow Walking and Peak Energy Expenditure to Gait Speed in Mid-to-Late Life SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Energy Expenditure; Walking Efficiency; Usual Gait Speed; Physical Function ID HEALTHY OLDER-ADULTS; FUNCTIONAL PERFORMANCE; OXYGEN-UPTAKE; AGE; INDEPENDENCE; EFFICIENCY; ATTITUDES; TREADMILL; MOBILITY; FRAILTY AB Schrack JA, Simonsick EM, Ferrucci L: The relationship of the energetic cost of slow walking and peak energy expenditure to gait speed in mid-to-late life. Am J Phys Med Rehabil 2013;92:28-35. Objective: Peak energy expenditure is highly correlated with usual gait speed; however, it is unknown whether the energetic cost of walking is also an important contributor to usual gait speed when considered as a component of peak walking capacity. Design: The energetic cost of 5 mins of slow treadmill walking (0.67 m/sec), peak overground walking energy expenditure, and usual gait speed over 6 m were assessed cross-sectionally in 405 adults aged 33 to 94 yrs in the Baltimore Longitudinal Study of Aging. Results: Mean (SD) energy expenditures during slow and peak sustained walking were 8.9 (1.4) and 18.38 (4.8) ml kg(-1) min(-1), respectively. Overall, the energetic cost of slow walking as a percentage of peak walking energy expenditure was strongly associated with usual gait speed (P < 0.001); however in stratified analyses, this association was maintained only in those with peak walking capacity below 18.3 ml kg(-1) min(-1) (P = 0.04), the threshold associated with independent living. Conclusions: In older persons with substantially reduced peak walking capacity, the energetic cost of walking is associated with gait speed, particularly when peak walking capacity nears the minimum level considered necessary for independent living. Thus, optimal habilitation in older frail persons may benefit from both improving fitness and reducing the energetic cost of walking. C1 [Schrack, Jennifer A.; Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21225 USA. [Simonsick, Eleanor M.] Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. RP Schrack, JA (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA. FU Intramural Research Program of the National Institutes of Health, National Institute on Aging FX Supported by the Intramural Research Program of the National Institutes of Health, National Institute on Aging. Data for these analyses were obtained from the Baltimore Longitudinal Study of Aging, a study performed by the National Institute on Aging. NR 38 TC 9 Z9 9 U1 1 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 EI 1537-7385 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2013 VL 92 IS 1 BP 28 EP 35 DI 10.1097/PHM.0b013e3182644165 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 057DO UT WOS:000312542500003 PM 22854908 ER PT J AU Sanz-Ortega, J Vocke, C Stratton, P Linehan, WM Merino, MJ AF Sanz-Ortega, Julian Vocke, Cathy Stratton, Pamela Linehan, William Marston Merino, Maria J. TI Morphologic and Molecular Characteristics of Uterine Leiomyomas in Hereditary Leiomyomatosis and Renal Cancer (HLRCC) Syndrome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE familial renal cancer syndrome; fumarate hydratase mutation; HLRCC; uterine leiomyoma ID FUMARATE HYDRATASE MUTATIONS; CELL-CANCER; CUTANEOUS LEIOMYOMATOSIS; FH; FAMILIES; TUMORS; FIBROIDS; SPECTRUM; KIDNEY; GENE AB Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a hereditary cancer syndrome in which affected individuals are predisposed to the development of multiple leiomyomas of the skin and uterus and aggressive forms of kidney cancer. Affected individuals harbor a germline heterozygous loss-of-function mutation of the fumarate hydratase (FH) gene. Uterine leiomyomas are present in up to 77% of women with this syndrome. Previous studies have shown that inactivation of the FH gene is unusual for nonsyndromic leiomyomas. Therefore, it might be possible to distinguish 2 genetic groups of smooth muscle tumors: the most common group of sporadic uterine leiomyomas without FH gene inactivation and the more unusual group of HLRCC leiomyomas in patients who harbor a germline mutation of FH, although the exact prevalence of hereditary HLRCC is unknown. We reviewed the clinical, morphologic, and genotypic features of uterine leiomyomas in 19 HLRCC patients with FH germline mutations. Patients with HLRCC syndrome were younger in age compared with those with regular leiomyomata. DNA was extracted by microdissection, and analysis of loss of heterozygosity (LOH) at 1q43 was performed. Uterine leiomyomas in HLRCC have young age of onset and are multiple, with size ranging from 1 to 8 cm. Histopathologically, HLRCC leiomyomas frequently had increased cellularity, multinucleated cells, and atypia. All cases showed tumor nuclei with large orangeophilic nucleoli surrounded by a perinucleolar halo similar to the changes found in HLRCC. Occasional mitoses were found in 3 cases; however, the tumors did not fulfill the criteria for malignancy. Our study also showed that LOH at 1q43 was frequent in HLRCC leiomyomas (8/10 cases), similarly to what has been previously found in renal cell carcinomas from HLRCC patients. LOH is considered to be the second hit that inactivates the FH gene. We conclude that uterine leiomyomas associated with HLRCC syndrome have characteristic morphologic features. Both, uterine leiomyomas and renal cell carcinoma share some morphologic nuclear changes and genotypic features in HLRCC patients. The specific morphologic features of the uterine leiomyomas that we describe may help in the identification of patients who may be part of the hereditary syndrome. C1 [Vocke, Cathy; Linehan, William Marston; Merino, Maria J.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, NIH, Bethesda, MD USA. RP Merino, MJ (reprint author), NCI, Urol Oncol Branch, 9000 Rockville Pike Bldg 10,Rm 2B44, Bethesda, MD 20892 USA. EM mjmerino@mail.nih.gov RI Sanz, Julian/G-5276-2013 FU Intramural NIH HHS [Z01 BC010696-03] NR 22 TC 27 Z9 29 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2013 VL 37 IS 1 BP 74 EP 80 DI 10.1097/PAS.0b013e31825ec16f PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 056KC UT WOS:000312486700009 PM 23211287 ER PT J AU Lasota, J Wang, ZF Kim, SY Helman, L Miettinen, M AF Lasota, Jerzy Wang, Zengfeng Kim, Su Young Helman, Lee Miettinen, Markku TI Expression of the Receptor for Type I Insulin-like Growth Factor (IGF1R) in Gastrointestinal Stromal Tumors An Immunohistochemical Study of 1078 Cases With Diagnostic and Therapeutic Implications SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastrointestinal stromal tumor; insulin-like growth factor 1 receptor; IGF1R; GIST; immunohistochemistry; succinate dehydrogenase; pediatric GIST ID CARNEY-STRATAKIS-SYNDROME; SUCCINATE-DEHYDROGENASE; THERAPEUTIC TARGET; MOLECULAR-GENETICS; PDGFRA MUTATIONS; SARCOMAS; CANCER; TRIAD; KIT; INHIBITORS AB A majority of gastrointestinal stromal tumors (GISTs) carry gain-of-function KIT or platelet-derived growth factor receptor a (PDGFRA) mutations. However, no mutational activation of KIT or PDGFRA has been identified in pediatric gastric GISTs, neurofibromatosis-1-associated GISTs, and a small subset of sporadic GISTs in adults [so-called wild-type (WT) GISTs]. Recently, pediatric gastric GISTs and some adult WT gastric GISTs have been found to have losses of the succinate dehydrogenase (SDH) complex, a Krebs cycle/electron transport chain interface protein, as seen by immunohistochemical loss of SDH subunit B (SDHB) expression. Moreover, recently, expression of the receptor for type I insulin-like growth factor (IGF1R) has been detected in pediatric and WT GISTs, although only a small number of cases have been analyzed. In this study, IGF1R expression was examined immunohistochemically in 1078 well-characterized GISTs representing different clinicogenetic categories and in 103 non-GIST gastrointestinal tumors. IGF1R expression was detected in 71/80 of SDH-deficient GISTs (SDHB-negative GISTs) but only in 9/625 (1%) of the SDHB-positive gastric GISTs. The latter often carried KIT or PDGFRA mutations and generally occurred in older patients. None of the 373 intestinal GISTs was IGF1R positive, whereas many primary intestinal sarcomas, including clear cell sarcomas, leiomyosarcomas, and undifferentiated sarcomas, were IGF1R positive. The consistent lack of IGF1R expression in intestinal GISTs should be considered an additional immunohistochemical marker in the differential diagnosis between GISTs and non-GIST sarcomas. Because inhibition of IGF1R signaling might become a therapeutic target in GISTs, screening for IGF1R expression may become important in the near future. C1 [Lasota, Jerzy] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Kim, Su Young; Helman, Lee] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Lasota, J (reprint author), NCI, Pathol Lab, NIH, 10 Ctr Dr,Room B1B47, Bethesda, MD 20892 USA. EM jerzy.lasota@nih.gov FU NIH/NCI Intramural Research Program FX Supported by the NIH/NCI Intramural Research Program. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article. NR 30 TC 29 Z9 30 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2013 VL 37 IS 1 BP 114 EP 119 DI 10.1097/PAS.0b013e3182613c86 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 056KC UT WOS:000312486700014 PM 22892600 ER PT J AU Benveniste, H Volkow, ND AF Benveniste, Helene Volkow, Nora D. TI Dopamine-enhancing Medications to Accelerate Emergence from General Anesthesia SO ANESTHESIOLOGY LA English DT Editorial Material ID TRAUMATIC BRAIN-INJURY; NEURONS; WAKEFULNESS; SKF-38393 C1 [Benveniste, Helene] SUNY Stony Brook, Dept Anesthesiol, Hlth Sci Ctr, Stony Brook, NY 11794 USA. [Volkow, Nora D.] NIDA, Bethesda, MD 20892 USA. RP Benveniste, H (reprint author), SUNY Stony Brook, Dept Anesthesiol, Hlth Sci Ctr, Stony Brook, NY 11794 USA. EM helene.benveniste@sbumed.org NR 12 TC 2 Z9 3 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JAN PY 2013 VL 118 IS 1 BP 5 EP 6 DI 10.1097/ALN.0b013e318278c8cd PG 2 WC Anesthesiology SC Anesthesiology GA 057BM UT WOS:000312536800002 PM 23208519 ER PT J AU Gore, AV Pham, V Butler, M Castranova, D Weinstein, BM AF Gore, Aniket, V Pham Van Butler, Matthew Castranova, Daniel Weinstein, Brant M. TI Epigenetic control of Hematopoietic Stem Cell development SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Gore, Aniket, V; Pham Van; Butler, Matthew; Castranova, Daniel; Weinstein, Brant M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 245 EP 245 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800022 ER PT J AU James, JM Nalbandian, A Mukoyama, Y AF James, Jennifer M. Nalbandian, Ani Mukoyama, Yosuke TI TGF beta-signaling regulates early lymphangio-genesis SO ANGIOGENESIS LA English DT Meeting Abstract C1 [James, Jennifer M.; Nalbandian, Ani; Mukoyama, Yosuke] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 248 EP 249 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800035 ER PT J AU Monzo, K Weinstein, BM AF Monzo, Kathryn Weinstein, Brant M. TI Vascular-specific translational profiling in zebrafish SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Monzo, Kathryn; Weinstein, Brant M.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 252 EP 252 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800048 ER PT J AU Onitsuka, I Nam, J Hatch, J Uchida, Y Mukoyama, Y AF Onitsuka, Izumi Nam, Joseph Hatch, John Uchida, Yutaka Mukoyama, Yosuke TI Coronary veins guide distal sympathetic axon projection via local secretion of NGF by vascular smooth muscle cells in the developing heart SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Onitsuka, Izumi; Nam, Joseph; Hatch, John; Uchida, Yutaka; Mukoyama, Yosuke] NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 257 EP 257 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800068 ER PT J AU Stratman, AN Pan, WJ Pham, VN Mikelis, CM Gutkind, JS Davis, GE Weinstein, BM AF Stratman, Amber N. Pan Weijun Pham, Van N. Mikelis, Constantionos M. Gutkind, J. Silvio Davis, George E. Weinstein, Brant M. TI CDP-diacylglycerol synthetase-controlled phosphoinositide availability limits VEGFA signaling and vascular morphogenesis SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Stratman, Amber N.; Pan Weijun; Pham, Van N.; Mikelis, Constantionos M.; Gutkind, J. Silvio; Weinstein, Brant M.] NIH, Bethesda, MD 20892 USA. [Davis, George E.] Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 257 EP 257 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800069 ER PT J AU Yu, JXA Weinstein, BM AF Yu Jianxin A Weinstein, Brant M. TI Single cell analysis of endothelial cell morphogenesis during vascular development SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Yu Jianxin A; Weinstein, Brant M.] NICHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 259 EP 259 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800076 ER PT J AU Swift, MR Weinstein, B AF Swift, Matthew R. Weinstein, Brant TI Upstream Regulators of COUP-TFII mediate vein identity SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Swift, Matthew R.; Weinstein, Brant] NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 262 EP 262 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800086 ER PT J AU St Hilaire, C Kyaw, MT Boehm, M AF St Hilaire, Cynthia Kyaw, Maung-Tin Boehm, Manfred TI Modulation of IGF2-mediated PI3K/MEK signaling is implicated in the vascular calcification of a rare monogenetic disease SO ANGIOGENESIS LA English DT Meeting Abstract C1 [St Hilaire, Cynthia; Kyaw, Maung-Tin; Boehm, Manfred] NHLBI, Bethesda, MD 20892 USA. RI St. Hilaire, Cynthia/I-4713-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 264 EP 264 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800093 ER PT J AU Xie, ZH Terai, K Iwaki, S Dudek, AZ Druey, KM AF Xie Zhihui Terai, Kaoru Iwaki, Shoko Dudek, Arkadiusz Z. Druey, Kirk M. TI Endothelial ETA expression in SCLS SO ANGIOGENESIS LA English DT Meeting Abstract C1 [Xie Zhihui; Iwaki, Shoko; Druey, Kirk M.] NIH, Bethesda, MD 20892 USA. [Terai, Kaoru; Dudek, Arkadiusz Z.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0969-6970 J9 ANGIOGENESIS JI Angiogenesis PD JAN PY 2013 VL 16 IS 1 BP 274 EP 274 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 058UA UT WOS:000312658800132 ER PT J AU Kim, JH Yamaori, S Tanabe, T Johnson, CH Krausz, KW Kato, S Gonzalez, FJ AF Kim, Jung-Hwan Yamaori, Satoshi Tanabe, Tomotaka Johnson, Caroline H. Krausz, Kristopher W. Kato, Shigeaki Gonzalez, Frank J. TI Implication of intestinal VDR deficiency in inflammatory bowel disease SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE Vitamin D receptor (VDR); Inflammatory bowel disease (IBD); Bile acid ID VITAMIN-D-RECEPTOR; ULCERATIVE-COLITIS; INNATE IMMUNITY; CROHNS-DISEASE; EXPRESSION; TAURINE; GENE; MICE; METABOLOMICS; RATS AB Background: To investigate the function of the intestinal Vdr gene in inflammatory bowel disease (IBD), in conjunction with the discovery of possible metabolic markers for IBD using intestine-specific Vdr knockout mice. Methods: Vdr(Delta IEpC) mice were generated, phenotyped and treated with a time-course of 3% dextran sulfate sodium (DSS) to induce colitis. Colitis was diagnosed by evaluating clinical symptoms and intestinal histopathology. Gene expression analysis was carried out. In addition, metabolic markers of IBD were explored by metabolomics. Results: Vdr(Delta IEpC) mice showed abnormal body size, colon structures and feces color. Calcium, collagen, and intestinal proliferation-related gene expression were all decreased, and serum alkaline phosphatase was highly increased. In the acute model which was treated with 3% DSS for six days, Vdr(Delta IEpC) mice showed a high score of IBD symptoms; enlarged mucosal layer and damaged muscularis layer. In the recovery experiment model, where mice were treated with 3% DSS for four days and water for three days. Vdr(Delta IEpC) mice showed a high score of IBD symptoms: severe damage of mucosal layer and increased expression of genes encoding proinflammatory cytokines. Feces metabolomics revealed decreased concentrations of taurine, taurocholic acid, taurodeoxycholic acid and cholic acid in Vdr(Delta IEpC) mice. Conclusions: Disruption of the intestinal Vdr gene showed phenotypical changes that may exacerbate IBD. These results suggest that VDR may play an important role in IBD. General significance VDR function has been implicated in IBD. This is of value for understanding the etiology of IBD and for development of diagnostic biomarkers for IBD. Published by Elsevier B.V. C1 [Kim, Jung-Hwan; Yamaori, Satoshi; Tanabe, Tomotaka; Johnson, Caroline H.; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kato, Shigeaki] Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo, Japan. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gonzalef@mail.nih.gov FU National Cancer Institute FX This work is supported by the National Cancer Institute Intramural Research Program. NR 43 TC 13 Z9 13 U1 1 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD JAN PY 2013 VL 1830 IS 1 BP 2118 EP 2128 DI 10.1016/j.bbagen.2012.09.020 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 056EE UT WOS:000312470400002 PM 23041070 ER PT J AU Adler, N Pantell, MS O'Donovan, A Blackburn, E Cawthon, R Koster, A Opresko, P Newman, A Harris, TB Epel, E AF Adler, Nancy Pantell, Matthew S. O'Donovan, Aoife Blackburn, Elizabeth Cawthon, Richard Koster, Annemarie Opresko, Patricia Newman, Anne Harris, Tamara B. Epel, Elissa TI Educational attainment and late life telomere length in the Health, Aging and Body Composition Study SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Socioeconomic status; Education; Telomere length; Race; Health disparities ID UNITED-STATES; SOCIOECONOMIC-STATUS; MORTALITY; DISPARITIES; STRESS; BLOOD; AGE; RACE/ETHNICITY; ASSOCIATION; EXPECTANCY AB Morbidity and mortality are greater among socially disadvantaged racial/ethnic groups and those of lower socioeconomic status (SES). Greater chronic stress exposure in disadvantaged groups may contribute to this by accelerating cellular aging, indexed by shorter age-adjusted telomere length. While studies consistently relate shorter leukocyte telomere length (LTL) to stress, the few studies, mostly from the UK, examining associations of LTL with SES have been mixed. The current study examined associations between educational attainment and LTL among 2599 high-functioning black and white adults age 70-79 from the Health, Aging and Body Composition Study. Multiple regression analyses tested associations of race/ethnicity, educational attainment and income with LTL, adjusting for potential confounders. Those with only a high school education had significantly shorter mean LTL (4806 basepairs) than those with post-high school education (4926 basepairs; B = 125, SE = 47.6, p =.009). A significant interaction of race and education (B = 207.8, SE = 98.7, p =.035) revealed more beneficial effects of post-high school education for blacks than for whites. Smokers had shorter LTL than non-smokers, but the association of education and LTL remained significant when smoking was covaried (B = 119.7, SE = 47.6, p = 012). While higher income was associated with longer LTL, the effect was not significant (p > .10). This study provides the first demonstration of an association between educational attainment and LTL in a US population where higher education appears to have a protective effect against telomere shortening, particularly in blacks. (C) 2012 Elsevier Inc. All rights reserved. C1 [Adler, Nancy; O'Donovan, Aoife; Blackburn, Elizabeth; Epel, Elissa] Univ Calif San Francisco, San Francisco, CA 94143 USA. [O'Donovan, Aoife] San Francisco VA Med Ctr, San Francisco, CA USA. [Cawthon, Richard] Univ Utah, Salt Lake City, UT 84112 USA. [Koster, Annemarie; Harris, Tamara B.] NIA, Bethesda, MD 20892 USA. [Opresko, Patricia; Newman, Anne] Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Adler, N (reprint author), 3333 Calif St,Ste 465, San Francisco, CA 94143 USA. EM nancy.adler@ucsf.edu RI Newman, Anne/C-6408-2013; Koster, Annemarie/E-7438-2010; OI Newman, Anne/0000-0002-0106-1150; Opresko, Patricia/0000-0002-6470-2189 FU NIH, National Institute on Aging; National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR [R01-NR012459] FX The authors thank the Health ABC Study staff at the Pittsburgh and Memphis study sites and at the UCSF Coordinating Center, as well as the Health ABC Study participants for their time and efforts. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. The study was conducted on behalf of the Health, Aging and Body Composition (Health ABC) Study and was funded National Institute on Aging (NIA) Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant R01-AG028050, and NINR Grant R01-NR012459. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 26 Z9 29 U1 1 U2 27 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2013 VL 27 BP 15 EP 21 DI 10.1016/j.bbi.2012.08.014 PG 7 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 058JE UT WOS:000312629100004 PM 22981835 ER PT J AU Brunssen, SH Moy, SS Toews, AD McPherson, CA Harry, GJ AF Brunssen, Susan H. Moy, Sheryl S. Toews, Arrel D. McPherson, Christopher A. Harry, G. Jean TI Interleukin-6 (IL-6) receptor/IL-6 fusion protein (Hyper IL-6) effects on the neonatal mouse brain: Possible role for IL-6 trans-signaling in brain development and functional neurobehavioral outcomes SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Interleukin-6; IL-6R; Developmental neurotoxicity; Learning; Social behavior; Neuroinflammation; Oligodendroglia; Myelin; Postnatal inflammation ID IMMUNE ACTIVATION; RAT-BRAIN; IN-VIVO; DESIGNER CYTOKINE; DOPAMINERGIC HYPERFUNCTION; PROTEOLIPID PROTEIN; PRENATAL INFECTION; GENE-EXPRESSION; AMNIOTIC-FLUID; CEREBRAL-PALSY AB Adverse neurodevelopmental outcomes are linked to perinatal production of inflammatory mediators, including interleukin 6 (IL-6). While a pivotal role for maternal elevation in IL-6 has been established in determining neurobehavioral outcomes in the offspring and considered the primary target mediating the fetal inflammatory response, questions remain as to the specific actions of IL-6 on the developing brain. CD-1 male mice received a subdural injection of the bioactive fusion protein, hyper 1L-6 (HIL-6) on postnatal-day (PND)4 and assessed from preweaning until adulthood. Immunohistochemical evaluation of astrocytes and microglia and mRNA levels for pro-inflammatory cytokines and host response genes indicated no evidence of an acute neuroinflammatory injury response. HIL-6 accelerated motor development and increased reactivity to stimulation and number of entries in a light/dark chamber, decreased ability to learn to withhold a response in passive avoidance, and effected deficits in social novelty behavior. No changes were observed in motor activity, pre-pulse startle inhibition, or learning and memory in the Morris water maze or radial arm maze, as have been reported for models of more severe developmental neuroinflammation. In young animals, mRNA levels for MBP and PLP/DM20 decreased and less complexity of MBP processes in the cortex was evident by immunohistochemistry. The non-hydroxy cerebroside fraction of cerebral lipids was increased. These results provide evidence for selective effects of IL-6 signaling, particularly trans-signaling, in the developing brain in the absence of a general neuroinflammatory response. These data contribute to our further understanding of the multiple aspects of IL-6 signaling in the developing brain. Published by Elsevier Inc. C1 [Brunssen, Susan H.; McPherson, Christopher A.; Harry, G. Jean] NIEHS, Natl Toxicol Program Lab, NIH, Res Triangle Pk, NC 27709 USA. [Brunssen, Susan H.] Univ N Carolina, Sch Nursing, Chapel Hill, NC 27515 USA. [Brunssen, Susan H.; Moy, Sheryl S.] Univ N Carolina, Carolina Inst Dev Disabil, Chapel Hill, NC 27515 USA. [Toews, Arrel D.] Univ N Carolina, Dept Cellular & Mol Biol, Chapel Hill, NC 27515 USA. RP Harry, GJ (reprint author), NIEHS, Natl Toxicol Program Lab, NIH, POB 12233,MD C1-04,Res Triangle Pk, Res Triangle Pk, NC 27709 USA. EM harry@niehs.nih.gov FU NIH [P30-NR03962, 5-P30-HD03110, F31 NR 07511]; Division of Intramural Research, NIEHS, NIH [1Z01ES101623] FX This work was supported by NIH P30-NR03962; 5-P30-HD03110; F31 NR 07511; Division of Intramural Research, NIEHS, NIH, (Z#1Z01ES101623). The authors thank James Clark, Page Meyers and Natasha Clayton, NIEHS for technical assistance and Dr. Todd Schwartz, UNC-CH for statistical assistance. NR 62 TC 9 Z9 10 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 EI 1090-2139 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2013 VL 27 BP 42 EP 53 DI 10.1016/j.bbi.2012.08.017 PG 12 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 058JE UT WOS:000312629100008 PM 22985907 ER PT J AU Saligan, LN Hsiao, CP Wang, D Wang, XM John, LS Kaushal, A Citrin, D Barb, JJ Munson, PJ Dionne, RA AF Saligan, L. N. Hsiao, C. P. Wang, D. Wang, X. M. John, L. St. Kaushal, A. Citrin, D. Barb, J. J. Munson, P. J. Dionne, R. A. TI Upregulation of alpha-synuclein during localized radiation therapy signals the association of cancer-related fatigue with the activation of inflammatory and neuroprotective pathways SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE Fatigue; Cancer-related fatigue; Genomic; Gene expression; Neuroinflammation ID PATIENT-CONTROLLED METHYLPHENIDATE; PLACEBO-CONTROLLED TRIAL; PARKINSONS-DISEASE; PROSTATE-CANCER; OXIDATIVE STRESS; DOUBLE-BLIND; BREAST-CANCER; MESSENGER-RNA; IN-VITRO; RADIOTHERAPY AB Purpose: Neuroinflammatory mechanisms are associated with fatigue in neurodegenerative conditions such as Parkinson's. The symptoms in Parkinson's including fatigue are thought to be related to alpha-synuclein overexpression. This study investigated genomic correlates of fatigue experienced by men with prostate cancer receiving external beam radiation therapy (EBRT). Patients and methods: Sixteen men with non-metastatic prostate cancer who were scheduled to receive EBRT were enrolled. Fatigue scores and blood were obtained at baseline (prior to EBRT, DO); one hour following initiation of EBRT (D1), day 7 (D7), day 14 (D14), midpoint (days 19-21, D21), completion (days 38-42, D42), and four weeks post-EBRT (days 68-72, D72). Gene expression profiling using microarray analysis was performed from peripheral blood and confirmatory qPCR and protein (ELISA) analyses verified the microarray results. Correlations between fatigue and gene/protein expressions were determined using a mixed model approach. Results: Microarray data showed significant, differential expression of 463 probesets following EBRT. SNCA had a 2.95-fold change at D21from baseline. SNCA expression was confirmed by qPCR (p < 0.001) and ELISA (p < 0.001) over time during EBRT. Fatigue scores were significantly correlated with SNCA gene expression on D14 (r = 0.55, p <0.05) and plasma a-synuclein concentrations on D42 of EBRT (r = 0.54, p = 0.04). Conclusion: Fatigue experienced during EBRT may be mediated by a-synuclein overexpression. Alpha-synuclein may serve as a useful biomarker to understand the mechanisms and pathways related to the development of fatigue in this population. Published by Elsevier Inc. C1 [Saligan, L. N.; Hsiao, C. P.; Wang, D.; Wang, X. M.; John, L. St.; Dionne, R. A.] NINR, NIH, Bethesda, MD 20892 USA. [Kaushal, A.; Citrin, D.] NCI, NIH, Bethesda, MD 20892 USA. [Barb, J. J.; Munson, P. J.] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Saligan, LN (reprint author), NINR, NIH, 9000 Rockville Pike,Bldg 10,Room 2-1339, Bethesda, MD 20892 USA. EM saliganl@mail.nih.gov FU Intramural NIH HHS [ZIA NR000019-01] NR 41 TC 14 Z9 14 U1 1 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JAN PY 2013 VL 27 BP 63 EP 70 DI 10.1016/j.bbi.2012.09.009 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 058JE UT WOS:000312629100010 PM 23022913 ER PT J AU Vickers, AJ Bennette, C Kibel, AS Black, A Izmirlian, G Stephenson, AJ Bochner, B AF Vickers, Andrew J. Bennette, Caroline Kibel, Adam S. Black, Amanda Izmirlian, Grant Stephenson, Andrew J. Bochner, Bernard TI Who should be included in a clinical trial of screening for bladder cancer? A decision analysis of data from the prostate, lung, colorectal, and ovarian cancer screening trial SO CANCER LA English DT Article DE bladder cancer; screening; tobacco; clinical trials; research design ID HEMATURIA; MEN; RISK; PRESENTATIONS AB BACKGROUND: Because of its relatively low incidence, bladder cancer screening might have a better ratio of benefits to harms if it is restricted to a high-risk population. Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial were used and simple decision analytic techniques were applied to compare different eligibility criteria for a screening trial. METHODS: For a variety of possible eligibility criteria, the percentage of the population aged 55 years to 74 years and classified as being at high risk for developing invasive or high-grade carcinoma, and therefore likely to benefit from screening, was calculated. Regression models were used to calculate a risk score based on age, sex, smoking history, and family history of bladder cancer. The reduction in cases was calculated given hypothetical risk reductions associated with screening. The trade-off between patients screened and tumors avoided was calculated as a net benefit. RESULTS: The 5-year probability of being diagnosed with invasive bladder cancer was 0.24%. Using a risk score > 6 or > 8 as the eligibility criterion for a trial was generally superior to including all older adults. In a typical scenario, a risk score > 6 would result in approximately 25% of the population being screened to prevent 57 invasive or high-grade bladder cancers per 100,000 population; screening the entire population would prevent only an additional 38 cases. CONCLUSIONS: Screening for bladder cancer can be optimized by restricting it to a subgroup of patients considered to be at elevated risk. Different eligibility criteria for a screening trial can be compared rationally using decision-analytic techniques. Cancer 2013. (c) 2012 American Cancer Society. C1 [Vickers, Andrew J.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. [Bennette, Caroline] Univ Washington, Pharmaceut Outcomes Res & Policy Program, Seattle, WA 98195 USA. [Kibel, Adam S.] Brigham & Womens Hosp, Dept Urol, Dana Farber Canc Inst, Boston, MA 02115 USA. [Black, Amanda] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Izmirlian, Grant] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Stephenson, Andrew J.] Cleveland Clin, Dept Urol, Cleveland, OH 44106 USA. [Bochner, Bernard] Mem Sloan Kettering Canc Ctr, Dept Urol, New York, NY 10021 USA. RP Vickers, AJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA. EM vickersa@mskcc.org OI Vickers, Andrew/0000-0003-1525-6503 FU Prostate Cancer Foundation; Sidney Kimmel Center for Prostate and Urologic Cancers; SPORE grant from the National Cancer Institute [P50-CA92629] FX Supported in part by funds from David H. Koch provided through the Prostate Cancer Foundation, the Sidney Kimmel Center for Prostate and Urologic Cancers, and a P50-CA92629 SPORE grant from the National Cancer Institute to Dr. P. T. Scardino. NR 16 TC 9 Z9 9 U1 1 U2 4 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 JAN 1 PY 2013 VL 119 IS 1 BP 143 EP 149 DI 10.1002/cncr.27692 PG 7 WC Oncology SC Oncology GA 057DT UT WOS:000312543000020 PM 22736219 ER PT J AU Hudgens, MG Taha, TE Omer, SB Jamieson, DJ Lee, H Mofenson, LM Chasela, C Kourtis, AP Kumwenda, N Ruff, A Bedri, A Jackson, JB Musoke, P Bollinger, RC Gupte, N Thigpen, MC Taylor, A van der Horst, C AF Hudgens, Michael G. Taha, Taha E. Omer, Saad B. Jamieson, Denise J. Lee, Hana Mofenson, Lynne M. Chasela, Charles Kourtis, Athena P. Kumwenda, Newton Ruff, Andrea Bedri, Abubaker Jackson, J. Brooks Musoke, Philippa Bollinger, Robert C. Gupte, Nikhil Thigpen, Michael C. Taylor, Allan van der Horst, Charles TI Pooled Individual Data Analysis of 5 Randomized Trials of Infant Nevirapine Prophylaxis to Prevent Breast-Milk HIV-1 Transmission SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE breast milk; HIV; nevirapine ID TO-CHILD TRANSMISSION; DOSE NEVIRAPINE; MORTALITY; BOTSWANA; MOTHERS; ZIDOVUDINE; INFECTION; PREGNANCY; DIARRHEA; BORN AB Background. In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission. Methods. Data from 5396 mother-infant pairs who participated in 5 randomized trials where the infant was HIV-1 negative at birth were pooled to estimate the efficacy of infant nevirapine prophylaxis to prevent breast-milk HIV-1 transmission. Four daily regimens were compared: nevirapine for 6 weeks, 14 weeks, or 28 weeks, or nevirapine plus zidovudine for 14 weeks. Results. The estimated 28-week risk of HIV-1 transmission was 5.8% (95% confidence interval [CI], 4.3%-7.9%) for the 6-week nevirapine regimen, 3.7% (95% CI, 2.5%-5.4%) for the 14-week nevirapine regimen, 4.8% (95% CI, 3.5%-6.7%) for the 14-week nevirapine plus zidovudine regimen, and 1.8% (95% CI, 1.0%-3.1%) for the 28-week nevirapine regimen (log-rank test for trend, P<.001). Cox regression models with nevirapine as a time-varying covariate, stratified by trial site and adjusted for maternal CD4 cell count and infant birth weight, indicated that nevirapine reduces the rate of HIV-1 infection by 71% (95% CI, 58%-80%; P<.001) and reduces the rate of HIV infection or death by 58% (95% CI, 45%-69%; P<.001). Conclusions. Extended prophylaxis with nevirapine or with nevirapine and zidovudine significantly reduces postnatal HIV-1 infection. Longer duration of prophylaxis results in a greater reduction in the risk of infection. C1 [Hudgens, Michael G.; Lee, Hana; van der Horst, Charles] Univ N Carolina, Chapel Hill, NC 27599 USA. [Taha, Taha E.; Kumwenda, Newton; Ruff, Andrea; Jackson, J. Brooks; Bollinger, Robert C.; Gupte, Nikhil] Johns Hopkins Univ, Baltimore, MD USA. [Omer, Saad B.] Emory Univ, Atlanta, GA 30322 USA. [Jamieson, Denise J.; Kourtis, Athena P.; Thigpen, Michael C.; Taylor, Allan] Ctr Dis Control & Prevent, Atlanta, GA USA. [Mofenson, Lynne M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA. [Chasela, Charles] Univ N Carolina Project, Lilongwe, Malawi. [Bedri, Abubaker] Univ Addis Ababa, Addis Ababa, Ethiopia. [Musoke, Philippa] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda. [Musoke, Philippa] Makerere Univ, Kampala, Uganda. RP Hudgens, MG (reprint author), Univ N Carolina, CB 7420,McGavran Greenberg Hall, Chapel Hill, NC 27599 USA. EM mhudgens@bios.unc.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU Prevention Research Centers Special Interest Project of the CDC [SIP 13-01 U48-CCU409660-09, SIP 26-04 U48-DP000059-01, SIP 22-09 U48-DP001944]; National Institute of Allergy and Infectious Diseases (NIAID); University of North Carolina Center for AIDS Research [P30-AI50410]; NIH Fogarty AIDS International Training and Research Program (DHHS/NIH/FIC) [5-D43 TW001039, 5-R24 TW007988]; Abbott Laboratories; GlaxoSmithKline; Boehringer Ingelheim; Roche Pharmaceuticals; Bristol-Myers Squibb; Elizabeth Glaser Pediatric AIDS Foundation; United Nations Children's Fund; World Food Program; Malawi Ministry of Health and Population; Johnson Johnson; US Agency for International Development; NIH, NIAID [R01AI45462, R01AI3857601A, R01AI34235]; NIH Fogarty International Center NIH Program of International Training [D43-TW0000]; CDC [5 U50 PS022061-05, U50/CC0222061]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH; NIH FX The Breastfeeding, Antiretrovirals and Nutrition (BAN) study was supported by the Prevention Research Centers Special Interest Project of the CDC (SIP 13-01 U48-CCU409660-09, SIP 26-04 U48-DP000059-01, and SIP 22-09 U48-DP001944), the National Institute of Allergy and Infectious Diseases (NIAID), the University of North Carolina Center for AIDS Research (P30-AI50410), the NIH Fogarty AIDS International Training and Research Program (DHHS/NIH/FIC 5-D43 TW001039 and 5-R24 TW007988), Abbott Laboratories, GlaxoSmithKline, Boehringer Ingelheim, Roche Pharmaceuticals, Bristol-Myers Squibb, the Elizabeth Glaser Pediatric AIDS Foundation, the United Nations Children's Fund, the World Food Program, the Malawi Ministry of Health and Population, Johnson & Johnson, and the US Agency for International Development. The SWEN study was supported by grants from the NIH, NIAID (R01AI45462, R01AI3857601A, R01AI34235) and the NIH Fogarty International Center NIH Program of International Training Grants in Epidemiology Related to AIDS (D43-TW0000). The PEPI study was supported by a Cooperative Agreement (5 U50 PS022061-05; award U50/CC0222061) from the CDC and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, NIH. The CDC and NIH were sponsors of the studies included in this pooled analysis.; During the follow-up phase of the BAN study, the University of North Carolina received cash grants from GlaxoSmithKline and Abbott Laboratories to conduct pharmacokinetic and resistance analysis substudies. In addition, GlaxoSmithKline, Abbott Laboratories, Boehringer Ingelheim, Bristol-Myers Squibb, and Roche Pharmaceuticals provided the study drugs. All authors: No reported conflicts. NR 22 TC 11 Z9 11 U1 1 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2013 VL 56 IS 1 BP 131 EP 139 DI 10.1093/cid/cis808 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AE UT WOS:000312605500025 PM 22997212 ER PT J AU Sassi, M Mueller, NJ Yazaki, H Oka, S Gianella, S Kovacs, JA AF Sassi, Monica Mueller, Nicolas J. Yazaki, Hirohisa Oka, Shinichi Gianella, Sara Kovacs, Joseph A. TI Pneumocystis jirovecii Genotypes Involved in Pneumocystis Pneumonia Outbreaks Among Renal Transplant Recipients Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID MOLECULAR EVIDENCE; TRANSMISSION C1 [Sassi, Monica; Kovacs, Joseph A.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. [Mueller, Nicolas J.; Gianella, Sara] Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland. [Yazaki, Hirohisa; Oka, Shinichi] Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo, Japan. [Oka, Shinichi] Kumamoto Univ, Ctr AIDS Res, Div 9, Kumamoto 860, Japan. RP Kovacs, JA (reprint author), Bldg 10,Rm 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@mail.nih.gov RI Kumamoto University, CAIDS/G-8446-2013; Mueller, Nicolas/B-6864-2013 OI Mueller, Nicolas/0000-0002-1059-3191 FU Intramural NIH HHS NR 7 TC 0 Z9 0 U1 0 U2 2 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 JAN 1 PY 2013 VL 56 IS 1 BP 166 EP U208 DI 10.1093/cid/cis814 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AE UT WOS:000312605500035 PM 22990850 ER PT J AU Dooley, KE Mitnick, C DeGroote, MA Obuku, E Hamilton, CD Makhene, M Shah, S Brust, JCM Durakovic, N Nuermberger, E AF Dooley, Kelly E. Mitnick, Carole DeGroote, Mary Ann Obuku, Ekwaro Hamilton, Carol D. Makhene, Mamodikoe Shah, Sarita Brust, James C. M. Durakovic, Nadza Nuermberger, Eric CA RESIST-TB TI Retooling Existing Tuberculosis Drugs for Children Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Dooley, Kelly E.] Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, Baltimore, MD 21287 USA. [Mitnick, Carole] Harvard Univ, Sch Med, Boston, MA USA. [DeGroote, Mary Ann] Colorado State Univ, Mycobacterial Res Labs, Ft Collins, CO 80523 USA. [Obuku, Ekwaro] AIDS Relief Programme, Kampala, Uganda. [Obuku, Ekwaro] Joint Clin Res Ctr, Kampala, Uganda. [Hamilton, Carol D.] Family Hlth Int, Hlth & Dev Sci, Durham, NC USA. [Makhene, Mamodikoe] NIH, Bethesda, MD 20892 USA. [Shah, Sarita; Brust, James C. M.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Durakovic, Nadza] Partners Hlth, Boston, MA USA. RP Dooley, KE (reprint author), Johns Hopkins Univ, Sch Med, Div Clin Pharmacol, 600 N Wolfe St,Osler 527, Baltimore, MD 21287 USA. EM kdooley1@jhmi.edu FU NIAID NIH HHS [R01 AI090820] NR 2 TC 0 Z9 0 U1 0 U2 3 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 JAN 1 PY 2013 VL 56 IS 1 BP 168 EP 169 DI 10.1093/cid/cis820 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 058AE UT WOS:000312605500037 PM 22990846 ER PT J AU Williams, KW Andrews, AL Heine, D Russell, WS Titus, MO AF Williams, Kelli W. Andrews, Annie L. Heine, Daniel Russell, W. Scott Titus, M. Olivia TI Parental Preference for Short- Versus Long-Course Corticosteroid Therapy in Children With Asthma Presenting to the Pediatric Emergency Department SO CLINICAL PEDIATRICS LA English DT Article DE asthma; steroids; dexamethasone; prednisone; parental preference ID ORAL DEXAMETHASONE; YOUNG-CHILDREN; EXACERBATIONS; PREDNISONE; TRIAL AB Asthma is the most common chronic condition affecting children and a prominent chief complaint in pediatric emergency departments (ED). We aimed to determine parental preference between short- and long-term courses of oral corticosteroids for use in children with mild to moderate asthma presenting to our pediatric ED with acute asthma exacerbations. We surveyed parents of asthmatic children who presented to our pediatric ED from August 2011 to April 2012. Questions characterized each patient's asthma severity, assessed parental preference among systemic steroid and inhaled medication delivery options for acute asthma management, and inquired about compliance, medication costs, and intention to follow up. The majority of our parents prefer the use of 1 to 2 days of steroids to 5 days for acute asthma exacerbations in the ED. Thus, dexamethasone is an attractive alternative to prednisone/prednisolone and should be considered in the management of acute asthma exacerbations in the ED. C1 [Williams, Kelli W.; Andrews, Annie L.; Heine, Daniel; Russell, W. Scott; Titus, M. Olivia] Med Univ S Carolina, Charleston, SC 29425 USA. RP Williams, KW (reprint author), NIAID, ICMOB, DCR, NIH, 10 Ctr Dr,Bldg 10,Room 12C103, Bethesda, MD 20892 USA. EM kelli.williams@nih.gov NR 14 TC 3 Z9 3 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0009-9228 J9 CLIN PEDIATR JI Clin. Pediatr. PD JAN PY 2013 VL 52 IS 1 BP 30 EP 34 DI 10.1177/0009922812461441 PG 5 WC Pediatrics SC Pediatrics GA 057JF UT WOS:000312558600005 PM 23034948 ER PT J AU Stahl, RG Hooper, MJ Balbus, JM Clements, W Fritz, A Gouin, T Helm, R Hickey, C Landis, W Moe, SJ AF Stahl, Ralph G., Jr. Hooper, Michael J. Balbus, John M. Clements, William Fritz, Alyce Gouin, Todd Helm, Roger Hickey, Christopher Landis, Wayne Moe, S. Jannicke TI The influence of global climate change on the scientific foundations and applications of Environmental Toxicology and Chemistry: Introduction to a SETAC international workshop SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE Global climate change; Chemical contaminant; SETAC Workshop; Risk assessment; Interaction ID ECOLOGICAL RISK-ASSESSMENT; PERSISTENT ORGANIC POLLUTANTS; CHEMICAL-EXPOSURE; CONTAMINANTS; FRAMEWORK; MANAGEMENT; DEPOSITION; INCREASES; TRANSPORT; SCIENCE AB This is the first of seven papers resulting from a Society of Environmental Toxicology and Chemistry (SETAC) international workshop titled The Influence of Global Climate Change on the Scientific Foundations and Applications of Environmental Toxicology and Chemistry. The workshop involved 36 scientists from 11 countries and was designed to answer the following question: How will global climate change influence the environmental impacts of chemicals and other stressors and the way we assess and manage them in the environment? While more detail is found in the complete series of articles, some key consensus points are as follows: (1) human actions (including mitigation of and adaptation to impacts of global climate change [GCC]) may have as much influence on the fate and distribution of chemical contaminants as does GCC, and modeled predictions should be interpreted cautiously; (2) climate change can affect the toxicity of chemicals, but chemicals can also affect how organisms acclimate to climate change; (3) effects of GCC may be slow, variable, and difficult to detect, though some populations and communities of high vulnerability may exhibit responses sooner and more dramatically than others; (4) future approaches to human and ecological risk assessments will need to incorporate multiple stressors and cumulative risks considering the wide spectrum of potential impacts stemming from GCC; and (5) baseline/reference conditions for estimating resource injury and restoration/rehabilitation will continually shift due to GCC and represent significant challenges to practitioners. Environ. Toxicol. Chem. 2013;32:1319. (c) 2012 SETAC C1 [Stahl, Ralph G., Jr.] DuPont Co Inc, Wilmington, DE USA. [Hooper, Michael J.] US Geol Survey, Columbia, MO USA. [Clements, William] Colorado State Univ, Ft Collins, CO 80523 USA. [Balbus, John M.] NIH, Bethesda, MD 20892 USA. [Fritz, Alyce] NOAA, Seattle, WA USA. [Gouin, Todd] Unilever, Sharnbrook, Beds, England. [Helm, Roger] US Fish & Wildlife Serv, Arlington, VA USA. [Hickey, Christopher] Natl Inst Water & Atmospher Res, Hamilton, New Zealand. [Landis, Wayne] Western Washington Univ, Bellingham, WA 98225 USA. [Moe, S. Jannicke] Norwegian Inst Water Res, Oslo, Norway. RP Stahl, RG (reprint author), DuPont Co Inc, Wilmington, DE USA. EM Ralph.g.stahl-jr@usa.dupont.com RI Hickey, Christopher/E-9931-2013; OI Moe, Jannicke/0000-0002-3681-3551; Hooper, Michael/0000-0002-4161-8961 NR 74 TC 18 Z9 18 U1 3 U2 59 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JAN PY 2013 VL 32 IS 1 BP 13 EP 19 DI 10.1002/etc.2037 PG 7 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 057EQ UT WOS:000312545700005 PM 23097130 ER PT J AU Balbus, JM Boxall, ABA Fenske, RA McKone, TE Zeise, L AF Balbus, John M. Boxall, Alistair B. A. Fenske, Richard A. McKone, Thomas E. Zeise, Lauren TI Implications of global climate change for the assessment and management of human health risks of chemicals in the natural environment SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Review DE Toxicology; Exposure pathway; Risk assessment; Vulnerability ID SAN-FRANCISCO BAY; POLYCHLORINATED-BIPHENYLS; PARTICULATE MATTER; AIR-POLLUTION; TEMPERATURE MODIFY; UNITED-STATES; NMMAPS DATA; HEAT-WAVE; MORTALITY; OZONE AB Global climate change (GCC) is likely to alter the degree of human exposure to pollutants and the response of human populations to these exposures, meaning that risks of pollutants could change in the future. The present study, therefore, explores how GCC might affect the different steps in the pathway from a chemical source in the environment through to impacts on human health and evaluates the implications for existing risk-assessment and management practices. In certain parts of the world, GCC is predicted to increase the level of exposure of many environmental pollutants due to direct and indirect effects on the use patterns and transport and fate of chemicals. Changes in human behavior will also affect how humans come into contact with contaminated air, water, and food. Dietary changes, psychosocial stress, and coexposure to stressors such as high temperatures are likely to increase the vulnerability of humans to chemicals. These changes are likely to have significant implications for current practices for chemical assessment. Assumptions used in current exposure-assessment models may no longer apply, and existing monitoring methods may not be robust enough to detect adverse episodic changes in exposures. Organizations responsible for the assessment and management of health risks of chemicals therefore need to be more proactive and consider the implications of GCC for their procedures and processes. Environ. Toxicol. Chem. 2013;32:6278. (c) 2012 SETAC C1 [Balbus, John M.] NIEHS, Bethesda, MD USA. [Boxall, Alistair B. A.] Univ York, Dept Environm, York YO10 5DD, N Yorkshire, England. [Fenske, Richard A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA. [McKone, Thomas E.] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. [Zeise, Lauren] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Sacramento, CA USA. RP Balbus, JM (reprint author), NIEHS, Bethesda, MD USA. EM john.balbus@nih.gov FU U.S. Department of Energy (DOE) [DE-AC02-05CH11231]; American Chemistry Council; Conestoga-Rover and Associates; E.I. du Pont de Nemours Co.; Environ Corp; Exponent; NIEHS Superfund Research Program; National Oceanic and Atmospheric Administration; National Council for Air and Stream Improvement; Norwegian Institute for Water Research; Research Council of Norway; Society of Environ Toxicol Chem; Johnson Foundation at Wingspread; Unilever; U.S. Department of Interior Natural Resource Damage Assessment and Restoration Program; U.S. Environmental Protection Agency; U.S. Fish and Wildlife Service; U.S. Geological Survey FX This article is the work of an employee or group of employees of the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), the California Office of Environmental Health Hazard Assessment (OEHHA), and the Lawrence Berkeley National Laboratory, which is operated by the U.S. Department of Energy (DOE) under contract DE-AC02-05CH11231; however, the statements, opinions, or conclusions contained here do not necessarily represent the statements, opinions, or conclusions of the NIEHS, NIH, DOE, U.S. government, OEHHA, California Environmental Protection Agency, or the state of California. The authors acknowledge funding for the Society of Environmental Toxicology and Chemistry international workshop, The Influence of Global Climate Change, on the Scientific Foundations and Applications of Environ Toxicol Chem, which was provided by the American Chemistry Council, Conestoga-Rover and Associates, E.I. du Pont de Nemours & Co., Environ Corp, Exponent, NIEHS Superfund Research Program, National Oceanic and Atmospheric Administration, National Council for Air and Stream Improvement, Norwegian Institute for Water Research, Research Council of Norway, Society of Environ Toxicol Chem, Johnson Foundation at Wingspread, Unilever, U.S. Department of Interior Natural Resource Damage Assessment and Restoration Program, U.S. Environmental Protection Agency, U.S. Fish and Wildlife Service, and U.S. Geological Survey. The authors would like to thank J. Lee of MDB, Inc. for her outstanding assistance with manuscript preparation and submission. NR 105 TC 27 Z9 28 U1 5 U2 128 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JAN PY 2013 VL 32 IS 1 BP 62 EP 78 DI 10.1002/etc.2046 PG 17 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 057EQ UT WOS:000312545700009 PM 23147420 ER PT J AU Dragnev, K You, M Wang, Y Lubet, R AF Dragnev, Konstantine You, Ming Wang, Yian Lubet, Ronald TI Lung cancer chemoprevention: difficulties, promise and potential agents? SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE chemoprevention; chemopreventive agents; lung cancer; NSAIDs ID GROWTH-FACTOR RECEPTOR; CHEMOTHERAPY-NAIVE PATIENTS; PHASE-II TRIAL; NF-KAPPA-B; BREAST-CANCER; POSTMENOPAUSAL WOMEN; FORMER SMOKERS; MOUSE MODELS; TAMOXIFEN THERAPY; RANDOMIZED-TRIAL AB Introduction: In a variety of cancers there is evidence that specific regimens can prevent or significantly delay the development of cancer. Thus, for breast cancer (ER+) use of SERMs or aromatase inhibitors can substantially decrease tumor incidence. For cervical cancer, HPV vaccination will inhibit long term cancer incidence. For colon cancer, the second greatest cancer killer, administration of aspirin and other NSAIDs decreases advanced colon adenomas in Phase II trials and epidemiologic data support their ability to prevent colon cancer. To date prevention trials in the area of lung cancer have shown minimal efficacy. Areas covered: The paper examines and discusses in greater detail certain promising agents which the authors have tested either preclinically and or in early phase clinical trials. These agents include RXR agonists, EGFr inhibitors, NSAIDs and Triterpenoids. Other agents including glucocorticoids, pioglitazone and iloprost are briefly mentioned. In addition, the paper presents various types of potential Phase II lung cancer prevention trials and describes their strengths and weaknesses. The potential use of various biomarkers as endpoints in trials e. g. histopathology, non-specific biomarkers (e. g., Ki67, cyclin D expression, apoptosis) and molecular biomarkers (e. g. specific phosphorylated proteins, gene expression etc.) is presented. Finally, we examine at least one approach, the use of aerosols, which may diminish the systemic toxicity associated with certain of these agents. Expert Opinion: The manuscript presents: a) a number of promising agents which appear applicable to further Phase II prevention trials; b) approaches to defining potential preventive agents as well; c) approaches which might mitigate the side effects associated with potential agents most specifically the use of aerosols. Finally, we discuss biomarker studies both preclinical and clinical which might help support potential Phase II trials. The particular appeal to the preclinical studies is that they can be followed to a tumor endpoint. We hope that this will give the reader further background and allow one to appreciate the potential and some of the hurdles associated with lung cancer chemoprevention. C1 [Dragnev, Konstantine; Lubet, Ronald] Dartmoth Med Sch, Hitchcock Canc Ctr, Lebanon, NH USA. [Lubet, Ronald] NCI, Rockville, MD 20852 USA. [You, Ming] Med Coll Wisconsin, Milwaukee, WI 53226 USA. [Wang, Yian] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. RP Lubet, R (reprint author), Dartmoth Med Sch, Hitchcock Canc Ctr, Lebanon, NH USA. EM rl57q@nih.gov FU Genentech; Ligand; Eisai pharmaceuticals; NIH [ROICA 139959, ROIAT005522, NOICN43308] FX K Dragnev has received funding from Genentech, Ligand and Eisai pharmaceuticals for clinical trials. M You and Y Wang have received NIH grants ROICA 139959 and ROIAT005522, and contract NOICN43308. R Lubet has no competing interests to declare. No funding was received in support of this manuscript. NR 79 TC 11 Z9 11 U1 0 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JAN PY 2013 VL 22 IS 1 BP 35 EP 47 DI 10.1517/13543784.2013.731392 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 052TP UT WOS:000312221700003 PM 23167766 ER PT J AU Soto-Pantoja, DR Stein, EV Rogers, NM Sharifi-Sanjani, M Isenberg, JS Roberts, DD AF Soto-Pantoja, David R. Stein, Erica V. Rogers, Natasha M. Sharifi-Sanjani, Maryam Isenberg, Jeffrey S. Roberts, David D. TI Therapeutic opportunities for targeting the ubiquitous cell surface receptor CD47 SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE autophagy; cancer immunotherapy; ionizing radiation; ischemia; macrophages; nitric oxide; reperfusion injury; thrombospondin-1; tissue perfusion ID INTEGRIN-ASSOCIATED PROTEIN; ISCHEMIA-REPERFUSION INJURY; NON-HODGKIN-LYMPHOMA; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-I; HUMAN T-CELLS; NITRIC-OXIDE; SIRP-ALPHA; TISSUE SURVIVAL; DENDRITIC CELLS AB Introduction: CD47 is a ubiquitously expressed cell surface receptor that serves as a counter-receptor for SIRPa in recognition of self by the innate immune system. Independently, CD47 also functions as an important signaling receptor for regulating cell responses to stress. Areas covered: We review the expression, molecular interactions, and pathophysiological functions of CD47 in the cardiovascular and immune systems. CD47 was first identified as a potential tumor marker, and we examine recent evidence that its dysregulation contributes to cancer progression and evasion of anti-tumor immunity. We further discuss therapeutic strategies for enhancing or inhibiting CD47 signaling and applications of such agents in preclinical models of ischemia and ischemia/reperfusion injuries, organ transplantation, pulmonary hypertension, radioprotection, and cancer. Expert opinion: Ongoing studies are revealing a central role of CD47 for conveying signals from the extracellular microenvironment that limit cell and tissue survival upon exposure to various types of stress. Based on this key function, therapeutics targeting CD47 or its ligands thrombospondin-1 and SIRPa could have broad applications spanning reconstructive surgery, engineering of tissues and biocompatible surfaces, vascular diseases, diabetes, organ transplantation, radiation injuries, inflammatory diseases, and cancer. C1 [Roberts, David D.] NCI, Biochem Pathol Sect, NIH, Ctr Canc Res,Lab Pathol, Bethesda, MD 20892 USA. [Rogers, Natasha M.; Sharifi-Sanjani, Maryam; Isenberg, Jeffrey S.] Univ Pittsburgh, Sch Med, Vasc Med Inst, Div Pulm Allergy & Crit Care Med, Pittsburgh, PA 15261 USA. [Stein, Erica V.] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Microbiol, Washington, DC 20037 USA. [Stein, Erica V.] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Immunol, Washington, DC 20037 USA. [Stein, Erica V.] George Washington Univ, Microbiol & Immunol Program, Inst Biomed Sci, Dept Trop Med, Washington, DC 20037 USA. RP Roberts, DD (reprint author), NCI, Biochem Pathol Sect, NIH, Ctr Canc Res,Lab Pathol, Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; OI Roberts, David/0000-0002-2481-2981; Stein, Erica/0000-0001-8778-8846 FU Intramural Research Program of the NIH/NCI; NCI; National Heart Lung and Blood Institute [R01HL108954 2, R01HL089658, 1P01HL103455]; American Heart Association [11BGIA7210001]; Institute for Transfusion Medicine; Hemophilia Center of Western Pennsylvania; Australian National Health and Medical Research Council [APP1016276] FX This work was supported by the Intramural Research Program of the NIH/NCI (D. D. R.), by a NCI Director's Career Development Innovation Award (D. R. S-P), by the National Heart Lung and Blood Institute (R01HL108954 2, R01HL089658, 1P01HL103455 to J.S.I.), the American Heart Association (11BGIA7210001 to J.S.I.), the Institute for Transfusion Medicine and the Hemophilia Center of Western Pennsylvania (to J.S.I.), and the Australian National Health and Medical Research Council (APP1016276 C.J. Martin Award to N.M.R.). NR 142 TC 14 Z9 16 U1 4 U2 35 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JAN PY 2013 VL 17 IS 1 BP 89 EP 103 DI 10.1517/14728222.2013.733699 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 056PJ UT WOS:000312502900009 PM 23101472 ER PT J AU Hiraki, LT Major, JM Chen, C Cornelis, MC Hunter, DJ Rimm, EB Simon, KC Weinstein, SJ Purdue, MP Yu, K Albanes, D Kraft, P AF Hiraki, Linda T. Major, Jacqueline M. Chen, Constance Cornelis, Marilyn C. Hunter, David J. Rimm, Eric B. Simon, Kelly C. Weinstein, Stephanie J. Purdue, Mark P. Yu, Kai Albanes, Demetrius Kraft, Peter TI Exploring the Genetic Architecture of Circulating 25-Hydroxyvitamin D SO GENETIC EPIDEMIOLOGY LA English DT Article DE genome-wide association; heritability; polygenic score; vitamin D ID GENOME-WIDE ASSOCIATION; PROSTATE-CANCER RISK; VITAMIN-D STATUS; BREAST-CANCER; MISSING HERITABILITY; MULTIPLE-SCLEROSIS; POLYGENIC SUSCEPTIBILITY; 1,25-DIHYDROXYVITAMIN-D; RADIOIMMUNOASSAY; POLYMORPHISMS AB The primary circulating form of vitamin D is 25-hydroxy vitamin D (25(OH)D), a modifiable trait linked with a growing number of chronic diseases. In addition to environmental determinants of 25(OH)D, including dietary sources and skin ultraviolet B (UVB) exposure, twin- and family-based studies suggest that genetics contribute substantially to vitamin D variability with heritability estimates ranging from 43% to 80%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) located in four gene regions associated with 25(OH)D. These SNPs collectively explain only a fraction of the heritability in 25(OH)D estimated by twin- and family-based studies. Using 25(OH)D concentrations and GWAS data on 5,575 subjects drawn from five cohorts, we hypothesized that genome-wide data, in the form of (1) a polygenic score comprised of hundreds or thousands of SNPs that do not individually reach GWAS significance, or (2) a linear mixed model for genome-wide complex trait analysis, would explain variance in measured circulating 25(OH)D beyond that explained by known genome-wide significant 25(OH)D-associated SNPs. GWAS identified SNPs explained 5.2% of the variation in circulating 25(OH)D in these samples and there was little evidence additional markers significantly improved predictive ability. On average, a polygenic score comprised of GWAS-identified SNPs explained a larger proportion of variation in circulating 25(OH)D than scores comprised of thousands of SNPs that were on average, nonsignificant. Employing a linear mixed model for genome-wide complex trait analysis explained little additional variability (range 022%). The absence of a significant polygenic effect in this relatively large sample suggests an oligogenetic architecture for 25(OH)D. C1 [Hiraki, Linda T.; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, Boston, MA 02115 USA. [Major, Jacqueline M.; Weinstein, Stephanie J.; Purdue, Mark P.; Yu, Kai; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Cornelis, Marilyn C.; Rimm, Eric B.; Simon, Kelly C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Hunter, David J.; Rimm, Eric B.; Simon, Kelly C.] Harvard Univ, Sch Med, Channing Lab, Dept Med, Boston, MA 02115 USA. [Hunter, David J.; Rimm, Eric B.; Simon, Kelly C.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Hiraki, LT (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Dept Epidemiol, 655 Huntington Ave,Bldg 2,Room 200, Boston, MA 02115 USA. EM lindahiraki@mail.harvard.edu RI Albanes, Demetrius/B-9749-2015; Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Canadian Institute of Health Research; GWAS as part of the Gene-Environment Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI) [U01HG004399]; NIH GEI [U01HG04424]; NIH [HL35464, CA55075, P01CA087969, 5U01HG004399-2, P01CA055075]; Merck/Rosetta Research Laboratories, North Wales, PA; Intramural Research Program of the National Cancer Institute at the National Institutes of Health; U.S. Public Health Service from the National Cancer Institute, Department of Health and Human Services [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C]; [N01-CO-12400] FX We thank P. Soule for assistance, and we thank the participants in the Nurses' Health Studies (NHS) and Health Professionals Follow-up Study (HPFS). This work was supported by the Canadian Institute of Health Research (Health Professionals Fellowship Award to L. H.). The NHS Cancer Genetic Markers of Susceptibility breast cancer GWAS was supported by N01-CO-12400. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS funded as part of the Gene-Environment Association Studies (GENEVA) under the National Institutes of Health (NIH) Genes, Environment, and Health Initiative (GEI). Genotyping was performed at the Broad Institute of the Massachusetts Institute of Technology and Harvard, with funding support from the NIH GEI (U01HG04424). The NHS/HPFS CHD GWAS was supported by HL35464 and CA55075 from the NIH with additional support for genotyping from Merck/Rosetta Research Laboratories, North Wales, PA. The NHS is supported by NIH grants P01CA087969 and 5U01HG004399-2, and the HPFS is supported by NIH grant P01CA055075. The ATBC work was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health. Additionally, this research was supported by U.S. Public Health Service contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and HHSN261201000006C from the National Cancer Institute, Department of Health and Human Services. The authors declare no conflict of interest. NR 45 TC 15 Z9 15 U1 1 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JAN PY 2013 VL 37 IS 1 BP 92 EP 98 DI 10.1002/gepi.21694 PG 7 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 057BY UT WOS:000312538100009 PM 23135809 ER PT J AU Rahman, M Greene, T Phillips, RA Agodoa, LY Bakris, GL Charleston, J Contreras, G Gabbai, F Hiremath, L Jamerson, K Kendrick, C Kusek, JW Lash, JP Lea, J Miller, ER Rostand, S Toto, R Wang, XL Wright, JT Appel, LJ AF Rahman, Mahboob Greene, Tom Phillips, Robert A. Agodoa, Lawrence Y. Bakris, George L. Charleston, Jeanne Contreras, Gabriel Gabbai, Francis Hiremath, Leena Jamerson, Kenneth Kendrick, Cynthia Kusek, John W. Lash, James P. Lea, Janice Miller, Edgar R., III Rostand, Stephen Toto, Robert Wang, Xulei Wright, Jackson T., Jr. Appel, Lawrence J. TI A Trial of 2 Strategies to Reduce Nocturnal Blood Pressure in Blacks With Chronic Kidney Disease SO HYPERTENSION LA English DT Article DE nocturnal blood pressure; chronic kidney disease; hypertension ID CARDIOVASCULAR RISK; HYPERTENSIVE SUBJECTS; DIPPING STATUS; HEART-RATE; PROGRESSION; BEDTIME; EVENTS; COHORT; TIME; CKD AB The objective of our study was to determine the effects of 2 antihypertensive drug dose schedules (PM dose and add-on dose) on nocturnal blood pressure (BP) in comparison with usual therapy (AM dose) in blacks with hypertensive chronic kidney disease and controlled office BP. In a 3-period, crossover trial, former participants of the African American Study of Kidney Disease were assigned to receive the following 3 regimens, each lasting 6 weeks, presented in random order: AM dose (once-daily antihypertensive medications taken in the morning), PM dose (once-daily antihypertensives taken at bedtime), and add-on dose (once-daily antihypertensives taken in the morning and an additional antihypertensive medication before bedtime [diltiazem 60-120 mg, hydralazine 25 mg, or additional ramipril 5 mg]). Ambulatory BP monitoring was performed at the end of each period. The primary outcome was nocturnal systolic BP. Mean age of the study population (n=147) was 65.4 years, 64% were men, and mean estimated glomerular filtration rate was 44.9 mL/min per 1.73 m(2). At the end of each period, mean (SE) nocturnal systolic BP was 125.6 (1.2) mm Hg in the AM dose, 123.9 (1.2) mm Hg in the PM dose, and 123.5 (1.2) mm Hg in the add-on dose. None of the pairwise differences in nocturnal, 24-hour, and daytime systolic BP was statistically significant. Among blacks with hypertensive chronic kidney disease, neither PM (bedtime) dosing of once-daily antihypertensive nor the addition of drugs taken at bedtime significantly reduced nocturnal BP compared with morning dosing of antihypertensive medications. (Hypertension. 2013;61:82-88.) circle Online Data Supplement C1 [Rahman, Mahboob; Wright, Jackson T., Jr.] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, Louis Stokes Cleveland VA Med Ctr, Cleveland, OH 44016 USA. [Greene, Tom] Univ Utah, Salt Lake City, UT USA. [Phillips, Robert A.] Univ Massachusetts, Amherst, MA 01003 USA. [Agodoa, Lawrence Y.] NIDDKD, NIH, Bethesda, MD 20892 USA. [Bakris, George L.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Charleston, Jeanne; Miller, Edgar R., III; Appel, Lawrence J.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Contreras, Gabriel] Univ Miami, Miller Sch Med, Miami, FL 33136 USA. [Gabbai, Francis] Univ Calif San Diego, San Diego, CA 92103 USA. [Hiremath, Leena] Ohio State Univ, Columbus, OH 43210 USA. [Jamerson, Kenneth] Univ Michigan, Ann Arbor, MI 48109 USA. [Kendrick, Cynthia; Wang, Xulei] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Lash, James P.] Univ Illinois, Champaign, IL 61820 USA. [Lea, Janice] Emory Univ, Atlanta, GA 30322 USA. [Rostand, Stephen] Univ Alabama, Tuscaloosa, AL USA. [Toto, Robert] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. RP Rahman, M (reprint author), Case Western Reserve Univ, Univ Hosp Case Med Ctr, Div Nephrol & Hypertens, Louis Stokes Cleveland VA Med Ctr, 11100 Euclid Ave, Cleveland, OH 44016 USA. EM Mahboob.Rahman@uhhospitals.org FU National Institute of Diabetes, Digestive and Kidney Disease; King Pharmaceuticals; National Institutes of Health (NIH); NIH; National Heart, Lung, and Blood Institute FX This study was supported by the National Institute of Diabetes, Digestive and Kidney Disease and an unrestricted grant from King Pharmaceuticals.; Dr Rahman has research support from National Institutes of Health (NIH) and has received honoraria from Boehringer Ingelheim. Dr Bakris has served as a consultant/advisory board for Takeda, Servier, Abbott, CVRx, Johnson and Johnson, Eli Lilly, and Medtronic. Dr Jamerson has research grant support from NIH, National Institute of Diabetes, Digestive and Kidney Diseases, and National Heart, Lung, and Blood Institute, serves on the speakers bureau for Daichi-Sankyo pharmaceuticals, has received honoraria from Boehringer-Ingelheim, Daichi-Sankyo, Forest, Novartis, and Xuma Pharm, and served as a consultant advisory board for Boehringer-Ingelheim, Daichi Sankyo, Forest, Pfizer, Novartis, Xoma pharm, and Invasc Therapeutics. Dr Rostand holds shares of common stock in Merck. Dr Toto has served on the speakers bureau for Amgen and Merck and has served as consultant/advisory board for Boehringer-Ingelheim and Amgen. Dr Wright has served as consultant/advisory board for Medtronics, Takeda, and Medical Letter. The other authors have no conflicts to report. NR 33 TC 21 Z9 22 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2013 VL 61 IS 1 BP 82 EP + DI 10.1161/HYPERTENSIONAHA.112.200477 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 055AD UT WOS:000312386200022 PM 23172931 ER PT J AU Rosano, C Watson, N Chang, YF Newman, AB Aizenstein, HJ Du, Y Venkatraman, V Harris, TB Barinas-Mitchell, E Sutton-Tyrrell, K AF Rosano, Caterina Watson, Nora Chang, YueFang Newman, Anne B. Aizenstein, Howard J. Du, Yan Venkatraman, Vijay Harris, Tamara B. Barinas-Mitchell, Emma Sutton-Tyrrell, Kim TI Aortic Pulse Wave Velocity Predicts Focal White Matter Hyperintensities in a Biracial Cohort of Older Adults SO HYPERTENSION LA English DT Article DE pulse wave velocity; small vessel disease; longitudinal; fractional anisotropy; community-dwelling elderly ID SMALL-VESSEL DISEASE; SYSTOLIC BLOOD-PRESSURE; ARTERIAL STIFFNESS; COGNITIVE DECLINE; ORGAN DAMAGE; HYPERTENSIVE PATIENTS; GRAY-MATTER; MR-IMAGES; BRAIN; ASSOCIATION AB Although the cross-sectional relationship of arterial stiffness with cerebral small vessel disease is consistently shown in middle-aged and young-old adults, it is less clear whether these associations remain significant over time in very old adults. We hypothesize that arterial stiffness is longitudinally associated with white matter characteristics, and associations are stronger within watershed areas. Neuroimaging was obtained in 2006-2008 from 303 elderly (mean age 82.9 years, 59% women, 41% black) with pulse wave velocity (PWV) measures in 1997-1998. Multivariable regression models estimated the coefficients for PWV (cm/sec) in relationship to presence, severity, and spatial distribution of white matter hyperintensities (WMH), gray matter volume, and fractional anisotropy from diffusion tensor, adjusting for demographic, cardiovascular risk factors, and diseases from 1997-1998 to 2006-2008. Higher PWV in 1997-1998 was associated with greater WMH volume in 2006-2008 within the left superior longitudinal fasciculus (age and total brain WMH adjusted, P=0.023), but not with WMH in other tracts or with fractional anisotropy or gray matter volume from total brain (P>0.2). Associations were stronger in blacks than in whites, remaining significant in fully adjusted models. Elderly with WMH in tracts related to processing speed and memory are more likely to have had higher PWV values 10 years prior, before neuroimaging data being available. Future studies should address whether arterial stiffness can serve as an early biomarker of covert brain structural abnormalities and whether early arterial stiffness control can promote successful brain aging, especially in black elderly. (Hypertension. 2013;61:160-165.) center dot Online Data Supplement C1 [Rosano, Caterina; Watson, Nora; Newman, Anne B.; Du, Yan; Barinas-Mitchell, Emma; Sutton-Tyrrell, Kim] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Chang, YueFang] Univ Pittsburgh, Dept Neurol Surg, Pittsburgh, PA 15260 USA. [Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. [Venkatraman, Vijay] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Rosano, C (reprint author), 130 N Bellefield Ave,Room 507, Pittsburgh, PA 15213 USA. EM rosanoc@edc.pitt.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010; Barinas-Mitchell, Emma/0000-0002-7280-7781 FU National Institutes of Health's National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIA [R01-AG028050]; National Institute of Nursing Research [R01-NR012459, R01 MH076079, P30 AG024827-06, R01 AG029232-01] FX This work was supported by National Institutes of Health's National Institute on Aging (NIA) contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grant R01-AG028050; National Institute of Nursing Research grant R01-NR012459, R01 MH076079, P30 AG024827-06, R01 AG029232-01; and in part by the Intramural Research Program of the NIA. NR 56 TC 24 Z9 25 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2013 VL 61 IS 1 BP 160 EP + DI 10.1161/HYPERTENSIONAHA.112.198069 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 055AD UT WOS:000312386200032 PM 23172923 ER PT J AU Ganapathi, SB Wei, SG Zaremba, A Lamb, FS Shears, SB AF Ganapathi, Sindura B. Wei, Shun-Guang Zaremba, Angelika Lamb, Fred S. Shears, Stephen B. TI Functional Regulation of ClC-3 in the Migration of Vascular Smooth Muscle Cells SO HYPERTENSION LA English DT Article DE calcium; chloride; inositol phosphate; CaMKII; atherosclerosis; restenosis ID ACTIVATED CHLORIDE CHANNELS; DEPENDENT PROTEIN-KINASE; INOSITOL 3,4,5,6-TETRAKISPHOSPHATE; ION CHANNELS; CL-CHANNEL; CALCIUM; EXPRESSION; PROLIFERATION; TRANSPORTERS; MODULATION AB Migration of vascular smooth muscle cells (VSMCs) into neointima contributes to atherosclerosis and restenosis. This migration requires coordinated plasmalemmal fluxes of water and ions. Here, we show that aortic VSMC migration depends on the regulation of transmembrane Cl-flux by ClC-3, a Cl- channel/transporter. The contribution of ClC-3 to plasmalemmal Cl- current was studied in VSMCs by electrophysiological recordings. Cl(-)current was negligible in cells perfused with 0 [Ca2+]. Raising intracellular [Ca2+] to 0.5 mu M activated a Cl-current (I-Cl.Ca), approximately half of which was eliminated on inhibition by KN-93 of calmodulin-dependent protein kinase II. I-Cl.Ca was also halved by inositol-3,4,5,6-tetrakisphosphate, a cellular signal with the biological function of specifically preventing calmodulin-dependent protein kinase II from activating I-Cl.Ca. Gene disruption of ClC-3 reduced I-Cl.Ca by 50%. Moreover, I-Cl.Ca in the ClC-3 null VSMCs was not affected by either KN-93 or inositol-3,4,5,6-tetrakisphosphate. We conclude that I-Cl.Ca is composed of 2 components, one is ClC-3 independent whereas the other is ClC-3 dependent, activated by calmodulin-dependent protein kinase II and inhibited by inositol-3,4,5,6-tetrakisphosphate. We also assayed VSMC migration in transwell assays. Migration was halved in ClC-3 null cells versus wild-type cells. In addition, inhibition of ClC-3 by niflumic acid, KN-93, or inositol-3,4,5,6-tetrakisphosphate each reduced cell migration in wild-type cells but not in ClC-3 null cells. These cell-signaling roles of ClC-3 in VSMC migration suggest new therapeutic approaches to vascular remodeling diseases. (Hypertension. 2013;61:174-179.) center dot Online Data Supplement C1 [Ganapathi, Sindura B.; Wei, Shun-Guang; Zaremba, Angelika; Shears, Stephen B.] NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. [Lamb, Fred S.] Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. [Wei, Shun-Guang] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA USA. RP Shears, SB (reprint author), NIEHS, Inositol Signaling Grp, Lab Signal Transduct, NIH,Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU National Institutes of Health/National Institute of Environmental Health Sciences; National Institutes of Health [RO1 HL62483] FX This work was supported by the Intramural Research Program of the National Institutes of Health/National Institute of Environmental Health Sciences and an National Institutes of Health RO1 grant to F.S.L (HL62483). NR 42 TC 5 Z9 6 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JAN PY 2013 VL 61 IS 1 BP 174 EP + DI 10.1161/HYPERTENSIONAHA.112.194209 PG 17 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 055AD UT WOS:000312386200034 PM 23150504 ER PT J AU Bork, K Cames, C Cournil, A Musyoka, F Ayassou, K Naidu, K Mepham, S Gichuhi, C Read, JS Gaillard, P de Vincenzi, I AF Bork, Kirsten Cames, Cecile Cournil, Amandine Musyoka, Faith Ayassou, Kossiwavi Naidu, Kevindra Mepham, Stephen Gichuhi, Christine Read, Jennifer S. Gaillard, Philippe de Vincenzi, Isabelle CA Kesho Bora Study Grp TI Infant Feeding Modes and Determinants Among HIV-1-Infected African Women in the Kesho Bora Study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE infant feeding; HIV/AIDS; Africa; prevention of mother-to-child transmission ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-FREE SURVIVAL; POSTNATAL TRANSMISSION; ANTIRETROVIRAL DRUGS; INFECTIOUS-DISEASES; PROSPECTIVE COHORT; POOLED ANALYSIS; LARGE OUTBREAK; BURKINA-FASO AB Objective: To assess breastfeeding modes and determinants in a prevention of mother-to-child transmission study. Design: HIV-1-infected pregnant women from 5 sites in Burkina Faso, Kenya, and South Africa were enrolled in the study that comprised 2 prospective cohorts and 1 randomized controlled trial. Women were counseled to either breastfeed exclusively up to 6 months or formula feed from birth. Methods: Determinants of breastfeeding initiation and continuation by 3 months postpartum were investigated using multiple logistic regression analysis. Neonatal morbidity was defined as mother-reported fever, diarrhea, or vomiting during the first month of life. Results: Among 1028, 781 women (76%) initiated breastfeeding and 565 of 995 (56%) were still breastfeeding at 3 months postpartum (30% exclusively, 18% predominantly, and 8% partially). Study site (Durban, Mombasa, and Nairobi compared with Bobo-Dioulasso), CD4 cell count (<200 cells/mm(3)), secondary schooling (compared with none), and emergency cesarean delivery (compared with vaginal delivery) were independently associated with a lower probability of ever breastfeeding. The odds of still breastfeeding by 3 months postpartum (among those breastfeeding by 1 month) were lower in Mombasa, Nairobi, and Somkhele (compared with Bobo-Dioulasso) and among infants with neonatal morbidity [0.60 (0.37-0.976)]. The odds of exclusive breastfeeding (EBF) by 3 months (if EBF by 1 month) were lower in Mombasa and Nairobi, in ill neonates [0.54 (0.31-0.93)] and boys [0.51 (0.34-0.77)]. Conclusions: EBF was of short duration, particularly for boys. The importance of neonatal morbidity for breastfeeding cessation requires further investigation. Infant feeding counseling might need adaptation to better support mothers of boys and ill neonates. C1 [Bork, Kirsten; Cames, Cecile; Cournil, Amandine] UM1, UMI233, IRD, F-34394 Montpellier 5, France. [Musyoka, Faith] ICRH, Mombasa, Kenya. [Ayassou, Kossiwavi] Ctr Muraz, Bobo Dioulasso, Burkina Faso. [Naidu, Kevindra] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Somkhele, South Africa. [Naidu, Kevindra; Mepham, Stephen] Univ KwaZulu Natal, Durban, South Africa. [Gichuhi, Christine] Africa Hosp, Nairobi, Kenya. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Gaillard, Philippe; de Vincenzi, Isabelle] WHO, CH-1211 Geneva, Switzerland. RP Bork, K (reprint author), UM1, UMI233, IRD, BP 64501, F-34394 Montpellier 5, France. EM kirsten.bork@ird.fr RI Van de Perre, Philippe/B-9692-2008; OI Van de Perre, Philippe/0000-0002-3912-0427; Bork, Kirsten/0000-0002-5909-7332; Njagi, Ephantus/0000-0002-1484-0241 FU Agence Nationale de Recherche sur le Sida et les hepatites virales (ANRS); Department for International Development (DFID); European and Developing Countries Clinical Trials Partnership (EDCTP); Thrasher Research Fund; Belgian Directorate General for International Cooperation; GlaxoSmithKline Foundation; Centers for Disease Control and Prevention; Eunice Kennedy Shriver National Institute of Child Health and Human Development; UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction; ANRS; UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP); WHO/HRP; EDCTP; DFID; UNICEF FX Supported by Agence Nationale de Recherche sur le Sida et les hepatites virales (ANRS), Department for International Development (DFID), European and Developing Countries Clinical Trials Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General for International Cooperation, GlaxoSmithKline Foundation, Centers for Disease Control and Prevention, Eunice Kennedy Shriver National Institute of Child Health and Human Development, and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction. The Bobo-Dioulasso site was funded by ANRS and UNDP/UNFPA/World Bank/WHO Special Programme of Research, Development and Research Training in Human Reproduction (WHO/HRP). The Mombasa site was funded by ANRS, WHO/HRP, EDCTP, Thrasher Research Fund, and Belgian Directorate General for International Cooperation. The Nairobi site was funded by the Centers for Disease Control and Prevention and the Eunice Kennedy Shriver National Institute of Child Health and Human Development through a cooperative agreement. The South African sites were funded by the DFID, EDCTP, UNICEF, and WHO/HRP. The Nutrition and laboratory coordination were funded by ANRS. The overall coordination and external monitoring was funded by WHO/HRP. NR 33 TC 7 Z9 7 U1 2 U2 12 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 JAN 1 PY 2013 VL 62 IS 1 BP 109 EP 118 DI 10.1097/QAI.0b013e318277005e PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 058PG UT WOS:000312645400023 PM 23075919 ER PT J AU Isukapalli, SS Brinkerhoff, CJ Xu, S Dellarco, M Landrigan, PJ Lioy, PJ Georgopoulos, PG AF Isukapalli, Sastry S. Brinkerhoff, Christopher J. Xu, Shu Dellarco, Michael Landrigan, Philip J. Lioy, Paul J. Georgopoulos, Panos G. TI Exposure indices for the National Children's Study: application to inhalation exposures in Queens County, NY SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE National Children's Study; exposure index; birth outcomes; inhalation exposures ID PREGNANCY OUTCOMES; DOSE ASSESSMENT; AIR-POLLUTION; QUALITY; SYSTEM AB Characterization of environmental exposures to population subgroups within the National Children's Study (NCS), or other large-scale human environmental health studies is essential for developing a high-quality data platform for subsequent investigations. A computational formulation utilizing the tiered exposure ranking framework is presented for calculating inhalation exposure indices (EIs) for population subgroups. This formulation employs a probabilistic approach and combines information from diverse, publicly available exposure-relevant databases and information on biological mechanisms, for ranking study locations or population subgroups with respect to potential for specific end point-related environmental exposures. These EIs capture and summarize, within a set of numerical values/ranges, complex distributions of potential exposures to multiple airborne contaminants. These estimates capture spatial and demographic variability within each study segment, and allow for the relative comparison of study locations based on different statistical metrics of exposures. The EI formulation was applied to characterize and rank segments within Queens County, NY, which is one of the Vanguard centers for the NCS. Inhalation EI estimates relevant to respiratory outcomes, and potentially to pregnancy outcomes (low birth weight and preterm birth rates) were calculated at the study segment level. Results indicate that there is substantial variability across the study segments in Queens County, NY, and within segments, and showed an exposure gradient across the study segments that can help guide and target environmental and personal exposure sampling efforts in this county. The results also serve as an example application of the EI for use in other exposure and outcome studies. Journal of Exposure Science and Environmental Epidemiology (2012) 23, 22-31; doi:10.1038/jes.2012.99; published online 17 October 2012 C1 [Isukapalli, Sastry S.; Brinkerhoff, Christopher J.; Xu, Shu; Lioy, Paul J.; Georgopoulos, Panos G.] EOHSI, Piscataway, NJ 08854 USA. [Dellarco, Michael] NICHD, NICHHD, Bethesda, MD 20892 USA. [Landrigan, Philip J.] Mt Sinai Sch Med, New York, NY 10029 USA. RP Lioy, PJ (reprint author), EOHSI, 170 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM plioy@eohsi.rutgers.edu FU National Children's Study Queens Vanguard Center; National Institute of Child Health and Human Development, National Institutes of Health [0258-325-4609]; NIEHS [P30ES005022] FX Support for the work presented here is provided by the National Children's Study Queens Vanguard Center, which is funded in whole or in part by the National Institute of Child Health and Human Development, National Institutes of Health, under Contract Number 0258-325-4609. Further support is provided by the NIEHS sponsored UMDNJ Center for Environmental Exposures and Disease, under Grant Number NIEHS P30ES005022. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. NR 22 TC 1 Z9 1 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD JAN-FEB PY 2013 VL 23 IS 1 BP 22 EP 31 DI 10.1038/jes.2012.99 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 057QE UT WOS:000312577300004 PM 23072768 ER PT J AU Deziel, NC Wei, WQ Abnet, CC Qiao, YL Sunderland, D Ren, JS Schantz, MM Zhang, Y Strickland, PT Abubaker, S Dawsey, SM Friesen, MC Roth, MJ AF Deziel, Nicole C. Wei, Wen-Qiang Abnet, Christian C. Qiao, You-Lin Sunderland, Deirdre Ren, Jian-Song Schantz, Michele M. Zhang, Yu Strickland, Paul T. Abubaker, Salahaddin Dawsey, Sanford M. Friesen, Melissa C. Roth, Mark J. TI A multi-day environmental study of polycyclic aromatic hydrocarbon exposure in a high-risk region for esophageal cancer in China SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE polycyclic aromatic hydrocarbons; cancer; China; dietary exposure; inhalation exposure; biomonitoring ID SQUAMOUS-CELL CARCINOMA; 1-HYDROXYPYRENE GLUCURONIDE; RESIDENTIAL AIR; URINE; AREA; IRAN; TOBACCO; CONTRIBUTE; ALCOHOL; LINXIAN AB Linzhou, China has one of the highest rates of esophageal squamous cell carcinoma in the world. Exposure to carcinogenic polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), may have a role in this increased risk. To better understand PAH sources, we measured PAHs in the air and food of 20 non-smokers over multiple days and compared the concentrations with a urinary PAH biomarker, 1-hydroxypyrene glucuronide (1-OHPG). Sampling occurred over 4 consecutive days. Kitchen air samples (days 2-3) and duplicate diet samples (days 1-4) were analyzed for 14 or more unique PAHs, including BaP. Daily urine samples (days 1-3) were analyzed for 1-OHPG. Mixed-effects models were used to evaluate the associations between air or food PAH concentrations and urine 1-OHPG concentrations. The median kitchen air BaP concentration was 10.2 ng/m(3) (interquartile range (IQR): 5.1-20.2 ng/m(3)). The median daily food BaP concentration and intake were 0.08 ng/g (IQR = 0.04-0.16 ng/g) and 86 ng/day (IQR = 41-142 ng/day), respectively. The median 1-OHPG concentration was 3.36 pmol/ml (IQR = 2.09-6.98 pmol/ml). In mixed-effects models, 1-OHPG concentration increased with same-day concentration of food BaP (P=0.07). Although PAH concentrations in air were not associated with 1-OHPG concentrations, the high concentrations of PAHs in both air and food suggest that they are both important routes of exposure to PAHs in this population. Further evaluation of the role of PAH exposure from air and food in the elevated rates of esophageal cancer in this region is warranted. Journal of Exposure Science and Environmental Epidemiology (2013) 23, 52-59; doi:10.1038/jes.2012.73; published online 18 July 2012 C1 [Deziel, Nicole C.; Friesen, Melissa C.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Wei, Wen-Qiang; Qiao, You-Lin; Zhang, Yu] Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. [Abnet, Christian C.; Ren, Jian-Song; Dawsey, Sanford M.; Roth, Mark J.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Sunderland, Deirdre] Univ Maryland, Chesapeake Biol Lab, Ctr Environm Sci, Solomons, MD 20688 USA. [Schantz, Michele M.] Natl Inst Stand & Technol, Analyt Chem Div, Gaithersburg, MD 20899 USA. [Strickland, Paul T.; Abubaker, Salahaddin] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. RP Deziel, NC (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8005, Bethesda, MD 20892 USA. EM dezielnc@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Friesen, Melissa/A-5362-2009 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843; FU NCI [N01-RC-47702]; Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; Cancer Institute, Chinese Academy of Medical Sciences FX This study was supported in part by NCI contract N01-RC-47702 to the Cancer Institute, Chinese Academy of Medical Sciences; in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH; and in part by the Cancer Institute, Chinese Academy of Medical Sciences. NR 36 TC 8 Z9 8 U1 2 U2 34 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD JAN-FEB PY 2013 VL 23 IS 1 BP 52 EP 59 DI 10.1038/jes.2012.73 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 057QE UT WOS:000312577300008 PM 22805987 ER PT J AU Morgan, RA AF Morgan, Richard A. TI Faster, Cheaper, Safer, T-cell Engineering SO JOURNAL OF IMMUNOTHERAPY LA English DT Editorial Material ID TRANSPOSON; SYSTEM C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, Bldg 10,CRC Rm 3-5940,10 Ctr Dr,MSC1201, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 9 TC 2 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JAN PY 2013 VL 36 IS 1 BP 1 EP 2 DI 10.1097/CJI.0b013e3182791257 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 058UL UT WOS:000312659900001 PM 23211627 ER PT J AU Mohammed, J Gunderson, AJ Khong, HH Koubek, RD Udey, MC Glick, AB AF Mohammed, Javed Gunderson, Andrew J. Khong, Hong-Hanh Koubek, Richard D. Udey, Mark C. Glick, Adam B. TI TGF beta 1 Overexpression by Keratinocytes Alters Skin Dendritic Cell Homeostasis and Enhances Contact Hypersensitivity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID EPIDERMAL LANGERHANS CELLS; STEADY-STATE CONDITIONS; TGF-BETA; IN-VIVO; TRANSGENIC MICE; NULL MICE; T-CELLS; PSORIASIS; EXPRESSION; MIGRATION AB Overexpression of transforming growth factor beta-1 (TGF beta 1) in mouse epidermis causes cutaneous inflammation and keratinocyte hyperproliferation. Here we examined acute effects of TGF beta 1 overproduction by keratinocytes on skin dendritic cells (DCs). TGF beta 1 induction for 2 and 4 days increased the numbers and CD86 expression of B220(+) plasmacytoid DCs (pDCs) and CD207(+)CD103(+), CD207(-)CD103(-)CD111D(+), and CD207(-)CD103(-)CD11b(-) dermal DCs (dDCs) in skin-draining lymph nodes (SDLNs). The dermis of TGF beta 1-overexpressing mice had significantly more pDCs, CD207(+)CD103(+) dDCs, and CD207(-)CD11b(+) dDCs in the absence of increased dermal proliferation. Application of dye, tetramethyl rhodamine iso-thiocyanate (TRITC), in dibutylpthalate (DBP) solution after TGF beta 1 induction increased the numbers of TRITC(+)CD207(-) dDCs in SDLNs, and augmented TRITC/DBP-induced Langerhans cell (LC) migration 72 hours post TRITC treatment. Consistent with this, LC migration was increased in vitro by TGF beta 1 overexpression in skin explants and by exogenous TGF beta 1 in culture media. Transient TGF beta 1 induction during DNFB sensitization increased contact hypersensitivity responses by 1.5-fold. Thus, elevated epidermal TGF beta 1 alone is sufficient to alter homeostasis of multiple cutaneous DC subsets, and enhance DC migration and immune responses to contact sensitizers. These results highlight a role for keratinocyte-derived TGF beta 1 in DC trafficking and in the initiation of skin inflammation. Journal of Investigative Dermatology (2013) 133, 135-143; doi:10.1038/jid.2012.241; published online 26 July 2012 C1 [Mohammed, Javed; Gunderson, Andrew J.; Khong, Hong-Hanh; Koubek, Richard D.; Glick, Adam B.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16801 USA. [Udey, Mark C.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Glick, AB (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, 201 Life Sci Bldg, University Pk, PA 16801 USA. EM abg11@psu.edu FU NCI [CA117957, 122109]; NIH, Center for Cancer Research, NCI FX We thank Dr Maria Gaiser for suggestions and technical help, and the Huck Institute Flow Cytometry Core Facility for help with flow cytometry. This study was funded by grants CA117957 and 122109 (AG) from the NCI and by the Intramural Research Program of the NIH, Center for Cancer Research, NCI (MCU). NR 46 TC 6 Z9 6 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2013 VL 133 IS 1 BP 135 EP 143 DI 10.1038/jid.2012.241 PG 9 WC Dermatology SC Dermatology GA 056GD UT WOS:000312475500020 PM 22832490 ER PT J AU Mabuchi, T Singh, TP Takekoshi, T Jia, GF Wu, XS Kao, MC Weiss, I Farber, JM Hwang, ST AF Mabuchi, Tomotaka Singh, Tej Pratap Takekoshi, Tomonori Jia, Guang-fu Wu, Xuesong Kao, Mandy C. Weiss, Ido Farber, Joshua M. Hwang, Sam T. TI CCR6 Is Required for Epidermal Trafficking of gamma delta-T Cells in an IL-23-Induced Model of Psoriasiform Dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID SKIN INFLAMMATION; PATHOGENESIS; IDENTIFICATION; CCL20; MICE; TH17; HYPERPLASIA; RECRUITMENT; EXPRESSION; CYTOKINES AB A subset of CC chemokine receptor-6(+) (CCR6(+)), gamma delta-low (GDL) Tcells that express Th17 cytokines in mouse skin participates in IL-23-induced psoriasiform dermatitis. We used CCR6-deficient (knockout, KO) and wild-type (WT) mice to analyze skin trafficking patterns of GDL T cells and function-blocking mAbs to determine the role of CCR6 in IL-23-mediated dermatitis. Herein, CCL20 was highly upregulated in IL-23-injected WT mouse ear skin as early as 24 hours after initial treatment, and large numbers of CCR6(+) cells were observed in the epidermis of IL-23-injected WT Mice. Anti-CCL20 mAbs reduced psoriasiform dermatitis and blocked recruitment of GDL T cells to the epidermis. In CCR6 KO mice, GDL T cells failed to accumulate in the epidermis after IL-23 treatment, but the total numbers of GDL T cells in the dermis of WT and CCR6 KO mice were equivalent. There was an similar to 70% reduction in the proportion of IL-22(+) GDL T cells in the dermis of CCR6 KO mice (vs. WT mice), suggesting that effector function and epidermal recruitment of GDLT ells are impaired in CCR6-deficient mice. Thus, these data show that CCR6 regulates epidermal trafficking of gamma delta-T-cell subsets in the skin and suggest the potential of CCR6 as a therapeutic target for psoriasis. Journal of investigative Dermatology (2013) 133, 164-171; doi :10.1038/jid.2012.260; published online 16 August 2012 C1 [Mabuchi, Tomotaka; Takekoshi, Tomonori; Jia, Guang-fu; Wu, Xuesong; Kao, Mandy C.; Hwang, Sam T.] Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. [Singh, Tej Pratap; Weiss, Ido; Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), Med Coll Wisconsin, Dept Dermatol, FEC4100,9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM sthwang@mcw.edu FU National Psoriasis Foundation; NIAID FX We are grateful to Mr Nathan Duncan, Lei Ma, and George Paragh (Department of Dermatology, MCW) for expert technical assistance and for many helpful suggestions. This work was supported by a Discovery Grant from the National Psoriasis Foundation to TM and STH, and Intramural Research Funds (NIAID) to JMF. NR 32 TC 31 Z9 33 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2013 VL 133 IS 1 BP 164 EP 171 DI 10.1038/jid.2012.260 PG 8 WC Dermatology SC Dermatology GA 056GD UT WOS:000312475500023 PM 22895364 ER PT J AU Ke, HN Augustine, CK Gandham, VD Jin, JY Tyler, DS Akiyama, SK Hall, RP Zhang, JY AF Ke, Hengning Augustine, Christina K. Gandham, Vineela D. Jin, Jane Y. Tyler, Douglas S. Akiyama, Steven K. Hall, Russell P. Zhang, Jennifer Y. TI CYLD Inhibits Melanoma Growth and Progression through Suppression of the JNK/AP-1 and beta 1-Integrin Signaling Pathways SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID NF-KAPPA-B; DEUBIQUITINATING ENZYME CYLD; TUMOR-NECROSIS-FACTOR; EPIDERMAL NEOPLASIA; GENE; INTEGRIN; ACTIVATION; EXPRESSION; APOPTOSIS; BINDING AB The molecular mechanisms mediating cylindromatosis (CYLD) tumor suppressor function appear to be manifold. Here, we demonstrate that, in contrast to the increased levels of phosphorylated c-Jun NH2-terminal kinase (pJNK), CYLD was decreased in a majority of the melanoma cell lines and tissues examined. Exogenous expression of CYLD but not its catalytically deficient mutant markedly inhibited melanoma cell proliferation and migration in vitro and subcutaneous tumor growth in vivo. In addition, the melanoma cells expressing exogenous CYLD were unable to form pulmonary tumor nodules following tail-vein injection. At the molecular level, CYLD decreased beta 1-integrin and inhibited pJNK induction by tumor necrosis factor-alpha or cell attachment to collagen IV. Moreover, CYLD induced an array of other molecular changes associated with modulation of the "malignant" phenotype, including a decreased expression of cyclin D1, N-cadherin, and nuclear Bcl3, and an increased expression of p53 and E-cadherin. Most interestingly, coexpression of the constitutively active MKK7 or c-Jun mutants with CYLD prevented the above molecular changes, and fully restored melanoma growth and metastatic potential in vivo. Our findings demonstrate that the JNK/activator protein 1 signaling pathway underlies the melanoma growth and metastasis that are associated with CYLD loss of function. Thus, restoration of CYLD and inhibition of JNK and beta 1-integrin function represent potential therapeutic strategies for treatment of malignant melanoma. Journal of Investigative Dermatology (2013) 133, 221-229; doi:10.1038/jid.2012.253; published online 26 July 2012 C1 [Ke, Hengning; Gandham, Vineela D.; Jin, Jane Y.; Hall, Russell P.; Zhang, Jennifer Y.] Duke Univ, Dept Dermatol, Durham, NC USA. [Augustine, Christina K.; Tyler, Douglas S.] Duke Univ, Dept Surg, Durham, NC USA. [Augustine, Christina K.; Tyler, Douglas S.] Durham Vet Affairs Med Ctr, Durham, NC USA. [Akiyama, Steven K.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Zhang, JY (reprint author), Duke Hosp S, Duke Med Ctr DUMC 3135, Room 4032,200 Trent Dr, Durham, NC 27710 USA. EM Jennifer.zhang@duke.edu FU NIH/NIAMS [R01AR057746]; Duke School of Medicine and Duke Dermatology; National Institute of Environmental Health Sciences FX This work was supported in part by NIH/NIAMS (R01AR057746) and grants from Duke School of Medicine and Duke Dermatology to JYZ and the Intramural Research Program of the National Institute of Environmental Health Sciences. We thank M. Angelica Selim (Duke University) for her guidance in histological analysis, and Chuan-Yuan Li, Kelly Nelson, and Shirley Zhang (Duke University) for suggestions and critical reading of the manuscript. We also thank Rene Bernard (Netherland Cancer Institute), Dirk Bohmann (University of Rochester Medical Center), and Michael Kracht (Medical School of Hanover, Hanover, NH) for sharing the CYLD, c-Jun, and MKK7 expression constructs, respectively. In addition, we are indebted to Jonathan L Cook and Stephen Ray (Duke University) for providing surgically discarded melanoma tissues. NR 40 TC 11 Z9 13 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X EI 1523-1747 J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JAN PY 2013 VL 133 IS 1 BP 221 EP 229 DI 10.1038/jid.2012.253 PG 9 WC Dermatology SC Dermatology GA 056GD UT WOS:000312475500029 PM 22832488 ER PT J AU Vanderver, A Tonduti, D Bernard, G Lai, JP Rossi, C Carosso, G Quezado, M Wong, K Schiffmann, R AF Vanderver, Adeline Tonduti, Davide Bernard, Genevieve Lai, Jinping Rossi, Christopher Carosso, Giovanni Quezado, Martha Wong, Kondi Schiffmann, Raphael TI More Than Hypomyelination in Pol-III Disorder SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Hypodontia; Hypogonadotropic hypogonadism; Hypomyelination; Leukodystrophy; Pol-III ID BLOOD-BRAIN-BARRIER; POLYMERASE-III; 4H SYNDROME; HYPOGONADOTROPIC HYPOGONADISM; CATALYTIC SUBUNIT; RNA; MUTATIONS; LEUKOENCEPHALOPATHY; LEUKODYSTROPHY; HYPODONTIA AB The 4H syndrome (hypomyelination, hypodontia, hypogonadotropic hypogonadism) is a newly recognized leukodystrophy. The classical form is characterized by the association of hypomyelination, abnormal dentition, and hypogonadotropic hypogonadism, but the recent identification of 2 genes responsible for the syndrome demonstrates that these 3 main characteristics can be variably combined among "Pol-III (polymerase III) Yrelated leukodystrophies.'' The pathophysiology of this group of diseases is still to be elucidated, and there are no neuropathologic descriptions of brain tissue. We report the clinical, neuroradiologic, and neuropathologic findings of a patient affected by 4H syndrome with confirmed POLR3A mutations. We found a marked loss of oligodendrocytes, varying in severity in different brain regions, and accompanied by severe loss of myelin, moderately severe loss of axons, and patchy perivascular regions of better preserved white matter. There was relatively mild white matter astrogliosis and microgliosis. A macrophage reaction involving viable normal-appearing oligodendroglia suggests the possibility of an immunologic process in this disorder. Cortical laminar astrogliosis and mineralization of Layers I and II in particular were present. Thus, despite the uniformly hypomyelinating pattern seen on magnetic resonance imaging, neuropathologic examination reveals a complex heterogeneous leukodystrophy with prominent neuroaxonal and glial involvement in this disorder. C1 [Vanderver, Adeline; Carosso, Giovanni] Childrens Natl Med Ctr, Ctr Genet Med, Washington, DC 20010 USA. [Tonduti, Davide] Univ Pavia, IRCCS C Mondino Natl Inst Neurol Fdn, Child Neurol & Psychiat Unit, I-27100 Pavia, Italy. [Bernard, Genevieve] McGill Univ, Montreal Childrens Hosp, Heath Ctr, Montreal, PQ H3H 1P3, Canada. [Lai, Jinping; Quezado, Martha] NIH, Dept Pathol, Bethesda, MD 20892 USA. [Rossi, Christopher] Childrens Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. [Wong, Kondi] UTHSCSA, Dept Pathol, San Antonio, TX USA. [Schiffmann, Raphael] Baylor Res Inst, Inst Metab Dis, Dallas, TX USA. RP Vanderver, A (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM avanderv@childrensnational.org RI tonduti, davide/K-1673-2016 OI tonduti, davide/0000-0001-9371-7454 FU National Institutes of Health; National Human Genome Research Institute; National Institute of Neurologic Disorders and Stroke; Myelin Disorders Bioregistry Project at Children's National Medical Center; Fondation sur les Leucodystrophies; Fondation Go; Montreal Children's Hospital, Montreal University Health Center Research Institutes; FRSQ (Fonds de Recherche en Sante du Quebec) FX This work was supported by the intramural program at the National Institutes of Health, the National Human Genome Research Institute, the National Institute of Neurologic Disorders and Stroke, and the Myelin Disorders Bioregistry Project at Children's National Medical Center. The contributions of Genevieve Bernard were supported by the Fondation sur les Leucodystrophies, the "Fondation Go," the Montreal Children's Hospital, Montreal University Health Center Research Institutes, and the FRSQ (Fonds de Recherche en Sante du Quebec). NR 37 TC 6 Z9 6 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JAN PY 2013 VL 72 IS 1 BP 67 EP 75 DI 10.1097/NEN.0b013e31827c99d2 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 059YJ UT WOS:000312741300008 PM 23242285 ER PT J AU Caplan, S Escobar, J Paris, M Alvidrez, J Dixon, JK Desai, MM Scahill, LD Whittemore, R AF Caplan, Susan Escobar, Javier Paris, Manuel Alvidrez, Jennifer Dixon, Jane K. Desai, Mayur M. Scahill, Lawrence D. Whittemore, Robin TI Cultural Influences on Causal Beliefs About Depression Among Latino Immigrants SO JOURNAL OF TRANSCULTURAL NURSING LA English DT Article DE causal beliefs; depression; Latinos/Hispanics; immigrants; illness perceptions ID MEXICAN-AMERICANS; HEALTH BELIEFS; CARE; ACCULTURATION; CURANDERISMO; HISPANICS; ETHNICITY; ATTITUDES; DISTRESS; FATALISM AB Purpose: This study describes causal beliefs about depression among Dominican, Colombian, and Ecuadorian immigrants. The authors describe participants' narratives about how particular supernatural or religious beliefs may contribute to or alleviate depression. Method: Latino primary care patients (n = 177) were interviewed with the Beliefs About Causes of Depression Scale, a list of 35 items rated from not at all important to extremely important. Participants had the option of expanding on responses using an informal conversational approach. Underlying themes of these explanatory comments were derived from narrative and content analysis. Results: Major themes that emerged were Psychosocial and Religious and Supernatural causal beliefs. A third theme emerged that represented the integration of these categories in the context of the immigrant experience. Discussion and Conclusions: This article adds to the understanding of cross-cultural beliefs about depression. Psychosocial stressors related to the immigrant experience and adverse life events were highly endorsed, but the meaning of these stressors was construed in terms of religious and cultural values. To provide culturally appropriate services, nurses should be aware of and discuss the patient's belief systems, illness interpretations, and expectations of treatment. C1 [Caplan, Susan] Rutgers State Univ, Newark, NJ 07102 USA. [Escobar, Javier] Univ Med & Dent New Jersey, New Brunswick, NJ USA. [Paris, Manuel; Dixon, Jane K.; Desai, Mayur M.; Scahill, Lawrence D.; Whittemore, Robin] Yale Univ, New Haven, CT USA. [Alvidrez, Jennifer] NIH, Bethesda, MD 20892 USA. RP Caplan, S (reprint author), Rutgers State Univ, Ackerson Hall,180 Univ Ave, Newark, NJ 07102 USA. EM susan.caplan@rutgers.edu OI Caplan, Susan/0000-0002-9656-784X; Scahill, Lawrence/0000-0001-5073-1707 FU Sigma Theta Tau International Honor Small Research grant, Indianapolis, Indiana FX This research was partially supported by a the Sigma Theta Tau International Honor Small Research grant, Indianapolis, Indiana. NR 59 TC 10 Z9 10 U1 0 U2 14 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-6596 J9 J TRANSCULT NURS JI J. Transcult. Nurs. PD JAN PY 2013 VL 24 IS 1 BP 68 EP 77 DI 10.1177/1043659612453745 PG 10 WC Nursing SC Nursing GA 052JD UT WOS:000312193000009 PM 22913985 ER PT J AU Wood, BJ Choyke, P Turkbey, B Pinto, P AF Wood, Bradford J. Choyke, Peter Turkbey, Baris Pinto, Peter TI Targeted Biopsy in the Detection of Prostate Cancer Using an Office Based Magnetic Resonance Ultrasound Fusion Device SO JOURNAL OF UROLOGY LA English DT Editorial Material C1 [Wood, Bradford J.] NCI, Ctr Intervent Oncol, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. [Choyke, Peter; Turkbey, Baris] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Wood, BJ (reprint author), NCI, Ctr Intervent Oncol, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA CL040011-05, ZIA CL040015-04, ZID BC011242-04] NR 2 TC 0 Z9 0 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2013 VL 189 IS 1 BP 92 EP 92 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 057ZZ UT WOS:000312604800031 PM 23158414 ER PT J AU Sirls, LT Richter, HE Litman, HJ Kenton, K Lemack, GE Lukacz, ES Kraus, SR Goldman, HB Weidner, A Rickey, L Norton, P Zyczynski, HM Kusek, JW AF Sirls, Larry T. Richter, Holly E. Litman, Heather J. Kenton, Kimberly Lemack, Gary E. Lukacz, Emily S. Kraus, Stephen R. Goldman, Howard B. Weidner, Alison Rickey, Leslie Norton, Peggy Zyczynski, Halina M. Kusek, John W. CA Urinary Incontinence Treatment TI The Effect of Urodynamic Testing on Clinical Diagnosis, Treatment Plan and Outcomes in Women Undergoing Stress Urinary Incontinence Surgery SO JOURNAL OF UROLOGY LA English DT Article DE urinary bladder, overactive; urinary incontinence, stress; diagnosis; urodynamics; suburethral slings ID PREDICT VOIDING DYSFUNCTION; QUALITY-OF-LIFE; HEALTH AB Purpose: We evaluated the influence of preoperative urodynamic studies on diagnoses, global treatment plans and outcomes in women treated with surgery for uncomplicated stress predominant urinary incontinence. Materials and Methods: We performed a secondary analysis from a multicenter, randomized trial of the value of preoperative urodynamic studies. Physicians provided diagnoses before and after urodynamic studies and global treatment plans, defined as proceeding with surgery, surgery type, surgical modification and nonoperative therapy. Treatment plan changes and surgical outcomes between office evaluation and office evaluation plus urodynamic studies were compared by the McNemar test. Results: Of 315 subjects randomized to urodynamic studies after office evaluation 294 had evaluable data. Urodynamic studies changed the office evaluation diagnoses in 167 women (56.8%), decreasing the diagnoses of overactive bladder-wet (41.6% to 25.2%, p < 0.001), overactive bladder-dry (31.4% to 20.8%, p = 0.002) and intrinsic sphincter deficiency (19.4% to 12.6%, p = 0.003) but increasing the diagnosis of voiding dysfunction (2.2% to 11.9%, p < 0.001). After urodynamic studies physicians canceled surgery in 4 of 294 women (1.4%), changed the incontinence procedure in 13 (4.4%) and planned to modify mid urethral sling tension (more or less obstructive) in 20 women (6.8%). Nonoperative treatment plans changed in 40 of 294 women (14%). Urodynamic study driven treatment plan changes were not associated with treatment success (OR 0.96, 95% CI 0.41, 2.25, p = 0.92) but they were associated with increased postoperative treatment for urge urinary incontinence (OR 3.23, 95% CI 1.46, 7.14, p = 0.004). Conclusions: Urodynamic studies significantly changed clinical diagnoses but infrequently changed the global treatment plan or influenced surgeon decision to cancel, change or modify surgical plans. Global treatment plan changes were associated with increased treatment for postoperative urgency urinary incontinence. C1 [Sirls, Larry T.] William Beaumont Hosp, Dept Urol, Royal Oak, MI 48073 USA. [Richter, Holly E.] Univ Alabama Birmingham, Birmingham, AL USA. [Litman, Heather J.] New England Res Inst, Watertown, MA 02172 USA. [Kenton, Kimberly] Loyola Univ, Chicago, IL 60611 USA. [Lemack, Gary E.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Kraus, Stephen R.] Univ Texas San Antonio, San Antonio, TX USA. [Lukacz, Emily S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Goldman, Howard B.] Cleveland Clin, Cleveland, OH 44106 USA. [Weidner, Alison] Duke Univ, Durham, NC USA. [Rickey, Leslie] Univ Maryland, Baltimore, MD 21201 USA. [Kusek, John W.] NIH, Bethesda, MD 20892 USA. [Norton, Peggy] Univ Utah, Salt Lake City, UT USA. [Zyczynski, Halina M.] Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. RP Sirls, LT (reprint author), William Beaumont Hosp, Dept Urol, Royal Oak, MI 48073 USA. EM lsirls@mac.com FU NIDDK NIH HHS [U01DK60401, U01DK60380, U01DK58229, U01 DK60397, U01 DK60379, U01 DK58234, U01 DK58231, U01 DK58225, U01 DK060393, U01 DK058225, U01 DK058231, U01 DK058234, U01 DK060379, U01 DK060397, U01 DK60395, U01 DK60393, U01 DK058229, U01 DK060380, U01 DK060395, U01 DK060401] NR 18 TC 22 Z9 26 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JAN PY 2013 VL 189 IS 1 BP 204 EP 209 DI 10.1016/j.juro.2012.09.050 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 057ZZ UT WOS:000312604800067 PM 22982425 ER PT J AU Xu, L Elkahloun, AG Candotti, F Grajkowski, A Beaucage, SL Petricoin, EF Calvert, V Juhl, H Mills, F Mason, K Shastri, N Chik, J Xu, C Rosenberg, AS AF Xu, Lai Elkahloun, Abdel G. Candotti, Fabio Grajkowski, Andrzej Beaucage, Serge L. Petricoin, Emanuel F. Calvert, Valerie Juhl, Hartmut Mills, Frederick Mason, Karen Shastri, Neal Chik, Josh Xu, Cynthia Rosenberg, Amy S. TI A Novel Function of RNAs Arising From the Long Terminal Repeat of Human Endogenous Retrovirus 9 in Cell Cycle Arrest SO JOURNAL OF VIROLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; P53 TUMOR-SUPPRESSOR; GENE-EXPRESSION; GERM-LINE; NF-Y; ACTIVATION; SP1; IDENTIFICATION; TRANSCRIPTION; PROMOTER AB The human genome contains approximately 50 copies of the replication-defective human endogenous retrovirus 9 (ERV-9) and thousands of copies of its solitary long term repeat (sLTR) element. While some sLTRs are located upstream of critical genes and have enhancer activity, other sLTRs are located within introns and may be transcribed as RNAs. We found that intronic RNAs arising from U3 sLTRs of ERV-9 were expressed as both sense (S) and antisense (AS) transcripts in all human cells tested but that expression levels differed in malignant versus nonmalignant cells. In nonmalignant cells, AS was expressed at higher levels than S and at higher levels than in malignant cells; in malignant cells, AS was expressed at amounts equivalent to those of S RNA. Critically, U3 AS RNA was found to physically bind to key transcription factors for cellular proliferation, including NF-Y, p53, and sp1, indicating that such RNA transcripts may function as decoy targets or traps for NF-Y and thus inhibit the growth of human cancer cells. Indeed, short U3 oligodeoxynucleotides (ODNs) based on these RNA sequences ably inhibited proliferation of cancer cell lines driven by cyclins B1/B2, the gene targets of NF-Y. C1 [Xu, Lai; Grajkowski, Andrzej; Beaucage, Serge L.; Mills, Frederick; Mason, Karen; Shastri, Neal; Chik, Josh; Xu, Cynthia; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Elkahloun, Abdel G.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Candotti, Fabio] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Petricoin, Emanuel F.; Calvert, Valerie] George Mason Univ, Ctr Appl Prote & Mol Med, Fairfax, VA 22030 USA. [Juhl, Hartmut] Indivumed GmbH, Hamburg, Germany. RP Rosenberg, AS (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Amy.Rosenberg@fda.hhs.gov FU NHGRI intramural program funds FX This work was supported by NHGRI intramural program funds (to Fabio Candotti). NR 44 TC 5 Z9 5 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 25 EP 36 DI 10.1128/JVI.01648-12 PG 12 WC Virology SC Virology GA 055ZB UT WOS:000312455500003 PM 23097441 ER PT J AU Costin, JM Zaitseva, E Kahle, KM Nicholson, CO Rowe, DK Graham, AS Bazzone, LE Hogancamp, G Sierra, MF Fong, RH Yang, ST Lin, L Robinson, JE Doranz, BJ Chernomordik, LV Michael, SF Schieffelin, JS Isern, S AF Costin, Joshua M. Zaitseva, Elena Kahle, Kristen M. Nicholson, Cindo O. Rowe, Dawne K. Graham, Amanda S. Bazzone, Lindsey E. Hogancamp, Greg Sierra, Marielys Figueroa Fong, Rachel H. Yang, Sung-Tae Lin, Li Robinson, James E. Doranz, Benjamin J. Chernomordik, Leonid V. Michael, Scott F. Schieffelin, John S. Isern, Sharon TI Mechanistic Study of Broadly Neutralizing Human Monoclonal Antibodies against Dengue Virus That Target the Fusion Loop SO JOURNAL OF VIROLOGY LA English DT Article ID FLAVIVIRUS-NAIVE ADULTS; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; DOMAIN-III; WEST-NILE; ANTIGENIC DETERMINANTS; CLINICAL-TRIAL; 4 SEROTYPES; VERO CELLS; VACCINE AB There are no available vaccines for dengue, the most important mosquito-transmitted viral disease. Mechanistic studies with anti-dengue virus (DENV) human monoclonal antibodies (hMAbs) provide a rational approach to identify and characterize neutralizing epitopes on DENV structural proteins that can serve to inform vaccine strategies. Here, we report a class of hMAbs that is likely to be an important determinant in the human humoral response to DENV infection. In this study, we identified and characterized three broadly neutralizing anti-DENV hMAbs: 4.8A, D11C, and 1.6D. These antibodies were isolated from three different convalescent patients with distinct histories of DENV infection yet demonstrated remarkable similarities. All three hMAbs recognized the E glycoprotein with high affinity, neutralized all four serotypes of DENV, and mediated antibody-dependent enhancement of infection in Fc receptor-bearing cells at subneutralizing concentrations. The neutralization activities of these hMAbs correlated with a strong inhibition of virus-liposome and intracellular fusion, not virus-cell binding. We mapped epitopes of these antibodies to the highly conserved fusion loop region of E domain II. Mutations at fusion loop residues W101, L107, and/or G109 significantly reduced the binding of the hMAbs to E protein. The results show that hMAbs directed against the highly conserved E protein fusion loop block viral entry downstream of virus-cell binding by inhibiting E protein-mediated fusion. Characterization of hMAbs targeting this region may provide new insights into DENV vaccine and therapeutic strategies. C1 [Costin, Joshua M.; Nicholson, Cindo O.; Rowe, Dawne K.; Graham, Amanda S.; Hogancamp, Greg; Sierra, Marielys Figueroa; Michael, Scott F.; Isern, Sharon] Florida Gulf Coast Univ, Dept Biol Sci, Ft Myers, FL USA. [Zaitseva, Elena; Yang, Sung-Tae; Chernomordik, Leonid V.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. [Kahle, Kristen M.; Fong, Rachel H.; Doranz, Benjamin J.] Integral Mol Inc, Philadelphia, PA USA. [Bazzone, Lindsey E.; Robinson, James E.; Schieffelin, John S.] Tulane Univ, Sch Med, Dept Pediat, Sect Pediat Infect Dis, New Orleans, LA 70112 USA. [Lin, Li] Tan Tock Seng Hosp, Communicable Dis Ctr, Singapore, Singapore. RP Isern, S (reprint author), Florida Gulf Coast Univ, Dept Biol Sci, Ft Myers, FL USA. EM sisern@fgcu.edu FU Defense Threat Reduction Agency [HDTRA1-08-1-0003, HDTRA1-09-1-0004, HDTRA1-10-1-0009]; National Science Foundation [CBET-0923030]; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH); National Institute of Allergy and Infectious Diseases (NIAID) NIH Intramural Biodefense Research grant; Intramural AIDS Targeted Antiviral Program; NIAID [HHSN272200900055C]; NIH Centers of Biomedical Research Excellence award [P20RR021970-06] FX This work was supported by the Defense Threat Reduction Agency under award numbers HDTRA1-08-1-0003, HDTRA1-09-1-0004, and HDTRA1-10-1-0009 and the National Science Foundation under grant number CBET-0923030 to S. I. and S. F. M.; the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health (NIH), and by a National Institute of Allergy and Infectious Diseases (NIAID) NIH Intramural Biodefense Research grant and the Intramural AIDS Targeted Antiviral Program to L. V. C.; by NIAID contract HHSN272200900055C to B.J.D.; and by NIH Centers of Biomedical Research Excellence award P20RR021970-06 to J.S.S. and J.E.R. NR 88 TC 35 Z9 35 U1 1 U2 23 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 52 EP 66 DI 10.1128/JVI.02273-12 PG 15 WC Virology SC Virology GA 055ZB UT WOS:000312455500005 PM 23077306 ER PT J AU Wolff, S Becker, S Groseth, A AF Wolff, Svenja Becker, Stephan Groseth, Allison TI Cleavage of the Junin Virus Nucleoprotein Serves a Decoy Function To Inhibit the Induction of Apoptosis during Infection SO JOURNAL OF VIROLOGY LA English DT Article ID LASSA-VIRUS; CASPASE CLEAVAGE; CELL-DEATH; VIRAL-PROTEINS; RNA ANALOGS; REPLICATION; IDENTIFICATION; TRANSCRIPTION; MITOCHONDRIA; ACTIVATION AB The regulation of apoptosis during infection is an important factor for host survival and, in some cases, also for the virus life cycle. At the same time, mechanisms to prevent the induction of apoptosis have been observed in numerous viral pathogens, but until now the role of apoptosis during arenavirus infection has not been investigated. Junin virus (JUNV) belongs to the New World arenavirus serogroup of the Arenaviridae and is the causative agent of Argentine hemorrhagic fever. We have demonstrated that infection with JUNV in cell culture does not induce apoptosis but leads to cleavage of the nucleoprotein (NP) into discrete products resembling caspase cleavage events. Similar specific NP degradation patterns were also observed in NP-transfected cell lines, and a closer examination of the sequence of NP showed several putative caspase cleavage motifs. Point mutations that abolished these cleavage motifs were consistent with the loss of certain cleavage products. Consistent with these data, further studies showed that treatment with a caspase inhibitor also reduced NP cleavage, indicating that the observed cleavage events were occurring as a result of caspase activity with NP as a substrate. Finally, we showed that expression of NP suppresses the cleavage of caspase 3 in cells treated with an apoptosis activator. Based on these findings, we propose that NP functions as a decoy substrate for caspase cleavage in order to inhibit the induction of apoptosis in JUNV-infected cells. C1 [Wolff, Svenja; Becker, Stephan; Groseth, Allison] Univ Marburg, Inst Virol, D-3550 Marburg, Germany. [Groseth, Allison] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT USA. RP Becker, S (reprint author), Univ Marburg, Inst Virol, D-3550 Marburg, Germany. EM becker@staff.uni-marburg.de RI Becker, Stephan/A-1065-2010 OI Becker, Stephan/0000-0002-2794-5659 FU Jurgen Manchot Stiftung; Canadian Institutes of Health Research; Philipps Universitat Marburg; Intramural Research Program of the NIH, NIAID FX This work was supported in part by fellowships from the Jurgen Manchot Stiftung (http://www.manchot.org) (to S. W.) and the Canadian Institutes of Health Research (http://www.cihr-irsc.gc.ca) (to A. G.). This research was also supported in part by the Philipps Universitat Marburg and the Intramural Research Program of the NIH, NIAID. NR 50 TC 7 Z9 7 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 224 EP 233 DI 10.1128/JVI.01929-12 PG 10 WC Virology SC Virology GA 055ZB UT WOS:000312455500018 PM 23077297 ER PT J AU Massimelli, MJ Majerciak, V Kruhlak, M Zheng, ZM AF Massimelli, Maria J. Majerciak, Vladimir Kruhlak, Michael Zheng, Zhi-Ming TI Interplay between Polyadenylate-Binding Protein 1 and Kaposi's Sarcoma-Associated Herpesvirus ORF57 in Accumulation of Polyadenylated Nuclear RNA, a Viral Long Noncoding RNA SO JOURNAL OF VIROLOGY LA English DT Article ID PABP-INTERACTING PROTEINS; POLY(A)-BINDING PROTEIN; MESSENGER-RNA; GENE-EXPRESSION; HOST SHUTOFF; 3C PROTEASE; IN-VITRO; TRANSLATION; CLEAVAGE; COMPLEX AB Polyadenylate-binding protein cytoplasmic 1 (PABPC1) is a cytoplasmic-nuclear shuttling protein important for protein translation initiation and both RNA processing and stability. We report that PABPC1 forms a complex with the Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein, which allows ORF57 to interact with a 9-nucleotide (nt) core element of KSHV polyadenylated nuclear (PAN) RNA, a viral long noncoding RNA (lncRNA), and increase PAN stability. The N-terminal RNA recognition motifs (RRMs) of PABPC1 are necessary for the direct interaction with ORF57. During KSHV lytic infection, the expression of viral ORF57 leads to a substantial decrease in overall PABPC1 expression, along with a shift in the cellular distribution of the remaining PABPC1 to the nucleus. Interestingly, PABPC1 and ORF57 have opposing functions in modulating PAN steady-state accumulation. The suppressive effect of PABPC1 specific to PAN expression is alleviated by small interfering RNA knockdown of PABPC1 or by overexpression of ORF57. Conversely, ectopic PABPC1 reduces ORF57 steady-state protein levels and induces aberrant polyadenylation of PAN and thereby indirectly inhibits ORF57-mediated PAN accumulation. However, E1B-AP5 (heterogeneous nuclear ribonucleoprotein U-like 1), which interacts with a region outside the 9-nt core to stimulate PAN expression, does not interact or even colocalize with ORF57. Unlike PABPC1, the nuclear distribution of E1B-AP5 remains unchanged by viral lytic infection or overexpression of ORF57. Together, these data indicate that PABPC1 is an important cellular target of viral ORF57 to directly upregulate PAN accumulation during viral lytic infection, and the ability of host PABPC1 to disrupt ORF57 expression is a strategic host counterbalancing mechanism. C1 [Massimelli, Maria J.; Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Kruhlak, Michael] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Lab, HIV & AIDS Malignancy Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural Research Program of the NCI, Center for Cancer Research, National Institutes of Health FX This work was supported by the Intramural Research Program of the NCI, Center for Cancer Research, National Institutes of Health. NR 72 TC 15 Z9 15 U1 0 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 243 EP 256 DI 10.1128/JVI.01693-12 PG 14 WC Virology SC Virology GA 055ZB UT WOS:000312455500020 PM 23077296 ER PT J AU Bosinger, SE Jochems, SP Folkner, KA Hayes, TL Klatt, NR Silvestri, G AF Bosinger, Steven E. Jochems, Simon P. Folkner, Kathryn A. Hayes, Timothy L. Klatt, Nichole R. Silvestri, Guido TI Transcriptional Profiling of Experimental CD8(+) Lymphocyte Depletion in Rhesus Macaques Infected with Simian Immunodeficiency Virus SIVmac239 SO JOURNAL OF VIROLOGY LA English DT Article ID V-GAMMA-9V-DELTA-2 T-CELLS; HUMAN NK CELLS; GENE-EXPRESSION; ALPHA-DEFENSINS; HIV-INFECTION; VACCINE DESIGN; AIDS VACCINE; REPLICATION; VIREMIA; ALPHA-DEFENSIN-1 AB CD8(+) T cells inhibit virus replication in SIV-infected rhesus macaques. However, it is unclear to what extent the viral suppression mediated by CD8(+) T cells reflects direct killing of infected cells as opposed to indirect, noncytolytic mechanisms. In this study, we used functional genomics to investigate noncytolytic mechanisms of in vivo viral suppression mediated by CD8(+) lymphocytes. Eight chronically SIVmac239-infected rhesus macaques underwent CD8(+) lymphocyte depletion, and RNA from whole blood was obtained prior to depletion, during the nadir of CD8(+) cell depletion, and after CD8(+) lymphocyte numbers had rebounded. We observed significant downregulation of the expression of genes encoding factors that can suppress SIV replication, including the CCR5-binding chemokine CCL5/RANTES and CCL4 and several members of the tripartite motif-containing (TRIM) family. Surprisingly, we also noted a strong, widespread downregulation of alpha- and theta-defensins with anti-HIV activity, which are not expressed by CD8(+) T cells. After cessation of depleting antibody treatment, we observed induction of a transcriptional signature indicative of B lymphocyte activation. Validation experiments demonstrated that animals during this period had elevated levels of B cells coupled with higher expression of the proliferative marker Ki67, indicating that CD8(+) depletion triggered a potent expansion of B cell numbers. Collectively, these data identify antiviral pathways perturbed by in vivo CD8(+) T cell depletion that may contribute to noncytolytic control of SIV replication. C1 [Bosinger, Steven E.; Jochems, Simon P.; Folkner, Kathryn A.; Hayes, Timothy L.; Silvestri, Guido] Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Jochems, Simon P.] Univ Utrecht, Infect & Immun Ctr Utrecht, Grad Sch Life Sci, Utrecht, Netherlands. [Klatt, Nichole R.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silvestri, G (reprint author), Emory Univ, Div Microbiol & Immunol, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. EM gsilves@emory.edu FU NIH [R01-AI90797]; Office of Research Infrastructure Programs [P51OD11107]; NCCR [P51RR169] FX This work was supported by NIH grant R01-AI90797 to G.S. and by Office of Research Infrastructure Programs P51OD11107 and (formerly) NCCR P51RR169. NR 65 TC 4 Z9 5 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 433 EP 443 DI 10.1128/JVI.01746-12 PG 11 WC Virology SC Virology GA 055ZB UT WOS:000312455500038 PM 23097439 ER PT J AU Chaipan, C Smith, JL Hu, WS Pathak, VK AF Chaipan, Chawaree Smith, Jessica L. Hu, Wei-Shau Pathak, Vinay K. TI APOBEC3G Restricts HIV-1 to a Greater Extent than APOBEC3F and APOBEC3DE in Human Primary CD4(+) T Cells and Macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTIDINE DEAMINASE APOBEC3H; BLOOD MONONUCLEAR-CELLS; FUSION INHIBITOR T-20; ANTIVIRAL ACTIVITY; ANTIRETROVIRAL FACTOR; VIF PROTEIN; IN-VIVO; ENZYME APOBEC3G; A MUTATIONS AB APOBEC3 proteins inhibit HIV-1 replication in experimental systems and induce hypermutation in infected patients; however, the relative contributions of several APOBEC3 proteins to restriction of HIV-1 replication in the absence of the viral Vif protein in human primary CD4(+) T cells and macrophages are unknown. We observed significant inhibition of HIV-1 Delta vif produced in 293T cells in the presence of APOBEC3DE (A3DE), APOBEC3F (A3F), APOBEC3G (A3G), and APOBEC3H haplotype II (A3H HapII) but not APOBEC3B (A3B), APOBEC3C (A3C), or APOBEC3H haplotype I (A3H HapI). Our previous studies showed that Vif amino acids (YRHHY44)-R-40 are important for inducing proteasomal degradation of A3G, whereas amino acids (DRMR17)-D-14 are important for degradation of A3F and A3DE. Here, we introduced substitution mutations of (YRHHY44)-Y-40 and (DRMR17)-D-14 in replication-competent HIV-1 to generate vif mutants NL4-3 YRHHY>A5 and NL4-3 DRMR>A4 to compare the antiviral activity of A3G to the combined antiviral activity of A3F and A3DE in activated CD4(+) T cells and macrophages. During the first 15 days (round 1), in which multiple cycles of viral replication occurred, both the NL4-3 YRHHY>A5 and NL4-3 DRMR>A4 mutants replicated in activated CD4(+) T cells and macrophages, and only the NL4-3 YRHHY>A5 mutant showed a 2- to 4-day delay in replication compared to the wild type. During the subsequent 27 days (round 2) of cultures initiated with peak virus obtained from round 1, the NL4-3 YRHHY>A5 mutant exhibited a longer, 8- to 10-day delay and the NL4-3 DRMR>A4 mutant exhibited a 2- to 6-day delay in replication compared to the wild type. The NL4-3 YRHHY>A5 and NL4-3 DRMR>A4 mutant proviruses displayed G-to-A hypermutations primarily in GG and GA dinucleotides as expected of A3G- and A3F- or A3DE-mediated deamination, respectively. We conclude that A3G exerts a greater restriction effect on HIV-1 than A3F and A3DE. C1 [Chaipan, Chawaree; Smith, Jessica L.; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. [Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. EM vinay.pathak@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 72 TC 44 Z9 47 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 444 EP 453 DI 10.1128/JVI.00676-12 PG 10 WC Virology SC Virology GA 055ZB UT WOS:000312455500039 PM 23097438 ER PT J AU Lopatin, U Blutt, SE Conner, ME Kelsall, BL AF Lopatin, Uri Blutt, Sarah E. Conner, Margaret E. Kelsall, Brian L. TI Lymphotoxin Alpha-Deficient Mice Clear Persistent Rotavirus Infection after Local Generation of Mucosal IgA SO JOURNAL OF VIROLOGY LA English DT Article ID PATCH DENDRITIC CELLS; SEVERE COMBINED IMMUNODEFICIENCY; B-CELLS; IMMUNE RESPONSIVENESS; LYMPHOID-TISSUES; SECRETING CELLS; PEYERS-PATCHES; GUT; MECHANISM; RESPONSES AB Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in infection by and immunity to rotavirus, lymphotoxin alpha-deficient (LT alpha(-/-)) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LT alpha(-/-) and wildtype mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal infection within 10 days, LT alpha(-/-) mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific IgA in both mouse strains. Induction of intestinal rotavirus-specific IgA in LT alpha(-/-) mice correlated with the (late) appearance of IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum IgA, implies that secretory rotavirus-specific IgA was produced locally. These findings indicate that serum IgG responses are insufficient and imply that local intestinal IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LT alpha-dependent lymphoid tissues are important for the generation of IgA-producing B cells in the intestine, they are not absolutely required in the setting of rotavirus infection. Moreover, the induction of local IgA-producing B cell responses can occur late after infection and in an LT alpha-independent manner. C1 [Lopatin, Uri; Kelsall, Brian L.] NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. [Blutt, Sarah E.; Conner, Margaret E.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [Blutt, Sarah E.; Conner, Margaret E.] Michael E DeBakey VA Med Ctr, Houston, TX USA. RP Kelsall, BL (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bkelsall@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases [R01 AI24998]; Office of Research and Development, Medical Research Service, Department of Veterans Affairs FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases grant R01 AI24998 (to M. E. C. and S. E. B) and a merit review grant from the Office of Research and Development, Medical Research Service, Department of Veterans Affairs (to M.E.C. and S.E.B.). NR 42 TC 7 Z9 7 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 524 EP 530 DI 10.1128/JVI.01801-12 PG 7 WC Virology SC Virology GA 055ZB UT WOS:000312455500047 PM 23097456 ER PT J AU Koh, Y Wu, XL Ferris, AL Matreyek, KA Smith, SJ Lee, K KewalRamani, VN Hughes, SH Engelman, A AF Koh, Yasuhiro Wu, Xiaolin Ferris, Andrea L. Matreyek, Kenneth A. Smith, Steven J. Lee, KyeongEun KewalRamani, Vineet N. Hughes, Stephen H. Engelman, Alan TI Differential Effects of Human Immunodeficiency Virus Type 1 Capsid and Cellular Factors Nucleoporin 153 and LEDGF/p75 on the Efficiency and Specificity of Viral DNA Integration SO JOURNAL OF VIROLOGY LA English DT Article ID PREINTEGRATION COMPLEXES; HIV-1 INTEGRASE; NUCLEAR IMPORT; HUMAN GENOME; REVERSE TRANSCRIPTION; NONDIVIDING CELLS; TARGET SITES; IN-VIVO; REPLICATION; INFECTION AB Retroviruses integrate into cellular DNA nonrandomly. Lentiviruses such as human immunodeficiency virus type 1 (HIV-1) favor the bodies of active genes and gene-enriched transcriptionally active regions of chromosomes. The interaction between lentiviral integrase and the cellular protein lens epithelium-derived growth factor (LEDGF)/p75 underlies the targeting of gene bodies, whereas recent research has highlighted roles for the HIV-1 capsid (CA) protein and cellular factors implicated in viral nuclear import, including transportin 3 (TNPO3) and nucleoporin 358 (NUP358), in the targeting of gene-dense regions of chromosomes. Here, we show that CA mutations, which include the substitution of Asp for Asn74 (N74D), significantly reduce the dependency of HIV-1 on LEDGF/p75 during infection and that this difference correlates with the efficiency of viral DNA integration. The distribution of integration sites mapped by Illumina sequencing confirms that the N74D mutation reduces integration into gene-rich regions of chromosomes and gene bodies and reveals previously unrecognized roles for NUP153 (another HIV-1 cofactor implicated in viral nuclear import) and LEDGF/p75 in the targeting of the viral preintegration complex to gene-dense regions of chromatin. A role for the CA protein in determining the dependency of HIV-1 on LEDGF/p75 during infection highlights a connection between the viral capsid and chromosomal DNA integration. C1 [Koh, Yasuhiro; Matreyek, Kenneth A.; Engelman, Alan] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Koh, Yasuhiro; Matreyek, Kenneth A.; Engelman, Alan] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Wu, Xiaolin] Frederick Natl Lab Canc Res, SAIC Frederick Inc, Lab Mol Technol, Frederick, MD USA. [Ferris, Andrea L.; Smith, Steven J.; Lee, KyeongEun; KewalRamani, Vineet N.; Hughes, Stephen H.] Frederick Natl Lab Canc Res, HIV Drug Resistance Program, Frederick, MD USA. RP Engelman, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM alan_engelman@dfci.harvard.edu OI Matreyek, Kenneth/0000-0001-9149-551X FU National Cancer Institute's Intramural Center for Cancer Research; National Institutes of Health (NIH) [AI039394, AI052014] FX This work was supported by the National Cancer Institute's Intramural Center for Cancer Research, which supports the HIV Drug Resistance Program (V.N.K. and S.H.H.), and National Institutes of Health (NIH) grants AI039394 and AI052014 (to A.E.). NR 66 TC 40 Z9 40 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 648 EP 658 DI 10.1128/JVI.01148-12 PG 11 WC Virology SC Virology GA 055ZB UT WOS:000312455500057 PM 23097450 ER PT J AU Lauck, M Sibley, SD Hyeroba, D Tumukunde, A Weny, G Chapman, CA Ting, N Switzer, WM Kuhn, JH Friedrich, TC O'Connor, DH Goldberg, TL AF Lauck, Michael Sibley, Samuel D. Hyeroba, David Tumukunde, Alex Weny, Geoffrey Chapman, Colin A. Ting, Nelson Switzer, William M. Kuhn, Jens H. Friedrich, Thomas C. O'Connor, David H. Goldberg, Tony L. TI Exceptional Simian Hemorrhagic Fever Virus Diversity in a Wild African Primate Community SO JOURNAL OF VIROLOGY LA English DT Article ID PHYLOGENETIC ANALYSIS; ALIGNMENT; EVOLUTION; SEQUENCE; MONKEYS AB Simian hemorrhagic fever virus (SHFV) is an arterivirus that causes severe disease in captive macaques. We describe two new SHFV variants subclinically infecting wild African red-tailed guenons (Cercopithecus ascanius). Both variants are highly divergent from the prototype virus and variants infecting sympatric red colobus (Procolobus rufomitratus). All known SHFV variants are monophyletic and share three open reading frames not present in other arteriviruses. Our data suggest a need to modify the current arterivirus classification. C1 [Sibley, Samuel D.; Friedrich, Thomas C.; Goldberg, Tony L.] Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. [Lauck, Michael; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Hyeroba, David; Tumukunde, Alex; Weny, Geoffrey; Chapman, Colin A.; Goldberg, Tony L.] Makerere Univ, Kampala, Uganda. [Chapman, Colin A.] McGill Univ, Dept Anthropol, Montreal, PQ, Canada. [Chapman, Colin A.] McGill Univ, Sch Environm, Montreal, PQ, Canada. [Ting, Nelson] Univ Oregon, Dept Anthropol, Eugene, OR 97403 USA. [Ting, Nelson] Univ Oregon, Inst Ecol & Evolut, Eugene, OR 97403 USA. [Switzer, William M.] Ctr Dis Control & Prevent, Natl Ctr HIV Hepatitis STD & TB Prevent, Div HIV AIDS Prevent, Branch Lab, Atlanta, GA USA. [Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Frederick, MD USA. [Friedrich, Thomas C.; O'Connor, David H.; Goldberg, Tony L.] Wisconsin Natl Primate Res Ctr, Madison, WI USA. RP Goldberg, TL (reprint author), Univ Wisconsin, Dept Pathobiol Sci, Madison, WI 53706 USA. EM tgoldberg@vetmed.wisc.edu RI Kuhn, Jens H./B-7615-2011; OI Kuhn, Jens H./0000-0002-7800-6045; Sibley, Samuel/0000-0002-6754-3187; o'connor, david/0000-0003-2139-470X; Friedrich, Thomas/0000-0001-9831-6895 FU NIH grant as part of the joint NIH-NSF Ecology of Infectious Disease program [TW009237]; UK Economic and Social Research Council; University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program through the Wisconsin Center for Infectious Disease (WisCID); NIAID [HHSN272200200016I] FX This work was funded by NIH grant TW009237 as part of the joint NIH-NSF Ecology of Infectious Disease program and the UK Economic and Social Research Council, and by the University of Wisconsin School of Medicine and Public Health from The Wisconsin Partnership Program through the Wisconsin Center for Infectious Disease (WisCID). J.H.K. performed this work as an employee of Tunnell Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under contract no. HHSN272200200016I. NR 26 TC 32 Z9 33 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2013 VL 87 IS 1 BP 688 EP 691 DI 10.1128/JVI.02433-12 PG 4 WC Virology SC Virology GA 055ZB UT WOS:000312455500062 PM 23077302 ER PT J AU Glazer, NL Lyass, A Esliger, DW Blease, SJ Freedson, PS Massaro, JM Murabito, JM Vasan, RS AF Glazer, Nicole L. Lyass, Asya Esliger, Dale W. Blease, Susan J. Freedson, Patty S. Massaro, Joseph M. Murabito, Joanne M. Vasan, Ramachandran S. TI Sustained and Shorter Bouts of Physical Activity Are Related to Cardiovascular Health SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE ACCELEROMETER; HEART DISEASE; EXERCISE; GUIDELINES ID CORONARY-HEART-DISEASE; METABOLIC SYNDROME; AMERICAN-COLLEGE; SPORTS-MEDICINE; SEDENTARY TIME; PUBLIC-HEALTH; OLDER-ADULTS; RISK-FACTORS; LIFE-STYLE; ACCELEROMETER AB GLAZER, N. L., A. LYASS, D. W. ESLIGER, S. J. BLEASE, P. S. FREEDSON, J. M. MASSARO, J. M. MURABITO, and R. S. VASAN. Sustained and Shorter Bouts of Physical Activity Are Related to Cardiovascular Health. Med. Sci. Sports Exerc., Vol. 45, No. 1, pp. 109-115, 2013. Purpose: Whereas greater physical activity (PA) is known to prevent cardiovascular disease (CVD), the relative importance of performing PA in sustained bouts of activity versus shorter bouts of activity on CVD risk is not known. The objective of this study was to investigate the relationship between moderate-to-vigorous PA (MVPA), measured in bouts >= 10 and <10 min, and CVD risk factors in a well-characterized community-based sample of white adults. Methods: We conducted a cross-sectional analysis of 2109 participants in the Third Generation Cohort of the Framingham Heart Study (mean age = 47 yr, 55% women) who underwent objective assessment of PA by accelerometry over 5-7 d. Total MVPA, MVPA done in bouts >= 10 min (MVPA(10+)), and MVPA done in bouts <10 min (MVPA(<10)) were calculated. MVPA exposures were related to individual CVD risk factors, including measures of adiposity and blood lipid and glucose levels, using linear and logistic regression. Results: Total MVPA was significantly associated with higher HDL levels and with lower triglycerides, BMI, waist circumference, and Framingham risk score (P < 0.0001). MVPA(<10) showed similar statistically significant associations with these CVD risk factors (P < 0.001). Compliance with national guidelines (>= 150 min of total MVPA) was significantly related to lower BMI, triglycerides, Framingham risk score, waist circumference, higher HDL, and a lower prevalence of obesity and impaired fasting glucose (P < 0.001 for all). Conclusions: Our cross-sectional observations on a large middle-age community-based sample confirm a positive association of MVPA with a healthier CVD risk factor profile and indicate that accruing PA in bouts <10 min may favorably influence cardiometabolic risk. Additional investigations are warranted to confirm our findings. C1 [Glazer, Nicole L.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA. [Lyass, Asya; Blease, Susan J.; Massaro, Joseph M.; Murabito, Joanne M.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Lyass, Asya; Massaro, Joseph M.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Esliger, Dale W.] Loughborough Univ Technol, Sch Sport Exercise & Hlth Sci, Loughborough LE11 3TU, Leics, England. [Freedson, Patty S.] Univ Massachusetts, Dept Kinesiol, Amherst, MA 01003 USA. [Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med, Boston, MA 02118 USA. RP Glazer, NL (reprint author), Boston Univ, Sch Med, Sect Prevent Med & Epidemiol, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA. EM nlglazer@bu.edu RI Esliger, Dale/E-1796-2016; OI Esliger, Dale/0000-0002-1236-6419; Murabito, Joanne/0000-0002-0192-7516; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU National Heart, Lung, and Blood Institute [NO-1 HC25195] FX The present investigation was supported in part by contract NO-1 HC25195 to Boston University from the National Heart, Lung, and Blood Institute. Drs. Murabito and Vasan equally contributed to this investigation. NR 40 TC 51 Z9 52 U1 6 U2 44 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD JAN PY 2013 VL 45 IS 1 BP 109 EP 115 DI 10.1249/MSS.0b013e31826beae5 PG 7 WC Sport Sciences SC Sport Sciences GA 057AW UT WOS:000312535200016 PM 22895372 ER PT J AU Wang, Y Yao, RS Gao, S Wen, WD Du, YQ Szabo, E Hu, M Lubet, RA You, M AF Wang, Yian Yao, Ruisheng Gao, Song Wen, Weidong Du, Yinqiu Szabo, Eva Hu, Ming Lubet, Ronald A. You, Ming TI Chemopreventive effect of a mixture of Chinese Herbs (antitumor B) on chemically induced oral carcinogenesis SO MOLECULAR CARCINOGENESIS LA English DT Article DE antitumor B; chemoprevention; oral cancer ID GROWTH-FACTOR RECEPTOR; SQUAMOUS-CELL CARCINOMA; INDUCED COLON CARCINOGENESIS; CITRUS LIMONOIDS OBACUNONE; IMMUNOHISTOCHEMICAL EXPRESSION; NECK-CANCER; EGFR; MICE; MATRINE; PROLIFERATION AB In this study, we evaluated chemopreventive efficacy of Antitumor B, a Chinese herbal mixture of six plants (Sophora tonkinensis, Polygonum bistorta, Prunella vulgaris, Sonchus arvensis L., Dictamnus dasycarpus, and Dioscorea bulbifera) on the development of 4-nitroquinoline-1-oxide (4NQO) induced oral squamous cell carcinomas in A/J mice. Antitumor B, delivered through diet, inhibited 4NQO-induced oral cancer development by 59.19%. The reduction of cell proliferation appears to be associated with efficacy of Antitumor B against 4NQO-induced oral cancer in A/J mice. The expression of epidermal growth factor receptor (EGFR) and phosphorylated EGFR (Tyr1173) were down-regulated by Antitumor B. Tissue distribution of Antitumor B was determined using obacunone, matrine, and maackiain as marker chemicals. We found significant amounts of obacunone, matrine, and maackiain in the blood after 1-wk treatment. The concentrations of these three compounds did not increase further at 18?wk, suggesting that plasma concentrations had reached a steady-state level at 1?wk. There was no significant body weight loss and there was no other obvious sign of toxicity in Antitumor B-treated mice. These results suggest that Antitumor B is a promising agent for human oral cancer chemoprevention. (c) 2011 Wiley Periodicals, Inc. C1 [Wang, Yian; Yao, Ruisheng; Wen, Weidong; Du, Yinqiu; You, Ming] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. [Gao, Song; Hu, Ming] Univ Houston, Coll Pharm, Dept Pharmacol & Pharmaceut Sci, Houston, TX 77030 USA. [Szabo, Eva; Lubet, Ronald A.] NCI, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Campus Box 8109,10130 Wohl Clin, St Louis, MO 63110 USA. NR 35 TC 7 Z9 7 U1 4 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JAN PY 2013 VL 52 IS 1 BP 49 EP 56 DI 10.1002/mc.20877 PG 8 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 058TM UT WOS:000312657100005 PM 22086836 ER PT J AU Chittajallu, R Pelkey, KA McBain, CJ AF Chittajallu, Ramesh Pelkey, Kenneth A. McBain, Chris J. TI Neurogliaform cells dynamically regulate somatosensory integration via synapse-specific modulation SO NATURE NEUROSCIENCE LA English DT Article ID INHIBITION; RECEPTOR; CORTEX; ACTIVATION; NEOCORTEX; RESPONSES; AMYGDALA; NEURONS; DRIVEN AB Despite the prevailing idea that neurogliaform cells produce a spatially unrestricted widespread inhibition, we demonstrate here that their activity attenuates thalamic-evoked feed-forward inhibition in layer IV barrel cortex but has no effect on feed-forward excitation. The result of this circuit selectivity is a dynamic regulation in the temporal window for integration of excitatory thalamic input, thus revealing a new role for neurogliaform cells in shaping sensory processing. C1 [Chittajallu, Ramesh; Pelkey, Kenneth A.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA. RP McBain, CJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA. EM mcbainc@mail.nih.gov FU National Institute of Child Health and Human Development; National Institute of Neurological Disorders and Stroke Intramural Programs FX We thank J. Isaac for comments, and M. Craig for the IGOR procedures used to automate analyses of the modeling data. This work was supported by the National Institute of Child Health and Human Development and National Institute of Neurological Disorders and Stroke Intramural Programs. NR 18 TC 20 Z9 20 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 EI 1546-1726 J9 NAT NEUROSCI JI Nat. Neurosci. PD JAN PY 2013 VL 16 IS 1 BP 13 EP U167 DI 10.1038/nn.3284 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 058KZ UT WOS:000312633900007 PM 23222912 ER PT J AU Rosenberg, HF Dyer, KD Foster, PS AF Rosenberg, Helene F. Dyer, Kimberly D. Foster, Paul S. TI Eosinophils: changing perspectives in health and disease SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID ALTERNATIVELY ACTIVATED MACROPHAGES; MAJOR BASIC-PROTEIN; SCHISTOSOMA-MANSONI INFECTION; RESPIRATORY SYNCYTIAL VIRUS; ALLERGIC LUNG INFLAMMATION; INNATE LYMPHOID-CELLS; MYALGIA-SYNDROME; T-CELLS; CATIONIC PROTEIN; MURINE MODEL AB Eosinophils have been traditionally perceived as terminally differentiated cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular pathways that control the development, trafficking and degranulation of eosinophils have improved our understanding of the immunomodulatory functions of these cells and their roles in promoting homeostasis. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of different diseases, including asthma and primary hypereosinophilic syndromes, and have also provided us with a more complete appreciation of the activities of these cells during parasitic infection. C1 [Rosenberg, Helene F.; Dyer, Kimberly D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Foster, Paul S.] Univ Newcastle, Prior Res Ctr Asthma & Resp Dis, Hunter Med Res Inst, Fac Hlth, Newcastle, NSW 2300, Australia. [Foster, Paul S.] Univ Newcastle, Sch Biomed Sci & Pharm, Fac Hlth, Newcastle, NSW 2300, Australia. RP Rosenberg, HF (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenberg@niaid.nih.gov RI Foster, Paul/G-5057-2013 FU NIAID Division of Intramural Research [AI000941, AI000943]; National Health and Medical Research Council of Australia; Harvard Club of Australia FX The authors thank R. Dreyfuss (Medical Arts Branch, Office of the Director, US National Institutes of Health (NIH)) for photographic images and E. R. Fischer (Research Technologies Section, Rocky Mountain Laboratories, US National Institute of Allergy and Infectious Diseases (NIAID), NIH) for preparing the transmission electron micrograph of the mouse eosinophil. H. F. R. receives funding from the NIAID Division of Intramural Research (grants AI000941 and AI000943); P. S. F. receives funding from the National Health and Medical Research Council of Australia and fellowship support from the Harvard Club of Australia. NR 171 TC 166 Z9 171 U1 4 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JAN PY 2013 VL 13 IS 1 BP 9 EP 22 DI 10.1038/nri3341 PG 14 WC Immunology SC Immunology GA 058QI UT WOS:000312648300010 PM 23154224 ER PT J AU Radulescu, E Sambataro, F Mattay, VS Callicott, JH Straub, RE Matsumoto, M Weinberger, DR Marenco, S AF Radulescu, Eugenia Sambataro, Fabio Mattay, Venkata S. Callicott, Joseph H. Straub, Richard E. Matsumoto, Mitsuyuki Weinberger, Daniel R. Marenco, Stefano TI Effect of Schizophrenia Risk-Associated Alleles in SREB2 (GPR85) on Functional MRI Phenotypes in Healthy Volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE emotion; hippocampal formation; amygdala; dorsolateral prefrontal cortex; single-nucleotide polymorphisms ID PROTEIN-COUPLED RECEPTORS; SEX-DIFFERENCES; AMYGDALA RESPONSE; BIPOLAR DISORDER; WORKING-MEMORY; BRAIN; ACTIVATION; FMRI; GENETICS; PERFORMANCE AB Genetic variants in GPR85 (SREB2: rs56080411 and rs56039557) have been associated with risk for schizophrenia. Here, we test the hypothesis that these variants impact on brain function in normal subjects, measured with functional magnetic resonance imaging (fMRI) paradigms that target regions with greatest SREB2 expression (hippocampal formation and amygdaloid complex). During a facial emotion recognition paradigm, a significant interaction of rs56080411 genotype by sex was found in the left amygdaloid complex (male risk allele carriers showed less activation than male homozygotes for the non-risk allele, while females showed the opposite pattern). During aversive encoding of an emotional memory paradigm, we found that risk allele carriers for rs56080411 had greater activation in the right inferior frontal gyrus. Trends in the same direction were present for rs56039557 in the right occipital cortex and right fusiform gyrus. During a working memory paradigm, a significant sex-by-genotype interaction was found with male risk allele carriers of rs56080411 having inefficient activation within the left dorsolateral prefrontal cortex (DLPFC), compared with same sex non-risk carriers, while females revealed an opposite pattern, despite similar levels of performance. These data suggest that risk-associated variants in SREB2 are associated with phenotypes similar to those found in patients with schizophrenia in the DLPFC and the amygdala of males, while the pattern is opposite in females. The findings in females and during the emotional memory paradigm are consistent with modulation by SREB2 of brain circuitries implicated in mood regulation and may be relevant to neuropsychiatric conditions other than schizophrenia. Neuropsychopharmacology (2013) 38, 341-349; doi:10.1038/npp.2012.184; published online 12 September 2012 C1 [Radulescu, Eugenia; Sambataro, Fabio; Mattay, Venkata S.; Callicott, Joseph H.; Straub, Richard E.; Weinberger, Daniel R.; Marenco, Stefano] NIMH, Clin Brain Disorders Branch, GCAP, IRP, Bethesda, MD 20892 USA. [Matsumoto, Mitsuyuki] Astellas Res Inst Amer LLC, CNS, Skokie, IL USA. RP Marenco, S (reprint author), NIMH, Clin Brain Disorders Branch, GCAP, IRP, 10 Ctr Dr,Bldg 10,Room 3C103, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008; Matsumoto, Mitsuyuki/G-3207-2012; Sambataro, Fabio/E-3426-2010; Callicott, Joseph/C-9102-2009 OI Marenco, Stefano/0000-0002-2488-2365; Matsumoto, Mitsuyuki/0000-0002-1172-2354; Sambataro, Fabio/0000-0003-2102-416X; Callicott, Joseph/0000-0003-1298-3334 FU NIMH IRP FX This work was entirely funded by the NIMH IRP to the Weinberger Laboratory. NR 51 TC 3 Z9 3 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2013 VL 38 IS 2 BP 341 EP 349 DI 10.1038/npp.2012.184 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 057QO UT WOS:000312578300009 PM 22968816 ER PT J AU Collins, MA Moon, KH Tajuddin, N Neafsey, EJ Kim, HY AF Collins, Michael A. Moon, Kwan-Hoon Tajuddin, Nuzhath Neafsey, Edward J. Kim, Hee-Yong TI Docosahexaenoic Acid (DHA) Prevents Binge Ethanol-Dependent Aquaporin-4 Elevations While Inhibiting Neurodegeneration: Experiments in Rat Adult-Age Entorhino-Hippocampal Slice Cultures SO NEUROTOXICITY RESEARCH LA English DT Article DE Organotypic; Neuroinflammation; Omega-3; AQP4; Alcohol; Neurodamage ID IN-VIVO; BRAIN EDEMA; NEURONAL DEGENERATION; OXIDATIVE STRESS; GENE-EXPRESSION; KAPPA-B; ASTROCYTES; INJURY; PHOSPHATIDYLSERINE; INTOXICATION AB Repetitive binge intoxication with ethanol (alcohol) in adult rats, mimicking chronic ethanol abuse in alcoholics, causes trauma-like brain edema and relatively selective neurodegeneration of hippocampal dentate granule cells and pyramidal neurons in the temporal cortex (especially entorhinal cortex). We have now modeled the aspects of this type of acquired brain damage in vitro with rat entorhino-hippocampal slice cultures of adult brain age (62 +/- A 3 days). When sequentially treated (four 16-h overnight exposures) with 100 mM ethanol, the slices display elevated levels of aquaporin-4 (AQP4) water channels accompanied by significant neurodegeneration. Increased AQP4 has been associated with neuroinflammatory responses including edema, pro-inflammatory cytokine elevations, arachidonic acid release, and oxidative stress. Co-treatment of ethanol-binged slice cultures with docosahexaenoic acid (DHA), an omega-3 fatty acid known to suppress brain damage from other insults, prevents both the AQP4 elevations and the neurodamage. Surmising that AQP4 augmentation is a causative neuroinflammatory component in this model, we are investigating several possibilities to explain the protective actions of the omega-3 fatty acid. Since the worldwide incidence of cognitive dysfunction and dementia from ethanol abuse and alcoholism is not inconsequential, DHA supplementation with chronic alcoholics could emerge to be a rational approach to potentially lessening brain disabilities. C1 [Collins, Michael A.; Moon, Kwan-Hoon; Tajuddin, Nuzhath; Neafsey, Edward J.] Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. [Kim, Hee-Yong] NIAAA, Lab Mol Signaling, NIH, Bethesda, MD 20892 USA. RP Collins, MA (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Mol Pharmacol & Therapeut, Maywood, IL 60153 USA. EM mcollin@lumc.edu FU NIH NIAAA [UO1 AA018279] FX This research is supported by NIH NIAAA UO1 AA018279. Dr. Peter Bergold, Downstate Medical Center, Brooklyn, and Dr. Philip E. Bickler, UCSF, San Francisco, are acknowledged for helpful advice in the preparation of adult-age brain slices. NR 36 TC 6 Z9 6 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD JAN PY 2013 VL 23 IS 1 BP 105 EP 110 DI 10.1007/s12640-012-9360-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 058WF UT WOS:000312664800009 PM 23184649 ER PT J AU van Veghel, D Cleynhens, J Pearce, LV Blumberg, PM Van Laere, K Verbruggen, A Bormans, G AF van Veghel, Daisy Cleynhens, Jan Pearce, Larry V. Blumberg, Peter M. Van Laere, Koen Verbruggen, Alfons Bormans, Guy TI Synthesis and biological evaluation of [C-11]SB366791: A new PET-radioligand for in vivo imaging of the TRPV1 receptor SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE TRPV1; Positron emission tomography; [C-11]SB366791 ID CENTRAL-NERVOUS-SYSTEM; VANILLOID RECEPTOR; CAPSAICIN RECEPTOR; BRAIN; ANTAGONIST; CHANNELS; RAT; PAIN; MICE; VR1 AB Introduction: The transient receptor potential vanilloid subfamily member 1 (TRPV1) receptor, a non-selective cation channel, is known for its key role in pain nociception and neurogenic inflammation. TRPV1 expression has been demonstrated in diverse tissues and an essential role for TRPV1 in various disorders has been suggested. A TRPV1-specific PET-radioligand can serve as a useful tool for further in vivo research in animals and directly in humans. In this study, we report the synthesis and biological evaluation of a carbon-11 labelled analogue of N-(3-methoxyphenyl)-4-chlorocinnamide (SB366791) which was reported as a specific high-affinity antagonist for TRPV1. Methods: The new tracer was evaluated with respect to log D and biodistribution in control, pretreated and TRPV1(-/-) mice. The percentage of radiometabolites of [C-11]SB366791 was determined in mouse plasma and brain. Results: [C-11] SB366791 was obtained in good yield (69%+/- 11%: isolated amoums 3034-5032 MBq) and high specific activity (390 +/- 215GBq/mu mol). The tracer was efficiently cleared from blood and all major organs via hepatobiliary and renal pathways. Initial brain uptake was high (1.6% ID) and wash-out from brain was rapid. The retention of [C-11] SB366791 in the trigeminal nerve of control mice was prominent. The in vitro binding affinity of SB366791 was determined to be 280 +/- 56 nM and 780 +/- 140 nM for human and rat TRPV1, respectively. Conclusions: [C-11] SB366791 has favourable biodistribution characteristics in mice. However the obtained low binding affinity for TRPV1 may not be sufficient to use the current compound as PET tracer. (C) 2013 Elsevier Inc. All rights reserved. C1 [van Veghel, Daisy; Cleynhens, Jan; Verbruggen, Alfons; Bormans, Guy] Katholieke Univ Leuven, Lab Radiopharm, BE-3000 Louvain, Belgium. [Pearce, Larry V.; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Van Laere, Koen] Univ Hosp, Div Nucl Med, Louvain, Belgium. RP Bormans, G (reprint author), Katholieke Univ Leuven, Lab Radiopharm, Campus Gasthuisberg O&N2,Herestr 49,Box 821, BE-3000 Louvain, Belgium. EM Guy.Bormans@pharm.kuleuven.be FU Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT); National Institutes of Health, National Cancer Institute, Centre for Cancer Research [Z1A BC 005270] FX We thank Julie Cornelis (Laboratory for Radiopharmacy, KU Leuven) for her skilful help with the animal experiments. This research was funded by a Ph.D. grant of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT), in part by in-vivo molecular imaging research (IMIR) and in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Centre for Cancer Research (project Z1A BC 005270). NR 35 TC 4 Z9 4 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD JAN PY 2013 VL 40 IS 1 BP 141 EP 147 DI 10.1016/j.nucmedbio.2012.08.011 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 055MG UT WOS:000312420000019 PM 23141549 ER PT J AU Volkow, ND Wang, GJ Tomasi, D Baler, RD AF Volkow, N. D. Wang, G. -J. Tomasi, D. Baler, R. D. TI Obesity and addiction: neurobiological overlaps SO OBESITY REVIEWS LA English DT Review DE Addiction; dopamine; obesity; prefrontal cortex ID VENTRAL TEGMENTAL AREA; BODY-MASS INDEX; DOPAMINE D2 RECEPTORS; NUCLEUS-ACCUMBENS DOPAMINE; MESSENGER-RNA EXPRESSION; DIET-INDUCED OBESITY; HIGH-CALORIE FOODS; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; CENTRAL AMYGDALA AB Drug addiction and obesity appear to share several properties. Both can be defined as disorders in which the saliency of a specific type of reward (food or drug) becomes exaggerated relative to, and at the expense of others rewards. Both drugs and food have powerful reinforcing effects, which are in part mediated by abrupt dopamine increases in the brain reward centres. The abrupt dopamine increases, in vulnerable individuals, can override the brain's homeostatic control mechanisms. These parallels have generated interest in understanding the shared vulnerabilities between addiction and obesity. Predictably, they also engendered a heated debate. Specifically, brain imaging studies are beginning to uncover common features between these two conditions and delineate some of the overlapping brain circuits whose dysfunctions may underlie the observed deficits. The combined results suggest that both obese and drug-addicted individuals suffer from impairments in dopaminergic pathways that regulate neuronal systems associated not only with reward sensitivity and incentive motivation, but also with conditioning, self-control, stress reactivity and interoceptive awareness. In parallel, studies are also delineating differences between them that centre on the key role that peripheral signals involved with homeostatic control exert on food intake. Here, we focus on the shared neurobiological substrates of obesity and addiction. C1 [Volkow, N. D.; Baler, R. D.] NIDA, NIH, Bethesda, MD 20892 USA. [Wang, G. -J.; Tomasi, D.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA. EM nvokowl@nida.nih.gov RI Tomasi, Dardo/J-2127-2015 FU Intramural NIH HHS [ZIA AA000550-09] NR 225 TC 182 Z9 185 U1 10 U2 119 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1467-7881 J9 OBES REV JI Obes. Rev. PD JAN PY 2013 VL 14 IS 1 BP 2 EP 18 DI 10.1111/j.1467-789X.2012.01031.x PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 057FB UT WOS:000312546900002 PM 23016694 ER PT J AU Lewis, JP Horenstein, RB Ryan, K O'Connell, JR Gibson, Q Mitchell, BD Tanner, K Chai, S Bliden, KP Tantry, US Peer, CJ Figg, WD Spencer, SD Pacanowski, MA Gurbel, PA Shuldiner, AR AF Lewis, Joshua P. Horenstein, Richard B. Ryan, Kathleen O'Connell, Jeffrey R. Gibson, Quince Mitchell, Braxton D. Tanner, Keith Chai, Sumbul Bliden, Kevin P. Tantry, Udaya S. Peer, Cody J. Figg, William D. Spencer, Shawn D. Pacanowski, Michael A. Gurbel, Paul A. Shuldiner, Alan R. TI The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE carboxylesterase 1; CES1; clopidogrel; percutaneous coronary intervention; pharmacogenetics ID MYOCARDIAL-INFARCTION; PLATELET REACTIVITY; THIOL METABOLITE; CYP2C19 GENOTYPE; GENETIC-VARIANTS; ESTERASE; IDENTIFICATION; OSELTAMIVIR; INHIBITION; ACTIVATION AB Introduction Carboxylesterase 1 (CES1) is the primary enzyme responsible for converting clopidogrel into biologically inactive carboxylic acid metabolites. Methods We genotyped a functional variant in CES1, G143E, in participants of the Pharmacogenomics of Anti-Platelet Intervention (PAPI) study (n=566) and in 350 patients with coronary heart disease treated with clopidogrel, and carried out an association analysis of bioactive metabolite levels, on-clopidogrel ADP-stimulated platelet aggregation, and cardiovascular outcomes. Results The levels of clopidogrel active metabolite were significantly greater in CES1 143E-allele carriers (P = 0.001). Consistent with these findings, individuals who carried the CES1 143E-allele showed a better clopidogrel response as measured by ADP-stimulated platelet aggregation in both participants of the PAPI study (P = 0.003) and clopidogrel-treated coronary heart disease patients (P = 0.03). No association was found between this single nucleotide polymorphism and baseline measures of platelet aggregation in either cohort. Conclusion Taken together, these findings suggest, for the first time, that genetic variation in CES1 may be an important determinant of the efficacy of clopidogrel. Pharmacogenetics and Genomics 23:1-8 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2013, 23: 1-8 C1 [Lewis, Joshua P.; Horenstein, Richard B.; Ryan, Kathleen; O'Connell, Jeffrey R.; Gibson, Quince; Mitchell, Braxton D.; Tanner, Keith; Chai, Sumbul; Shuldiner, Alan R.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Lewis, Joshua P.; Horenstein, Richard B.; Ryan, Kathleen; O'Connell, Jeffrey R.; Gibson, Quince; Mitchell, Braxton D.; Tanner, Keith; Chai, Sumbul; Shuldiner, Alan R.] Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA. [Bliden, Kevin P.; Tantry, Udaya S.; Gurbel, Paul A.] Sinai Hosp Baltimore, Sinai Ctr Thrombosis Res, Baltimore, MD USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, Bethesda, MD 20892 USA. [Spencer, Shawn D.] NCI, SAIC Frederick Inc, Appl & Dev Res, Frederick, MD USA. [Pacanowski, Michael A.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. RP Shuldiner, AR (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Rm 494, Baltimore, MD 21201 USA. EM ashuldin@medicine.umaryland.edu RI Figg Sr, William/M-2411-2016; OI Mitchell, Braxton/0000-0003-4920-4744 FU National Institutes of Health [U01 GM074518, U01 GM074518-05S1, U01 HL105198]; University of Maryland General Clinical Research Center [M01 RR 16500]; General Clinical Research Centers Program, National Center for Research Resources (NCRR), NIH; Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC); Sinai Hospital of Baltimore; NIH; Astra Zeneca; Daiichi-Sankyo; Bayer Healthcare; Eli Lilly; Haemonetics; Pozen; Sanofi-Aventis FX This investigation was supported by National Institutes of Health grants U01 GM074518, U01 GM074518-05S1, and U01 HL105198, the University of Maryland General Clinical Research Center, Grant M01 RR 16500, General Clinical Research Centers Program, National Center for Research Resources (NCRR), NIH, the Baltimore Veterans Administration Geriatric Research and Education Clinical Center (GRECC), and Sinai Hospital of Baltimore.; Dr Shuldiner receives grant support from NIH to study the pharmacogenomics of antiplatelet therapy. He is also a consultant for United States Diagnostic Standards Inc. Dr Gurbel receives grant support from Astra Zeneca, Daiichi-Sankyo, Bayer Healthcare, Eli Lilly, Haemonetics, Pozen, and Sanofi-Aventis; and Honoraria/Consulting income from Accumetrics, Astra Zeneca, Bayer Healthcare, Boehringer Ingelheim, Daiichi-Sankyo, Eli Lilly, Merck, Pozen, Novartis, CSL Limited, and Sanofi-Aventis. For the remaining authors there are no conflicts of interest. NR 32 TC 52 Z9 56 U1 2 U2 31 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD JAN PY 2013 VL 23 IS 1 BP 1 EP 8 DI 10.1097/FPC.0b013e32835aa8a2 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 056OJ UT WOS:000312499800001 PM 23111421 ER PT J AU Menge, T Gerber, M Wataha, K Reid, W Guha, S Cox, CS Dash, P Reitz, MS Khakoo, AY Pati, S AF Menge, Tyler Gerber, Michael Wataha, Kathryn Reid, William Guha, Sushovan Cox, Charles S., Jr. Dash, Pramod Reitz, Marvin S., Jr. Khakoo, Aarif Y. Pati, Shibani TI Human Mesenchymal Stem Cells Inhibit Endothelial Proliferation and Angiogenesis via Cell-Cell Contact Through Modulation of the VE-Cadherin/beta-Catenin Signaling Pathway SO STEM CELLS AND DEVELOPMENT LA English DT Article ID STROMAL CELLS; MYOCARDIAL-INFARCTION; PARACRINE MECHANISMS; KAPOSIS-SARCOMA; MODEL; DELIVERY; DISEASE; PERMEABILITY; SECRETION; PERFUSION AB Over the past 10 years, a great deal has been learned about the fundamental biology and therapeutic application of bone marrow-derived human mesenchymal stem cells (MSCs). Intravenous administration of these cells is the preferred route for therapeutic delivery of MSCs. Vascular endothelial cells (ECs) are the first cell type that MSCs encounter following IV administration. However, little is known about the biological consequences of interactions between MSCs and ECs, and if any therapeutic benefit results from this interaction. We show that MSCs exert potent stabilizing effects on ECs using an in vitro coculture system. Such effects include decreased EC proliferation and the reduction of EC vascular network formation in matrigel. Interestingly, these effects appear to require EC-MSC contact and result in enhanced colocalization of VE-Cadherin and beta-catenin at the cell membrane. Disruption of the VE-Cadherin/beta-catenin interaction abrogates the observed effects. As a functional in vivo correlate, we show that intravenously administered MSCs strongly inhibit angiogenesis in a matrigel plug assay. Taken together, these results identify a novel mechanism of action of MSCs that involves a contact-dependent EC interaction. These findings are relevant to intravenous use of MSCs and provide insight into further optimizing therapeutic strategies involving MSCs. C1 [Menge, Tyler; Wataha, Kathryn; Pati, Shibani] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Gerber, Michael] Univ Texas Houston, Dept Surg, Hlth Sci Ctr UTHSC, Houston, TX USA. [Reid, William] NIH, Lab Diagnost Radiol Res & Imaging Serv, Ctr Clin, Bethesda, MD 20892 USA. [Guha, Sushovan] Univ Texas MD Anderson Canc Ctr, Dept Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA. [Cox, Charles S., Jr.] Univ Texas Houston, Dept Pediat Surg, Hlth Sci Ctr UTHSC, Houston, TX USA. [Dash, Pramod] Univ Texas Houston, Dept Neurobiol & Anat, Hlth Sci Ctr UTHSC, Houston, TX USA. [Reitz, Marvin S., Jr.] Univ Maryland, Inst Human Virol, Baltimore, MD 21201 USA. [Khakoo, Aarif Y.] Amgen Inc, San Francisco, CA USA. [Pati, Shibani] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Pati, S (reprint author), Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM spati@bloodsystems.org FU K18 grant from NHLBI [K18HL102256] FX We are grateful to Dr. Randall Moon (University of Washington, Seattle) for the kind gift of the plasmids for Wnt3a. Also, we would like to thank Scott Holmes for his expertise in graphic art design. This work was supported by a K18 grant from NHLBI: K18HL102256. NR 25 TC 19 Z9 21 U1 1 U2 21 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1547-3287 J9 STEM CELLS DEV JI Stem Cells Dev. PD JAN PY 2013 VL 22 IS 1 BP 148 EP 157 DI 10.1089/scd.2012.0165 PG 10 WC Cell & Tissue Engineering; Hematology; Medicine, Research & Experimental; Transplantation SC Cell Biology; Hematology; Research & Experimental Medicine; Transplantation GA 057VT UT WOS:000312592900014 PM 22734943 ER PT J AU Prokhorov, AV Hudmon, KS Marani, SK Bondy, ML Gatus, LA Spitz, MR Wilkinson, AV Hammond, SK Koehly, LM AF Prokhorov, Alexander V. Hudmon, Karen Suchanek Marani, Salma K. Bondy, Melissa L. Gatus, Leticia A. Spitz, Margaret R. Wilkinson, Anna V. Hammond, S. Katharine Koehly, Laura M. TI Eliminating second-hand smoke from Mexican-American households: Outcomes from Project Clean Air-Safe Air (CASA) SO ADDICTIVE BEHAVIORS LA English DT Article DE Smoking; Second-hand smoke; Prevention; Cessation; Exposure ID ENVIRONMENTAL RISK-FACTORS; SECONDHAND SMOKE; HEART-DISEASE; RANDOMIZED-TRIAL; EXPOSURE; CHILDREN; STROKE; ADULTS; HOME; AGE AB Exposure to second-hand smoke (SHS) is a major public health problem and a risk factor for morbidity and mortality. The objective of this randomized trial was to estimate the impact of a culturally-sensitive intervention to reduce SHS exposure in Mexican-American households. Method: A total of 91 households (with a child under 18 years of age and two adults, one of whom was a smoker) were recruited from a population-based cohort of Mexican-American households and randomized to receive the experimental intervention (EI: n = 47) or standard care (SC; n = 44). Of these 74 households (83%) provided baseline, 6-month, and 12-month survey and nicotine monitor data (EI. n = 39; SC, n = 35). The EI materials, designed to increase the participants' likelihood of adopting a smoke-free indoor home air policy, included one culturally-appropriate bilingual comic book for children and two fotonovelas for adults. Results: Ambient nicotine levels significantly decreased over the 12 study months (F = 136, DF = 147; p < 0.001): with a significantly greater decrease in the EI households compared to the SC households (F = 4.1, DF = 72; p < 0.05). At 12 months, 73% of EI households had banned smoking vs. 56% of SC households. Ambient nicotine levels, measured using nicotine air sampling monitors, were significantly associated with self-reported SHS exposure at the 12-month follow-up. Knowledge of the health effects of SHS increaser from baseline to 6 and 12 months in the EI condition but not in the SC condition (F = 6.0, DF = 238; p < 0.01), aid smokers and quitters in the EI group reported an increased perception of health vulnerability compared to those in the SC group. Conclusion: Our low-cost intervention impacted SHS-related knowledge and exposure among Mexican Americans. This culturally-appropriate intervention has the potential to decrease SHS-related health problems in the target population substantially. Published by Elsevier Ltd. C1 [Prokhorov, Alexander V.] Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, Houston, TX 77030 USA. [Prokhorov, Alexander V.; Gatus, Leticia A.] Univ Texas MD Anderson Canc Ctr, Dept Ctr Res Minor Hlth, Houston, TX 77030 USA. [Hudmon, Karen Suchanek] Purdue Univ, Dept Pharm Practice, Coll Pharm, W Lafayette, IN 47907 USA. [Bondy, Melissa L.; Spitz, Margaret R.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Wilkinson, Anna V.] Univ Texas Hlth Sci Houston, Sch Publ Hlth, Austin, TX USA. [Wilkinson, Anna V.] Michael & Susan Dell Ctr Hlth Living, Austin, TX USA. [Hammond, S. Katharine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. RP Prokhorov, AV (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Behav Sci, Unit 1330, 1155 Pressler St, Houston, TX 77030 USA. EM aprokhor@mdanderson.org FU Flight Attendant Medical Research Institute (FAMRI) [052374]; National Human Genome Research Institute at the NIH [Z01HG200335]; 76th legislature to The University of Texas MD Anderson Cancer Center; Caroline W. Law Fund for Cancer Prevention; Dan Duncan Family Institute for Risk Assessment and Cancer Prevention FX Flight Attendant Medical Research Institute ($300K; Dr. Prokhorov, Principal Investigator; FAMRI #052374).; This study was partially supported by the Intramural Research Program of the National Human Genome Research Institute at the NIH (Z01HG200335; Dr. Koehly, Principal Investigator).; The Mono a Mono cohort receives funds collected pursuant to the Comprehensive Tobacco Settlement of 1998 and appropriated by the 76th legislature to The University of Texas MD Anderson Cancer Center; by the Caroline W. Law Fund for Cancer Prevention, and by the Dan Duncan Family Institute for Risk Assessment and Cancer Prevention. NR 32 TC 15 Z9 15 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD JAN PY 2013 VL 38 IS 1 BP 1485 EP 1492 DI 10.1016/j.addbeh.2012.06.023 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 054QM UT WOS:000312358300013 PM 23085392 ER PT J AU Shirota, Y Yarboro, C Fischer, R Pham, TH Lipsky, P Illei, GG AF Shirota, Yuko Yarboro, Cheryl Fischer, Randy Pham, Tuyet-Hang Lipsky, Peter Illei, Gabor G. TI Impact of anti-interleukin-6 receptor blockade on circulating T and B cell subsets in patients with systemic lupus erythematosus SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID MARROW STROMAL CELLS; DISEASE-ACTIVITY; PLASMA-CELLS; TERMINAL DIFFERENTIATION; INTERLEUKIN-6; EXPRESSION; LYMPHOCYTES; ACTIVATION; IL-6; ADHESION AB Background Circulating plasmablasts/plasma cells and activated B and T cells are increased in systemic lupus erythematosus (SLE). Interleukin (IL)-6 induces differentiation of B cells into antibody-forming cells and of T cells into effector cells. Objective To examine the hypothesis that blocking IL-6 would reverse some of the immune abnormalities present in SLE. Methods Fifteen patients with SLE with mild-to moderate disease activity were treated with biweekly infusions of tocilizumab, a humanised anti-IL-6 receptor monoclonal antibody for 12 weeks. Lymphocyte subsets (analysed by flow cytometry) and serum immunoglobulin levels were compared at baseline and at weeks 6 and 12. Results Tocilizumab decreased activated T and B cells, the frequency of CD27(high)CD38(high)IgD-plasmablasts/plasma cells and IgD-CD27+ post-switched memory B cells as well as IgG+ memory B cell, whereas it increased the frequency of IgD+CD27-antigen-inexperienced B cells. Among antigen-inexperienced IgD +CD27-B cells, CD38(low) mature naive B cells increased significantly and CD38(Intermediate)CD5+ pre-naive B cells showed a decreasing trend, whereas CD38(high)CD5+ transitional type 1 B cells did not change. Most of the changes occurred in patients who had abnormal values at baseline. IgG, IgA, IgG1 and IgG3 serum levels decreased albeit within the normal range. The frequency of CD4 +CD45RA+CCR7+ naive T cells increased. Conclusions In vivo blockade of the IL-6 receptor decreases lymphocyte activation and restores B and T cell homoeostasis by either blocking differentiation and/or trafficking in patients with SLE and leads to normalisation of the abnormal B and T cell subsets seen at baseline. C1 [Shirota, Yuko; Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Shirota, Yuko; Yarboro, Cheryl; Pham, Tuyet-Hang; Illei, Gabor G.] NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. [Fischer, Randy] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Illei, GG (reprint author), Natl Inst Dent & Craniofacial Res, Sjogrens Syndrome Clin, Mol Physiol & Therapeut Branch, NIH, 10 Ctr Dr,Room 1N 110, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov FU National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Dental and Craniofacial Research FX We thank Drs Ruth Fritsch-Stork, Gary Sims, Rachel Ettinger and Xavier Valencia for their helpful advice in designing the antibody panels for the flow cytometry. The study was done under a Collaborative Research and Development Agreement between the National Institute of Arthritis and Musculoskeletal and Skin Diseases and Chugai, Pharma USA and was supported by the intramural research programmes of the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the National Institute of Dental and Craniofacial Research. NR 44 TC 46 Z9 53 U1 0 U2 9 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2013 VL 72 IS 1 BP 118 EP 128 DI 10.1136/annrheumdis-2012-201310 PG 11 WC Rheumatology SC Rheumatology GA 055IB UT WOS:000312407800019 PM 22858586 ER PT J AU Porter, SA Pedley, A Massaro, JM Vasan, RS Hoffmann, U Fox, CS AF Porter, Stacy A. Pedley, Alison Massaro, Joseph M. Vasan, Ramachandran S. Hoffmann, Udo Fox, Caroline S. TI Aminotransferase Levels Are Associated With Cardiometabolic Risk Above and Beyond Visceral Fat and Insulin Resistance The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE cardiometabolic risk factors; insulin resistance; liver function tests; obesity; visceral fat ID SERUM ALANINE AMINOTRANSFERASE; LIVER-DISEASE; METABOLIC SYNDROME; NONALCOHOLIC STEATOHEPATITIS; TRANSAMINASE-ACTIVITY; ADIPONECTIN; DYSLIPIDEMIA; PREVALENCE; SPECTRUM; GLUCOSE AB Objective-We sought to characterize associations between aminotransferase levels and cardiometabolic risk after accounting for visceral adipose tissue and insulin resistance. Methods and Results-Participants (n=2621) from the Framingham Heart Study (mean age 51, 49.8% women) were included. Sex-specific linear and logistic regressions were used to evaluate associations between aminotransferase levels and cardiometabolic risk factors. In multivariable models, increased alanine aminotransferase levels were associated with elevated blood pressure, fasting plasma glucose, and triglycerides and lower high-density lipoprotein levels (all P <= 0.007). Furthermore, each 1-SD increase in alanine aminotransferase corresponded to an increased odds of hypertension, diabetes mellitus, the metabolic syndrome, impaired fasting glucose, and insulin resistance estimated by the homeostasis model assessment of insulin resistance (odds ratio, 1.29-1.85, all P <= 0.002). Associations with alanine aminotransferase persisted after additional adjustment for visceral adipose tissue, insulin resistance, and body mass index with the exception of high-density lipoprotein cholesterol in both sexes and blood pressure in women. Results were materially unchanged when moderate drinkers were excluded, when the sample was restricted to those with alanine aminotransferase <40 U/L, and when the sample was restricted to those without diabetes mellitus. Similar trends were observed for aspartate aminotransferase levels, but associations were more modest. Conclusion-Aminotransferase levels are correlated with multiple cardiometabolic risk factors above and beyond visceral adipose tissue and insulin resistance. (Arterioscler Thromb Vasc Biol. 2013;33:139-146.) C1 [Massaro, Joseph M.; Vasan, Ramachandran S.; Fox, Caroline S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Porter, Stacy A.; Pedley, Alison; Fox, Caroline S.] NHLBI, Ctr Populat Studies, Framingham, MA USA. [Porter, Stacy A.] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA. [Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. [Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA. [Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@Nhlbi.nih.gov OI Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU Boston University School of Medicine; National Heart, Lung, and Blood Institute's Framingham Heart Study [N01-HC-25195] FX This work was supported by the Boston University School of Medicine and the National Heart, Lung, and Blood Institute's Framingham Heart Study (contract N01-HC-25195). NR 37 TC 14 Z9 15 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2013 VL 33 IS 1 BP 139 EP + DI 10.1161/ATVBAHA.112.300075 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 055CJ UT WOS:000312392500021 PM 23162012 ER PT J AU Otto, M AF Otto, Michael TI Coagulase-negative staphylococci as reservoirs of genes facilitating MRSA infection SO BIOESSAYS LA English DT Article DE CRISPR; horizontal gene transfer; MRSA; Staphylococcus aureus; Staphylococcus epidermidis ID CATABOLIC MOBILE ELEMENT; CASSETTE CHROMOSOME MEC; COMMUNITY-ASSOCIATED MRSA; METHICILLIN RESISTANCE; VIRULENCE DETERMINANTS; SURVEILLANCE PROGRAM; AUREUS INFECTIONS; GENOME SEQUENCE; IMMUNE EVASION; NASAL CARRIAGE AB Recent research has suggested that Staphylococcus epidermidis is a reservoir of genes that, after horizontal transfer, facilitate the potential of Staphylococcus aureus to colonize, survive during infection, or resist antibiotic treatment, traits that are notably manifest in methicillin-resistant S. aureus (MRSA). S. aureus is a dangerous human pathogen and notorious for acquiring antibiotic resistance. MRSA in particular is one of the most frequent causes of morbidity and death in hospitalized patients. S. aureus is an extremely versatile pathogen with a multitude of mechanisms to cause disease and circumvent immune defenses. In contrast, most other staphylococci, such as S. epidermidis, are commonly benign commensals and only occasionally cause disease. Recent findings highlight the key importance of efforts to better understand how genes of staphylococci other than S. aureus contribute to survival in the human host, how they are transferred to S. aureus, and why this exchange appears to be uni-directional. C1 NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA. RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU National Institute of Allergy and Infectious Diseases (NIAID), U. S. National Institutes of Health (NIH) FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases (NIAID), U. S. National Institutes of Health (NIH). NR 68 TC 45 Z9 48 U1 2 U2 30 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2013 VL 35 IS 1 BP 4 EP 11 DI 10.1002/bies.201200112 PG 8 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 053VI UT WOS:000312302600005 PM 23165978 ER PT J AU Lee, IY Gruber, TD Samuels, A Yun, M Nam, B Kang, M Crowley, K Winterroth, B Boshoff, HI Barry, CE AF Lee, Ill-Young Gruber, Todd D. Samuels, Amanda Yun, Minhan Nam, Bora Kang, Minseo Crowley, Kathryn Winterroth, Benjamin Boshoff, Helena I. Barry, Clifton E., III TI Structure-activity relationships of antitubercular salicylanilides consistent with disruption of the proton gradient via proton shuttling SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Tuberculosis; Salicylanilide; Proton gradient; Antibacterial ID MYCOBACTERIUM-TUBERCULOSIS; INTRABACTERIAL PH; INHIBITORS; MITOCHONDRIA; DESIGN AB A series of salicylanilides was synthesized based on a high-throughput screening hit against Mycobacterium tuberculosis. A free phenolic hydroxyl on the salicylic acid moeity is required for activity, and the structure-activity relationship of the aniline ring is largely driven by the presence of electron withdrawing groups. We synthesized 94 analogs exploring substitutions of both rings and the linker region in this series and we have identified multiple compounds with low micromolar potency. Unfortunately, cytotoxicity in a murine macrophage cell line trends with antimicrobial activity, suggesting a similar mechanism of action. We propose that salicylanilides function as proton shuttles that kill cells by destroying the cellular proton gradient, limiting their utility as potential therapeutics. Published by Elsevier Ltd. C1 [Gruber, Todd D.; Samuels, Amanda; Crowley, Kathryn; Winterroth, Benjamin; Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. [Lee, Ill-Young; Yun, Minhan; Nam, Bora; Kang, Minseo] Korea Res Inst Chem Technol, Pharmacol Res Ctr, Taejon 305600, South Korea. RP Barry, CE (reprint author), NIAID, TB Res Sect, LCID, NIH, 33 North Dr,Bldg 33,Rm 2W20D, Bethesda, MD 20892 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU National Institute of Allergy and Infectious Disease; National Institutes of Health; Bill and Melinda Gates Foundation; Korea Research Institute of Chemical and Technology; Ministry of Education, Science and Technology of Korea FX We thank Anton Simeonov, Paul Shinn, Adam Yasgar, Carleen Klumpp, and Ajit Jadhav for construction and help with screening and analysis of the NCGC library. We also thank Gwendolyn Marriner for helpful discussions, Noel Whittaker for HRMS data collection, and Kathryn Soucy for assistance in data collection. This work was funded (in part) by the Intramural Research Program of the National Institute of Allergy and Infectious Disease, National Institutes of Health, the Bill and Melinda Gates Foundation, the Korea Research Institute of Chemical and Technology, and the Ministry of Education, Science and Technology of Korea. NR 30 TC 18 Z9 18 U1 0 U2 41 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2013 VL 21 IS 1 BP 114 EP 126 DI 10.1016/j.bmc.2012.10.056 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 053MJ UT WOS:000312275500010 PM 23211970 ER PT J AU Kozma, E Jayasekara, PS Squarcialupi, L Paoletta, S Moro, S Federico, S Spalluto, G Jacobson, KA AF Kozma, Eszter Jayasekara, P. Suresh Squarcialupi, Lucia Paoletta, Silvia Moro, Stefano Federico, Stephanie Spalluto, Giampiero Jacobson, Kenneth A. TI Fluorescent ligands for adenosine receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Review DE Purine; G protein-coupled receptor; Fluorescence; Membrane proteins; Binding; Screening ID SINGLE LIVING CELLS; PROTEIN-COUPLED RECEPTOR; CORRELATION SPECTROSCOPY; GPCR LIGANDS; BINDING; DERIVATIVES; AGONISTS; ANTAGONISTS; POTENT; PROBES AB Interest is increasing in developing fluorescent ligands for characterization of adenosine receptors (ARs), which hold a promise of usefulness in the drug discovery process. The size of a strategically labeled AR ligand can be greatly increased after the attachment of a fluorophore. The choice of dye moiety (e. g. Alexa Fluor 488), attachment point and linker length can alter the selectivity and potency of the parent molecule. Fluorescent derivatives of adenosine agonists and antagonists (e.g. XAC and other heterocyclic antagonist scaffolds) have been synthesized and characterized pharmacologically. Some are useful AR probes for flow cytometry, fluorescence correlation spectroscopy, fluorescence microscopy, fluorescence polarization, fluorescence resonance energy transfer, and scanning confocal microscopy. Thus, the approach of fluorescent labeled GPCR ligands, including those for ARs, is a growing dynamic research field. Published by Elsevier Ltd. C1 [Kozma, Eszter; Jayasekara, P. Suresh; Squarcialupi, Lucia; Paoletta, Silvia; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Moro, Stefano] Univ Padua, Dipartimento Sci Farmaco, MMS, I-35131 Padua, Italy. [Federico, Stephanie; Spalluto, Giampiero] Univ Trieste, Dipartimento Sci Chim & Farmaceut, I-34127 Trieste, Italy. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; Federico, Stephanie/0000-0003-2800-5287 FU NIDDK Intramural Research program; Hungarian-American Enterprise Scholarship Foundation (HAESF); University of Padova, Italy; Italian Ministry for University and Research (MIUR), Rome, Italy FX Support from the NIDDK Intramural Research program is acknowledged. E.K. thanks the Hungarian-American Enterprise Scholarship Foundation (HAESF) for financial support. The work coordinated by S.M. was carried out with financial support from the University of Padova, Italy, and the Italian Ministry for University and Research (MIUR), Rome, Italy. NR 50 TC 14 Z9 14 U1 0 U2 47 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X EI 1464-3405 J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2013 VL 23 IS 1 BP 26 EP 36 DI 10.1016/j.bmcl.2012.10.112 PG 11 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 053JO UT WOS:000312267700002 PM 23200243 ER PT J AU Zhang, P Jorgensen, TN Loland, CJ Newman, AH AF Zhang, Peng Jorgensen, Trine Nygaard Loland, Claus J. Newman, Amy Hauck TI A rhodamine-labeled citalopram analogue as a high-affinity fluorescent probe for the serotonin transporter SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Fluorescent ligand; Citalopram; SERT; Rhodamine ID DOPAMINE TRANSPORTER; MONOAMINE TRANSPORTERS; CONFORMATIONAL-CHANGES; NEURONS; SPECTROSCOPY; ACTIVATION; RECEPTOR; SERIES; CELLS AB A novel fluorescent ligand was synthesized as a high-affinity, high specificity probe for visualizing the serotonin transporter (SERT). The rhodamine fluorophore was extended from an aniline substitution on the 5-position of the dihydroisobenzofuran ring of citalopram (2, 1-(3-(dimethylamino)propyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile), using an ethylamino linker. The resulting rhodamine-labeled ligand 8 inhibited [H-3]5-HT uptake in COS-7 cells (K-i = 225 nM) with similar potency to the tropane-based JHC 1-064 (1), but with higher specificity towards the SERT relative to the transporters for dopamine and norepinephrine. Visualization of the SERT with compound 8 was demonstrated by confocal microscopy in HEK293 cells stably expressing EGFP-SERT. Published by Elsevier Ltd. C1 [Zhang, Peng; Newman, Amy Hauck] NIDA, Mol Targets & Medicat Discovery Branch, Med Chem Sect, Intramural Res Program,NIH, Baltimore, MD 21224 USA. [Jorgensen, Trine Nygaard; Loland, Claus J.] Univ Copenhagen, Mol Neuropharmacol Lab, DK-2200 Copenhagen N, Denmark. [Jorgensen, Trine Nygaard; Loland, Claus J.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Neurosci & Pharmacol, Ctr Pharmacogen, DK-2200 Copenhagen N, Denmark. RP Newman, AH (reprint author), NIDA, Mol Targets & Medicat Discovery Branch, Med Chem Sect, Intramural Res Program,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov RI Loland, Claus/E-5975-2014 OI Loland, Claus/0000-0002-1773-1446 FU NIDA-Intramural Research Program; Center for Pharmacogenomics, University of Copenhagen, NIH [P01 DA 12408]; Lundbeck Foundation; University of Copenhagen FX This work was funded by the NIDA-Intramural Research Program (A.H.N.), the Center for Pharmacogenomics, University of Copenhagen, NIH Grant P01 DA 12408, The Lundbeck Foundation and University of Copenhagen Program of Excellence (C.J.L). The Danish Council for Independent Research, Sapere Aude Program (C.J.L.) NR 23 TC 7 Z9 7 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD JAN 1 PY 2013 VL 23 IS 1 BP 323 EP 326 DI 10.1016/j.bmcl.2012.10.089 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 053JO UT WOS:000312267700059 PM 23168018 ER PT J AU Romero, R AF Romero, R. TI Progesterone to prevent preterm birth in twin gestations: what is the next step forward? SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; DOUBLE-BLIND; CERVICAL LENGTH; VAGINAL PROGESTERONE; PARTURITION SYNDROME; WOMEN; RISK; DELIVERY; MULTICENTER C1 [Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, R.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu FU Intramural NIH HHS [ZIA HD002400-21] NR 28 TC 10 Z9 11 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD JAN PY 2013 VL 120 IS 1 BP 1 EP 4 DI 10.1111/1471-0528.12019 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 053VX UT WOS:000312304300002 PM 23237263 ER PT J AU Pacher, P AF Pacher, Pal TI Towards the use of non-psychoactive cannabinoids for prostate cancer SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE Cannabis sativa; cannabidiol; cannabinoid; cancer; prostate; phytocannabinoids; non-psychoactive ID ENDOCANNABINOID SYSTEM; TARGET AB The palliative effects of Cannabis sativa (marijuana), and its putative main active ingredient, ?9-tetrahydrocannabinol (THC), which include appetite stimulation, attenuation of nausea and emesis associated with chemo- or radiotherapy, pain relief, mood elevation, and relief from insomnia in cancer patients, are well-known. Because of the adverse psychoactive effects of THC, numerous recent preclinical studies have been focused on investigating other non-psychoactive constituents of C. sativa, such as cannabidiol, for potential therapeutic use. In this issue of the British Journal of Pharmacology, De Petrocellis and colleagues present comprehensive evidence that plant-derived cannabinoids, especially cannabidiol, are potent inhibitors of prostate carcinoma viability in vitro. They also showed that the extract was active in vivo, either alone or when administered with drugs commonly used to treat prostate cancer (the anti-mitotic chemotherapeutic drug docetaxel (Taxotere) or the anti-androgen bicalutamide (Casodex)) and explored the potential mechanisms behind these antineoplastic effects. Linked Article This article is a commentary on De Petrocellis et?al., pp. 79102 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.02027.x C1 [Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress & Tissue Injury, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC 9413,Room 2N-17, Rockville, MD 20852 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU NIH/NIAAA FX This publication was supported by the Intramural Research Program of NIH/NIAAA to Dr Pacher. Drug and receptor nomenclature follows Alexander et al., (2011). NR 15 TC 3 Z9 4 U1 3 U2 51 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JAN PY 2013 VL 168 IS 1 BP 76 EP 78 DI 10.1111/j.1476-5381.2012.02121.x PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 057EI UT WOS:000312544900011 PM 22849856 ER PT J AU Grodzinski, P AF Grodzinski, Piotr TI Themed issue on Cancer Nanotechnology SO INTEGRATIVE BIOLOGY LA English DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Grodzinski, P (reprint author), NCI, 6116 Execut Blvd,Suite 300, Bethesda, MD 20892 USA. EM grodzinp@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 12 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2013 VL 5 IS 1 BP 17 EP 18 DI 10.1039/c2ib90050e PG 2 WC Cell Biology SC Cell Biology GA 055BY UT WOS:000312391300002 PM 23179042 ER PT J AU Meng, J Liang, XJ Chen, XY Zhao, YL AF Meng, Jie Liang, Xingjie Chen, Xiaoyuan Zhao, Yuliang TI Biological characterizations of [Gd@C-82(OH)(22)](n) nanoparticles as fullerene derivatives for cancer therapy SO INTEGRATIVE BIOLOGY LA English DT Review ID MATRIX-METALLOPROTEINASE INHIBITORS; TUMOR-BEARING MICE; IN-VIVO; BIODISTRIBUTION; PERSPECTIVES; MODULATION; DELIVERY; TISSUES; DAMAGE; CELLS AB Malignant tumor disease is one of the leading causes of human death in many countries. Currently, chemotherapy is considered highly efficient for cancer treatment. However, the clinical application of conventional chemotherapeutic agents is limited because of their high toxicity. With the development of nanotechnology, engineered nanomaterials have been widely and increasingly used in biomedical fields such as biomedicine. Thus, the use of engineered nanomaterials has become a promising approach to cancer treatment. Many newly fabricated nanomaterials with unique characteristics exhibit favorable therapeutic and diagnostic properties, implying their enormous potential as biomedical candidates. [Gd@C-82(OH)(22)](n) is a new type of metallofullerenol nanoparticle with high anti-tumor activity but low toxicity. In this article, the properties and biological effects of [Gd@C-82(OH)(22)](n) are summarized, and their possible mechanisms are analyzed. C1 [Meng, Jie; Liang, Xingjie] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China. [Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA. [Zhao, Yuliang] Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Inst High Energy Phys, Beijing 100190, Peoples R China. RP Meng, J (reprint author), Chinese Acad Sci, Key Lab Biomed Effects Nanomat & Nanosafety, Natl Ctr Nanosci & Technol China, Beijing 100190, Peoples R China. FU Chinese Natural Science Foundation [30970784, 81171455, 31100720, 31000451]; National Key Basic Research Program of China [2009CB930200]; Chinese Academy of Sciences (CAS) "Hundred Talents Program" [07165111ZX]; CAS Knowledge Innovation Program; Chinese Academy of Science visiting professorship for senior international scientists [Y2022911ZX] FX This work was financially supported by Chinese Natural Science Foundation project (No. 30970784, 81171455, 31100720 and 31000451), National Key Basic Research Program of China (2009CB930200), Chinese Academy of Sciences (CAS) "Hundred Talents Program" (07165111ZX) and CAS Knowledge Innovation Program, and Chinese Academy of Science visiting professorship for senior international scientists (Y2022911ZX). NR 30 TC 28 Z9 30 U1 7 U2 97 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2013 VL 5 IS 1 BP 43 EP 47 DI 10.1039/c2ib20145c PG 5 WC Cell Biology SC Cell Biology GA 055BY UT WOS:000312391300005 PM 22961501 ER PT J AU Crist, RM Grossman, JH Patri, AK Stern, ST Dobrovolskaia, MA Adiseshaiah, PP Clogston, JD McNeil, SE AF Crist, Rachael M. Grossman, Jennifer Hall Patri, Anil K. Stern, Stephan T. Dobrovolskaia, Marina A. Adiseshaiah, Pavan P. Clogston, Jeffrey D. McNeil, Scott E. TI Common pitfalls in nanotechnology: lessons learned from NCI's Nanotechnology Characterization Laboratory SO INTEGRATIVE BIOLOGY LA English DT Article ID PLASMA-PROTEIN BINDING; IN-VITRO; NANOPARTICLE FORMULATIONS; ENDOTOXIN REMOVAL; PARTICLE-SIZE; NICKEL; TOXICITY; RADIATION; SURFACES; C-60 AB The Nanotechnology Characterization Laboratory's (NCL) unique set-up has allowed our lab to handle and test a variety of nanoparticle platforms intended for the delivery of cancer therapeutics and/or imaging contrast agents. Over the last six years, the NCL has characterized more than 250 different nanomaterials from more than 75 different investigators. These submitted nanomaterials stem from a range of backgrounds and experiences, including government, academia and industry. This has given the NCL a unique and valuable opportunity to observe trends in nanoparticle safety and biocompatibility, as well as note some of the common mistakes and oversights of nanoformulation. While not exhaustive, this article aims to share some of the most common pitfalls observed by the NCL as they relate to nanoparticle synthesis, purification, characterization and analysis. C1 [Crist, Rachael M.; Grossman, Jennifer Hall; Patri, Anil K.; Stern, Stephan T.; Dobrovolskaia, Marina A.; Adiseshaiah, Pavan P.; Clogston, Jeffrey D.; McNeil, Scott E.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. RP Crist, RM (reprint author), SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA. EM ncl@mail.nih.gov RI Nanotechnology Characterization Lab, NCL/K-8454-2012; Crist, Rachael/K-7603-2012 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The NCL would like to thank the technical staff for assistance with all of the projects highlighted in the article: Chris McLeland, Tim Potter, Barry Neun, Sarah Skoczen, Matt Hansen, Sonny Man, and Jamie Rodriguez. The NCL also appreciates the support of SAIC-Frederick, Inc.'s Electron Microscopy Lab and Laboratory Animal Sciences Program. Finally, the NCL would like to express our gratitude to all the collaborators submitting nanoparticles to the NCL. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 40 TC 72 Z9 72 U1 3 U2 70 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1757-9694 J9 INTEGR BIOL-UK JI Integr. Biol. PY 2013 VL 5 IS 1 BP 66 EP 73 DI 10.1039/c2ib20117h PG 8 WC Cell Biology SC Cell Biology GA 055BY UT WOS:000312391300007 PM 22772974 ER PT J AU Dotson, VM Zonderman, AB Kraut, MA Resnick, SM AF Dotson, Vonetta M. Zonderman, Alan B. Kraut, Michael A. Resnick, Susan M. TI Temporal relationships between depressive symptoms and white matter hyperintensities in older men and women SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE depression; aging; elderly; vascular disease; sex differences; longitudinal studies ID LATE-LIFE DEPRESSION; APOLIPOPROTEIN-E GENOTYPE; CEREBRAL-BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; DEFINED VASCULAR DEPRESSION; SCALE CES-D; MAJOR DEPRESSION; GERIATRIC DEPRESSION; CEREBROVASCULAR-DISEASE; CARDIOVASCULAR HEALTH AB Objective Associations between vascular disease and depression in late life, including increased white matter hyperintensities (WMHs), have been reported. Whether depression is an etiology or a consequence of vascular disease is still unknown. We investigated the temporal relationship between depressive symptoms and WMHs in older men and women. Methods We utilized data from 90 dementia-free older adults (39 women, 51 men), 57?years of age and older at baseline, from the neuroimaging substudy of the Baltimore Longitudinal Study of Aging. Participants were followed for up to 8?years. Ratings of white matter disease burden were available for the first, last, and at least one interim visit, and participants completed the Center for Epidemiologic Studies Depression Scale (CES-D) annually. Statistical models, performed separately in men and women, examined whether depressive symptoms predicted subsequent WMH ratings or WMHs predicted subsequent depressive symptoms. Results The total CES-D score was not associated with WMHs in men or women. In men, the CES-D depressed mood subscale predicted accelerating longitudinal increases in WMHs at older ages, but WMHs did not predict subsequent depressive symptoms. In women, there were no significant associations between the CES-D depressed mood subscale and WMHs. Conclusions White matter disease may be a consequence of depressed mood in men but not in women. Intervention strategies for depression may slow the progression of white matter disease in older men. These results add to previous findings documenting sex differences in the correlates of depressive disorders in late life. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Dotson, Vonetta M.; Zonderman, Alan B.; Resnick, Susan M.] NIA, Lab Personal & Cognit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Kraut, Michael A.] Johns Hopkins Med Inst, Dept Radiol, Baltimore, MD 21205 USA. RP Dotson, VM (reprint author), Univ Florida, Dept Clin & Hlth Psychol, Gainesville, FL 32610 USA. EM vonetta@phhp.ufl.edu RI Dotson, Vonetta/K-6090-2015; OI Dotson, Vonetta/0000-0002-3043-3320; Zonderman, Alan B/0000-0002-6523-4778 FU National Institute on Aging Intramural Research Program of the National Institutes of Health FX The National Institute on Aging Intramural Research Program of the National Institutes of Health supported this research. The authors wish to thank Yang An, M. S. for assistance with the statistical analyses. NR 89 TC 5 Z9 5 U1 5 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD JAN PY 2013 VL 28 IS 1 BP 66 EP 74 DI 10.1002/gps.3791 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 051QB UT WOS:000312141000008 PM 22415749 ER PT J AU Frank-Kamenetskii, M Trifonov, E Zhurkin, V Danilov, V Sarma, M Sarma, R AF Frank-Kamenetskii, Maxim Trifonov, Edward Zhurkin, Victor Danilov, Victor Sarma, Mukti Sarma, Ramaswamy TI Valery (Chrom) Ivanov In memoriam SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Biographical-Item C1 [Sarma, Mukti; Sarma, Ramaswamy] SUNY Albany, Dept Chem, Albany, NY 12222 USA. [Frank-Kamenetskii, Maxim] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA. [Trifonov, Edward] Univ Haifa, Inst Evolut, IL-31999 Haifa, Israel. [Zhurkin, Victor] NCI, Bethesda, MD 20892 USA. [Danilov, Victor] Natl Acad Sci Ukraine, Inst Mol Biol & Genet, Kiev, Ukraine. RP Sarma, R (reprint author), SUNY Albany, Dept Chem, Albany, NY 12222 USA. EM rhs07@albany.edu NR 1 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD JAN 1 PY 2013 VL 31 IS 1 SI SI BP 125 EP 127 DI 10.1080/07391102.2013.745267 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 055VY UT WOS:000312447100013 PM 23171071 ER PT J AU Adeyemo, A Tayo, BO Luke, A Ogedegbe, O Durazo-Arvizu, R Cooper, RS AF Adeyemo, Adebowale Tayo, Bamidele O. Luke, Amy Ogedegbe, Olugbenga Durazo-Arvizu, Ramon Cooper, Richard S. TI The Nigerian antihypertensive adherence trial: a community-based randomized trial SO JOURNAL OF HYPERTENSION LA English DT Article DE adherence; antihypertensive; compliance trial; randomized trial ID MEDICATION COMPLIANCE; HYPERTENSION CONTROL; TANZANIA; URBAN; RIBOFLAVIN; MORTALITY; THERAPY; DESIGN; IMPACT; CARE AB Background: Research in industrialized countries has demonstrated that a key factor limiting the control of hypertension is poor patient adherence and that the most successful interventions for long-term adherence employ multiple strategies. Very little data exist on this question in low-income countries, wherein medication-taking behavior may be less well developed. Method: We conducted a treatment adherence trial of 544 patients [mean age similar to 63 years, mean blood pressure (BP) similar to 168/92 mmHg] with previously untreated hypertension in urban and rural Nigeria. Eligible participants were randomized to one of two arms: clinic management only, or clinic management and home visits. Both interventions included three elements: a community based, nurse-led treatment program with physician backup; facilitation of clinic visits and health education; and the use of diuretics and a beta blocker as needed. After initial diagnosis, the management protocol was implemented by a nurse with physician backup. Participants were evaluated monthly for 6 months. Results: Medication adherence was assessed with pill count and urine testing. Drop-out rates, by treatment group, ranged from 12 to 28%. Among participants who completed the 6-month trial, overall adherence was high (similar to 77% of participants took >98% of prescribed pills). Adherence did not differ by treatment arm, but was better at the rural than the urban site and among those with higher baseline BP. Hypertension control (BP <140/90 mmHg) was achieved in approximately 66% of participants at 6 months. Conclusion: This community-based intervention confirms relatively modest default rates compared with industrialized societies, and suggests that medication adherence can be high in developing world settings in clinic attenders. C1 [Tayo, Bamidele O.; Luke, Amy; Durazo-Arvizu, Ramon; Cooper, Richard S.] Loyola Univ Chicago, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. [Adeyemo, Adebowale] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA. [Ogedegbe, Olugbenga] NYU, Langone Med Ctr, Ctr Healthful Behav Change, New York, NY USA. RP Cooper, RS (reprint author), Loyola Univ Chicago, Stritch Sch Med, Dept Prevent Med & Epidemiol, 2160 S 1st Ave, Maywood, IL 60153 USA. EM rcooper@lumc.edu OI Adeyemo, Adebowale/0000-0002-3105-3231 FU Fogarty Training Grant [D43TW009140]; National Institutes of Health (NIH) grant from the NHLBI [R01 HL67883] FX Many thanks to the research and field staff at the Institute of Child Health, University of Ibadan, and the staff and participants at the field sites in Igbo-Ora, Idere and Idekan. O.O. was supported in part, by Fogarty Training Grant D43TW009140; This work was supported by National Institutes of Health (NIH) grant from the NHLBI (R01 HL67883). NR 24 TC 13 Z9 14 U1 1 U2 11 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 JAN PY 2013 VL 31 IS 1 BP 201 EP 207 DI 10.1097/HJH.0b013e32835b0842 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 052PV UT WOS:000312211400029 PM 23137954 ER PT J AU Kimura, AK Kim, HY AF Kimura, Atsuko Kakio Kim, Hee-Yong TI Phosphatidylserine synthase 2: high efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid SO JOURNAL OF LIPID RESEARCH LA English DT Article DE mass spectrometry; plasmalogen; membranes; omega-3 fatty acids; phospholipids ID HAMSTER OVARY CELLS; TUMOR BLOOD-VESSELS; FATTY-ACIDS; ANIONIC PHOSPHOLIPIDS; SUBSTRATE PREFERENCE; INCREASED EXPOSURE; MASS-SPECTROMETRY; MAMMALIAN-CELLS; APOPTOTIC CELLS; NERVOUS-SYSTEM AB Phosphatidylserine (PS), the major anionic phospholipid in eukaryotic cell membranes, is synthesized by the integral membrane enzymes PS synthase 1 (PSS1) and 2 (PSS2). PSS2 is highly expressed in specific tissues, such as brain and testis, where docosahexaenoic acid (DHA, 22:6n-3) is also highly enriched. The purpose of this work was to characterize the hydrocarbon-chain preference of PSS2 to gain insight on the specialized role of PSS2 in PS accumulation in the DHA-abundant tissues. Flag-tagged PSS2 was expressed in HEK cells and immunopurified in a functionally active form. Purified PSS2 utilized both PE plasmalogen and diacyl PE as substrates. Nevertheless, the latter was six times better utilized, indicating the importance of an ester linkage at the sn-1 position. Although no sn-1 fatty acyl preference was noted, PSS2 exhibited significant preference toward DHA compared with 18:1 or 20:4 at the sn-2 position. Preferential production of DHA-containing PS (DHA-PS) was consistently observed with PSS2 purified from a variety of cell lines as well as with microsomes from mutant cells in which PS synthesis relies primarily on PSS2.(jlr) These findings suggest that PSS2 may play a key role in PS accumulation in brain and testis through high activity toward DHA-containing substrates that are abundant in these tissues.-Kimura, A. K., and H.-Y. Kim. Phosphatidylserine synthase 2: high efficiency for synthesizing phosphatidylserine containing docosahexaenoic acid. J. Lipid Res. 2013. 54: 214-222. C1 [Kimura, Atsuko Kakio; Kim, Hee-Yong] NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Kim, HY (reprint author), NIAAA, Lab Mol Signaling, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. EM hykim@nih.gov FU Intramural Research Program of the National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. NR 46 TC 2 Z9 2 U1 3 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JAN PY 2013 VL 54 IS 1 BP 214 EP 222 DI 10.1194/jlr.M031989 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 055BI UT WOS:000312389600020 PM 23071296 ER PT J AU Zwingenberger, AL Vernau, W Sh, C Yan, W Chen, X Gordon, IK Kent, MS AF Zwingenberger, Allison L. Vernau, William Sh, Changying Yan, Wensheng Chen, Xinbin Gordon, Ira K. Kent, Michael S. TI Development and characterization of 5 canine B-cell lymphoma cell lines (vol 36, pg 601, 2011) SO LEUKEMIA RESEARCH LA English DT Correction C1 [Zwingenberger, Allison L.; Sh, Changying; Yan, Wensheng; Chen, Xinbin; Kent, Michael S.] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, Davis, CA 95616 USA. [Vernau, William] Univ Calif Davis, Sch Vet Med, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA. [Gordon, Ira K.] NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Zwingenberger, AL (reprint author), Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, 1 Shields Ave, Davis, CA 95616 USA. EM azwingen@ucdavis.edu NR 1 TC 1 Z9 1 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD JAN PY 2013 VL 37 IS 1 BP 120 EP 120 DI 10.1016/j.leukres.2012.09.007 PG 1 WC Oncology; Hematology SC Oncology; Hematology GA 052KP UT WOS:000312196800021 ER PT J AU Petraitis, V Petraitiene, R Antachopoulos, C Hughes, JE Cotton, MP Kasai, M Harrington, S Gamaletsou, MN Bacher, JD Kontoyiannis, DP Roilides, E Walsh, TJ AF Petraitis, Vidmantas Petraitiene, Ruta Antachopoulos, Charalampos Hughes, Johanna E. Cotton, Margaret P. Kasai, Miki Harrington, Susan Gamaletsou, Maria N. Bacher, John D. Kontoyiannis, Dimitrios P. Roilides, Emmanuel Walsh, Thomas J. TI Increased virulence of Cunninghamella bertholletiae in experimental pulmonary mucormycosis: correlation with circulating molecular biomarkers, sporangiospore germination and hyphal metabolism SO MEDICAL MYCOLOGY LA English DT Article DE Cunninghamella bertholletiae; rabbits; virulence; pulmonary mucormycosis ID NOSOCOMIAL FUNGAL-INFECTIONS; QUANTITATIVE CULTURE; ZYGOMYCOSIS; ASPERGILLOSIS; EPIDEMIOLOGY; LEUKEMIA; PATIENT; TISSUE; GRANULOCYTOPENIA; PNEUMONIA AB Members of the order Mucorales are emerging invasive molds that cause infections in immunocompromised patients. However, little is known about the relation between different species of Mucorales and their virulence in invasive pulmonary mucormycosis. Based upon our earlier epidemiological studies, we hypothesized that Cunninghamella bertholletiae would demonstrate increased virulence. Therefore, we studied the relative virulence of C. bertholletiae (CB), Rhizopus oryzae (RO), R. microsporus (RM), and Mucor circinelloides (MC) in experimental invasive pulmonary mucormycosis in persistently neutropenic rabbits in relation to the fungi in vitro sporangiospore germination rate and hyphal metabolic activity. Rabbits infected with CB demonstrated (1) higher lung weights in comparison to RM (P <= 0.05), RO and MC (P <= 0.001), (2) pulmonary infarcts in comparison to RO and MC (P <= 0.001), (3) tissue fungal burden (CFU/g) vs. MC (P <= 0.001), and (4) the lowest survival of 0% (0/18), in comparison to 16% (3/18, P <= 0.01) of RM, 81% (21/26) of RO, and 83% (15/18) of MC-infected rabbits (P <= 0.001). Serum PCR concentration-time-curve showed the greatest amplitude for CB. Virulence correlated directly with sporangiospore germination rate at 4 h among species, i.e., CB (67-85%) > RM (14-56%) > RO (4-30%) > MC (0%), and hyphal metabolic activity, i.e., CB (1.22-1.51) > MC (0.54-0.64) = RM (0.38-0.41) = RO (0.37-0.59). C. bertholletiae was significantly more virulent in experimental invasive pulmonary mucormycosis than R. microsporus, R. oryzae, and M. circinelloides. In vivo virulence correlated with species-dependent differences of in vitro germination rate and hyphal metabolic activity. C1 [Petraitis, Vidmantas; Petraitiene, Ruta; Gamaletsou, Maria N.; Walsh, Thomas J.] Weill Cornell Univ, Med Ctr, Div Infect Dis, Transplantat Oncol Infect Dis Program, New York, NY 10065 USA. [Petraitis, Vidmantas; Petraitiene, Ruta; Antachopoulos, Charalampos; Hughes, Johanna E.; Cotton, Margaret P.; Kasai, Miki; Roilides, Emmanuel; Walsh, Thomas J.] NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Harrington, Susan] Albany Med Ctr, Clin Microbiol Lab, Albany, NY USA. [Harrington, Susan] NIH Clin Ctr, Dept Lab Med, Bethesda, MD USA. [Gamaletsou, Maria N.] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Bacher, John D.] NIH, Surg Serv, Div Vet Resources, Vet Resources Program,Off Res Serv, Bethesda, MD 20892 USA. [Kontoyiannis, Dimitrios P.] Univ Texas MD Anderson Canc Ctr, Dept Infect Dis Infect Control & Employee Hlth, Houston, TX 77030 USA. [Antachopoulos, Charalampos; Roilides, Emmanuel] Aristotle Univ Thessaloniki, Dept Pediat 3, Sch Med, Hippokrat Hosp, GR-54006 Thessaloniki, Greece. RP Walsh, TJ (reprint author), Weill Cornell Univ, Med Ctr, Div Infect Dis, Transplantat Oncol Infect Dis Program, 1300 York Ave,Rm A-421, New York, NY 10065 USA. EM thw2003@med.cornell.edu NR 39 TC 9 Z9 9 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JAN PY 2013 VL 51 IS 1 BP 72 EP 82 DI 10.3109/13693786.2012.690107 PG 11 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 052UG UT WOS:000312223400010 PM 22686246 ER PT J AU Paterson, LM Kornum, BR Nutt, DJ Pike, VW Knudsen, GM AF Paterson, Louise M. Kornum, Birgitte R. Nutt, David J. Pike, Victor W. Knudsen, Gitte M. TI 5-HT radioligands for human brain imaging with PET and SPECT SO MEDICINAL RESEARCH REVIEWS LA English DT Review DE 5-HT; PET; SPECT; radioligand ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO EVALUATION; SEROTONIN TRANSPORTER BINDING; TEMPORAL-LOBE EPILEPSY; OBSESSIVE-COMPULSIVE DISORDER; MAJOR DEPRESSIVE DISORDER; NOR-BETA-CIT; TEST-RETEST REPRODUCIBILITY; CENTRAL-NERVOUS-SYSTEM; 2A RECEPTOR-BINDING AB The serotonergic system plays a key modulatory role in the brain and is the target for many drug treatments for brain disorders either through reuptake blockade or via interactions at the 14 subtypes of 5-HT receptors. This review provides the history and current status of radioligands used for positron emission tomography (PET) and single photon emission computerized tomography (SPECT) imaging of human brain serotonin (5-HT) receptors, the 5-HT transporter (SERT), and 5-HT synthesis rate. Currently available radioligands for in vivo brain imaging of the 5-HT system in humans include antagonists for the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 receptors, and for SERT. Here we describe the evolution of these radioligands, along with the attempts made to develop radioligands for additional serotonergic targets. We describe the properties needed for a radioligand to become successful and the main caveats. The success of a PET or SPECT radioligand can ultimately be assessed by its frequency of use, its utility in humans, and the number of research sites using it relative to its invention date, and so these aspects are also covered. In conclusion, the development of PET and SPECT radioligands to image serotonergic targets is of high interest, and successful evaluation in humans is leading to invaluable insight into normal and abnormal brain function, emphasizing the need for continued development of both SPECT and PET radioligands for human brain imaging. (C) 2011 Wiley Periodicals, Inc. Med Res Rev., 33, No. 1, 54-111, 2013 C1 [Kornum, Birgitte R.; Knudsen, Gitte M.] Rigshosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark. [Kornum, Birgitte R.; Knudsen, Gitte M.] Rigshosp, Ctr Integrated Mol Brain Imaging, DK-2100 Copenhagen, Denmark. [Kornum, Birgitte R.; Knudsen, Gitte M.] Univ Copenhagen, DK-2100 Copenhagen, Denmark. [Paterson, Louise M.; Nutt, David J.] Univ London Imperial Coll Sci Technol & Med, Div Expt Med, Neuropsychopharmacol Unit, London, England. [Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Knudsen, GM (reprint author), Rigshosp, Neurobiol Res Unit, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. EM gitte@nru.dk RI Knudsen, Gitte/C-1368-2013; Kornum, Birgitte/K-9193-2015; OI Knudsen, Gitte/0000-0003-1508-6866; Kornum, Birgitte/0000-0002-2515-9451; nutt, david/0000-0002-1286-1401 FU National Institutes of Health; Lundbeck Foundation; H. Lundbeck A/S; Intramural Research Program of the National Institutes of Health (NIMH) FX Contract grant sponsor: National Institutes of Health, Lundbeck Foundation and H. Lundbeck A/S.; V.W.P. is supported by the Intramural Research Program of the National Institutes of Health (NIMH). The authors acknowledge the Lundbeck Foundation and H. Lundbeck A/S for providing the financial support that enabled this review to be written and the METPETS (Measuring Endogenous Neurotransmitters by PET and SPECT) consortium members for sharing their recent research. The METPETS consortium is a collaborative network of European neuroscientists who have come together with the aim of developing tracers to image neurotransmitter release in the human brain. See http://www.p1vital.com/consortium_metpets.html. NR 418 TC 52 Z9 53 U1 0 U2 36 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0198-6325 J9 MED RES REV JI Med. Res. Rev. PD JAN PY 2013 VL 33 IS 1 BP 54 EP 111 DI 10.1002/med.20245 PG 58 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 057IL UT WOS:000312556400004 PM 21674551 ER PT J AU Lehner, KR Baumann, MH AF Lehner, Kurt R. Baumann, Michael H. TI Psychoactive 'Bath Salts': Compounds, Mechanisms, and Toxicities SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID LEGAL HIGHS; MEPHEDRONE C1 [Lehner, Kurt R.; Baumann, Michael H.] NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. RP Lehner, KR (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD USA. EM mbaumann@mail.nih.gov FU Intramural NIH HHS NR 6 TC 11 Z9 11 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2013 VL 38 IS 1 BP 243 EP 244 DI 10.1038/npp.2012.162 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 051BP UT WOS:000312099500023 PM 23147485 ER PT J AU Cadet, JL Jayanthi, S AF Cadet, Jean Lud Jayanthi, Subramaniam TI Epigenetics of Methamphetamine-Induced Changes in Glutamate Function SO NEUROPSYCHOPHARMACOLOGY LA English DT Editorial Material ID MECHANISMS C1 [Cadet, Jean Lud; Jayanthi, Subramaniam] NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Baltimore, MD USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Res Branch, NIH, DHHS, Bayview Blvd, Baltimore, MD USA. EM jcadet@intra.nida.nih.gov NR 5 TC 7 Z9 7 U1 1 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JAN PY 2013 VL 38 IS 1 BP 248 EP 249 DI 10.1038/npp.2012.169 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 051BP UT WOS:000312099500028 PM 23147489 ER PT J AU Blair, KS Vythilingam, M Crowe, SL McCaffrey, DE Ng, P Wu, CC Scaramozza, M Mondillo, K Pine, DS Charney, DS Blair, RJR AF Blair, K. S. Vythilingam, M. Crowe, S. L. McCaffrey, D. E. Ng, P. Wu, C. C. Scaramozza, M. Mondillo, K. Pine, D. S. Charney, D. S. Blair, R. J. R. TI Cognitive control of attention is differentially affected in trauma-exposed individuals with and without post-traumatic stress disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Anxiety; post-traumatic stress disorder; fMRI; fronto-parietal cortex; top down attention control ID AMYGDALA RESPONSE; PREFRONTAL CORTEX; VISUAL-ATTENTION; FEARFUL FACES; PTSD; INFORMATION; EMOTION; FMRI; MODULATION; MECHANISMS AB Background. This study aimed to determine whether patients with post-traumatic stress disorder (PTSD) show difficulty in recruitment of the regions of the frontal and parietal cortex implicated in top-down attentional control in the presence and absence of emotional distracters. Method. Unmedicated individuals with PTSD (n=14), and age-, IQ- and gender-matched individuals exposed to trauma (n= 15) and healthy controls (n= 19) were tested on the affective number Stroop task. In addition, blood oxygen level-dependent responses, as measured via functional magnetic resonance imaging, were recorded. Results. Patients with PTSD showed disrupted recruitment of lateral regions of the superior and inferior frontal cortex as well as the parietal cortex in the presence of negative distracters. Trauma-comparison individuals showed indications of a heightened ability to recruit fronto-parietal regions implicated in top-down attentional control across distracter conditions. Conclusions. These results are consistent with suggestions that emotional responsiveness can interfere with the recruitment of regions implicated in top-down attentional control; the heightened emotional responding of patients with PTSD may lead to the heightened interference in the recruitment of these regions. C1 [Blair, K. S.; Vythilingam, M.; Crowe, S. L.; McCaffrey, D. E.; Ng, P.; Wu, C. C.; Scaramozza, M.; Mondillo, K.; Pine, D. S.; Blair, R. J. R.] NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Charney, D. S.] Mt Sinai Sch Med, New York, NY USA. RP Blair, KS (reprint author), NIMH, NIH, Dept Hlth & Human Serv, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. EM peschark@mail.nih.gov FU National Institutes of Health, NIMH FX This research was supported by the Intramural Research Program of the National Institutes of Health, NIMH. NR 46 TC 16 Z9 16 U1 6 U2 41 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 JAN PY 2013 VL 43 IS 1 BP 85 EP 95 DI 10.1017/S0033291712000840 PG 11 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 053GX UT WOS:000312260500008 PM 22571775 ER PT J AU Bertelsen, RJ Longnecker, MP Lovik, M Calafat, AM Carlsen, KH London, SJ Carlsen, KCL AF Bertelsen, R. J. Longnecker, M. P. Lovik, M. Calafat, A. M. Carlsen, K-H. London, S. J. Carlsen, K. C. Lodrup TI Triclosan exposure and allergic sensitization in Norwegian children SO ALLERGY LA English DT Article DE allergy; antibacterial; asthma; rhinitis; triclosan ID URINARY CONCENTRATIONS; CARE PRODUCTS; TOXICITY; PHENOLS; ASTHMA; LIMIT AB Background Exposure to the synthetic antimicrobial chemical, triclosan, used in personal care products, has been hypothesized to lead to allergic disease. We investigated whether triclosan exposure was associated with allergic sensitization and symptoms in 10-year-old Norwegian children. Methods Urinary concentrations of triclosan were measured in one first morning void from 623 children, collected during 20012004. Logistic regression models, controlling for urine specific gravity, parental allergic disease, maternal education, and household income, were fitted for allergic sensitization (either skin prick test positivity or serum-specific IgE = 0.35 kU/l to at least one of 15 evaluated inhalant and food allergens), current rhinitis, and current asthma (questionnaire and exercise challenge test). Results The adjusted odds ratio (aOR) for allergic sensitization among those in the fourth quartile of triclosan concentration was 2.0 [95% confidence interval (CI): 1.1, 3.4] compared with the reference group (= 36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. C1 [Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Tuan, Rocky S.] NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Alexander, Peter G.; Taboas, Juan M.; Tuan, Rocky S.] Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, Pittsburgh, PA 15219 USA. [Melvin, Gary M.] NIAMSD, Off Sci & Technol, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Manner, Paul A.] Univ Washington, Dept Orthopaed & Sports Med, Seattle, WA 98195 USA. RP Tuan, RS (reprint author), Univ Pittsburgh, Sch Med, Dept Orthopaed Surg, Ctr Cellular & Mol Engn, 450 Technol Dr,Room 221, Pittsburgh, PA 15219 USA. EM rst13@pitt.edu FU Intramural Research Program of the NIH [Z01 AR41131]; Commonwealth of Pennsylvania Department of Health [SAP 4100050913] FX Supported in part by the Intramural Research Program of the NIH (Z01 AR41131) and the Commonwealth of Pennsylvania Department of Health (SAP 4100050913). NR 45 TC 5 Z9 5 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1947-6035 EI 1947-6043 J9 CARTILAGE JI Cartilage PD JAN PY 2013 VL 4 IS 1 BP 52 EP 62 DI 10.1177/1947603512455195 PG 11 WC Orthopedics SC Orthopedics GA V36NJ UT WOS:000209218200006 PM 26069650 ER PT J AU Chan, CYX Khan, AA Choi, JHH Ng, CMD Cadeiras, M Deng, M Ping, PP AF Chan, C. Y. X'avia Khan, Anjum A. Choi, J. H. Howard Ng, C. M. Dominic Cadeiras, Martin Deng, Mario Ping, Peipei TI Technology platform development for targeted plasma metabolites in human heart failure SO CLINICAL PROTEOMICS LA English DT Article DE Heart disease; Targeted human plasma metabolomics; Sample preparation AB Background: Heart failure is a multifactorial disease associated with staggeringly high morbidity and motility. Recently, alterations of multiple metabolites have been implicated in heart failure; however, the lack of an effective technology platform to assess these metabolites has limited our understanding on how they contribute to this disease phenotype. We have successfully developed a new workflow combining specific sample preparation with tandem mass spectrometry that enables us to extract most of the targeted metabolites. 19 metabolites were chosen ascribing to their biological relevance to heart failure, including extracellular matrix remodeling, inflammation, insulin resistance, renal dysfunction, and cardioprotection against ischemic injury. Results: In this report, we systematically engineered, optimized and refined a protocol applicable to human plasma samples; this study contributes to the methodology development with respect to deproteinization, incubation, reconstitution, and detection with mass spectrometry. The deproteinization step was optimized with 20% methanol/ethanol at a plasma: solvent ratio of 1:3. Subsequently, an incubation step was implemented which remarkably enhanced the metabolite signals and the number of metabolite peaks detected by mass spectrometry in both positive and negative modes. With respect to the step of reconstitution, 0.1% formic acid was designated as the reconstitution solvent vs. 6.5 mM ammonium bicarbonate, based on the comparable number of metabolite peaks detected in both solvents, and yet the signal detected in the former was higher. By adapting this finalized protocol, we were able to retrieve 13 out of 19 targeted metabolites from human plasma. Conclusions: We have successfully devised a simple albeit effective workflow for the targeted plasma metabolites relevant to human heart failure. This will be employed in tandem with high throughput liquid chromatography mass spectrometry platform to validate and characterize these potential metabolic biomarkers for diagnostic and therapeutic development of heart failure patients. C1 [Chan, C. Y. X'avia; Choi, J. H. Howard; Ng, C. M. Dominic; Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, NHLBI Prote Ctr, Los Angeles, CA 90095 USA. [Chan, C. Y. X'avia; Choi, J. H. Howard; Ng, C. M. Dominic; Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, NHLBI Prote Ctr, Los Angeles, CA 90095 USA. [Khan, Anjum A.] Thermo Fisher Sci, San Jose, CA 95134 USA. [Cadeiras, Martin; Deng, Mario] UCLA Med Ctr, Ronald Reagan UCLA Med Ctr, Los Angeles, CA 90095 USA. RP Ping, PP (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, NHLBI Prote Ctr, Los Angeles, CA 90095 USA. EM PPing@mednet.ucla.edu OI Ping, Peipei/0000-0003-3583-3881 FU NHLBI Proteomics Center Award [HHSN268201000035C] FX The work was made possible by the support from both the NHLBI Proteomics Center Award (HHSN268201000035C), as well as an endorsement from Theodore C. Laubisch at UCLA to Dr. Peipei Ping. NR 49 TC 3 Z9 3 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1542-6416 EI 1559-0275 J9 CLIN PROTEOM JI Clin. Proteom. PY 2013 VL 10 AR 7 DI 10.1186/1559-0275-10-7 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA V42YQ UT WOS:000209649500017 PM 23826926 ER PT B AU Colberg-Poley, AM Williamson, CD AF Colberg-Poley, Anamaris M. Williamson, Chad D. BE Reddehase, MJ TI Intracellular Sorting and Trafficking of Cytomegalovirus Proteins during Permissive Infection SO CYTOMEGALOVIRUSES: FROM MOLECULAR PATHOGENESIS TO INTERVENTION, VOL I LA English DT Article; Book Chapter ID SIGNAL RECOGNITION PARTICLE; NUCLEAR-LOCALIZATION SIGNAL; VIRAL-DNA REPLICATION; EARLY GENE-EXPRESSION; MITOCHONDRIA-ASSOCIATED MEMBRANES; POLYMERASE PROCESSIVITY FACTOR; IMMEDIATE-EARLY PROTEINS; METHIONINE-RICH DOMAIN; HERPES-SIMPLEX-VIRUS; OPEN READING FRAME AB As with most DNA viruses, which require nuclear and cytoplasmic phases of virion maturation, proper and coordinated trafficking of viral proteins is crucial for the CMV life cycle. Trafficking of CMV proteins enables jumpstarting its infection, partly determines whether lytic or latent infection is established, promotes nuclear and cytoplasmic assembly of virions, and enhances their stability and egress. To allow complex processes including viral DNA replication, packaging, nuclear and cytoplasmic egress, trafficking of CMV proteins is temporally and spatially regulated by modifications, particularly phosphorylation, and by interactions between viral or cellular proteins. Thus, orchestrated recruitment and colocalization of necessary components to enable functions are assured. In addition to conventional nuclear and cytoplasmic trafficking of viral proteins, HCMV encodes an antiapoptotic UL37 exon 1 protein or viral mitochondria-localized inhibitor of apoptosis, which circuitously traffics from the ER to mitochondria and through ER subdomains known as mitochondria-associated membranes. By this unconventional trafficking, HCMV is able to commandeer ER-mitochondrial cross-talk as well as mitochondrial functions, metabolism, antiviral responses, and apoptosis. The importance of proper intracellular trafficking of some key HCMV proteins such as those required for its DNA replication and assembly is supported by the deleterious effects of their inhibition on HCMV permissive growth. C1 [Colberg-Poley, Anamaris M.] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Williamson, Chad D.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Colberg-Poley, AM (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. EM acolberg-poley@childrensnational.org; chad.williamson@nih.gov NR 330 TC 3 Z9 3 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-84-3; 978-1-908230-19-5 PY 2013 BP 196 EP 229 PG 34 WC Biochemistry & Molecular Biology; Virology SC Biochemistry & Molecular Biology; Virology GA BF6BZ UT WOS:000382949000013 ER PT B AU Croteau, DL Bohr, VA AF Croteau, Deborah L. Bohr, Vilhelm A. BE Madhusudan, S Wilson, DM TI Overview of DNA Repair Pathways SO DNA REPAIR AND CANCER: FROM BENCH TO CLINIC LA English DT Article; Book Chapter ID CLASS-SWITCH RECOMBINATION; HUMAN MITOCHONDRIAL-DNA; HUMAN MISMATCH REPAIR; POLYMERASE-BETA; MAMMALIAN MITOCHONDRIA; DAMAGE RESPONSE; MUTATIONS; CELLS; MECHANISM; CANCER C1 [Croteau, Deborah L.; Bohr, Vilhelm A.] NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM croteau@mail.nih.gov; BohrV@grc.nia.nih.gov NR 63 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-7744-2; 978-1-4665-7743-5 PY 2013 BP 1 EP 24 D2 10.1201/b14587 PG 24 WC Oncology SC Oncology GA BC5UA UT WOS:000353575000003 ER PT B AU Banerjee, T Bharti, SK Brosh, RM AF Banerjee, Taraswi Bharti, Sanjay Kumar Brosh, Robert M., Jr. BE Madhusudan, S Wilson, DM TI Fanconi Anemia, Interstrand Cross-Link Repair, and Cancer SO DNA REPAIR AND CANCER: FROM BENCH TO CLINIC LA English DT Article; Book Chapter ID SISTER-CHROMATID EXCHANGES; BLOOMS-SYNDROME; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; GENE-PRODUCT; PATHWAY; CELLS; INHIBITORS; CONNECTS; THERAPY C1 [Banerjee, Taraswi; Bharti, Sanjay Kumar; Brosh, Robert M., Jr.] NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, Baltimore, MD 21224 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM broshr@mail.nih.gov NR 50 TC 1 Z9 1 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-7744-2; 978-1-4665-7743-5 PY 2013 BP 310 EP 324 D2 10.1201/b14587 PG 15 WC Oncology SC Oncology GA BC5UA UT WOS:000353575000012 ER PT B AU Urick, ME Bell, DW AF Urick, Mary Ellen Bell, Daphne W. BE Madhusudan, S Wilson, DM TI Tumor Genetics and Personalized Medicine SO DNA REPAIR AND CANCER: FROM BENCH TO CLINIC LA English DT Article; Book Chapter ID CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; ACUTE LYMPHOBLASTIC-LEUKEMIA; PHASE-II TRIAL; ANAPLASTIC LYMPHOMA KINASE; GASTROINTESTINAL STROMAL TUMORS C1 [Urick, Mary Ellen; Bell, Daphne W.] NHGRI, NIH, Bethesda, MD 20892 USA. RP Bell, DW (reprint author), NHGRI, NIH, Bldg 50,MSC 8000, Bethesda, MD 20892 USA. EM belldaph@mail.nih.gov NR 397 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-7744-2; 978-1-4665-7743-5 PY 2013 BP 564 EP 628 D2 10.1201/b14587 PG 65 WC Oncology SC Oncology GA BC5UA UT WOS:000353575000018 ER PT J AU Bagci, U Foster, B Miller-Jaster, K Luna, B Dey, B Bishai, WR Jonsson, CB Jain, S Mollura, DJ AF Bagci, Ulas Foster, Brent Miller-Jaster, Kirsten Luna, Brian Dey, Bappaditya Bishai, William R. Jonsson, Colleen B. Jain, Sanjay Mollura, Daniel J. TI A computational pipeline for quantification of pulmonary infections in small animal models using serial PET-CT imaging SO EJNMMI RESEARCH LA English DT Article DE Quantitative analysis; Pulmonary infections; Small animal models; PET-CT; Image segmentation; H1N1; Tuberculosis AB Background: Infectious diseases are the second leading cause of death worldwide. In order to better understand and treat them, an accurate evaluation using multi-modal imaging techniques for anatomical and functional characterizations is needed. For non-invasive imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), there have been many engineering improvements that have significantly enhanced the resolution and contrast of the images, but there are still insufficient computational algorithms available for researchers to use when accurately quantifying imaging data from anatomical structures and functional biological processes. Since the development of such tools may potentially translate basic research into the clinic, this study focuses on the development of a quantitative and qualitative image analysis platform that provides a computational radiology perspective for pulmonary infections in small animal models. Specifically, we designed (a) a fast and robust automated and semi-automated image analysis platform and a quantification tool that can facilitate accurate diagnostic measurements of pulmonary lesions as well as volumetric measurements of anatomical structures, and incorporated (b) an image registration pipeline to our proposed framework for volumetric comparison of serial scans. This is an important investigational tool for small animal infectious disease models that can help advance researchers' understanding of infectious diseases. Methods: We tested the utility of our proposed methodology by using sequentially acquired CT and PET images of rabbit, ferret, and mouse models with respiratory infections of Mycobacterium tuberculosis (TB), H1N1 flu virus, and an aerosolized respiratory pathogen (necrotic TB) for a total of 92, 44, and 24 scans for the respective studies with half of the scans from CT and the other half from PET. Institutional Administrative Panel on Laboratory Animal Care approvals were obtained prior to conducting this research. First, the proposed computational framework registered PET and CT images to provide spatial correspondences between images. Second, the lungs from the CT scans were segmented using an interactive region growing (IRG) segmentation algorithm with mathematical morphology operations to avoid false positive (FP) uptake in PET images. Finally, we segmented significant radiotracer uptake from the PET images in lung regions determined from CT and computed metabolic volumes of the significant uptake. All segmentation processes were compared with expert radiologists' delineations (ground truths). Metabolic and gross volume of lesions were automatically computed with the segmentation processes using PET and CT images, and percentage changes in those volumes over time were calculated. Standardized uptake value (SUV) analysis from PET images was conducted as a complementary quantitative metric for disease severity assessment. Thus, severity and extent of pulmonary lesions were examined through both PET and CT images using the aforementioned quantification metrics outputted from the proposed framework. Results: Each animal study was evaluated within the same subject class, and all steps of the proposed methodology were evaluated separately. We quantified the accuracy of the proposed algorithm with respect to the state-of-the-art segmentation algorithms. For evaluation of the segmentation results, dice similarity coefficient (DSC) as an overlap measure and Haussdorf distance as a shape dissimilarity measure were used. Significant correlations regarding the estimated lesion volumes were obtained both in CT and PET images with respect to the ground truths (R-2 = 0.8922, p < 0.01 and R-2 = 0.8664, p < 0.01, respectively). The segmentation accuracy (DSC (%)) was 93.4 +/- 4.5% for normal lung CT scans and 86.0 +/- 7.1% for pathological lung CT scans. Experiments showed excellent agreements (all above 85%) with expert evaluations for both structural and functional imaging modalities. Apart from quantitative analysis of each animal, we also qualitatively showed how metabolic volumes were changing over time by examining serial PET/CT scans. Evaluation of the registration processes was based on precisely defined anatomical landmark points by expert clinicians. An average of 2.66, 3.93, and 2.52 mm errors was found in rabbit, ferret, and mouse data (all within the resolution limits), respectively. Quantitative results obtained from the proposed methodology were visually related to the progress and severity of the pulmonary infections as verified by the participating radiologists. Moreover, we demonstrated that lesions due to the infections were metabolically active and appeared multi-focal in nature, and we observed similar patterns in the CT images as well. Consolidation and ground glass opacity were the main abnormal imaging patterns and consistently appeared in all CT images. We also found that the gross and metabolic lesion volume percentage follow the same trend as the SUV-based evaluation in the longitudinal analysis. Conclusions: We explored the feasibility of using PET and CT imaging modalities in three distinct small animal models for two diverse pulmonary infections. We concluded from the clinical findings, derived from the proposed computational pipeline, that PET-CT imaging is an invaluable hybrid modality for tracking pulmonary infections longitudinally in small animals and has great potential to become routinely used in clinics. Our proposed methodology showed that automated computed-aided lesion detection and quantification of pulmonary infections in small animal models are efficient and accurate as compared to the clinical standard of manual and semi-automated approaches. Automated analysis of images in pre-clinical applications can increase the efficiency and quality of pre-clinical findings that ultimately inform downstream experimental design in human clinical studies; this innovation will allow researchers and clinicians to more effectively allocate study resources with respect to research demands without compromising accuracy. C1 [Bagci, Ulas; Foster, Brent; Miller-Jaster, Kirsten; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Bethesda, MD 20892 USA. [Bagci, Ulas; Foster, Brent; Miller-Jaster, Kirsten; Mollura, Daniel J.] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Luna, Brian; Dey, Bappaditya; Bishai, William R.; Jain, Sanjay] Johns Hopkins Univ, Sch Med, Ctr TB Res, Baltimore, MD 21231 USA. [Bishai, William R.] KwaZulu Natal Res Inst TB & HIV, Durban, South Africa. [Bishai, William R.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Jonsson, Colleen B.] Univ Louisville, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Jonsson, Colleen B.] Univ Louisville, Ctr Predict Med Biodefense & Emerging Infect Dis, Louisville, KY 40202 USA. [Jain, Sanjay] Johns Hopkins Univ, Sch Med, Dept Med, Ctr Infect & Inflammat Imaging Res, Baltimore, MD 21287 USA. [Jain, Sanjay] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21231 USA. RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Bldg 10, Bethesda, MD 20892 USA. EM ulas.bagci@nih.gov OI Bagci, Ulas/0000-0001-7379-6829; Dey, Bappaditya/0000-0003-2728-4683; Luna, PhD, Brian/0000-0001-6718-4551 FU Center for Infectious Disease Imaging (CIDI); Intramural Research Program of the National Institutes of Health; NIH [OD006492]; HHMI, NIAD [R01AI079590, R01A1035272] FX This study is supported by the Center for Infectious Disease Imaging (CIDI) and Intramural Research Program of the National Institutes of Health. Dr Jain acknowledges the NIH Director's New Inventor Award (OD006492). The rabbit infection study is funded by HHMI, NIAD R01AI079590, and R01A1035272. NR 47 TC 14 Z9 14 U1 1 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2191-219X J9 EJNMMI RES JI EJNMMI Res. PY 2013 VL 3 AR UNSP 55 DI 10.1186/2191-219X-3-55 PG 20 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V39UL UT WOS:000209435800055 PM 23879987 ER PT J AU Bagci, U Kramer-Marek, G Mollura, DJ AF Bagci, Ulas Kramer-Marek, Gabriela Mollura, Daniel J. TI Automated computer quantification of breast cancer in small-animal models using PET-guided MR image co-segmentation SO EJNMMI RESEARCH LA English DT Article DE Image segmentation; Computer quantification; FDG-PET; MRI/PET; Breast cancer; Small-animal models; Co-segmentation; Volume quantification; Random walk AB Background: Care providers use complementary information from multiple imaging modalities to identify and characterize metastatic tumors in early stages and perform surveillance for cancer recurrence. These tasks require volume quantification of tumor measurements using computed tomography (CT) or magnetic resonance imaging (MRI) and functional characterization through positron emission tomography (PET) imaging. In vivo volume quantification is conducted through image segmentation, which may require both anatomical and functional images available for precise tumor boundary delineation. Although integrating multiple image modalities into the segmentation process may improve the delineation accuracy and efficiency, due to variable visibility on image modalities, complex shape of metastatic lesions, and diverse visual features in functional and anatomical images, a precise and efficient segmentation of metastatic breast cancer remains a challenging goal even for advanced image segmentation methods. In response to these challenges, we present here a computer-assisted volume quantification method for PET/MRI dual modality images using PET-guided MRI co-segmentation. Our aims in this study were (1) to determine anatomical tumor volumes automatically from MRI accurately and efficiently, (2) to evaluate and compare the accuracy of the proposed method with different radiotracers (F-18-Z(HER2)-Affibody and F-18-flourodeoxyglucose (F-18-FDG)), and (3) to confirm the proposed method's determinations from PET/MRI scans in comparison with PET/CT scans. Methods: After the Institutional Administrative Panel on Laboratory Animal Care approval was obtained, 30 female nude mice were used to construct a small-animal breast cancer model. All mice were injected with human breast cancer cells and HER2-overexpressing MDA-MB-231HER2-Luc cells intravenously. Eight of them were selected for imaging studies, and selected mice were imaged with MRI, CT, and F-18-FDG-PET at weeks 9 and 10 and then imaged with F-18-Z(HER2)-Affibody-PET 2 days after the scheduled structural imaging (MRI and CT). After CT and MR images were co-registered with corresponding PET images, all images were quantitatively analyzed by the proposed segmentation technique. Automatically determined anatomical tumor volumes were compared to radiologist-derived reference truths. Observer agreements were presented through Bland-Altman and linear regression analyses. Segmentation evaluations were conducted using true-positive (TP) and false-positive (FP) volume fractions of delineated tissue samples, as complied with the state-of-the-art evaluation techniques for image segmentation. Moreover, the PET images, obtained using different radiotracers, were examined and compared using the complex wavelet-based structural similarity index (CWSSI). Results: PET/MR dual modality imaging using the F-18-Z(HER2)-Affibody imaging agent provided diagnostic image quality in all mice with excellent tumor delineations by the proposed method. The F-18-FDG radiotracer did not show accurate identification of the tumor regions. Structural similarity index (CWSSI) between PET images using F-18-FDG and F-18-Z(HER2)-Affibody agents was found to be 0.7838. MR showed higher diagnostic image quality when compared to CT because of its better soft tissue contrast. Significant correlations regarding the anatomical tumor volumes were obtained between both PET-guided MRI co-segmentation and reference truth (R-2 = 0.92, p < 0.001 for PET/MR, and R-2 = 0.84, p < 0.001, for PET/CT). TP and FP volume fractions using the automated co-segmentation method in PET/MR and PET/CT were found to be (TP 97.3%, FP 9.8%) and (TP 92.3%, FP 17.2%), respectively. Conclusions: The proposed PET-guided MR image co-segmentation algorithm provided an automated and efficient way of assessing anatomical tumor volumes and their spatial extent. We showed that although the F-18-Z(HER2)-Affibody radiotracer in PET imaging is often used for characterization of tumors rather than detection, sensitivity and specificity of the localized radiotracer in the tumor region were informative enough; therefore, roughly determined tumor regions from PET images guided the delineation process well in the anatomical image domain for extracting accurate tumor volume information. Furthermore, the use of F-18-FDG radiotracer was not as successful as the F-18-Z(HER2)-Affibody in guiding the delineation process due to false-positive uptake regions in the neighborhood of tumor regions; hence, the accuracy of the fully automated segmentation method changed dramatically. Last, we qualitatively showed that MRI yields superior identification of tumor boundaries when compared to conventional CT imaging. C1 [Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Bethesda, MD 20892 USA. [Bagci, Ulas; Mollura, Daniel J.] NIH, Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Kramer-Marek, Gabriela] Inst Canc Res, London SW3 6JB, England. RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Bldg 10, Bethesda, MD 20892 USA. EM ulas.bagci@nih.gov OI Bagci, Ulas/0000-0001-7379-6829 FU Center for Infectious Disease Imaging (CIDI); Intramural Research Program of the National Institutes of Health (NIH) FX This study is supported by the Center for Infectious Disease Imaging (CIDI) and Intramural Research Program of the National Institutes of Health (NIH). We thank Brent Foster and the anonymous reviewers for their constructive comments which helped us to improve the manuscript. NR 25 TC 3 Z9 3 U1 1 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2191-219X J9 EJNMMI RES JI EJNMMI Res. PY 2013 VL 3 AR UNSP 49 DI 10.1186/2191-219X-3-49 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V39UL UT WOS:000209435800049 PM 23829944 ER PT J AU Shetty, HU Morse, CL Zhang, Y Pike, VW AF Shetty, H. Umesha Morse, Cheryl L. Zhang, Yi Pike, Victor W. TI Characterization of fast-decaying PET radiotracers solely through LC-MS/MS of constituent radioactive and carrier isotopologues SO EJNMMI RESEARCH LA English DT Article DE PET radiotracers; Carbon-11; Specific radioactivity; LC-MS/MS AB Background: The characterization of fast-decaying radiotracers that are labeled with carbon-11 (t(1/2) = 20.38 min), including critical measurement of specific radioactivity (activity per mole at a specific time) before release for use in positron-emission tomography (PET), has relied heavily on chromatographic plus radiometric measurements, each of which may be vulnerable to significant errors. Thus, we aimed to develop a mass-specific detection method using sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) for identifying C-11-labeled tracers and for verifying their specific radioactivities. Methods: The LC-MS/MS was tuned and set up with methods to generate and measure the product ions specific for carbon-11 species and M + 1 carrier (predominantly the carbon-13 isotopologue) in four C-11-labeled tracers. These radiotracers were synthesized and then analyzed before extensive carbon-11 decay. The peak areas of carbon-11 species and M + 1 carrier from the LC-MS/MS measurement and the calculated abundances of carbon-12 carrier and M + 1 radioactive species gave the mole fraction of carbon-11 species in each sample. This value upon multiplication with the theoretical specific radioactivity of carbon-11 gave the specific radioactivity of the radiotracer. Results: LC-MS/MS of each C-11-labeled tracer generated the product ion peaks for carbon-11 species and M + 1 carrier at the expected LC retention time. The intensity of the radioactive peak diminished as time elapsed and was undetectable after six half-lives of carbon-11. Measurements of radiotracer-specific radioactivity determined solely by LC-MS/MS at timed intervals gave a half-life for carbon-11 (20.43 min) in excellent agreement with the value obtained radiometrically. Additionally, the LC-MS/MS measurement gave specific radioactivity values (83 to 505 GBq/mu mol) in good agreement with those from conventional radiometric methods. Conclusions: C-11-Labeled tracers were characterized at a fundamental level involving isolation and mass detection of extremely low-abundance carbon-11 species along with the M + 1 carrier counterpart. This LC-MS/MS method for characterizing fast-decaying radiotracers is valuable in both the development and production of PET radiopharmaceuticals. C1 [Shetty, H. Umesha; Morse, Cheryl L.; Zhang, Yi; Pike, Victor W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Shetty, HU (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C351,10 Ctr Dr,MSC 1003, Bethesda, MD 20892 USA. EM shettyu@mail.nih.gov FU Intramural Research Program of National Institutes of Health (NIMH) FX This research was supported by the Intramural Research Program of the National Institutes of Health (NIMH). We thank our colleagues for their helpful suggestions. NR 26 TC 0 Z9 1 U1 2 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2191-219X J9 EJNMMI RES JI EJNMMI Res. PY 2013 VL 3 AR UNSP 3 DI 10.1186/2191-219X-3-3 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V39UL UT WOS:000209435800003 PM 23311872 ER PT J AU Zanotti-Fregonara, P Barth, VN Zoghbi, SS Liow, JS Nisenbaum, E Siuda, E Gladding, RL Rallis-Frutos, D Morse, C Tauscher, J Pike, VW Innis, RB AF Zanotti-Fregonara, Paolo Barth, Vanessa N. Zoghbi, Sami S. Liow, Jeih-San Nisenbaum, Eric Siuda, Edward Gladding, Robert L. Rallis-Frutos, Denise Morse, Cheryl Tauscher, Johannes Pike, Victor W. Innis, Robert B. TI C-11-LY2428703, a positron emission tomographic radioligand for the metabotropic glutamate receptor 1, is unsuitable for imaging in monkey and human brains SO EJNMMI RESEARCH LA English DT Article DE mGluR1; PET; Kinetic modeling; Dosimetry AB Background: A recent study from our laboratory demonstrated that C-11-LY2428703, a new positron emission tomographic radioligand for metabotropic glutamate receptor 1 (mGluR1), has promising in vitro properties and excellent in vivo performance for imaging rat brain. The present study evaluated C-11-LY2428703 for imaging mGluR1 in monkey and human brains. Methods: Rhesus monkeys were imaged at baseline and after administration of an mGluR1 blocking agent to calculate nonspecific binding, as well as after the administration of permeability glycoprotein (P-gp) and breast cancer resistance protein (BCRP) blockers to assess whether C-11-LY2428703 is a substrate for efflux transporters at the blood-brain barrier. Human imaging was performed at baseline in three healthy volunteers, and arterial input function was measured. Results: Overall brain uptake was low in monkeys, though slightly higher in the cerebellum, where mGluR1s are concentrated. However, the uptake was not clearly displaceable in the scans after mGluR1 blockade. Brain penetration of the ligand did not increase after P-gp and BCRP blockade. Brain uptake was similarly low in all human subjects (mean V-T with a two-tissue compartment model, 0.093 +/- 0.012 mL/cm(3)) and for all regions, including the cerebellum. Conclusions: Despite promising in vitro and in vivo results in rodents, C-11-LY2428703 was unsuitable for imaging mGluR1s in monkey or human brain because of low brain uptake, which was likely caused by high binding to plasma proteins. C1 [Zanotti-Fregonara, Paolo; Zoghbi, Sami S.; Liow, Jeih-San; Gladding, Robert L.; Rallis-Frutos, Denise; Morse, Cheryl; Pike, Victor W.; Innis, Robert B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Barth, Vanessa N.; Nisenbaum, Eric; Siuda, Edward; Tauscher, Johannes] Eli Lilly & Co, Indianapolis, IN 46225 USA. RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM innisr@mail.nih.gov RI Tauscher, Johannes/M-5976-2016 FU Intramural Research Program of the National Institute of Mental Health National Institutes of Health (IRP-NIMH-NIH) FX This work was supported in part by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH). The authors are grateful to the PET Department (Chief, Dr. Peter Herscovitch) of the NIH Clinical Center for PET scanning in humans, to Nancy Goebl (Eli Lilly) for logistical support, to Alicia E. Woock for assistance in plasma analysis, and to Ioline Henter (NIMH) for excellent editorial assistance. NR 29 TC 3 Z9 3 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 2191-219X J9 EJNMMI RES JI EJNMMI Res. PY 2013 VL 3 AR UNSP 47 DI 10.1186/2191-219X-3-47 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V39UL UT WOS:000209435800047 PM 23758896 ER PT J AU Chen, GB Lustig, A Weng, NP AF Chen, Guobing Lustig, Ana Weng, Nan-ping TI T cell aging: a review of the transcriptional changes determined from genome-wide analysis SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE aging; thymocytes; T cells; naive and memory T cells; CD28(-) T cells AB Age carries a detrimental impact on T cell function. In the past decade, analyses of the genome-scale transcriptional changes of T cells during aging have yielded a large amount of data and provided a global view of gene expression changes in T cells from aged hosts as well as subsets of T cells accumulated with age. Here, we aim to review the changes of gene expression in thymocytes and peripheral mature T cells, as well as the subsets of T cells accumulated with age, and discuss the gene networks and signaling pathways that are altered with aging in T cells. We also discuss future direction for furthering the understanding of the molecular basis of gene expression alterations in aged T cells, which could potentially provide opportunities for gene-based clinical interventions. C1 [Chen, Guobing; Lustig, Ana; Weng, Nan-ping] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA. RP Weng, NP (reprint author), NIA, Lab Mol Biol & Immunol, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov RI Chen, Guobing/D-9572-2012 OI Chen, Guobing/0000-0002-2401-6168 FU Intramural Research Program of the National Institute on Aging, NIH FX We thank Christina Slota for proof reading the manuscript. This research work was supported by the Intramural Research Program of the National Institute on Aging, NIH. NR 42 TC 14 Z9 14 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 121 DI 10.3389/fimmu.2013.00121 PG 11 WC Immunology SC Immunology GA V38WS UT WOS:000209374100120 PM 23730304 ER PT J AU Cho, KJ Roche, PA AF Cho, Kyung-Jin Roche, Paul A. TI Regulation of VEIC class II-peptide complex expression by ubiquitination SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE MHC class II; March-I; ubiquitination; degradation; endocytosis; recycling AB MHC class II (MHC-II) molecules are present on antigen presenting cells (APCs) and these molecules function by binding antigenic peptides and presenting these peptides to antigenspecific CD4(+) T cells. APCs continuously generate and degrade MHC-II molecules, and ubiquitination of MHC-II has recently been shown to be a key regulator of MHC-II expression in dendritic cells (DCs). In this mini-review we will examine the mechanism by which the E3 ubiquitin ligase March-1 regulates MHC-II expression on APCs and will discuss the functional consequences of altering MHC-II ubiquitination. C1 [Cho, Kyung-Jin; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4836, Bethesda, MD 20892 USA. EM paul.roche@nih.gov FU National Institutes of Health FX Our work cited in this mini-review was supported by the Intramural Research Program of the National Institutes of Health. NR 29 TC 5 Z9 5 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 369 DI 10.3389/fimmu.2013.00369 PG 3 WC Immunology SC Immunology GA V38WS UT WOS:000209374100360 PM 24312092 ER PT J AU Cichocki, F Miller, JS Anderson, SK Bryceson, YT AF Cichocki, Frank Miller, Jeffrey S. Anderson, Stephen K. Bryceson, Yenan T. TI Epigenetic regulation of NK cell differentiation and effector functions SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE NK cell; epigenetics; transcription factors; development; memory AB Upon maturation, natural killer (NK) cells acquire effector functions and regulatory receptors. New insights suggest a considerable functional heterogeneity and dynamic regulation of receptor expression in mature human NK cell subsets based on different developmental axes. Such processes include acquisition of lytic granules as well as regulation of cytokine production in response to exogenous cytokine stimulation or target cell interactions. One axis is regulated by expression of inhibitory receptors for self-MHC class I molecules, whereas other axes are less well defined but likely are driven by different activating receptor engagements or cytokines. Moreover, the recent identification of long-lived NK cell subsets in mice that are able to expand and respond rapidly following a secondary viral challenge suggest previously unappreciated plasticity in the programming of NK cell differentiation. Here, we review advances in our understanding of mature NK cell development and plasticity with regards to regulation of cellular function. Furthermore, we highlight some of the major questions that remain pertaining to the epigenetic changes that underlie the differentiation and functional specialization of NK cells and the regulation of their responses. C1 [Cichocki, Frank; Bryceson, Yenan T.] Karolinska Inst, Karolinska Univ Hosp Huddinge, Dept Med, Ctr Infect Med, S-14186 Stockholm, Sweden. [Cichocki, Frank; Miller, Jeffrey S.] Univ Minnesota, Ctr Canc, Adult Div Hematol Oncol & Transplantat, Minneapolis, MN USA. [Anderson, Stephen K.] NCI, Expt Immunol Lab, Canc & Inflammat Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Cichocki, F (reprint author), Karolinska Inst, Karolinska Univ Hosp, Dept Med, Ctr Infect Med, F59, S-14186 Stockholm, Sweden. EM frank.cichocki@ki.se OI Anderson, Stephen/0000-0002-7856-4266; Miller, Jeffrey S/0000-0002-0339-4944; Bryceson, Yenan/0000-0002-7783-9934 FU Swedish Research Council; Swedish Cancer Foundation; Swedish Children's Cancer Foundation; Ake Olsson Foundation for Hematological Research; Histiocytosis Association; Jeansson's Foundation; Ake Wiberg's Foundation; Clas Groschinsky's Memorial Fund; Karolinska Institute Research Foundation; Frontiers in Biomedical Research Fellowship FX This work was supported by the Swedish Research Council, Swedish Cancer Foundation, Swedish Children's Cancer Foundation, Ake Olsson Foundation for Hematological Research, Histiocytosis Association, Jeansson's Foundation, Ake Wiberg's Foundation, Clas Groschinsky's Memorial Fund, the Karolinska Institute Research Foundation, and the Frontiers in Biomedical Research Fellowship. NR 65 TC 19 Z9 19 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 55 DI 10.3389/fimmu.2013.00055 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100055 PM 23450696 ER PT J AU Devaiah, BN Singer, DS AF Devaiah, Ballachanda N. Singer, Dinah S. TI CIITA and its dual roles in MAC gene transcription SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE CIITA; MHC transcription; NLR/CATERPILLER proteins; enhanceosome; TAF1; general transcription factors AB Class II transactivator (CIITA) is a transcriptional coactivator that regulates gamma-interferon-activated transcription of Major Histocompatibility Complex (MHC) class I and II genes. As such, it plays a critical role in immune responses: CIITA deficiency results in aberrant MHC gene expression and consequently in autoimmune diseases such as Type II bare lymphocyte syndrome. Although CIITA does not bind DNA directly, it regulates MHC transcription in two distinct ways as a transcriptional activator and as a general transcription factor. As an activator, CIITA nucleates an enhanceosome consisting of the DNA binding transcription factors RFX, cyclic AMP response element binding protein, and NF-Y As a general transcription factor, CIITA functionally replaces the TFIID component, TAF1. Like TAF1, CIITA possesses acetyltransferase (AT) and kinase activities, both of which contribute to proper transcription of MHC class I and II genes. The substrate specificity and regulation of the CIITA AT and kinase activities also parallel those of TAF1. In addition, CIITA is tightly regulated by its various regulatory domains that undergo phosphorylation and influence its targeted localization. Thus, a complex picture of the mechanisms regulating CIITA function is emerging suggesting that CIITA has dual roles in transcriptional regulation which are summarized in this review. C1 [Devaiah, Ballachanda N.; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 4836, Bethesda, MD 20892 USA. EM dinah.singer@nih.gov FU Intramural Research Program of the Center for Cancer Research (CCR), National Cancer Institute, NIH FX We thank Dr. Paul Roche for his critical review of this manuscript. We also thank members of our lab for helpful discussions and apologize to researchers whose work may not be cited due to lack of space. This research was supported by the Intramural Research Program of the Center for Cancer Research (CCR), National Cancer Institute, NIH. NR 50 TC 19 Z9 20 U1 2 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 476 DI 10.3389/fimmu.2013.00476 PG 6 WC Immunology SC Immunology GA V38WS UT WOS:000209374100464 PM 24391648 ER PT J AU Kanevskiy, LM Telford, WG Sapozhnikov, AM Kovalenko, EI AF Kanevskiy, Leonid M. Telford, William G. Sapozhnikov, Alexander M. Kovalenko, Elena I. TI Lipopolysaccharide induces IFN-gamma production in human NK cells SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE NK cells; lipopolysaccharide; cytokine production; cytotoxicity; flow cytometry AB Natural killer (NK) cells have been shown to play a regulatory role in sepsis. According to the current view, NK cells become activated via macrophages or dendritic cells primed by lipopolysaccharide (LPS). Recently, TLR4 gene expression was detected in human NK cells suggesting the possibility of a direct action of LPS on NK cells. In this study, effects of LPS on NK cell cytokine production and cytotoxicity were studied using highly purified human NK cells. LPS was shown to induce IFN-gamma production in the presence of 1152 in NK cell populations containing >98% CD56(+) cells. Surprisingly, in the same experiments LPS decreased NK cell degranulation. No significant expression of markers related to blood dendritic cells, monocytes on or B lymphocytes in the NK cell preparations was observed; the portions of HLA-DRbright, CD14(+) CD3(+), and CD20(+) cells amounted to less than 0.1% within the cell populations. No more than 0.2% of NK cells were shown to be slightly positive for surface TLR4 in our experimental system, although intracellular staining revealed moderate amounts of TLR4 inside the NK cell population. These cells were negative for surface CD14, the receptor participating in LPS recognition byTLR4. Incubation of NK cells with 1152 or/and LPS did not lead to an increase in TLR4 surface expression. TLR4(-)CD56(+) NK cells isolated by cell sorting secreted IFN-gamma in response to LPS. Antibody to TLR4 did not block the LPS-induced increase in IFN-gamma production. We have also shown that R-e-form of LPS lacking outer core oligosaccharide and 0-antigen induces less cytokine production in NK cells than full-length LPS. We speculate that the polysaccharide fragments of LPS molecule may take part in LPS-induced IFN-gamma production by NK cells. Collectively our data suggest the existence of a mechanism of LPS direct action on NK cells distinct from established TLR4-mediated signaling. C1 [Kanevskiy, Leonid M.; Sapozhnikov, Alexander M.; Kovalenko, Elena I.] Russian Acad Sci, Lab Cell Interact, Dept Immunol, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. [Telford, William G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kovalenko, EI (reprint author), Russian Acad Sci, Lab Cell Interact, Dept Immunol, Shemyakin Ovchinnikov Inst Bioorgan Chem, Miklukho Maklaya 16-10, Moscow 117997, Russia. EM kovalenelen@gmail.com RI Kovalenko, Elena/S-2086-2016 FU Ministry of Education and Science of the Russian Federation [16.740.11.0200]; Russian Academy of Sciences FX This work was supported by Ministry of Education and Science of the Russian Federation (grant #16.740.11.0200), Programs of Russian Academy of Sciences "Molecular and Cellular Biology" and "Fundamental Investigations of Nanotechnologies and Nanomaterials." NR 36 TC 16 Z9 18 U1 0 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 11 DI 10.3389/fimmu.2013.00011 PG 10 WC Immunology SC Immunology GA V38WS UT WOS:000209374100011 PM 23372571 ER PT J AU Kerkar, SP AF Kerkar, Sid P. TI "Model T" cells: a time-tested vehicle for gene therapy SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE gene therapy; cancer; immunotherapy; T cells; inflammation; chimeric-antigen receptors; cytokines; severe combined immunodeficiency AB T lymphocytes first carried foreign genes safely into humans over two decades ago. Since these pioneering studies, scientific techniques to better understand the genomic landscape of cells has directly led to a more sophisticated appreciation of the diversity, functional complexity, and therapeutic potential of T cells. Through the use of mouse models, we now know the function of the many genes that are critical for T cells to recognize foreign, mutated, or self-antigens and the factors responsible for the lineage diversification of T cells that lead to inhibitory or stimulatory immune responses. This knowledge combined with well-established modalities to introduce genes into T cells allows for the design of effector and memory CD8 and CD4 T lymphocytes specific for viral, fungal, bacterial, parasitic, and tumor-antigens and to design regulatory lymphocytes specific for the self-antigens responsible for autoimmune and inflammatory diseases. Here, I review strategies for designing the ideal T cell by introducing genes controlling (1) the secretion of cytokines/chemokines and their receptors, (2)T-cell receptor specificity, (3) chimeric-antigen receptors that enable for the recognition of surface antigens in an MHC-independent fashion, (4) co-stimulatory/inhibitory surface molecules, and (5) disease defining single-gene factors. C1 [Kerkar, Sid P.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kerkar, SP (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH Clin Ctr, Room 2838,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM kerkars@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The author has no conflicting financial interests. NR 76 TC 5 Z9 5 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 304 DI 10.3389/fimmu.2013.00304 PG 7 WC Immunology SC Immunology GA V38WS UT WOS:000209374100298 PM 24098300 ER PT J AU Leitner, WW Wali, T Costero-Saint Denis, A AF Leitner, Wolfgang W. Wali, Tonu Costero-Saint Denis, Adriana TI Is arthropod saliva the Achilles' heel of vector-borne diseases? SO FRONTIERS IN IMMUNOLOGY LA English DT Editorial Material DE vector-borne disease; vaccine; arthropod saliva; immunomodulation; malaria; leishmaniasis; dengue; Lyme disease C1 [Leitner, Wolfgang W.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Wali, Tonu; Costero-Saint Denis, Adriana] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Leitner, WW (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wleitner@niaid.nih.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 26 TC 4 Z9 4 U1 0 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 255 DI 10.3389/fimmu.2013.00255 PG 3 WC Immunology SC Immunology GA V38WS UT WOS:000209374100251 PM 24009609 ER PT J AU Limou, S Zagury, JF AF Limou, Sophie Zagury, Jean-Francois TI Immunogenetics: genome-wide association non-progressive HIV and viral load control: HLA genes and beyond SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE genome-wide association study; SNP; HIV-1; viral control; long-term non-progression; chemokine receptors region; HLA AB Very early after the identification of the human immunodeficiency virus (HIV), host genetics factors were anticipated to play a role in viral control and disease progression. As early as the mid-1990s, candidate gene studies demonstrated a central role for the chemokine co-receptor/ligand (e.g., CCR5) and human leukocyte antigen (HLA) systems. In the last decade, the advent of genome-wide arrays opened a new era for unbiased genetic exploration of the genome and brought big expectations for the identification of new unexpected genes and pathways involved in HIV/AIDS. More than 15 genome-wide association studies targeting various HIV-linked phenotypes have been published since 2007. Surprisingly, only the two HIV-chemokine co-receptors and HLA loci have exhibited consistent and reproducible statistically significant genetic associations. In this chapter, we will review the findings from the genome-wide studies focusing especially on non-progressive and HIV control phenotypes, and discuss the current perspectives. C1 [Limou, Sophie] Frederick Natl Lab Canc Res, Basic Res Lab, Basic Sci Program, Frederick, MD USA. [Zagury, Jean-Francois] Conservatoire Natl Arts & Metiers, Lab Genom Bioinformat & Applicat EA 4627, Chaire Bioinformat, Paris, France. RP Limou, S (reprint author), Frederick Natl Lab, POB B,Bldg 560,Room 11-84, Frederick, MD 21702 USA. EM sophie.limou@nih.gov; zagury@cnam.fr FU Federal funds from Frederick National Laboratory for Cancer Research, National Institutes of Health [HHSN261200800001E] FX We are very grateful to Dr. Cheryl A. Winkler and Dr. Nicolas Vince for their advice and careful reading of the manuscript. This project has been funded in whole or in part with Federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 97 TC 10 Z9 10 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 118 DI 10.3389/fimmu.2013.00118 PG 13 WC Immunology SC Immunology GA V38WS UT WOS:000209374100117 PM 23750159 ER PT J AU Mavragani, CP Niewold, TB Chatzigeorgiou, A Danielides, S Thomas, D Kirou, KA Kamper, E Kaltsas, G Crow, MK AF Mavragani, Clio P. Niewold, Timothy B. Chatzigeorgiou, Antonis Danielides, Stamatina Thomas, Dimitrios Kirou, Kyriakos A. Kamper, Elli Kaltsas, Grigorios Crow, Mary K. TI Increased serum type I interferon activity in organ-specific autoimmune disorders: clinical imaging, and serological associations SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE type I interferon; autoimmune thyroid disease; organ-specific autoimmunity; type I diabetes AB Background: Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (AID) and type I diabetes (T1DM). Methods: We studied 39 patients with AID and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 AID patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in AID patients. Results: Serum type I IFN activity was increased in patients with AID and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). AID patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels. Conclusion: Serum type I IFN activity is increased in AID and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ specific autoimmunity. C1 [Mavragani, Clio P.; Kirou, Kyriakos A.; Crow, Mary K.] Hosp Special Surg, Mary Kirkland Ctr Lupus Res, New York, NY 10021 USA. [Mavragani, Clio P.; Chatzigeorgiou, Antonis; Kamper, Elli] Univ Athens, Sch Med, Dept Physiol, GR-11527 Athens, Greece. [Niewold, Timothy B.] Mayo Clin, Div Rheumatol, Rochester, MN USA. [Niewold, Timothy B.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Danielides, Stamatina; Thomas, Dimitrios; Kaltsas, Grigorios] Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. [Danielides, Stamatina] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA. RP Mavragani, CP (reprint author), Univ Athens, Sch Med, Dept Physiol, M Asias 75, GR-11527 Athens, Greece. EM kmauragan@med.uoa.gr OI Niewold, Timothy/0000-0003-3532-6660 FU New York Chapter of the Arthritis Foundation; NIH CTSA K12 [RR025000-02]; NIAID Clinical Research Loan Repayment [AI071651]; Arthritis Foundation Post-Doctoral Fellowship Award; Arthritis National Research Foundation; NIH [AI059893]; Alliance for Lupus Research; Lupus Research Institute; Mary Kirkland Center for Lupus Research FX A Stavros Niarchos Fellowship from the New York Chapter of the Arthritis Foundation to Clio P. Mavragani; NIH CTSA K12 Scholar Award RR025000-02, NIAID Clinical Research Loan Repayment AI071651, Arthritis Foundation Post-Doctoral Fellowship Award, and Arthritis National Research Foundation Scholar Award grants to Timothy B. Niewold; and grants from the NIH (AI059893), the Alliance for Lupus Research, the Lupus Research Institute, and the Mary Kirkland Center for Lupus Research to Mary K. Crow. The authors would also like to thank Prof. HM Moutsopoulos, MD, for valuable guidance and advice. NR 48 TC 7 Z9 7 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 238 DI 10.3389/fimmu.2013.00238 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100234 PM 23966997 ER PT J AU Metenou, S Nutman, TB AF Metenou, Simon Nutman, Thomas B. TI Regulatory T cell subsets in filarial infection and their function SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE tTregs; pTregs; Tr1; Th3; filarial infection; O. volvulus; W. bancrofti; B. malayi AB Filarial infections in humans are chronic infections that cause significant morbidity. The chronic nature of these infections with continuous antigen release is associated with a parasite-specific T cell hypo-responsiveness that may over time also affect the immune responses to bystander antigens. Previous studies have shown the filarial parasite antigen-specific T cells hypo-responsiveness is mediated by regulatory cytokines -IL-10 and TGF-beta in particular. Recent studies have suggested that the modulated/regulated T cell responses associated with patent filarial infection may reflect an expansion of regulatoryT cells (Tregs) that include both Tregs induced in peripheral circulation or pTregs and the thymus-derived Tregs or tTregs. Although much is known about the phenotype of these regulatory populations, the mechanisms underlying their expansion and their mode of action in filarial and other infections remain unclear. Nevertheless there are data to suggest that while many of these regulatory cells are activated in an antigen-specific manner the ensuing effectors of this activation are relatively non-specific and may affect a broad range of immune cells. This review will focus on the subsets and function of regulatory T cells in filarial infection. C1 [Metenou, Simon; Nutman, Thomas B.] NIH, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIH, Helminth Immunol Sect, Parasit Dis Lab, 4 Ctr Dr Bldg 4 Room B1-03, Bethesda, MD 20892 USA. EM tnutman@naiaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 141 TC 18 Z9 18 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 305 DI 10.3389/fimmu.2013.00305 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100299 PM 24137161 ER PT J AU Nunes, JA Guittard, G AF Nunes, Jacques A. Guittard, Geoffrey TI An emerging role for Pl5P in T cell biology SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE Pl5P; PtdIns5P; phosphoinositide; T cell signaling; Dok proteins AB Phosphoinositides are critical regulators in cell biology. Phosphatidylinositol 4,5-bisphosphate, also known as PI(4,5)P-2 or PIP2, was the first variety of phosphoinositide to enter in the T cell signaling scene. Phosphatidylinositol bis-phosphates are the substrates for different types of enzymes such as phospholipases C (beta and gamma isoforms) and phosphoinositide 3-kinases (PI3K class IA and IB) that are largely involved in signal transduction. However until recently, only a few studies highlighted phosphatidylinositol monophosphates as signaling molecules. This was mostly due to the difficulty of detection of some of these phosphoinositides, such as phosphatidylinositol 5-phosphate, also known as Pl5P. Some compelling evidence argues for a role of Pl5P in cell signaling and/or cell trafficking. Recently, we reported the detection of a Pl5P increase upon TCR triggering. Here, we describe the current knowledge of the role of Pl5P in T cell signaling. The future challenges that will be important to achieve in order to fully characterize the role of Pl5P in T cell biology, will be discussed. C1 [Nunes, Jacques A.] Ctr Rech Cancerol Marseille, CNRS, UMR7258, Immunol & Canc, Marseille, France. [Nunes, Jacques A.] Ctr Rech Cancerol Marseille, INSERM, U1068, Immunol & Canc, Marseille, France. [Nunes, Jacques A.] Inst J Paoli I Calmettes, Immunol & Canc, F-13009 Marseille, France. [Nunes, Jacques A.] Aix Marseille Univ, Ctr Rech Cancerol Marseille, Marseille, France. [Guittard, Geoffrey] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, Bethesda, MD 20892 USA. RP Nunes, JA (reprint author), Ctr Rech Cancerol, BP30059,27 Bd Lei Roure, F-13273 Marseille 09, France. EM jacques.nunes@inserm.fr NR 73 TC 4 Z9 4 U1 0 U2 0 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 80 DI 10.3389/fimmu.2013.00080 PG 7 WC Immunology SC Immunology GA V38WS UT WOS:000209374100079 PM 23565114 ER PT J AU Oliveira, F de Carvalho, AM de Oliveira, CI AF Oliveira, Fabiano de Carvalho, Augusto M. de Oliveira, Camila I. TI Sand-fly saliva-Leishmania-man: the trigger trio SO FRONTIERS IN IMMUNOLOGY LA English DT Review DE sand-fly; saliva; Leishmania; vaccine; leishmaniasis AB Leishmaniases are worldwide diseases transmitted to the vertebrate host by the bite of an infected sand-fly. Sand-fly biting and parasite inoculation are accompanied by the injection of salivary molecules, whose immunomodulatory properties are actively being studied. This mini review focuses on how the interactions between sand-fly saliva and the immune system may shape the outcome of infection, given its immunomodulatory properties, in experimental models and in the endemic area. Additionally, we approach the recent contributions regarding the identification of individual salivary components and how these are currently being considered as additional components of a vaccine against leishmaniasis. C1 [Oliveira, Fabiano] NIAID, Vector Biol Sect, Lab Malaria & Vector Res, NIH, Rockville, MD USA. [de Carvalho, Augusto M.; de Oliveira, Camila I.] FlOCRUZ, Lab Imunoparasitol, Ctr Pesquisas Goncalo Moniz, BR-40196710 Salvador, BA, Brazil. [de Oliveira, Camila I.] Inst Nacl Ciencia & Tecnol Invest Imunol Iii INCT, Salvador, BA, Brazil. RP de Oliveira, CI (reprint author), FlOCRUZ, Lab Imunoparasitol, Ctr Pesquisas Goncalo Moniz, Rua Waldemar Falcao,121 Candeal, BR-40196710 Salvador, BA, Brazil. EM camila@bahia.fiocruz.br OI DE OLIVEIRA, CAMILA INDIANI/0000-0002-7868-5164 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank Brenda Rae Marshall, DPSS, NIAID, for editing. Because Fabiano Oliveira is a government employe and this is a government work, the work is in the public domain in the U.S. Notwithstanding any other agreements, the NIH reserves the right to provide the work to Pub Med Central for display and use by the public, and Pub Med Central may tag or modify the work consistent with its customary practices. You can establish rights outside of the U.S. subject to a government use license. NR 93 TC 11 Z9 11 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 375 DI 10.3389/fimmu.2013.00375 PG 8 WC Immunology SC Immunology GA V38WS UT WOS:000209374100366 PM 24312093 ER PT J AU van den Berg, HA Ladell, K Miners, K Laugel, B Llewellyn-Lacey, S Clement, M Cole, DK Gostick, E Wooldridge, L Sewell, AK Bridgeman, JS Price, DA AF van den Berg, Hugo A. Ladell, Kristin Miners, Kelly Laugel, Bruno Llewellyn-Lacey, Sian Clement, Mathew Cole, David K. Gostick, Emma Wooldridge, Linda Sewell, Andrew K. Bridgeman, John S. Price, David A. TI Cellular-level versus receptor-level response threshold hierarchies in T-cell activation SO FRONTIERS IN IMMUNOLOGY LA English DT Article DE T-cell activation; T-cell cross-reactivity; T-cell receptor AB Peptide-MHC (pM HC) ligand engagement by T-cell receptors (TCRs) elicits a variety of cellular responses, some of which require substantially more TCR-mediated stimulation than others. This threshold hierarchy could reside at the receptor level, where different response pathways branch off at different stages of the TCR/CD3 triggering cascade, or at the cellular level, where the cumulative TCR signal registered by the T-cell is compared to different threshold values. Alternatively, dual-level thresholds could exist. In this study, we show that the cellular hypothesis provides the most parsimonious explanation consistent with data obtained from an in-depth analysis of distinct functional responses elicited in a clonal T-cell system by a spectrum of biophysically defined altered peptide ligands across a range of concentrations. Further, we derive a mathematical model that describes how ligand density, affinity, and off-rate all affect signaling in distinct ways. However, under the kinetic regime prevailing in the experiments reported here, the TCR/pMHC class I (pMHCI) dissociation rate was found to be the main governing factor. The CD8 coreceptor modulated the TCR/pMHCI interaction and altered peptide ligand potency. Collectively, these findings elucidate the relationship between TCR/pMHCI kinetics and cellular function, thereby providing an integrated mechanistic understanding of T-cell response profiles. C1 [van den Berg, Hugo A.] Univ Warwick, Coventry CV4 7AL, W Midlands, England. [Ladell, Kristin; Miners, Kelly; Laugel, Bruno; Llewellyn-Lacey, Sian; Clement, Mathew; Cole, David K.; Gostick, Emma; Wooldridge, Linda; Sewell, Andrew K.; Bridgeman, John S.; Price, David A.] Cardiff Univ, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. [Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP van den Berg, HA (reprint author), Univ Warwick, Coventry CV4 7AL, W Midlands, England. EM hugo@maths.warwick.ac.uk RI Ladell, Kristin/K-2475-2013; Ladell, Kristin/C-8301-2013; OI Ladell, Kristin/0000-0002-9856-2938; Sewell, Andrew/0000-0003-3194-3135; Cole, David/0000-0003-0028-9396 FU Biotechnology and Biological Sciences Research Council [BB/H001085/1] FX This work was supported by the Biotechnology and Biological Sciences Research Council (grant BB/H001085/1). The authors are grateful to Brenda Hartman (NIH/VRC) for expert assistance with graphics. NR 68 TC 8 Z9 8 U1 1 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-3224 J9 FRONT IMMUNOL JI Front. Immunol. PY 2013 VL 4 AR UNSP 250 DI 10.3389/fimmu.2013.00250 PG 13 WC Immunology SC Immunology GA V38WS UT WOS:000209374100246 PM 24046768 ER PT J AU Lowekamp, BC Chen, DT Ibanez, L Blezek, D AF Lowekamp, Bradley C. Chen, David T. Ibanez, Luis Blezek, Daniel TI The Design of SimpleITK SO FRONTIERS IN NEUROINFORMATICS LA English DT Article DE software design; Insight Toolkit; segmentation; software development; image processing software; image processing and analysis AB SimpleITK is a new interface to the Insight Segmentation and Registration Toolkit (ITK) designed to facilitate rapid prototyping, education and scientific activities via high level programming languages. ITK is a templated C++ library of image processing algorithms and frameworks for biomedical and other applications, and it was designed to be generic, flexible and extensible. Initially, ITK provided a direct wrapping interface to languages such as Python and Tcl through the WrapITK system. Unlike WrapITK, which exposed ITK's complex templated interface, SimpleITK was designed to provide an easy to use and simplified interface to ITK's algorithms. It includes procedural methods, hides ITK's demand driven pipeline, and provides a template-less layer. Also SimpleITK provides practical conveniences such as binary distribution packages and overloaded operators. Our user-friendly design goals dictated a departure from the direct interface wrapping approach of WrapITK, toward a new facade class structure that only exposes the required functionality, hiding ITK's extensive template use. Internally SimpleITK utilizes a manual description of each filter with code-generation and advanced C++ meta-programming to provide the higher-level interface, bringing the capabilities of ITK to a wider audience. C1 [Lowekamp, Bradley C.; Chen, David T.] Natl Lib Med, Off High Performance Comp & Commun, NIH, Bethesda, MD 20894 USA. [Lowekamp, Bradley C.; Chen, David T.] Med Sci & Comp, Rockville, MD USA. [Ibanez, Luis] Kitware Inc, Clifton Pk, NY USA. [Blezek, Daniel] Mayo Clin & Mayo Grad Sch Med, Dept Biomed Engn, Rochester, MN USA. RP Lowekamp, BC (reprint author), Natl Lib Med, Off High Performance Comp & Commun, BLDG 38A RM B1N30,8600 Rockville Pike, Bethesda, MD 20894 USA. EM blowekamp@mail.nih.gov FU National Library of Medicine under the American Reinvestment and Recovery Act (ARRA) [HHSN276201000488P, HHSN276201000490P]; National Library of Medicine's intramural research program FX This work was funded in part by National Library of Medicine contract awards HHSN276201000488P and HHSN276201000490P under the American Reinvestment and Recovery Act (ARRA) along with the National Library of Medicine's intramural research program. NR 23 TC 13 Z9 13 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-5196 J9 FRONT NEUROINFORM JI Front. Neuroinformatics PY 2013 VL 7 AR UNSP 45 DI 10.3389/fninf.2013.00045 PG 14 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA V36JA UT WOS:000209207300042 PM 24416015 ER PT J AU Romero, JR Mercado, M Beiser, AS Pikula, A Seshadri, S Kelly-Hayes, M Wolf, PA Kase, CS AF Romero, Jose Rafael Mercado, Melissa Beiser, Alexa S. Pikula, Aleksandra Seshadri, Sudha Kelly-Hayes, Margaret Wolf, Philip A. Kase, Carlos S. TI Transient global amnesia and neurological events: the Framingham Heart Study SO FRONTIERS IN NEUROLOGY LA English DT Article DE transient global amnesia; cerebrovascular disease; stroke; TIA; Brain MRI AB Background/objective:Transient global amnesia (TGA) is a temporary amnestic syndrome characterized by lack of other focal neurological deficits. Cerebrovascular disease, migraine and seizures have been suggested as underlying mechanisms. TGA may be a risk factor for cerebrovascular or other neurological events. We studied the relation of TGA, vascular risk factors, brain magnetic resonance imaging (MRI) indices of subclinical ischemia and neurological events in a community-based sample. Design/setting: A total of 12 TGA cases were ascertained using standard criteria by experienced neurologists, and matched to 41 stroke- and seizure-free controls. Vascular risk factors, brain MRI findings, and subsequent cerebrovascular or seizure events were compared in cases and controls. Participants: Framingham Heart Study (FHS) original and offspring cohort participants were included. Results: No significant differences between the groups were observed in the prevalence of vascular risk factors, or brain MRI measures. Few incident stroke/transient ischemic attacks (TIA) (one event among the cases and four in controls) or subsequent seizures occurred in either group. Head CT during the acute event (n=11) and brain MRI (n=7) were negative for acute abnormalities. Electroencephalograms (EEG) (n=5) were negative for epileptiform activity. Extracranial vascular studies were negative for significant stenosis in all cases. Conclusion: In our community-based study TGA was not related to traditional vascular risk factors, or cerebrovascular disease. However, our study is limited by small sample size and power, and larger studies are required to exclude an association. C1 [Romero, Jose Rafael; Mercado, Melissa; Beiser, Alexa S.; Pikula, Aleksandra; Seshadri, Sudha; Wolf, Philip A.; Kase, Carlos S.] Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. [Romero, Jose Rafael; Beiser, Alexa S.; Pikula, Aleksandra; Seshadri, Sudha; Kelly-Hayes, Margaret; Wolf, Philip A.; Kase, Carlos S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Beiser, Alexa S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Romero, JR (reprint author), Boston Univ, Sch Med, Dept Neurol, 72 East Concord St,C-329, Boston, MA 02118 USA. EM joromero@bmc.org OI Seshadri, Sudha/0000-0001-6135-2622; Pikula, Aleksandra/0000-0002-8378-5522; Beiser, Alexa/0000-0001-8551-7778 FU Framingham Heart Study's National Heart, Lung, and Blood Institute [N01-HC-25195]; National Institute of Neurological Disorders and Stroke [R01 NS17950]; National Institute on Aging [R01 AG16495, AG08122, AG033193, AG031287] FX This work (design and conduct of the study, collection and management of the data) was supported by the Framingham Heart Study's National Heart, Lung, and Blood Institute contract (N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (R01 NS17950) and from the National Institute on Aging (R01 AG16495; AG08122; AG033193; AG031287). NR 10 TC 6 Z9 6 U1 1 U2 1 PU FRONTIERS MEDIA SA PI LAUSANNE PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND SN 1664-2295 J9 FRONT NEUROL JI Front. Neurol. PY 2013 VL 4 AR 47 DI 10.3389/fneur.2013.00047 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V42QT UT WOS:000209629000046 PM 23675365 ER PT J AU Murray, EA Rudebeck, PH AF Murray, Elisabeth A. Rudebeck, Peter H. TI The drive to strive: goal generation based on current needs SO FRONTIERS IN NEUROSCIENCE LA English DT Review DE orbitofrontal cortex; macaque; reward; reinforcer devaluation; selective satiation; prefrontal cortex; anthropoid primates; amygdala ID ORBITAL PREFRONTAL CORTEX; PRIMATE ORBITOFRONTAL CORTEX; MEDIODORSAL THALAMIC NUCLEUS; ANTERIOR CINGULATE CORTEX; SENSORY-SPECIFIC SATIETY; RHESUS-MONKEYS FAIL; REINFORCER DEVALUATION; DECISION-MAKING; FRONTAL-CORTEX; MACAQUE MONKEY AB Hungry animals are influenced by a multitude of different factors when foraging for sustenance. Much of the work on animal foraging has focused on factors relating to the amount of time and energy animals expend searching for and harvesting foods. Models that emphasize such factors have been invaluable in determining when it is beneficial for an animal to search for pastures new. When foraging, however, animals also have to determine how to direct their search. For what food should they forage? There is no point searching for more of a particular food when you are sated from eating it. Here we review work in macaques and humans that has sought to reveal the neural circuits critical for determining the subjective value of different foods and associated objects in our environment and tracking this value over time. There is mounting evidence that a network composed of the orbitofrontal cortex (OFC), amygdala, and medial thalamus is critical for linking objects in the environment with food value and adjusting those valuations in real time based on current biological needs. Studies using temporary inactivation methods have revealed that the amygdala and OFC play distinct yet complementary roles in this valuation process. Such a network for determining the subjective value of different foods and, by extension, associated objects, must interact with systems that determine where and for how long to forage. Only by efficiently incorporating these two factors into their decisions will animals be able to achieve maximal fitness. C1 [Murray, Elisabeth A.; Rudebeck, Peter H.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Neuropsychol Lab, Bldg 49,Suite 1B80,49 Convent Dr, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov OI Rudebeck, Peter/0000-0002-1411-7555; Murray, Elisabeth/0000-0003-1450-1642 FU Intramural Research Program of the National Institute of Mental Health FX This work was supported by the Intramural Research Program of the National Institute of Mental Health. We thank Dr. Steven P. Wise for comments on an earlier version of the manuscript. NR 105 TC 13 Z9 13 U1 3 U2 9 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 112 DI 10.3389/fnins.2013.00112 PG 12 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300111 PM 23818876 ER PT J AU Raucci, F Tiong, JD Wray, S AF Raucci, Franca Tiong, Jean D. Wray, Susan TI P75 nerve growth factor receptors modulate development of GnRH neurons and olfactory ensheating cells SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE LHRH neurons; olfactory ensheathing cells; migration; olfactory system; development ID HORMONE-RELEASING HORMONE; MICE LACKING; LHRH NEURONS; RAT-BRAIN; MIGRATION; SYSTEM; EXPRESSION; PERIPHERIN; CULTURES; MOUSE AB Temporal and spatial localization of nerve growth factor receptor (p75NGFR) in the developing olfactory system and gonadotropin-releasing hormone-1 (GnRH) system was characterized and its role analyzed using p75NGFR null mice and nasal explants. Prenatally, p75NGFR was expressed by GnRH neurons and olfactory ensheathing cells (OECs). In p75NGFR null mice, no change in the number of GnRH cells was detected as compared to wild-type. However, in null mice, a shift in the distribution of GnRH neurons was found, with a small population of GnRH cells migrating further caudally toward the median eminence. Additionally, a reduction of both GAD67 positive olfactory axons and GEAR positive OEC fibers occurred. Acute administration of a p75NGFR blocker to GnRH cells maintained in vitro increased migration rate, consistent with the change in distribution detected in p75NGFR null mice. Chronic inhibition of p75NGFR caused an attenuation of olfactory axon fasciculation and a decrease in OEC density, again mimicking the changes detected in null mice. However, a reduction in GnRH cell number was found after chronic treatment that not observed in KO animals suggesting indirect changes occur during chronic treatment in vitro and/or a compensatory mechanism occurs in vivo that prevents loss of GnRH neurons in the absence of p75NGFR. C1 [Raucci, Franca; Tiong, Jean D.; Wray, Susan] NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bldg 35,Rm 3A 1012, Bethesda, MD 20892 USA. EM wrays@ninds.nih.gov OI wray, susan/0000-0001-7670-3915 FU Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health [ZIA NS002824-21] FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health, ZIA NS002824-21. NR 49 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 262 DI 10.3389/fnins.2013.00262 PG 14 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300258 PM 24409113 ER PT J AU Smith, JF Chen, KW Pillai, AS Horwitz, B AF Smith, Jason F. Chen, Kewei Pillai, Ajay S. Horwitz, Barry TI Identifying effective connectivity parameters in simulated fMRI: a direct comparison of switching linear dynamic system, stochastic dynamic causal, and multivariate autoregressive models SO FRONTIERS IN NEUROSCIENCE LA English DT Article DE effective connectivity; fMRI BOLD; modeling and simulation; parameter estimation ID PRINCIPAL COMPONENT ANALYSIS; BOLD HEMODYNAMIC-RESPONSES; GRANGER CAUSALITY; FUNCTIONAL CONNECTIVITY; STRUCTURAL EQUATION; MAXIMUM-LIKELIHOOD; BRAIN CONNECTIVITY; BALLOON MODEL; TIME-SERIES; NETWORK AB The number and variety of connectivity estimation methods is likely to continue to grow over the coming decade. Comparisons between methods are necessary to prune this growth to only the most accurate and robust methods. However, the nature of connectivity is elusive with different methods potentially attempting to identify different aspects of connectivity. Commonalities of connectivity definitions across methods upon which base direct comparisons can be difficult to derive. Here, we explicitly define "effective connectivity" using a common set of observation and state equations that are appropriate for three connectivity methods: dynamic causal modeling (DCM), multivariate autoregressive modeling (MAR), and switching linear dynamic systems for fMRI (sLDSf). In addition while deriving this set, we show how many other popular functional and effective connectivity methods are actually simplifications of these equations. We discuss implications of these connections for the practice of using one method to simulate data for another method. After mathematically connecting the three effective connectivity methods, simulated fMRI data with varying numbers of regions and task conditions is generated from the common equation. This simulated data explicitly contains the type of the connectivity that the three models were intended to identify. Each method is applied to the simulated data sets and the accuracy of parameter identification is analyzed. All methods perform above chance levels at identifying correct connectivity parameters. The sLDSf method was superior in parameter estimation accuracy to both DCM and MAR for all types of comparisons. C1 [Smith, Jason F.; Horwitz, Barry] Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modelling Sect, NIH, Bethesda, MD 20894 USA. [Chen, Kewei] Banner Good Samaritan Med Ctr, Positron Emiss Tomography Ctr, Phoenix, AZ USA. [Chen, Kewei] Banner Good Samaritan Med Ctr, Banner Alzheimers Dis Inst, Phoenix, AZ USA. [Chen, Kewei] Arizona State Univ, Dept Math & Stat, Tempe, AZ USA. [Chen, Kewei] Arizona Alzheimers Dis Consortium, Tempe, AZ USA. [Pillai, Ajay S.] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Smith, JF (reprint author), Natl Inst Deafness & Other Commun Disorders, Brain Imaging & Modelling Sect, NIH, 10 Ctr Dr,Room 5d39, Bethesda, MD 20894 USA. EM smithjas@nidcd.nih.gov RI Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU intramural program at the National Institute on Deafness and Communication Disorders at the National Institutes of Health FX This work was supported by the intramural program at the National Institute on Deafness and Communication Disorders at the National Institutes of Health. NR 105 TC 2 Z9 2 U1 0 U2 8 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1662-453X J9 FRONT NEUROSCI-SWITZ JI Front. Neurosci. PY 2013 VL 7 AR 70 DI 10.3389/fnins.2013.00070 PG 17 WC Neurosciences SC Neurosciences & Neurology GA AW9HF UT WOS:000346567300070 PM 23717258 ER PT J AU Kochunov, P Du, X Moran, LV Sampath, H Wijtenburg, SA Yang, Y Rowland, LM Stein, EA Hong, LE AF Kochunov, Peter Du, Xiaoming Moran, Lauren V. Sampath, Hemalatha Wijtenburg, S. Andrea Yang, Yihong Rowland, Laura M. Stein, Elliot A. Hong, L. Elliot TI Acute nicotine administration effects on fractional anisotropy of cerebral white matter and associated attention performance SO FRONTIERS IN PHARMACOLOGY LA English DT Article DE nicotine; DTI-FA; white matter; acute change; cognition; processing speed; attention ID CENTRAL-NERVOUS-SYSTEM; ATTENUATED MR SIGNAL; CIGARETTE-SMOKING; ACETYLCHOLINE-RECEPTOR; MICROSTRUCTURAL INTEGRITY; SPATIAL STATISTICS; TOBACCO-SMOKE; HUMAN BRAIN; IN-VITRO; DIFFUSION AB Introduction: Nicotinic acetylcholine receptors are present in the cerebral white matter (WM). We hypothesized that WM response to nicotine can be detected by diffusion tensor imaging (DTI); and that such responses may be associated with nicotine-led cognitive enhancement in sustained attention. Methods: A randomized, nicotine-placebo patch, crossover, double-blind clinical trial in two non-overlapping cohorts of smokers was used to test the hypothesis. The discovery cohort consisted of 39 subjects (N = 20/19 controls/schizophrenic patients, age = 36.8 10.1 years) and the replication cohorts consisted of 38 healthy smokers (31.7 10.5 years). WM integrity was measured by fractional anisotropy (FA) values for the whole brain and nine preselected WM tracts using tract-based-spatial-statistics. Results: Nicotine significantly enhanced FA values for the genu of corpus callosum compared with placebo (Delta FA(genu)) (p = 0.01) in smokers with low recent smoking exposure as measured by low average cotinine level. This finding was replicated in the second cohort (p = 0.02). Delta FA(genu) values explained 22% of variance in performance of a sustained attention task during the nicotine session (p = 0.006). However, this effect was limited to schizophrenia patients (r = 0.62 and 0.09; p = 0.003 and 0.7 for patients and controls, respectively). Conclusion: Acute pharmacological influence of nicotine patch on WM integrity appeared present, but was dependent on nicotine intake from recent smoking. Change in the WM integrity in the genu of corpus callosum was associated with a significant proportion of variability of nicotine-led changes in sustained attention/working memory of the smokers. Further studies will be necessary to understand biophysical underpinning of the nicotine-related changes in FA. C1 [Kochunov, Peter; Du, Xiaoming; Moran, Lauren V.; Sampath, Hemalatha; Wijtenburg, S. Andrea; Rowland, Laura M.; Hong, L. Elliot] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Kochunov, Peter] Univ Maryland, Dept Phys, Baltimore, MD 21201 USA. [Yang, Yihong; Stein, Elliot A.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Baltimore, MD USA. RP Kochunov, P (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, 655 W Baltimore St, Baltimore, MD 21201 USA. EM pkochunov@mprc.umaryland.edu RI Du, Xiaoming/M-3918-2016 OI Du, Xiaoming/0000-0001-7206-5282 FU National Institute of Health [K01EB006395, R01EB01561, R01DA027680, R01MH085646]; National Institute on Drug Abuse Intramural Research Program FX This research was supported by National Institute of Health grants K01EB006395 and R01EB01561 to Peter Kochunov and R01DA027680 and R01MH085646 to L. Elliott Hong, and the National Institute on Drug Abuse Intramural Research Program. NR 61 TC 10 Z9 10 U1 1 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PY 2013 VL 4 AR 117 DI 10.3389/fphar.2013.00117 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX6CS UT WOS:000347011700115 PM 24065920 ER PT J AU Zajicek, A Barrett, JS AF Zajicek, Anne Barrett, Jeffrey S. TI The grand challenges in obstetric and pediatric pharmacology SO FRONTIERS IN PHARMACOLOGY LA English DT Editorial Material DE obstetrics; pediatrics; pharmacology; medications; therapeutics C1 [Zajicek, Anne] Eunice Kennedy Shriver Nat Inst Child Hlth & Huma, NIH, Bethesda, MD 20892 USA. [Barrett, Jeffrey S.] Sanofi, Interdisciplinary Pharmacometr Program, Philadelphia, PA USA. RP Zajicek, A (reprint author), Eunice Kennedy Shriver Nat Inst Child Hlth & Huma, NIH, Bethesda, MD 20892 USA. EM zajiceka@mail.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1663-9812 J9 FRONT PHARMACOL JI Front. Pharmacol. PY 2013 VL 4 AR 170 DI 10.3389/fphar.2013.00170 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA AX6CS UT WOS:000347011700164 PM 24416021 ER PT J AU Boonstra, TW He, BJ Daffertshofer, A AF Boonstra, Tjeerd W. He, Biyu J. Daffertshofer, Andreas TI Scale-free dynamics and critical phenomena activity in cortical SO FRONTIERS IN PHYSIOLOGY LA English DT Editorial Material ID NEURONAL AVALANCHES; NETWORKS C1 [Boonstra, Tjeerd W.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. [Boonstra, Tjeerd W.] Black Dog Inst, Sydney, NSW, Australia. [Boonstra, Tjeerd W.; Daffertshofer, Andreas] Vrije Univ Amsterdam, Res Inst MOVE, Amsterdam, Netherlands. [He, Biyu J.] NINDS, NIH, Bethesda, MD 20892 USA. RP Boonstra, TW (reprint author), Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. EM t.boonstra@unsw.edu.au OI Boonstra, Tjeerd/0000-0002-6969-7243 NR 18 TC 1 Z9 1 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 4 AR 79 DI 10.3389/fphys.2013.00079 PG 2 WC Physiology SC Physiology GA AX2LA UT WOS:000346774000077 PM 23596422 ER PT J AU Chen, H Martin, B Daimon, CM Maudsley, S AF Chen, Hongyu Martin, Bronwen Daimon, Caitlin M. Maudsley, Stuart TI Effective use of latent semantic indexing and computational linguistics in biological and biomedical applications SO FRONTIERS IN PHYSIOLOGY LA English DT Review DE latent semantic indexing; data mining; computational linguistics; molecular interactions; drug discovery ID SINGULAR-VALUE DECOMPOSITION; MEDICAL LITERATURES; ABSTRACTS; SEARCH; GENES; TOOL AB Text mining is rapidly becoming an essential technique for the annotation and analysis of large biological data sets. Biomedical literature currently increases at a rate of several thousand papers per week, making automated information retrieval methods the only feasible method of managing this expanding corpus. With the increasing prevalence of open-access journals and constant growth of publicly-available repositories of biomedical literature, literature mining has become much more effective with respect to the extraction of biomedically-relevant data In recent years, text mining of popular databases such as MEDLINE has evolved from basic term searches to more sophisticated natural language processing techniques, indexing and retrieval methods, structural analysis and integration of literature with associated metadata. In this review, we will focus on Latent Semantic Indexing (LSI), a computational linguistics technique increasingly used for a variety of biological purposes. It is noted for its ability to consistently outperform benchmark Boolean text searches and co-occurrence models at information retrieval and its power to extract indirect relationships within a data set. LSI has been used successfully to formulate new hypotheses, generate novel connections from existing data, and validate empirical data C1 [Chen, Hongyu; Maudsley, Stuart] NIA, Neurosci Lab, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. [Martin, Bronwen; Daimon, Caitlin M.] NIA, Lab Clin Invest, Metab Unit, NIH, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Neurosci Lab, Receptor Pharmacol Unit, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 45 TC 6 Z9 6 U1 0 U2 6 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 4 AR 8 DI 10.3389/fphys.2013.00008 PG 6 WC Physiology SC Physiology GA AX2LA UT WOS:000346774000008 PM 23386833 ER PT J AU Martin, B Chen, HY Daimon, CM Chadwick, W Siddiqui, S Maudsley, S AF Martin, Bronwen Chen, Hongyu Daimon, Caitlin M. Chadwick, Wayne Siddiqui, Sana Maudsley, Stuart TI Plurigon: three dimensional visualization and classification of high-dimensionality data SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE Plurigon; three dimensional; data visualization; data classification; multivariate data vectors; algorithms; systems biology; bioinformatics ID ALZHEIMERS-DISEASE; RECEPTOR; BETA; DISORDERS; FRAMEWORK; INSIGHTS; TOPOLOGY; COMPLEX; POINTS; MODEL AB High-dimensionality data is rapidly becoming the norm for biomedical sciences and many other analytical disciplines. Not only is the collection and processing time for such data becoming problematic, but it has become increasingly difficult to form a comprehensive appreciation of high-dimensionality data. Though data analysis methods for coping with multivariate data are well-documented in technical fields such as computer science, little effort is currently being expended to condense data vectors that exist beyond the realm of physical space into an easily interpretable and aesthetic form. To address this important need, we have developed Plurigon, a data visualization and classification tool for the integration of high-dimensionality visualization algorithms with a user-friendly, interactive graphical interface. Unlike existing data visualization methods, which are focused on an ensemble of data points, Plurigon places a strong emphasis upon the visualization of a single data point and its determining characteristics. Multivariate data vectors are represented in the form of a deformed sphere with a distinct topology of hills, valleys, plateaus, peaks, and crevices. The gestalt structure of the resultant Plurigon object generates an easily-appreciable model. User interaction with the Plurigon is extensive; zoom, rotation, axial and vector display, feature extraction, and anaglyph stereoscopy are currently supported. With Plurigon and its ability to analyze high-complexity data, we hope to see a unification of biomedical and computational sciences as well as practical applications in a wide array of scientific disciplines. Increased accessibility to the analysis of high-dimensionality data may increase the number of new discoveries and breakthroughs, ranging from drug screening to disease diagnosis to medical literature mining. C1 [Martin, Bronwen; Daimon, Caitlin M.] NIA, Metab Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Chen, Hongyu; Chadwick, Wayne; Siddiqui, Sana; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. We would also like to thank Doug Hansen for photographic assistance and Kevin G. Becker, William H. Wood 3rd, Elin Lehrmann and Yongqing Zhang for their assistance with microarray data collection. NR 65 TC 4 Z9 4 U1 1 U2 3 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 4 AR 190 DI 10.3389/fphys.2013.00190 PG 17 WC Physiology SC Physiology GA AX2LA UT WOS:000346774000187 PM 23885241 ER PT J AU Qasba, P Larkin, J AF Qasba, Pankaj Larkin, Jennie TI NHLBI support of systems biology SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE NHLBI; NIH; funding opportunity; systems biology research; portfolio analysis ID NETWORK MEDICINE; HUMAN-DISEASE; DNA AB The National Heart, Lung, and Blood Institute (NHLBI) has recognized the importance of the systems biology approach for understanding normal physiology and perturbations associated with heart, lung, blood, and sleep diseases and disorders. In 2006, NHLBI announced the Exploratory Program in Systems Biology program, followed in 2010 by the NHLBI Systems Biology Collaborations program. The goal of these programs is to support collaborative teams of investigators in using experimental and computational strategies to integrate the component parts of biological networks and pathways into computational models that are based firmly on and validated using experimental data. These validated models are then applied to gain insights into the mechanisms of altered system function in disease, to generate novel hypotheses regarding these mechanisms that can be tested experimentally, and to then use the results of experiments to refine the models. This perspective reviews the history of dedicated systems biology programs at NHLBI and reviews some promising directions for future research in this area. C1 [Qasba, Pankaj] NHLBI, Blood Dis Branch, Div Blood Dis & Resources, HHS,NIH, Bethesda, MD 20892 USA. [Larkin, Jennie] NHLBI, Adv Technol & Surg Branch, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. RP Qasba, P (reprint author), NHLBI, Blood Dis Branch, Div Blood Dis & Resources, HHS,NIH, Bldg 10, Bethesda, MD 20892 USA. EM pq5h@nih.gov NR 17 TC 0 Z9 0 U1 0 U2 2 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 4 AR 299 DI 10.3389/fphys.2013.00299 PG 4 WC Physiology SC Physiology GA AX2LA UT WOS:000346774000296 PM 24298257 ER PT J AU Chen, HY Martin, B Cai, H Fiori, JL Egan, JM Siddiqui, S Maudsley, S AF Chen, Hongyu Martin, Bronwen Cai, Huan Fiori, Jennifer L. Egan, Josephine M. Siddiqui, Sana Maudsley, Stuart TI Pancreas plus plus : automated quantification of pancreatic islet cells in microscopy images SO FRONTIERS IN PHYSIOLOGY LA English DT Article DE pancreas; islets of Langerhans; alpha-cells; beta-cells; quantification; software; algorithm ID ENDOCRINE PANCREAS; INSULIN-SECRETION; DIABETES-MELLITUS; PREGNANCY; ONSET; MASS; PROLIFERATION; LANGERHANS; ADAPTATION; GROWTH AB The microscopic image analysis of pancreatic Islet of Langerhans morphology is crucial for the investigation of diabetes and metabolic diseases. Besides the general size of the islet, the percentage and relative position of glucagon-containing alpha-, and insulin-containing beta-cells is also important for pathophysiological analyses, especially in rodents. Hence, the ability to identify, quantify and spatially locate peripheral, and "involuted" alpha-cells in the islet core is an important analytical goal. There is a dearth of software available for the automated and sophisticated positional quantification of multiple cell types in the islet core. Manual analytical methods for these analyses, while relatively accurate, can suffer from a slow throughput rate as well as user-based biases. Here we describe a newly developed pancreatic islet analytical software program, Pancreas++, which facilitates the fully automated, non-biased, and highly reproducible investigation of islet area and alpha- and beta-cell quantity as well as position within the islet for either single or large batches of fluorescent images. We demonstrate the utility and accuracy of Pancreas++ by comparing its performance to other pancreatic islet size and cell type (alpha, beta) quantification methods. Our Pancreas++ analysis was significantly faster than other methods, while still retaining low error rates and a high degree of result correlation with the manually generated reference standard. C1 [Chen, Hongyu; Siddiqui, Sana; Maudsley, Stuart] NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA. [Martin, Bronwen; Cai, Huan] NIA, Metab Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Fiori, Jennifer L.; Egan, Josephine M.] NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Receptor Pharmacol Unit, Neurosci Lab, NIH, 251 Bayview Blvd,Suite 100, Baltimore, MD 21224 USA. EM maudsleyst@mail.nih.gov RI Cai, Huan/B-6578-2016 OI Cai, Huan/0000-0001-7731-8891 FU Intramural Research Program of the National Institute on Aging, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. NR 22 TC 2 Z9 2 U1 0 U2 1 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-042X J9 FRONT PHYSIOL JI Front. Physiol. PY 2013 VL 3 AR UNSP 482 DI 10.3389/fphys.2012.00482 PG 9 WC Physiology SC Physiology GA AX2KX UT WOS:000346773600006 ER PT B AU Yang, SX Dancey, JE AF Yang, Sherry X. Dancey, Janet E. BE Yand, SX Dancey, JE TI Overview: Therapeutic Biomarkers in Cancer SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; HER2-POSITIVE BREAST-CANCER; TYROSINE KINASE INHIBITORS; ADJUVANT CHEMOTHERAPY; AMERICAN-SOCIETY; DRUG DEVELOPMENT; POLY(ADP-RIBOSE) POLYMERASE; PREDICTIVE BIOMARKERS C1 [Yang, Sherry X.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Dancey, Janet E.] Ontario Inst Canc Res, High Impact Clin Trials, Toronto, ON, Canada. RP Yang, SX (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. EM Sherry.Yang@nih.gov; janet.dancey@oicr.on.ca NR 77 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 1 EP 29 PG 29 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300002 ER PT B AU Yang, SX Dancey, JE AF Yang, Sherry X. Dancey, Janet E. BE Yand, SX Dancey, JE TI Handbook of - THERAPEUTIC BIOMARKERS IN CANCER Preface SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Editorial Material; Book Chapter C1 [Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Dancey, Janet E.] Queens Univ, Dept Oncol, Kingston, ON K7L 3N6, Canada. [Dancey, Janet E.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Yang, SX (reprint author), NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP XIX EP XIX PG 1 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300001 ER PT B AU McShane, LM Korn, EL Freidlin, B AF McShane, Lisa M. Korn, Edward L. Freidlin, Boris BE Yand, SX Dancey, JE TI Statistical Considerations in the Development and Evaluation of Therapeutic Biomarkers in Cancer SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID PHASE-II TRIALS; CELL LUNG-CANCER; OUTCOME-ADAPTIVE RANDOMIZATION; CLINICAL-TRIALS; END-POINTS; NONCYTOTOXIC AGENTS; PROGNOSTIC-FACTORS; SIGNATURE DESIGN; PROGRESSION-FREE; PROSTATE-CANCER C1 [McShane, Lisa M.; Korn, Edward L.; Freidlin, Boris] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP McShane, LM (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM mcshanel@ctep.nci.nih.gov; korne@ctep.nci.nih.gov; freidlinb@ctep.nci.nih.gov NR 50 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 31 EP 58 PG 28 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300003 ER PT B AU Chen, HX AF Chen, Helen X. BE Yand, SX Dancey, JE TI Role of Biomarkers in Clinical Development of Cancer Therapies SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID METASTATIC COLORECTAL-CANCER; LUNG-CANCER; INHIBITOR; SIGNATURES; MUTATIONS; GEFITINIB C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Chen, HX (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, 6130 Execut Blvd,EPN 7131, Bethesda, MD 20892 USA. EM Helen.Chen@nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 59 EP 75 PG 17 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300004 ER PT B AU Wedam, SB Lipkowitz, S AF Wedam, Suparna B. Lipkowitz, Stanley BE Yand, SX Dancey, JE TI HER-2 as a Prognostic and Predictive Biomarker in Cancer SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID EPIDERMAL-GROWTH-FACTOR; METASTATIC BREAST-CANCER; IN-SITU HYBRIDIZATION; TOPOISOMERASE-II-ALPHA; CELL LUNG-CANCER; EPITHELIAL OVARIAN-CANCER; OF-AMERICAN-PATHOLOGISTS; RANDOMIZED PHASE-II; HUMANIZED ANTI-HER2 ANTIBODY; PRIMARY PERITONEAL CARCINOMA C1 [Wedam, Suparna B.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lipkowitz, Stanley] NCI, Lab Cellular & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wedam, SB (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Suparna.Wedam@fda.hhs.gov; lipkowis@mail.nih.gov NR 197 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 77 EP 120 PG 44 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300005 ER PT B AU Yang, SX AF Yang, Sherry X. BE Yand, SX Dancey, JE TI Hormone Receptors and Endocrine Therapy in Breast Cancer SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID PATHOLOGISTS GUIDELINE RECOMMENDATIONS; ONCOLOGY-TECHNOLOGY-ASSESSMENT; AROMATASE INHIBITOR THERAPY; RANDOMIZED CLINICAL-TRIAL; LIGAND-BINDING ASSAY; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; PHASE-III; AMERICAN-SOCIETY; ADJUVANT TAMOXIFEN C1 NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Yang, SX (reprint author), NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. EM Sherry.Yang@nih.gov NR 116 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 121 EP 153 PG 33 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300006 ER PT B AU Reece, KM Figg, WD AF Reece, K. M. Figg, W. D. BE Yand, SX Dancey, JE TI UGT1A1 Polymorphisms and Mutations Lead to Irinotecan-Induced Toxicity SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID CRIGLER-NAJJAR-SYNDROME; COLORECTAL-CANCER; GILBERTS-SYNDROME; RACIAL VARIABILITY; GENE; PHARMACOGENETICS; METABOLISM; PROMOTER; HYPERBILIRUBINEMIA; PHARMACOKINETICS C1 [Reece, K. M.] NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. [Figg, W. D.] NCI, Clin Pharmacol Core, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Reece, KM (reprint author), NCI, Mol Pharmacol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kelie.reece@nih.gov; wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 46 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 353 EP 368 PG 16 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300013 ER PT B AU Weil, MK Kummar, S Doroshow, JH Chen, A AF Weil, Marcie K. Kummar, Shivaani Doroshow, James H. Chen, Alice BE Yand, SX Dancey, JE TI BRCA Mutation and PARP Inhibitors SO HANDBOOK OF THERAPEUTIC BIOMARKERS IN CANCER LA English DT Article; Book Chapter ID POLY(ADP-RIBOSE) POLYMERASE INHIBITOR; ADVANCED SOLID TUMORS; DNA-DAMAGING AGENTS; OVARIAN-CANCER; GENE-EXPRESSION; SPORADIC BREAST; STRAND BREAKS; HOMOLOGOUS RECOMBINATION; SOMATIC MUTATIONS; MALIGNANT GLIOMA C1 [Weil, Marcie K.; Kummar, Shivaani; Doroshow, James H.; Chen, Alice] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Weil, MK (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. EM chenali@mail.nih.gov NR 98 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-981-4364-66-9; 978-981-4364-65-2 PY 2013 BP 417 EP 447 PG 31 WC Oncology SC Oncology GA BC7QB UT WOS:000355142300016 ER PT B AU Friedman, JE AF Friedman, Judith E. BE Gausemeier, B MullerWille, S Ramsden, E TI THE DISAPPEARANCE OF THE CONCEPT OF ANTICIPATION IN THE POST-WAR WORLD SO HUMAN HEREDITY IN THE TWENTIETH CENTURY SE Studies for the Society for the Social History of Medicine LA English DT Proceedings Paper CT Workshop on Human Heredity in the Twentieth Century CY SEP 02-04, 2010 CL Univ Exeter, Exeter, ENGLAND HO Univ Exeter C1 [Friedman, Judith E.] Max Planck Inst Hist Sci, Berlin, Germany. [Friedman, Judith E.] NIH, Bethesda, MD 20892 USA. RP Friedman, JE (reprint author), Max Planck Inst Hist Sci, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PICKERING & CHATTO PUBL PI LONDON PA 21 BLOOMSBURY WAY, LONDON, WC1A 2TH, ENGLAND BN 978-1-317-31921-4; 978-1-84893-426-9 J9 STUD SOC SOC HIST ME PY 2013 IS 15 BP 153 EP 164 PG 12 WC Genetics & Heredity; History & Philosophy Of Science SC Genetics & Heredity; History & Philosophy of Science GA BD8IH UT WOS:000363959900012 ER PT J AU Gulley, JL AF Gulley, James L. TI Therapeutic vaccines The ultimate personalized therapy? SO HUMAN VACCINES & IMMUNOTHERAPEUTICS LA English DT Editorial Material DE antigen cascade; antigen spreading; epitope spreading; personalized medicine; precision medicine; immunotherapy; individualized therapy; cancer vaccine ID RESISTANT PROSTATE-CANCER; RADIATION-THERAPY; ANTIGEN CASCADE; IMMUNOTHERAPY; COMBINATION; VACCINATION AB Personalized therapy is directed at obtaining maximal therapeutic effect on diseased tissue with minimal off-target side effects. Many classes of therapeutics have attempted to reach this ideal, only to fall well short. Therapeutic vaccines represent a novel class of therapies that can induce a dynamic immune response that, in theory, can continue to adapt and expand following initiation of vaccination. This adaptability, through epitope spreading or antigen cascade, can continuously refine a therapeutic immune response, making it more relevant to the patient's tumor. This active, dynamic, iterative process can continue long after the vaccine course has been completed. Recent clinical trials have provided further insight into the clinical activity of therapeutic vaccines, and offer guidance on clinical expectations following vaccine. The ongoing active sculpting of the immune response, along with the lack of significant side effects, uniquely positions therapeutic vaccines as perhaps the ultimate in personalized therapy. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 20 TC 12 Z9 13 U1 2 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 2164-5515 EI 2164-554X J9 HUM VACC IMMUNOTHER JI Human Vaccines Immunother. PD JAN PY 2013 VL 9 IS 1 BP 219 EP 221 DI 10.4161/hv.22106 PG 3 WC Biotechnology & Applied Microbiology; Immunology SC Biotechnology & Applied Microbiology; Immunology GA 098VR UT WOS:000315577700039 ER PT S AU Fay, MP Hunsberger, SA AF Fay, Michael P. Hunsberger, Sally A. BE Chen, DG Sun, J Peace, KE TI Practical Issues on Using Weighted Logrank Tests with Interval-Censored Events in Clinical Trials SO INTERVAL-CENSORED TIME-TO-EVENT DATA: METHODS AND APPLICATIONS SE Chapman & Hall-CRC Biostatistics Series LA English DT Article; Book Chapter ID FAILURE TIME DATA; LOG-RANK TEST; MAXIMUM-LIKELIHOOD; MULTIPLE IMPUTATION; ALGORITHM; COMPUTATION; CONSISTENCY; INFERENCE; MODEL C1 [Fay, Michael P.; Hunsberger, Sally A.] NCI, NIAID, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NCI, NIAID, Bethesda, MD 20892 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2154-4298 BN 978-1-4665-0428-8; 978-1-4665-0425-7 J9 CH CRC BIOSTAT SER JI Chapman & Hall-CRC Biostat. Ser. PY 2013 BP 345 EP 375 PG 31 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA BE2HN UT WOS:000369243500014 ER PT S AU Tanpaiboon, P Sloan, JL Callahan, PF McAreavey, D Hart, PS Lichter-Konecki, U Zand, D Venditti, CP AF Tanpaiboon, Pranoot Sloan, Jennifer L. Callahan, Patrick F. McAreavey, Dorothea Hart, P. Suzanne Lichter-Konecki, Uta Zand, Dina Venditti, Charles P. BE Zschocke, J Gibson, KM Brown, G Morava, E Peters, V TI Noncompaction of the Ventricular Myocardium and Hydrops Fetalis in Cobalamin C Disease SO JIMD REPORTS, VOL 10 SE JIMD Reports LA English DT Article; Book Chapter ID HEMOLYTIC-UREMIC SYNDROME; METHYLMALONIC ACIDURIA; NON-COMPACTION; CBLC-TYPE; CONGENITAL DEFECT; HOMOCYSTINURIA; HYPERTRABECULATION/NONCOMPACTION; CARDIOMYOPATHY; DELETION; ASSOCIATION AB Cobalamin C disease (cblC), a form of combined methylmalonic acidemia and hyperhomocysteinemia caused by mutations in the MMACHC gene, may be the most common inborn error of intracellular cobalamin metabolism. The clinical manifestations of cblC disease are diverse and range from intrauterine growth retardation to adult onset neurological disease. The occurrence of structural heart defects appears to be increased in cblC patients and may be related to the function of the MMACHC enzyme during cardiac embryogenesis, a concept supported by the observation that Mmachc is expressed in the bulbis cordis of the developing mouse heart. Here we report an infant who presented with hydrops fetalis, ventricular dysfunction, and echocardiographic evidence of LVNC, a rare congenital cardiomyopathy. Metabolic evaluations, complementation studies, and mutation analysis confirmed the diagnosis of cblC disease. These findings highlight an intrauterine cardiac phenotype that can be displayed in cblC disease in association with nonimmune hydrops. C1 [Tanpaiboon, Pranoot; Lichter-Konecki, Uta; Zand, Dina] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC USA. [Sloan, Jennifer L.; Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA. [Callahan, Patrick F.] Child Cardiol Associates, Fairfax, VA 22031 USA. [McAreavey, Dorothea] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Hart, P. Suzanne] NHGRI, Off Clin Director, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bldg 49,Room 4A18, Bethesda, MD 20892 USA. EM venditti@mail.nih.gov NR 43 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-642-37334-3; 978-3-642-37333-6 J9 JIMD REP PY 2013 VL 10 BP 33 EP 38 DI 10.1007/8904_2012_197 D2 10.1007/978-3-642-37334-3 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8SB UT WOS:000376974300005 PM 23430797 ER PT S AU Stabler, SP Korson, M Jethva, R Allen, RH Kraus, JP Spector, EB Wagner, C Mudd, SH AF Stabler, Sally P. Korson, Mark Jethva, Reena Allen, Robert H. Kraus, Jan P. Spector, Elaine B. Wagner, Conrad Mudd, S. Harvey BE Zschocke, J Gibson, KM Brown, G Morava, E TI Metabolic Profiling of Total Homocysteine and Related Compounds in Hyperhomocysteinemia: Utility and Limitations in Diagnosing the Cause of Puzzling Thrombophilia in a Family SO JIMD REPORTS, VOL 11 SE JIMD Reports LA English DT Article; Book Chapter ID CYSTATHIONINE-BETA-SYNTHASE; CHROMATOGRAPHY-MASS-SPECTROMETRY; S-ADENOSYLHOMOCYSTEINE; FOLATE-DEFICIENCY; MEGALOBLASTIC-ANEMIA; BIRTH PREVALENCE; MOLECULAR-BASIS; HOMOCYSTINURIA; SERUM; THROMBOSIS AB We describe a family illustrating the diagnostic difficulties occurring when pyridoxine-responsive cystathionine beta-synthase (CBS) deficiency presents with thrombotic disease without associated ocular, skeletal, or CNS abnormalities, a situation increasingly recognized. This family had several thromboembolic episodes in two generations with apparently inconstant elevations of plasma total homocysteine (tHcy). When taking (sometimes even low amounts) of pyridoxine, the affected family members had low-normal tHcy and normal values for cystathionine, methionine, and cysteine. Withdrawal of vitamin therapy was necessary before lower cystathionine, elevated methionine, and decreased cysteine became apparent, a pattern suggestive of CBS deficiency, leading to the finding that the affected members were each compound heterozygotes for CBS p.G307S and p.P49L. To assist more accurate diagnosis of adults presenting with thrombophilia found to have elevated tHcy, the patterns of methionine-related metabolites in CBS-deficient patients are compared in this article to those in patients with homocysteine remethylation defects, including inborn errors of folate or cobalamin metabolism, and untreated severe cobalamin or folate deficiency. Usually serum cystathionine is low in subjects with CBS deficiency and elevated in those with remethylation defects. S-Adenosylmethionine and S-adenosylhomocysteine are often markedly elevated in CBS deficiency when tHcy is above 100 umol/L. We conclude that there are likely other undiagnosed, highly B6-responsive adult patients with CBS deficiency, and that additional testing of cystathionine, total cysteine, methionine, and S-adenosylmethionine will be helpful in diagnosing them correctly and distinguishing CBS deficiency from remethylation defects. C1 [Stabler, Sally P.; Allen, Robert H.] Univ Colorado, Div Hematol, Dept Med, Sch Med, 12700 E 19th Ave,Room 9122,Bldg RC2, Aurora, CO 80045 USA. [Korson, Mark] Tufts Med Ctr, Div Genet & Metab, Dept Pediat, Boston, MA USA. [Jethva, Reena] St Christophers Hosp Children, Dept Pediat, Neurol Sect, Philadelphia, PA 19133 USA. [Kraus, Jan P.; Spector, Elaine B.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA. [Wagner, Conrad] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. [Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Stabler, SP (reprint author), Univ Colorado, Div Hematol, Dept Med, Sch Med, 12700 E 19th Ave,Room 9122,Bldg RC2, Aurora, CO 80045 USA. EM Sally.Stabler@ucdenver.edu NR 49 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 2192-8304 BN 978-3-642-37328-2; 978-3-642-37327-5 J9 JIMD REP PY 2013 VL 11 BP 149 EP 163 DI 10.1007/8904_2013_235 D2 10.1007/978-3-642-37328-2 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity SC Endocrinology & Metabolism; Genetics & Heredity GA BE8TQ UT WOS:000377027800021 PM 23733603 ER PT J AU Cao, VY Ye, YZ Mastwal, SS Lovinger, DM Costa, RM Wang, KH AF Cao, Vania Y. Ye, Yizhou Mastwal, Surjeet S. Lovinger, David M. Costa, Rui M. Wang, Kuan H. TI In Vivo Two-photon Imaging Of Experience-dependent Molecular Changes In Cortical Neurons SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS LA English DT Article DE Neuroscience; Issue 71; Medicine; Anatomy; Neurobiology; Surgery; Cerebral Cortex; Frontal Cortex; Stereotaxic Techniques; Molecular Imaging; Neuronal Plasticity; Neurosciences; In Vivo Imaging; Two-photon Microscopy; Experience-dependent Gene Expression; Arc-GFP Mice; Cranial Window; in situ hybridization; immunohistochemistry; animal model AB The brain's ability to change in response to experience is essential for healthy brain function, and abnormalities in this process contribute to a variety of brain disorders(1,2). To better understand the mechanisms by which brain circuits react to an animal's experience requires the ability to monitor the experience-dependent molecular changes in a given set of neurons, over a prolonged period of time, in the live animal. While experience and associated neural activity is known to trigger gene expression changes in neurons(1,2), most of the methods to detect such changes do not allow repeated observation of the same neurons over multiple days or do not have sufficient resolution to observe individual neurons(3,4). Here, we describe a method that combines in vivo two-photon microscopy with a genetically encoded fluorescent reporter to track experience-dependent gene expression changes in individual cortical neurons over the course of day-to-day experience. One of the well-established experience-dependent genes is Activity-regulated cytoskeletal associated protein (Arc) (5,6). The transcription of Arc is rapidly and highly induced by intensified neuronal activity(3), and its protein product regulates the endocytosis of glutamate receptors and long-term synaptic plasticity(7). The expression of Arc has been widely used as a molecular marker to map neuronal circuits involved in specific behaviors(3). In most of those studies, Arc expression was detected by in situ hybridization or immunohistochemistry in fixed brain sections. Although those methods revealed that the expression of Arc was localized to a subset of excitatory neurons after behavioral experience, how the cellular patterns of Arc expression might change with multiple episodes of repeated or distinctive experiences over days was not investigated. In vivo two-photon microscopy offers a powerful way to examine experience-dependent cellular changes in the living brain(8,9). To enable the examination of Arc expression in live neurons by two-photon microscopy, we previously generated a knock-in mouse line in which a GFP reporter is placed under the control of the endogenous Arc promoter(10). This protocol describes the surgical preparations and imaging procedures for tracking experience-dependent Arc-GFP expression patterns in neuronal ensembles in the live animal. In this method, chronic cranial windows were first implanted in Arc-GFP mice over the cortical regions of interest. Those animals were then repeatedly imaged by two-photon microscopy after desired behavioral paradigms over the course of several days. This method may be generally applicable to animals carrying other fluorescent reporters of experience-dependent molecular changes(4). C1 [Cao, Vania Y.; Ye, Yizhou; Mastwal, Surjeet S.; Wang, Kuan H.] NIMH, Unit Neural Circuits & Adapt Behaviors, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. [Cao, Vania Y.] Brown Univ, Dept Neurosci, Grad Partnership Program, NIH, Providence, RI 02912 USA. RP Wang, KH (reprint author), NIMH, Unit Neural Circuits & Adapt Behaviors, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. EM wkuan@mail.nih.gov RI Wang, Kuan Hong/J-1150-2016 OI Wang, Kuan Hong/0000-0002-2249-5417 FU NIMH Division of Intramural Research Programs; Genes, Cognition and Psychosis Program; NIMH Intramural Research Program; NIAAA Division of Intramural Clinical and Biological Research Program FX The authors would like to thank L. Belluscio for surgery filming equipment, D. Kwon for filming assistance, K. Liu for video editing assistance, and K. MacLeod for all background music. K. W. acknowledges the generous support of the NIMH Division of Intramural Research Programs and the Genes, Cognition and Psychosis Program. This work was supported by the NIMH Intramural Research Program (V.C., Y.Y., S.M. K.W.) and the NIAAA Division of Intramural Clinical and Biological Research Program (V.C., R.M.C., D.M.L.). NR 20 TC 0 Z9 0 U1 1 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 JAN PY 2013 IS 71 AR UNSP e50148 DI 10.3791/50148 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V36QO UT WOS:000209226200040 ER PT B AU Dwyer, J AF Dwyer, Johanna BE Rippe, JM TI Nutrition 101 The Concept of Nutritional Status and Guides for Nutrient Intakes, Eating Patterns, and Nutrition SO LIFESTYLE MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID INDEX C1 [Dwyer, Johanna] Tufts Univ, Off Dietary Supplements, NIH, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Univ, Sch Med, Dept Med & Community Hlth, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Ctr Aging, Boston, MA 02111 USA. [Dwyer, Johanna] Tufts Med Ctr, Frances Stern Nutr Ctr, Boston, MA USA. [Dwyer, Johanna] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Dwyer, J (reprint author), Tufts Univ, Off Dietary Supplements, NIH, Boston, MA 02111 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-4544-8; 978-1-4398-4542-4 PY 2013 BP 103 EP 117 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BF6FT UT WOS:000383033900009 ER PT B AU Starke-Reed, P McDade-Ngutter, C Hubbard, VS AF Starke-Reed, Pamela McDade-Ngutter, Crystal Hubbard, Van S. BE Rippe, JM TI Healthy People 2020 Highlights in the Nutrition and Weight Status Focus Area SO LIFESTYLE MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID SUGAR-SWEETENED BEVERAGES; UNITED-STATES; NEIGHBORHOOD CHARACTERISTICS; IRON-DEFICIENCY; FOOD STORES; CHILD-CARE; OBESITY PREVENTION; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; NUTRIENT INTAKE C1 [Starke-Reed, Pamela; McDade-Ngutter, Crystal; Hubbard, Van S.] NIH, Div Nutr Res Coordinat, Bldg 10, Bethesda, MD 20892 USA. RP Starke-Reed, P (reprint author), NIH, Div Nutr Res Coordinat, Bldg 10, Bethesda, MD 20892 USA. NR 61 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-4544-8; 978-1-4398-4542-4 PY 2013 BP 119 EP 130 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BF6FT UT WOS:000383033900010 ER PT B AU Croft, BY Tsui, BMW AF Croft, Barbara Y. Tsui, Benjamin M. W. BE Analoui, M Bronzino, JD Peterson, DR TI Nuclear Medicine SO MEDICAL IMAGING: PRINCIPLES AND PRACTICES LA English DT Article; Book Chapter ID EMISSION-COMPUTED-TOMOGRAPHY; ALGEBRAIC RECONSTRUCTION TECHNIQUES; ENERGY-WEIGHTED ACQUISITION; SCATTER RESPONSE FUNCTION; CEREBRAL-BLOOD-FLOW; SCINTILLATION-CAMERA; 3-DIMENSIONAL RECONSTRUCTION; IMAGE-RECONSTRUCTION; COMPENSATION TECHNIQUES; DETECTOR RESPONSE C1 [Croft, Barbara Y.] NIH, Bethesda, MD 20892 USA. [Tsui, Benjamin M. W.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD USA. RP Croft, BY (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 90 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7103-4; 978-1-4398-7102-7 PY 2013 PG 31 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BD7FI UT WOS:000362981200008 ER PT B AU Hassan, M Kainerstorfer, J Chernomordik, V Vogel, A Gannot, I Little, RF Yarchoan, R Gandjbakhche, AH AF Hassan, Moinuddin Kainerstorfer, Jana Chernomordik, Victor Vogel, Abby Gannot, Israel Little, Richard F. Yarchoan, Robert Gandjbakhche, Amir H. BE Diakides, M Bronzino, JD Peterson, DR TI Noninvasive Infrared Imaging for Functional Monitoring of Disease Processes SO MEDICAL INFRARED IMAGING: PRINCIPLES AND PRACTICES LA English DT Article; Book Chapter ID TISSUE OPTICAL-PROPERTIES; RESOLVED TRANSILLUMINATION EXPERIMENTS; ENDOTHELIAL GROWTH-FACTOR; ANISOTROPIC RANDOM-WALKS; HIGHLY SCATTERING MEDIA; DOMAIN PHOTON MIGRATION; IN-VIVO FLUORESCENCE; SKIN BLOOD-FLOW; KAPOSIS-SARCOMA; QUANTITATIVE ASSESSMENT C1 [Hassan, Moinuddin] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Kainerstorfer, Jana; Chernomordik, Victor; Little, Richard F.; Yarchoan, Robert; Gandjbakhche, Amir H.] NIH, Bethesda, MD 20892 USA. [Vogel, Abby] Georgia Inst Technol, Atlanta, GA 30332 USA. [Gannot, Israel] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Hassan, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 120 TC 0 Z9 0 U1 0 U2 1 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7250-5; 978-1-4398-7249-9 PY 2013 PG 31 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BC6MS UT WOS:000354125200020 ER PT J AU Abeliovich, H Zarei, M Rigbolt, KT Youle, RJ Dengjel, J AF Abeliovich, H. Zarei, M. Rigbolt, K. T. Youle, R. J. Dengjel, J. TI A role for mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Abeliovich, H.] Hebrew Univ Jerusalem, Biochem & Food Sci, Rehovot, Israel. [Zarei, M.; Rigbolt, K. T.; Dengjel, J.] Univ Freiburg, FRIAS, D-79106 Freiburg, Germany. [Youle, R. J.] NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 198 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705480 ER PT J AU Altan-Bonnet, N Ilnytska, O Santiana, M Chen, YH Hsu, NY Du, WL Belov, G Viktorova, E Moore, C Dixon, J Brinker, A Storch, J AF Altan-Bonnet, N. Ilnytska, O. Santiana, M. Chen, Y-H. Hsu, N-Y. Du, W-L. Belov, G. Viktorova, E. Moore, C. Dixon, J. Brinker, A. Storch, J. TI Endocytic machinery regulates viral replication through remodeling the host cell cholesterol landscape. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Altan-Bonnet, N.; Santiana, M.; Chen, Y-H.; Du, W-L.] NIH, Bethesda, MD 20892 USA. [Altan-Bonnet, N.; Ilnytska, O.; Hsu, N-Y.] Rutgers State Univ, Newark, NJ 07102 USA. [Belov, G.; Viktorova, E.] Univ Maryland, College Pk, MD 20742 USA. [Moore, C.] GlaxoSmithKline, Raleigh, NC USA. [Dixon, J.; Brinker, A.; Storch, J.] Rutgers State Univ, New Brunswick, NJ 08903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 31 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705313 ER PT J AU Anton, OM Tagaya, Y Long, EO AF Anton, O. M. Tagaya, Y. Long, E. O. TI IL-15 trans-presentation is regulated by NK inhibitory receptors and regulates activating response in NK cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Anton, O. M.; Long, E. O.] NIAID, NIH, Rockville, MD USA. [Tagaya, Y.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 828 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701153 ER PT J AU Baibakov, B Burkart, A Dean, J AF Baibakov, B. Burkart, A. Dean, J. TI Sperm bind with taxon-specificity to ZP2 which is cleaved post-fertilization by ovastacin to prevent polyspermy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Baibakov, B.; Burkart, A.; Dean, J.] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 749 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701075 ER PT J AU Bang, JY Jang, M Heo, JH Yoo, TJ Tsuji, PA Carlson, BA Gladyshev, VN Hatfield, DL Lee, BJ AF Bang, J-Y. Jang, M. Heo, J-H. Yoo, T-J. Tsuji, P. A. Carlson, B. A. Gladyshev, V. N. Hatfield, D. L. Lee, B. J. TI Deficiency in the 15-kDa selenoprotein induces membrane blebbing through Rho-dependent ROCK pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Bang, J-Y.; Jang, M.; Heo, J-H.; Yoo, T-J.; Lee, B. J.] Seoul Natl Univ, Seoul, South Korea. [Tsuji, P. A.] Towson Univ, Towson, MD USA. [Carlson, B. A.; Hatfield, D. L.] NIH, Bethesda, MD 20892 USA. [Gladyshev, V. N.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 618 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700361 ER PT J AU Beach, JR Shao, L Betzig, E Hammer, JA AF Beach, J. R. Shao, L. Betzig, E. Hammer, J. A., III TI Non-muscle Myosin II Isoforms Co-polymerize in Living Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Beach, J. R.; Hammer, J. A., III] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Shao, L.; Betzig, E.] HHMI, Ashburn, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 374 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700116 ER PT J AU Billington, N Heissler, S Guzik-Lendrum, S Sellers, J AF Billington, N. Heissler, S. Guzik-Lendrum, S. Sellers, J. TI Interaction of myosin 18A with nonmuscle myosin 2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Billington, N.; Heissler, S.; Guzik-Lendrum, S.; Sellers, J.] NHLBI, NIH, Bethesda, MD 20892 USA. [Guzik-Lendrum, S.] Rensselaer Polytech Inst, Troy, NY USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 373 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700115 ER PT J AU Bor, B Espinoza, S Heimsath, E Schnur, E Van Engelenburg, S Ritter, A Waxse, B Lippincott-Schwartz, J AF Bor, B. Espinoza, S. Heimsath, E. Schnur, E. Van Engelenburg, S. Ritter, A. Waxse, B. Lippincott-Schwartz, J. TI Dissecting the wound healing response pathway in vertebrate and invertebrate cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Bor, B.; Espinoza, S.; Heimsath, E.; Schnur, E.; Van Engelenburg, S.; Ritter, A.; Waxse, B.; Lippincott-Schwartz, J.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Van Engelenburg, S.; Ritter, A.; Waxse, B.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 797 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701122 ER PT J AU Browder, K Lee, SK Kipfell, EA Sandilos-Rega, JK Thomas, G AF Browder, K. Lee, S. K. Kipfell, E. A. Sandilos-Rega, J. K. Thomas, G. TI Protein Phosphatase 2A B" subunit (PR72) binds directly to beta(Heavy)-spectrin and plays a role in cell polarity and endocytosis in Drosophila SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Browder, K.; Thomas, G.] Penn State Univ, University Pk, PA 16802 USA. [Lee, S. K.] NIH, Baltimore, MD USA. [Kipfell, E. A.] Cleveland Clin, Cleveland, OH 44106 USA. [Sandilos-Rega, J. K.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1283 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702187 ER PT J AU Brownlee, C McLamarrah, T Buster, D Nguyen, A Dibble, T Rusan, N Thompson, P Rogers, GC AF Brownlee, C. McLamarrah, T. Buster, D. Nguyen, A. Dibble, T. Rusan, N. Thompson, P. Rogers, G. C. TI Cell cycle-dependent regulation of the centriole protein Ana2/STIL SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Brownlee, C.; McLamarrah, T.; Buster, D.; Nguyen, A.; Dibble, T.; Thompson, P.; Rogers, G. C.] Univ Arizona, Tucson, AZ USA. [Rusan, N.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1704 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703199 ER PT J AU Bruno, RD Boulanger, CA Anderson, L Lydon, J Smith, GH AF Bruno, R. D. Boulanger, C. A. Anderson, L. Lydon, J. Smith, G. H. TI Paracrine rescued lobulogenesis in PR null mammary outgrowths by redirected testicular cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Bruno, R. D.; Boulanger, C. A.; Anderson, L.; Smith, G. H.] NCI, CCR, NIH, Bethesda, MD 20892 USA. [Lydon, J.] Baylor Coll Med, Cell Biol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1441 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702345 ER PT J AU Burman, B Burgess, R Zhang, Z Lieb, J Misteli, T AF Burman, B. Burgess, R. Zhang, Z. Lieb, J. Misteli, T. TI Epigenetics of Chromosomal Breakage Sites and Translocations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Burman, B.; Burgess, R.; Misteli, T.] NCI, NIH, Bethesda, MD 20892 USA. [Burman, B.] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. [Zhang, Z.; Lieb, J.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 110 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705392 ER PT J AU Burman, B Burgess, R Zhang, Z Lieb, J Misteli, T AF Burman, B. Burgess, R. Zhang, Z. Lieb, J. Misteli, T. TI Epigenetics of Chromosomal Breakage Sites and Translocations SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Burman, B.; Burgess, R.; Misteli, T.] NCI, NIH, Bethesda, MD 20892 USA. [Burman, B.] Tufts Univ, Sackler Sch Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. [Zhang, Z.; Lieb, J.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2544 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705254 ER PT J AU Burnette, DT Sengupta, P Lippincott-Schwartz, J AF Burnette, D. T. Sengupta, P. Lippincott-Schwartz, J. TI Mitosis and Meiosis ePoster Talks SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Burnette, D. T.; Sengupta, P.; Lippincott-Schwartz, J.] NICHD, CMBP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 156 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705438 ER PT J AU Burnette, DT Sengupta, P Lippincott-Schwartz, J AF Burnette, D. T. Sengupta, P. Lippincott-Schwartz, J. TI High resolution imaging of Golgi protein trafficking through the ER during mitosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Burnette, D. T.; Sengupta, P.; Lippincott-Schwartz, J.] NICHD, CMBP, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 822 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701147 ER PT J AU Byrd, AS O'Brien, XM Johnson, CM Zarember, KA Sampaio, EP Holland, SM Reichner, JS AF Byrd, A. S. O'Brien, X. M. Johnson, C. M. Zarember, K. A. Sampaio, E. P. Holland, S. M. Reichner, J. S. TI Characterization of NETosis in patients with primary immunodeficiencies: evidence for a ROS-independent pathway SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Byrd, A. S.; O'Brien, X. M.; Johnson, C. M.; Reichner, J. S.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Surg Res,Dept Surg,Grad Program Pathobiol, Providence, RI 02903 USA. [Zarember, K. A.] NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. [Sampaio, E. P.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2158 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704264 ER PT J AU Caceres, M Park, KS Romero, A Recabarren, T Almarza, O Leiva-Salcedo, E Trimmer, JS Cerda, O AF Caceres, M. Park, K-S. Romero, A. Recabarren, T. Almarza, O. Leiva-Salcedo, E. Trimmer, J. S. Cerda, O. TI The Ca2+ activated non-selective cationic channel TRPM4 enhances cellular migration and contractility by modulating the focal adhesions dynamics SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Caceres, M.; Romero, A.; Recabarren, T.; Almarza, O.; Cerda, O.] Univ Chile, Fac Med, Programa Biol Celular & Mol, ICBM, Santiago 7, Chile. [Park, K-S.] Kyung Hee Univ, Dept Physiol, Sch Med, Seoul, South Korea. [Leiva-Salcedo, E.] NICHD, Sect Cellular Signaling, Program Dev Biol, NIH, Bethesda, MD USA. [Cerda, O.] Univ Calif Davis, Dept Neurobiol Physiol & Behav, Davis, CA 95616 USA. [Cerda, O.] Univ Calif Davis, Dept Membrane Biol, Coll Biol Sci, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 679 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701005 ER PT J AU Case, LB Shtengel, G Baird, MA Davidson, M Campbell, SL Hess, H Waterman, CM AF Case, L. B. Shtengel, G. Baird, M. A. Davidson, M. Campbell, S. L. Hess, H. Waterman, C. M. TI Two distinct populations of vinculin molecules interact with paxillin and talin at focal adhesions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Case, L. B.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Case, L. B.; Campbell, S. L.] Univ N Carolina, Chapel Hill, NC USA. [Shtengel, G.; Hess, H.] HHMI, Janelia Farm, Ashburn, VA USA. [Baird, M. A.; Davidson, M.] Florida State Univ, Magnet Lab, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 43 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705325 ER PT J AU Case, LB Shtengel, G Baird, MA Davidson, M Campbell, SL Hess, H Waterman, CM AF Case, L. B. Shtengel, G. Baird, M. A. Davidson, M. Campbell, S. L. Hess, H. Waterman, C. M. TI Two distinct populations of vinculin molecules interact with paxillin and talin at focal adhesions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Case, L. B.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Case, L. B.; Campbell, S. L.] Univ N Carolina, Chapel Hill, NC USA. [Shtengel, G.; Hess, H.] HHMI, Janelia Farm, Ashburn, VA USA. [Baird, M. A.; Davidson, M.] Florida State Univ, Magnet Lab, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 662 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700405 ER PT J AU Chen, AK Sengupta, P Waki, K Van Engelenburg, SB Ochiya, T Ablan, SD Freed, EO Lippincott-Schwartz, J AF Chen, A. K. Sengupta, P. Waki, K. Van Engelenburg, S. B. Ochiya, T. Ablan, S. D. Freed, E. O. Lippincott-Schwartz, J. TI MicroRNA binding to the HIV-1 Gag protein inhibits virus production through an RNA interference (RNAi)-independent mechanism SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chen, A. K.] Peking Univ, Biomed Engn, Beijing 100871, Peoples R China. [Chen, A. K.; Sengupta, P.; Van Engelenburg, S. B.; Lippincott-Schwartz, J.] NICHD, NIH, Bethesda, MD USA. [Waki, K.; Ablan, S. D.; Freed, E. O.] NCI, NIH, Frederick, MD 21701 USA. [Ochiya, T.] NCCRI, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2268 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704374 ER PT J AU Chen, J Liu, J AF Chen, J. Liu, J. TI Spatial-Temporal Regulation of the Mitotic Spindle Assembly Checkpoint SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chen, J.; Liu, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1746 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703241 ER PT J AU Chen, Y Lippincott-Schwartz, J AF Chen, Y. Lippincott-Schwartz, J. TI Insulin responsiveness of endosomal GLUT4 vesicles revealed by a novel GLUT4 probe SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chen, Y.; Lippincott-Schwartz, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 454 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700196 ER PT J AU Chen, YH Wimmer, E Paul, AV David, A Yewdell, JW Altan-Bonnet, N AF Chen, Y-H. Wimmer, E. Paul, A. V. David, A. Yewdell, J. W. Altan-Bonnet, N. TI Spatio-temporal dynamics of enteroviral RNA translation, synthesis and encapsidation revealed by super-resolution imaging. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Chen, Y-H.; Altan-Bonnet, N.] NHLBI, NIH, Bethesda, MD 20892 USA. [Chen, Y-H.] Rutgers State Univ, Newark, NJ 07102 USA. [Wimmer, E.; Paul, A. V.] SUNY Stony Brook, Stony Brook, NY 11794 USA. [David, A.; Yewdell, J. W.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1528 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703023 ER PT J AU Christensen, EA Marlarl, S Pedersen, GA Koffman, JS Nejsum, LN AF Christensen, E. A. Marlarl, S. Pedersen, G. A. Koffman, J. S. Nejsum, L. N. TI Measuring diffusion coefficients of aquaporin-2 and aquaporin-3 proteins in lateral versus basal membranes using functionalized substrates and kICS analysis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Christensen, E. A.; Marlarl, S.; Pedersen, G. A.; Koffman, J. S.; Nejsum, L. N.] Aarhus Univ, Aarhus, Denmark. [Christensen, E. A.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 838 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701163 ER PT J AU Cinghu, S Yellaboina, S Freudenberg, JM Ghosh, S Zheng, X Oldfield, AJ Lackford, BL Zaykin, DV Hu, G Jothi, R AF Cinghu, S. Yellaboina, S. Freudenberg, J. M. Ghosh, S. Zheng, X. Oldfield, A. J. Lackford, B. L. Zaykin, D. V. Hu, G. Jothi, R. TI Nucleolin maintains embryonic stem cell homeostasis by shielding against differentiation-inducing redox-imbalance induced oxidative stress SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Cinghu, S.; Yellaboina, S.; Freudenberg, J. M.; Ghosh, S.; Zheng, X.; Oldfield, A. J.; Lackford, B. L.; Zaykin, D. V.; Hu, G.; Jothi, R.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI Hu, Guang/E-7474-2016 OI Hu, Guang/0000-0003-0437-4723 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 706 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701032 ER PT J AU Cohen, S Rambold, AS Lipppincott-Schwartz, J AF Cohen, S. Rambold, A. S. Lipppincott-Schwartz, J. TI Cells respond to starvation by increased flux of lipids through lipid droplets SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Cohen, S.; Rambold, A. S.; Lipppincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2352 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705062 ER PT J AU Cole, NB Karabasheva, D Donaldson, JG AF Cole, N. B. Karabasheva, D. Donaldson, J. G. TI Endocytic trafficking and turnover of plasma membrane proteins using the SNAP-tag labeling system SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Cole, N. B.; Karabasheva, D.; Donaldson, J. G.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702179 ER PT J AU Crawley, SW Shifrin, DA Larson, NEG McConnell, RE Benesh, AE Mao, S Zheng, Q Millis, BA Kachar, B Tyska, MJ AF Crawley, S. W. Shifrin, D. A. Larson, N. E. Grega McConnell, R. E. Benesh, A. E. Mao, S. Zheng, Q. Millis, B. A. Kachar, B. Tyska, M. J. TI Protocadherins form Ca2+-dependent intermicrovillar adhesion links that are required for brush border assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Crawley, S. W.; Shifrin, D. A.; Larson, N. E. Grega; McConnell, R. E.; Benesh, A. E.; Mao, S.; Tyska, M. J.] Vanderbilt Univ, Med Ctr, Cell & Dev Biol, Nashville, TN 37235 USA. [Zheng, Q.] Case Western Reserve Univ, Dept Otolaryngol Head & Neck Surg, Cleveland, OH 44106 USA. [Millis, B. A.; Kachar, B.] NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 39 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705321 ER PT J AU Crawley, SW Shifrin, DA Larson, NEG McConnell, RE Benesh, AE Mao, S Zheng, Q Millis, BA Kachar, B Tyska, MJ AF Crawley, S. W. Shifrin, D. A. Larson, N. E. Grega McConnell, R. E. Benesh, A. E. Mao, S. Zheng, Q. Millis, B. A. Kachar, B. Tyska, M. J. TI Protocadherins form Ca2+-dependent intermicrovillar adhesion links that are required for brush border assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Crawley, S. W.; Shifrin, D. A.; Larson, N. E. Grega; McConnell, R. E.; Benesh, A. E.; Mao, S.; Tyska, M. J.] Vanderbilt Univ, Med Ctr, Cell & Dev Biol, Nashville, TN USA. [Zheng, Q.] Case Western Reserve Univ, Dept Otolaryngol Head & Neck Surg, Cleveland, OH 44106 USA. [Millis, B. A.; Kachar, B.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2184 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704290 ER PT J AU Cruse, G Music, S Bradding, P Gilfillan, AM Metcalfe, DD AF Cruse, G. Music, S. Bradding, P. Gilfillan, A. M. Metcalfe, D. D. TI MS4A4 is a Rab-interacting endosomal membrane protein that regulates receptor trafficking and function SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Cruse, G.; Music, S.; Gilfillan, A. M.; Metcalfe, D. D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. [Bradding, P.] Univ Leicester, Dept Infect Immun & Inflammat, Leicester, Leics, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2034 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704140 ER PT J AU Dennis, MK Mantegazza, AR Setty, SG Saldana, RAL Delevoye, C Sviderskaya, EV Bennett, DC Raposo, G Marks, MS AF Dennis, M. K. Mantegazza, A. R. Setty, S. G. Saldana, R. A. Linares Delevoye, C. Sviderskaya, E. V. Bennett, D. C. Raposo, G. Marks, M. S. TI SNARE dynamics during melanosome biogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Dennis, M. K.; Mantegazza, A. R.; Marks, M. S.] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA. [Setty, S. G.] Indian Inst Sci, Microbiol & Cell Biol, Bangalore 560012, Karnataka, India. [Saldana, R. A. Linares] NHGRI, NIH, Bethesda, MD 20892 USA. [Delevoye, C.; Raposo, G.] Inst Curie, Ctr Rech, Paris, France. [Delevoye, C.; Raposo, G.] Ctr Natl Rech Sci, Struct & Membrane Compartments, Paris, France. [Sviderskaya, E. V.; Bennett, D. C.] St Georges Univ London, Div Basic Med Sci, Ctr Mol & Metab Signalling, London, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 816 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701141 ER PT J AU Desai, R Zhang, C Yamada, K Karuri, NW AF Desai, R. Zhang, C. Yamada, K. Karuri, N. W. TI The effect of fibronectin PEGylation site on proteolytic stability, cell adhesion and cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Desai, R.; Zhang, C.; Karuri, N. W.] IIT, Chem & Biol Engn, Chicago, IL 60616 USA. [Yamada, K.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2168 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704274 ER PT J AU Dobrinskikh, E Okamura, K Kopp, JB Doctor, B Blaine, J AF Dobrinskikh, E. Okamura, K. Kopp, J. B. Doctor, B. Blaine, J. TI Human podocytes perform polarized, caveolae-dependent albumin endocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Dobrinskikh, E.; Okamura, K.; Doctor, B.; Blaine, J.] Univ Colorado Denver, Aurora, CO USA. [Kopp, J. B.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1993 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704100 ER PT J AU Doyle, AD Matsumoto, K Yamada, KM AF Doyle, A. D. Matsumoto, K. Yamada, K. M. TI Matrix-dependent regulation of cellular mechanotransduction in 3D microenvironments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Doyle, A. D.; Matsumoto, K.; Yamada, K. M.] NIDCR, Lab Cel & Dev Biol, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 151 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705433 ER PT J AU Doyle, AD Matsumoto, K Yamada, KM AF Doyle, A. D. Matsumoto, K. Yamada, K. M. TI Matrix-dependent regulation of cellular mechanotransduction in 3D microenvironments SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Doyle, A. D.; Matsumoto, K.; Yamada, K. M.] NIDCR, Lab Cel & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 661 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700404 ER PT J AU Ebrahim, S Millis, B Ma, X Kawamoto, S Adelstein, R Kachar, B AF Ebrahim, S. Millis, B. Ma, X. Kawamoto, S. Adelstein, R. Kachar, B. TI NMII sarcomeric network regulates epithelial apical junctions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ebrahim, S.; Millis, B.; Kachar, B.] NIDCD, NIH, Bethesda, MD USA. [Ma, X.; Kawamoto, S.; Adelstein, R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1311 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702215 ER PT J AU Elia, N Fabrikant, G Kozlov, M Lippincott-Schwartz, J AF Elia, N. Fabrikant, G. Kozlov, M. Lippincott-Schwartz, J. TI Mechanistic model for ESCRT-mediated membrane constriction and scission in animal cytokinesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Elia, N.] Ben Gurion Univ Negev, Life Sci, IL-84105 Beer Sheva, Israel. [Fabrikant, G.; Kozlov, M.] Tel Aviv Univ, IL-69978 Tel Aviv, Israel. [Lippincott-Schwartz, J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2496 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705206 ER PT J AU Ezan, J Lasvaux, L Gezer, A Novakovic, A May-Simera, H Belotti, E Lhoumeau, AC Birnbaumer, L Beer-Hammer, S Borg, JP Lebivic, A Nurnberg, B Sans, NA Montcouquiol, M AF Ezan, J. Lasvaux, L. Gezer, A. Novakovic, A. May-Simera, H. Belotti, E. Lhoumeau, A-C. Birnbaumer, L. Beer-hammer, S. Borg, J-P. Lebivic, A. Nurnberg, B. Sans, N. A. Montcouquiol, M. TI Primary Cilium Migration Depends on G-protein Signaling Control of Subapical Cytoskeleton SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ezan, J.; Lasvaux, L.; Gezer, A.; Sans, N. A.; Montcouquiol, M.] INSERM, Planar Polar & Plast Grp, U862, Bordeaux, France. [Novakovic, A.; Beer-hammer, S.; Nurnberg, B.] Univ Tubingen, Tubingen, Germany. [May-Simera, H.] NEI, NIH, Bethesda, MD 20892 USA. [Belotti, E.; Lhoumeau, A-C.; Borg, J-P.] CNRS, INSERM, Umr7258, U1068, Marseille, France. [Birnbaumer, L.] NIEHS, NIH, Bethesda, MD USA. [Lebivic, A.] CNRS, Umr7288, Marseille, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1196 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702100 ER PT J AU Fischer, RS Elliott, H Myers, K Chen, C Adelstein, R Waterman, C Danuser, G AF Fischer, R. S. Elliott, H. Myers, K. Chen, C. Adelstein, R. Waterman, C. Danuser, G. TI Myosin II mediates cellular branching, morphogenesis, and migration in 3D by controlling membrane curvature SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Fischer, R. S.; Waterman, C.] NHLBI, LCCB, NIH, Bethesda, MD 20892 USA. [Elliott, H.; Danuser, G.] Harvard Univ, Sch Med, Cell Biol, Boston, MA USA. [Myers, K.] Univ Sci, Philadelphia, PA USA. [Chen, C.] Univ Penn, Bioengn, Philadelphia, PA 19104 USA. [Adelstein, R.] NHLBI, Mol Cardiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1316 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702220 ER PT J AU Fredriksson, K Van Itallie, CM Aponte, A Anderson, JM AF Fredriksson, K. Van Itallie, C. M. Aponte, A. Anderson, J. M. TI Proteomic analysis of proteins surrounding Claudin-4 and Occludin SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Fredriksson, K.; Van Itallie, C. M.; Aponte, A.; Anderson, J. M.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1410 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702314 ER PT J AU Golden, A Fabritius, A Fuchsman, A Shrestha, S AF Golden, A. Fabritius, A. Fuchsman, A. Shrestha, S. TI Strategies for studying disease genes in C-elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Golden, A.; Fabritius, A.; Fuchsman, A.; Shrestha, S.] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2322 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705032 ER PT J AU Harunaga, JS Doyle, AD Conti, M Adelstein, RS Yamada, KM AF Harunaga, J. S. Doyle, A. D. Conti, M. Adelstein, R. S. Yamada, K. M. TI Rapid Expansion of Embryonic Epithelia Requires Extensive Basement Membrane Perforation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Harunaga, J. S.; Doyle, A. D.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Conti, M.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1424 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702328 ER PT J AU Hasegawa, K Ryu, SJ Cekan, P Tubman, E Odde, D Kalab, P AF Hasegawa, K. Ryu, S. J. Cekan, P. Tubman, E. Odde, D. Kalab, P. TI Analysis of chromosome gain-driven activation of mitotic RanGTP gradient SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Hasegawa, K.; Ryu, S. J.; Cekan, P.; Kalab, P.] NCI, Lab Cellular & Mol Biol, NIH, Bethesda, MD 20892 USA. [Hasegawa, K.; Tubman, E.; Odde, D.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA. [Tubman, E.; Odde, D.] Univ Minnesota, Dept Biomed Engn, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 943 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701267 ER PT J AU Heissler, SM Billington, N Sellers, JR AF Heissler, S. M. Billington, N. Sellers, J. R. TI Myosin-3B and its Light Chains SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Heissler, S. M.; Billington, N.; Sellers, J. R.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1161 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702065 ER PT J AU Hong, AST Sellers, JR AF Hong, A. S-T. Sellers, J. R. TI Drosophila Myosin7a in phagocytosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Hong, A. S-T.; Sellers, J. R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1169 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702073 ER PT J AU Huang, S Wang, C Frankowski, K Patnaik, S Schoenen, F Titus, S Ferrer, M Zheng, W Southall, N Wen, Y Aube, J Marugan, J AF Huang, S. Wang, C. Frankowski, K. Patnaik, S. Schoenen, F. Titus, S. Ferrer, M. Zheng, W. Southall, N. Wen, Y. Aube, J. Marugan, J. TI PNCs associate with structure and function of the nucleolus and Pol III SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Huang, S.; Wang, C.; Wen, Y.] Northwestern Univ, Feinberg Sch Med, Cell & Mol Biol, Chicago, IL 60611 USA. [Frankowski, K.; Schoenen, F.; Aube, J.] Univ Kansas, Specialized Chem Ctr, Lawrence, KS 66045 USA. [Patnaik, S.; Titus, S.; Ferrer, M.; Zheng, W.; Southall, N.; Marugan, J.] NIH, NIH Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 246 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705528 ER PT J AU Iyer, J Peel, N O'Rourke, S Bowerman, B O'Connell, K AF Iyer, J. Peel, N. O'Rourke, S. Bowerman, B. O'Connell, K. TI CSTL-2 is required for centrosome duplication in C. elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Iyer, J.; O'Connell, K.] NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. [Peel, N.] Coll New Jersey, Dept Biol, Ewing, NJ USA. [O'Rourke, S.; Bowerman, B.] Univ Oregon, Inst Mol Biol, Eugene, OR 97403 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 992 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701316 ER PT J AU Jang, SI Ong, HL Alevizos, I Ambudkar, IS AF Jang, S-I. Ong, H-L. Alevizos, I. Ambudkar, I. S. TI Regulation of AQP5 Expression by Calcium-Calcineurin-NFAT Signaling Pathway in Primary Salivary Gland Acinar Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Jang, S-I.; Ong, H-L.; Alevizos, I.; Ambudkar, I. S.] NIDCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1370 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702274 ER PT J AU Jaramillo-Lambert, A Golden, A AF Jaramillo-Lambert, A. Golden, A. TI Identification and characterization of paternal-effect embryonic lethal mutants in C. elegans SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Jaramillo-Lambert, A.; Golden, A.] NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 754 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701080 ER PT J AU Johnson, D Wilson, J Donaldson, J AF Johnson, D. Wilson, J. Donaldson, J. TI Characterization of Endocytosis in T cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Johnson, D.; Donaldson, J.] NHLBI, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [Johnson, D.; Wilson, J.] Univ Arizona, Cellular & Mol Med, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1267 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702171 ER PT J AU Joo, E Yamada, KM AF Joo, E. Yamada, K. M. TI Myosin phosphatase regulates actomyosin contractility and microtubule acetylation to modulate integrin adhesions and matrix assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Joo, E.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 568 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700311 ER PT J AU Kee, AJ Tran, L Yang, L Genel, F Weigert, R Gunning, P Hardeman, E AF Kee, A. J. Tran, L. Yang, L. Genel, F. Weigert, R. Gunning, P. Hardeman, E. TI Identification of a novel Golgi-associated actin filament population that is important for maintaining Golgi morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kee, A. J.; Tran, L.; Yang, L.; Genel, F.; Hardeman, E.] Univ New S Wales, Sch Med Sci, Neuromuscular & Regenerat Med Unit, Sydney, NSW, Australia. [Weigert, R.] Natl Inst Dent & Craniofacial Res, Intracellular Membrane Trafficking Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. [Gunning, P.] Univ New S Wales, Sch Med Sci, Oncol Res Unit, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1119 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702023 ER PT J AU Khalaj, M Abbasi, A Yamanishi, H Akiyama, K Kikuchi, S Hirose, M Yuzuriha, M Magari, M Degheidy, H Abe, K Ogura, A Hashimoto, H Kunieda, T AF Khalaj, M. Abbasi, A. Yamanishi, H. Akiyama, K. Kikuchi, S. Hirose, M. Yuzuriha, M. Magari, M. Degheidy, H. Abe, K. Ogura, A. Hashimoto, H. Kunieda, T. TI A missense mutation in Rev7 disrupts formation of Pol zeta and impairs mouse development and replication dependent ICL DNA repair SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Khalaj, M.; Abbasi, A.] NIH, Bethesda, MD 20892 USA. [Khalaj, M.; Abbasi, A.; Yamanishi, H.; Akiyama, K.; Magari, M.; Kunieda, T.] Okayama Univ, Okayama, Japan. [Kikuchi, S.; Hashimoto, H.] Yokohama City Univ, Yokohama, Kanagawa 232, Japan. [Hirose, M.; Yuzuriha, M.; Abe, K.; Ogura, A.] Riken Bioresource Ctr, Tsukuba, Ibaraki, Japan. [Degheidy, H.] FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 987 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701311 ER PT J AU Kim, J Li, S Ren, Y Kee, YS Zhang, G Robinson, D Chen, EH AF Kim, J. Li, S. Ren, Y. Kee, Y-S. Zhang, G. Robinson, D. Chen, E. H. TI Podosome invasion triggers Myosin II-mediated mechanosensory response and cortical resistance in cell-cell fusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kim, J.; Li, S.; Chen, E. H.] Johns Hopkins Univ, Sch Med, Mol Biol & Genet, Baltimore, MD USA. [Ren, Y.; Kee, Y-S.; Robinson, D.] Johns Hopkins Univ, Sch Med, Cell Biol, Baltimore, MD USA. [Zhang, G.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 38 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705320 ER PT J AU Kim, TS Park, JE Shukla, A Rhee, K Loncarek, J Erikson, RL Lee, KS AF Kim, T-S. Park, J-E. Shukla, A. Rhee, K. Loncarek, J. Erikson, R. L. Lee, K. S. TI Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kim, T-S.; Park, J-E.; Lee, K. S.] NCI, Bethesda, MD 20892 USA. [Shukla, A.; Loncarek, J.] NCI, Frederick, MD 21701 USA. [Rhee, K.] Seoul Natl Univ, Seoul, South Korea. [Erikson, R. L.] Harvard Univ, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1688 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703183 ER PT J AU Kong, D Farmer, V Loncarek, J AF Kong, D. Farmer, V. Loncarek, J. TI Plk1 promotes disengagement and reduplication of structurally immature procentrioles SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kong, D.; Farmer, V.; Loncarek, J.] NCI, Frederick, MD 21701 USA. RI Kong, Dong/O-4465-2016 OI Kong, Dong/0000-0002-7144-3808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1699 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703194 ER PT J AU Kruhlak, MJ Khurana, S Nyswaner, K Oberdoerffer, P AF Kruhlak, M. J. Khurana, S. Nyswaner, K. Oberdoerffer, P. TI DNA break-induced chromatin condensation promotes BRCA1 repair factor choice through a novel repressive chromatin module. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kruhlak, M. J.; Khurana, S.; Oberdoerffer, P.] NIH, Bethesda, MD 20892 USA. [Nyswaner, K.] Frederick Natl Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2434 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705144 ER PT J AU Kutys, ML Yamada, KM AF Kutys, M. L. Yamada, K. M. TI A novel matrix-specific mechanism of active RhoA suppression is required for 3D collagen migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kutys, M. L.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 140 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705422 ER PT J AU Kutys, ML Yamada, KM AF Kutys, M. L. Yamada, K. M. TI A novel matrix-specific mechanism of active RhoA suppression is required for 3D collagen migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Kutys, M. L.; Yamada, K. M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1375 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702279 ER PT J AU Larson, CL Beare, P Howe, D Heinzen, RA AF Larson, C. L. Beare, P. Howe, D. Heinzen, R. A. TI A Coxiella burnetii effector protein subverts clathrin-mediated vesicular trafficking for pathogen vacuole biogenesis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Larson, C. L.; Beare, P.; Howe, D.; Heinzen, R. A.] NIAID, Rocky Mt Lab, Lab Intracellular Parasites, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 34 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705316 ER PT J AU Lerit, DA Poulton, JS Peifer, M Rusan, NM AF Lerit, D. A. Poulton, J. S. Peifer, M. Rusan, N. M. TI Novel Pericentrin structures orchestrate the PCM in rapidly dividing embryos SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lerit, D. A.; Rusan, N. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Poulton, J. S.; Peifer, M.] Univ N Carolina, Dept Biol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 994 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701318 ER PT J AU Lu, Q Insinna, C Rahajeng, J Caplan, S Jackson, PK Westlake, CJ AF Lu, Q. Insinna, C. Rahajeng, J. Caplan, S. Jackson, P. K. Westlake, C. J. TI Primary cilium assembly initiation regulation by Rab and EHD proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lu, Q.; Insinna, C.; Westlake, C. J.] NCI, Lab Cell & Dev Signaling, NIH, Frederick, MD 21701 USA. [Rahajeng, J.; Caplan, S.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68182 USA. [Rahajeng, J.; Caplan, S.] Univ Nebraska Med Ctr, Eppley Canc Ctr, Omaha, NE 68182 USA. [Jackson, P. K.] Stanford Univ, Stanford, CA 94305 USA. RI Lu, Quanlong/M-4436-2015 OI Lu, Quanlong/0000-0002-4261-5121 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 96 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705378 ER PT J AU Lu, Q Insinna, C Rahajeng, J Caplan, S Jackson, PK Westlake, CJ AF Lu, Q. Insinna, C. Rahajeng, J. Caplan, S. Jackson, P. K. Westlake, C. J. TI Primary cilium assembly initiation regulation by Rab and EHD proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Lu, Q.; Insinna, C.; Westlake, C. J.] NCI, Lab Cell & Dev Signaling, NIH, Frederick, MD 21701 USA. [Rahajeng, J.; Caplan, S.] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Omaha, NE USA. [Rahajeng, J.; Caplan, S.] Univ Nebraska Med Ctr, Eppley Canc Ctr, Omaha, NE USA. [Jackson, P. K.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 419 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700161 ER PT J AU Ma, X Adelstein, RS AF Ma, X. Adelstein, R. S. TI A Point Mutation in Myh10 Causes Major Defects in Heart Development and Body Wall Closure SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Ma, X.; Adelstein, R. S.] NHLBI, LMC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 371 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700113 ER PT J AU Madsen, DH Leonard, D Masedunskas, A Moyer, A Jurgensen, HJ Peters, DE Amornphimoltham, P Selvaraj, A Yamada, SS Brenner, DA Burgdorf, S Engelholm, LH Behrendt, N Holmbeck, K Weigert, R Bugge, TH AF Madsen, D. H. Leonard, D. Masedunskas, A. Moyer, A. Jurgensen, H. J. Peters, D. E. Amornphimoltham, P. Selvaraj, A. Yamada, S. S. Brenner, D. A. Burgdorf, S. Engelholm, L. H. Behrendt, N. Holmbeck, K. Weigert, R. Bugge, T. H. TI A novel M2-like macrophage mediated intracellular collagen degradation pathway identified by intravital imaging SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Madsen, D. H.; Leonard, D.; Masedunskas, A.; Moyer, A.; Jurgensen, H. J.; Peters, D. E.; Amornphimoltham, P.; Selvaraj, A.; Yamada, S. S.; Holmbeck, K.; Weigert, R.; Bugge, T. H.] NIDCR, NIH, Bethesda, MD USA. [Jurgensen, H. J.; Engelholm, L. H.; Behrendt, N.] Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. [Brenner, D. A.] UCSD, Dept Med, La Jolla, CA USA. [Burgdorf, S.] Univ Bonn, Life & Med Sci Inst, Bonn, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 208 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705490 ER PT J AU Maldonado-Baez, L Cole, NB Johnson, D Donaldson, JG AF Maldonado-Baez, L. Cole, N. B. Johnson, D. Donaldson, J. G. TI Cellular factors mediating endosomal sorting of Clathrin-independent endocytic cargo proteins SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Maldonado-Baez, L.; Cole, N. B.; Johnson, D.; Donaldson, J. G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA. [Johnson, D.] Univ Arizona, Cellular & Mol Med, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2033 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704139 ER PT J AU Malide, D Metais, JY Dunbar, CE AF Malide, D. Metais, J-Y. Dunbar, C. E. TI Dynamic clonal analysis of murine hematopoietic stem and progenitor cells marked by 5 fluorescent proteins using confocal and multiphoton microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Malide, D.] NHLBI, Light Microscopy Core Facil, NIH, Bethesda, MD 20892 USA. [Metais, J-Y.; Dunbar, C. E.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 204 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705486 ER PT J AU Manor, U Bartholomew, S Higgs, H Spudich, J Lippincott-Schwartz, J AF Manor, U. Bartholomew, S. Higgs, H. Spudich, J. Lippincott-Schwartz, J. TI A novel splice isoform of the actin-regulatory protein Spire1 regulates mitochondria morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Manor, U.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Bethesda, MD USA. [Bartholomew, S.; Spudich, J.] Stanford Univ, Sch Med, Dept Biochem, Palo Alto, CA 94304 USA. [Higgs, H.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 59 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705341 ER PT J AU Manor, U Bartholomew, S Higgs, H Spudich, J Lippincott-Schwartz, J AF Manor, U. Bartholomew, S. Higgs, H. Spudich, J. Lippincott-Schwartz, J. TI A novel splice isoform of the actin-regulatory protein Spire1 regulates mitochondria morphology SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Manor, U.; Lippincott-Schwartz, J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Organelle Biol, Bethesda, MD USA. [Bartholomew, S.; Spudich, J.] Stanford Univ, Sch Med, Dept Biochem, Palo Alto, CA 94304 USA. [Higgs, H.] Geisel Sch Med Dartmouth, Dept Biochem, Hanover, NH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1572 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703067 ER PT J AU Manoussaki, D Shin, W Waterman, CM Chadwick, RS AF Manoussaki, D. Shin, W. Waterman, C. M. Chadwick, R. S. TI Determination of Membrane Tension and F-Actin Polymerization Width at a Protrusive Edge of a Lamellipod by AFM SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Manoussaki, D.] Tech Univ Crete, Hania, Greece. [Shin, W.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. [Chadwick, R. S.] NIDCD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1317 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702221 ER PT J AU Markowitz, MA Adelstein, RS AF Markowitz, M. A. Adelstein, R. S. TI How Much Information Is Too Much Information? The Challenges Associated with Sharing Results from Whole-Exomic and Whole-Genomic Sequencing with Research Subjects SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Markowitz, M. A.; Adelstein, R. S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1817 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703312 ER PT J AU Martina, JA Diab, H Li, L Lim, JA Patange, S Raben, N Puertollano, R AF Martina, J. A. Diab, H. Li, L. Lim, J-A. Patange, S. Raben, N. Puertollano, R. TI TFE3 is activated in response to nutrient deprivation and regulates autophagy, lysosomal biogenesis, and cellular clearance SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Martina, J. A.; Diab, H.; Patange, S.; Puertollano, R.] NHLBI, Lab Cell Biol, CBPC, NIH, Bethesda, MD 20892 USA. [Li, L.; Lim, J-A.; Raben, N.] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 64 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705346 ER PT J AU Mukherjee, K Wu, D Sackett, DL Bane, SL AF Mukherjee, K. Wu, D. Sackett, D. L. Bane, S. L. TI Tyrosine Hydrazide is a Substrate for Tubulin Tyrosine Ligase and a Suitable Vehicle for Fluorescent Labeling of Microtubules in Live Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Mukherjee, K.; Wu, D.; Bane, S. L.] SUNY Binghamton, Binghamton, NY USA. [Sackett, D. L.] NICHHD, NIH, Bethesda, MD 20892 USA. RI Bane, Susan/C-1414-2013 OI Bane, Susan/0000-0002-4270-6314 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1972 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704079 ER PT J AU Murugesan, S Yi, J Shao, L Betzig, E Wu, X Hammer, JA AF Murugesan, S. Yi, J. Shao, L. Betzig, E. Wu, X. Hammer, J. A. TI Investigating the mechanism of actin arc formation in the Jurkat T cell SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Murugesan, S.; Yi, J.; Wu, X.; Hammer, J. A.] NIH, Bethesda, MD 20892 USA. [Shao, L.; Betzig, E.] HHMI, Janelia Farm Res Campus, Ashburn, VA USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1104 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702008 ER PT J AU O'Brien, J Li, H Kothmann, WW AF O'Brien, J. Li, H. Kothmann, W. W. TI Molecular Design Principles of Electrical Synaptic Plasticity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [O'Brien, J.; Li, H.] Univ Texas Hlth Sci Ctr Houston, Ophthalmol & Visual Sci, Houston, TX 77030 USA. [O'Brien, J.] Univ Texas Houston, Grad Sch Biomed Sci, Houston, TX USA. [Kothmann, W. W.] NINDS, Synapt Physiol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1873 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703368 ER PT J AU Pasapera-Limon, AM Plotnikov, SV Fischer, RS Case, LB Egelhoff, T Waterman, CM AF Pasapera-Limon, A. M. Plotnikov, S. V. Fischer, R. S. Case, L. B. Egelhoff, T. Waterman, C. M. TI Rac1 and Integrin activation induce myosin IIA heavy chain phosphorylation to regulate association with focal adhesions and cell migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Pasapera-Limon, A. M.; Plotnikov, S. V.; Fischer, R. S.; Case, L. B.; Waterman, C. M.] NHLBI, Cell Biol, NIH, Bethesda, MD 20892 USA. [Egelhoff, T.] Cleveland Clin, Cell & Mol Med, Lerner Res Inst NC 10, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 678 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701004 ER PT J AU Perry, EA Phelix, C LeBaron, R AF Perry, E. A. Phelix, C. LeBaron, R. TI Dose dependent increase in collagen-I gene expression by transforming growth factor-beta 1 in the human periodontal ligament: an in silico experiment on periodontitis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Perry, E. A.] Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. [Phelix, C.; LeBaron, R.] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. RI Phelix, Clyde/L-8048-2015 OI Phelix, Clyde/0000-0002-6703-514X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1803 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703298 ER PT J AU Petrie, RJ Koo, H Doyle, AD Yamada, KM AF Petrie, R. J. Koo, H. Doyle, A. D. Yamada, K. M. TI Generation of compartmentalized pressure by a nuclear piston drives 3D cell motility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Petrie, R. J.; Koo, H.; Doyle, A. D.; Yamada, K. M.] NIDCR, NIH, Bethesda, MD USA. [Koo, H.] Univ Rochester, Dept Dent, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 185 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705467 ER PT J AU Petrie, RJ Koo, H Doyle, AD Yamada, KM AF Petrie, R. J. Koo, H. Doyle, A. D. Yamada, K. M. TI Generation of compartmentalized pressure by a nuclear piston drives 3D cell motility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Petrie, R. J.; Koo, H.; Doyle, A. D.; Yamada, K. M.] NIDCR, NIH, Bethesda, MD USA. [Koo, H.] Univ Rochester, Dept Dent, Rochester, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2116 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704222 ER PT J AU RenvoisE, B Chang, J Blackstone, C Pierson, TM AF RenvoisE, B. Chang, J. Blackstone, C. Pierson, T. M. TI Spastic Paraplegias SPG15 and SPG11 are Lysosomal Disorders SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [RenvoisE, B.; Chang, J.; Blackstone, C.] NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. [Pierson, T. M.] Cedars Sinai Med Ctr, Pediat & Neurol, Los Angeles, CA 90048 USA. [Pierson, T. M.] Cedars Sinai Med Ctr, Regenerat Med Inst, Los Angeles, CA 90048 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 2004 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704110 ER PT J AU Sengupta, P van Engelenburg, S Johnson, M Lippincott-Schwartz, J AF Sengupta, P. van Engelenburg, S. Johnson, M. Lippincott-Schwartz, J. TI Temporal and spatial remodeling of host cell plasma-membrane during HIV assembly revealed by quantitative superresolution microscopy SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sengupta, P.; van Engelenburg, S.; Lippincott-Schwartz, J.] NICHD, CBMP, NIH, Bethesda, MD USA. [Johnson, M.] Univ Missouri, Mol Microbiol & Immunol, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 271 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700014 ER PT J AU Shiba, Y Kametaka, S Waguri, S Presley, J Randazzo, PA AF Shiba, Y. Kametaka, S. Waguri, S. Presley, J. Randazzo, P. A. TI ArfGAP3 regulates the Transport of Cation-Independent Mannose 6-phosphate Receptor in the post-Golgi compartment SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shiba, Y.; Randazzo, P. A.] NCI, NIH, Bethesda, MD 20892 USA. [Kametaka, S.; Waguri, S.] Fukushima Med Univ, Dept Anat & Histol, Fukushima, Japan. [Presley, J.] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1238 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702142 ER PT J AU Shukla, AK Farmer, V Loncarek, J AF Shukla, A. K. Farmer, V. Loncarek, J. TI Centriole disengagement in the absence of microtubules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Shukla, A. K.; Farmer, V.; Loncarek, J.] Frederick Natl Lab Canc Res, Lab Prot Dynam & Signaling, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1689 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703184 ER PT J AU Sirenko, O Kristen, RR Behl, M Parham, F Anson, B Cromwell, EF Tice, RR AF Sirenko, O. Kristen, R. R. Behl, M. Parham, F. Anson, B. Cromwell, E. F. Tice, R. R. TI In vitro Assessment of Environmental Compound-Induced Cardiotoxicity Potential Using Human Induced Pluripotent Stem Cell (iPSC)-Derived Cardiomyocytes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Sirenko, O.; Cromwell, E. F.] Mol Devices LLC, Sunnyvale, CA USA. [Kristen, R. R.; Behl, M.; Parham, F.; Tice, R. R.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC USA. [Behl, M.] Kelly Govt Solut, Res Triangle Pk, NC USA. [Anson, B.] Cellular Dynam Int, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1086 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701410 ER PT J AU Skau, CT Waterman, CM AF Skau, C. T. Waterman, C. M. TI A novel actin-adhesion structure involved in nuclear positioning requires the formin FMN2 SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Skau, C. T.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 665 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700408 ER PT J AU Skau, CT Plotnikov, S Waterman, CM AF Skau, C. T. Plotnikov, S. Waterman, C. M. TI The formin INF2 is a focal adhesion protein that mediates maturation and stress fiber assembly SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Skau, C. T.; Plotnikov, S.; Waterman, C. M.] NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 306 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700048 ER PT J AU Takagi, Y Farrow, RE Billington, N Nagy, A Batters, C Yang, Y Sellers, JR Molloy, JE AF Takagi, Y. Farrow, R. E. Billington, N. Nagy, A. Batters, C. Yang, Y. Sellers, J. R. Molloy, J. E. TI Myosin-10 produces its power-stroke in two phases and moves processively along a single actin filament under low-load SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Takagi, Y.; Billington, N.; Nagy, A.; Yang, Y.; Sellers, J. R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. [Farrow, R. E.; Batters, C.; Molloy, J. E.] MRC Natl Inst Med Res, Div Phys Biochem, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1170 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702074 ER PT J AU Tanda, S Salles, FT Andrade, L Grati, M Plona, KL Gagnon, LH Johnson, KR Kachar, B Berryman, MA AF Tanda, S. Salles, F. T. Andrade, L. Grati, M. Plona, K. L. Gagnon, L. H. Johnson, K. R. Kachar, B. Berryman, M. A. TI CLIC5 is part of a multiprotein complex that functions to stabilize membrane-cytoskeletal attachments at the base of mechanosensory hair cell stereocilia SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Tanda, S.; Plona, K. L.] Ohio Univ, Biol Sci, Athens, OH 45701 USA. [Tanda, S.; Berryman, M. A.] Ohio Univ, Interdisciplinary Program Mol & Cellular Biol, Athens, OH 45701 USA. [Salles, F. T.] Stanford Univ, Sch Med, Otolaryngol, Stanford, CA 94305 USA. [Salles, F. T.; Andrade, L.; Grati, M.; Kachar, B.] NIDCD, Lab Cell Struct & Dynam, NIH, Bethesda, MD USA. [Andrade, L.] Univ Fed Rio de Janeiro, Inst Biomed Sci, Rio De Janeiro, Brazil. [Grati, M.] Univ Miami, Miller Sch Med, Otolaryngol, Miami, FL 33136 USA. [Plona, K. L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Gagnon, L. H.; Johnson, K. R.] Jackson Lab, Bar Harbor, ME 04609 USA. [Berryman, M. A.] Ohio Univ, Heritage Coll Osteopath, Biomed Sci, Athens, OH 45701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1827 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703322 ER PT J AU Thievessen, I Fakhri, N Steinwachs, J McIsaac, S Gao, L Chen, BC Betzig, E Oldenbourg, R Fabry, B Waterman, CM AF Thievessen, I. Fakhri, N. Steinwachs, J. McIsaac, S. Gao, L. Chen, B-C. Betzig, E. Oldenbourg, R. Fabry, B. Waterman, C. M. TI Vinculin is required for cell polarization, migration and ECM-remodeling in 3D collagen matrix SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Thievessen, I.; Steinwachs, J.; Fabry, B.] Univ Erlangen Nurnberg, Chair Phys & Med Technol, D-91054 Erlangen, Germany. [Thievessen, I.; Waterman, C. M.] NHLBI, Lab Cell & Tissue Morphodynam, NIH, Bethesda, MD 20892 USA. [Fakhri, N.] Univ Gottingen, Inst Phys 3, Biophys, D-37073 Gottingen, Germany. [McIsaac, S.] Princeton Univ, Lewis Sigler Inst, Princeton, NJ 08544 USA. [Gao, L.; Chen, B-C.; Betzig, E.] Janelia Farm Res Campus, Ashburn, VA USA. [Oldenbourg, R.] Marine Biol Lab, Cellular Dynam Programm, Woods Hole, MA 02543 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 230 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705512 ER PT J AU Thievessen, I Fakhri, N Steinwachs, J McIsaac, S Gao, L Chen, BC Betzig, E Oldenbourg, R Fabry, B Waterman, CM AF Thievessen, I. Fakhri, N. Steinwachs, J. McIsaac, S. Gao, L. Chen, B-C. Betzig, E. Oldenbourg, R. Fabry, B. Waterman, C. M. TI Vinculin is required for cell polarization, migration and ECM-remodeling in 3D collagen matrix SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Thievessen, I.; Steinwachs, J.; Fabry, B.] Univ Erlangen Nurnberg, Chair Phys & Med Technol, D-91054 Erlangen, Germany. [Thievessen, I.; Waterman, C. M.] NHLBI, Lab Cell & Tissue Morphodynam, NIH, Bethesda, MD 20892 USA. [Fakhri, N.] Univ Gottingen, Inst Phys 3, Biophys, Gottingen, Germany. [McIsaac, S.] Princeton Univ, Lewis Sigler Inst, Princeton, NJ 08544 USA. [Gao, L.; Chen, B-C.; Betzig, E.] Janelia Farm Res Campus, Ashburn, VA USA. [Oldenbourg, R.] Marine Biol Lab, Cellular Dynam Programm, Woods Hole, MA 02543 USA. RI Fabry, Ben/C-5496-2013 OI Fabry, Ben/0000-0003-1737-0465 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1374 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702278 ER PT J AU Valm, AM Cohen, S Sengupta, P Davidson, MW Schwartz, JL AF Valm, A. M. Cohen, S. Sengupta, P. Davidson, M. W. Schwartz, J. Lippincott TI Unraveling the organelle interactome through spectral imaging and pair correlation analysis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Valm, A. M.; Cohen, S.; Sengupta, P.; Schwartz, J. Lippincott] NICHD, NIH, Bethesda, MD USA. [Davidson, M. W.] Florida State Univ, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 796 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701121 ER PT J AU Verma, SK Leikina, E Chernomordik, LV AF Verma, S. K. Leikina, E. Chernomordik, L. V. TI Isolation of Cell Fusion Stage in Osteoclast Formation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Verma, S. K.; Leikina, E.; Chernomordik, L. V.] NICHD, Sect Membrane Biol, Program Phys Biol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 688 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348701014 ER PT J AU Vilboux, T Lev, A Malicdan, M Simon, A Sood, R Anikster, Y Klein, C Gahl, W Somech, R AF Vilboux, T. Lev, A. Malicdan, M. Simon, A. Sood, R. Anikster, Y. Klein, C. Gahl, W. Somech, R. TI Mutations in the VPS45 gene cause a new congenital neutrophil defect syndrome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Vilboux, T.; Malicdan, M.; Gahl, W.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Lev, A.; Simon, A.; Somech, R.] Jeffrey Modell Fdn, Pediat Immunol Serv, Tel Aviv, Israel. [Sood, R.] NHGRI, Zebrafish Core Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. [Anikster, Y.] Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, Tel Hashomer, Israel. [Anikster, Y.] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. [Klein, C.] Univ Munich, Dept Pediat, Dr von Hauner Childrens Hosp, Munich, Germany. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1530 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348703025 ER PT J AU Wang, A Zhang, Y Liu, C Adelstein, R AF Wang, A. Zhang, Y. Liu, C. Adelstein, R. TI Study of the Mechanism and Applications of a Newly Discovered Genomic Locus with a High (95%) Gene Targeting Frequency SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wang, A.; Zhang, Y.; Adelstein, R.] NHLBI, Lab Mol Cardiol, Bethesda, MD 20892 USA. [Liu, C.] NHLBI, Transgen Mouse Core Facil, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 294 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700036 ER PT J AU Wu, X Masedunskas, A Weigert, R Hammer, JA AF Wu, X. Masedunskas, A. Weigert, R. Hammer, J. A. TI Visualizing melanosome transfer in vivo SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wu, X.; Hammer, J. A.] NHLBI, NIH, Bethesda, MD 20892 USA. [Masedunskas, A.; Weigert, R.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1989 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348704096 ER PT J AU Wu, Z Plotnikov, S Waterman, CM Liu, J AF Wu, Z. Plotnikov, S. Waterman, C. M. Liu, J. TI Two distinct actin networks dictate traction peak oscillation within single focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wu, Z.; Liu, J.] NHLBI, Theoret Cellular Phys Sect, BBC, NIH, Bethesda, MD 20892 USA. [Plotnikov, S.; Waterman, C. M.] NHLBI, Lab Cell & Tissue Morphodynam, CPCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 83 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348705365 ER PT J AU Wu, Z Plotnikov, S Waterman, CM Liu, J AF Wu, Z. Plotnikov, S. Waterman, C. M. Liu, J. TI Two distinct actin networks dictate traction peak oscillation within single focal adhesions. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Wu, Z.; Liu, J.] NHLBI, Theoret Cellular Phys Sect, BBC, NIH, Bethesda, MD 20892 USA. [Plotnikov, S.; Waterman, C. M.] NHLBI, Lab Cell & Tissue Morphodynam, CPCB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 664 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348700407 ER PT J AU Xavier, CP Melikova, M Baljinnyam, B Chuman, Y Uren, A Rubin, J AF Xavier, C. P. Melikova, M. Baljinnyam, B. Chuman, Y. Ueren, A. Rubin, J. TI Secreted Frizzled-Related Protein Potentiation versus Inhibition of Wnt3a/beta-catenin Signaling SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Xavier, C. P.; Melikova, M.; Baljinnyam, B.; Rubin, J.] NCI, LCMB, NIH, Bethesda, MD 20892 USA. [Chuman, Y.] Hokkaido Univ, Fac Sci, Dept Chem, Sapporo, Hokkaido 060, Japan. [Ueren, A.] Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1358 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702262 ER PT J AU Xu, Y Cai, M Liu, Y Lee, JG Huang, L Ye, Y AF Xu, Y. Cai, M. Liu, Y. Lee, J-G. Huang, L. Ye, Y. TI A UBL dependent protein interaction network regulates ER-associated protein degradation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Xu, Y.; Liu, Y.; Lee, J-G.; Ye, Y.] NIDDK, Lab Mol Biol, Bethesda, MD 20892 USA. [Cai, M.] NIDDK, Lab Chem Phys, Bethesda, MD 20892 USA. [Huang, L.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1483 PG 1 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702387 ER PT J AU Zhang, M March, ME Lane, WS Long, EO AF Zhang, M. March, M. E. Lane, W. S. Long, E. O. TI A Proteomics Approach to Identify the Integrin-dependent Signaling Pathway for Granule Polarization in Natural Killer Cells SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 [Zhang, M.; March, M. E.; Long, E. O.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Lane, W. S.] FAS Ctr Syst Biol, Harvard Mass Spectrometry & Prote Resource Lab, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 EI 1939-4586 J9 MOL BIOL CELL JI Mol. Biol. Cell PY 2013 VL 24 MA 1282 PG 2 WC Cell Biology SC Cell Biology GA V38MY UT WOS:000209348702186 ER PT B AU Buvat, I Benoit, D Jan, S AF Buvat, Irene Benoit, Didier Jan, Sebastien BE Ljungberg, M Strand, SE King, MA TI GATE: A Toolkit for Monte Carlo Simulations in Tomography and Radiation Therapy SO MONTE CARLO CALCULATIONS IN NUCLEAR MEDICINE, 2ND EDITION: APPLICATIONS IN DIAGNOSTIC IMAGING SE Series in Medical Physics and Biomedical Engineering LA English DT Article; Book Chapter ID SMALL ANIMAL PET; ROTATING SLAT COLLIMATOR; LAYER PHOSWICH DETECTOR; INTER-CRYSTAL SCATTER; TIME-OF-FLIGHT; RESPONSE FUNCTION; MOUSE PHANTOM; RECONSTRUCTION; SYSTEM; VALIDATION C1 [Buvat, Irene] UCL, London WC1E 6BT, England. [Buvat, Irene] NIH, Bethesda, MD 20892 USA. [Buvat, Irene] French Ctr Natl Rech Sci CNRS, Paris, France. [Benoit, Didier] French CNRS Ctr Natl Rech Sci, CPPM, Marseilles, France. [Benoit, Didier] Univ Paris 11, CNRS Natl Inst Nucl & Particle Phys IN2P3, Orsay, France. [Jan, Sebastien] French Atom Commiss CEA, Grenoble, France. RP Buvat, I (reprint author), Neurobiol & Cancerol CNRS Lab, Mol Imaging Team Imaging & Modelling, Quantificat, Orsay, France. NR 78 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-4110-5; 978-1-4398-4109-9 J9 SER MED PHYS BIOMED PY 2013 BP 129 EP 152 PG 24 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BC7UC UT WOS:000355211800009 ER PT B AU Buvat, I AF Buvat, Irene BE Ljungberg, M Strand, SE King, MA TI Design of Molecular Imaging Systems Assisted by the Monte Carlo Methods SO MONTE CARLO CALCULATIONS IN NUCLEAR MEDICINE, 2ND EDITION: APPLICATIONS IN DIAGNOSTIC IMAGING SE Series in Medical Physics and Biomedical Engineering LA English DT Article; Book Chapter ID GAMMA-CAMERA ARCHITECTURE; DEDICATED PET SYSTEM; ANIMAL PET; SLAT COLLIMATOR; SIMULATION PLATFORM; STRIP DETECTOR; ROTATING SLAT; RESOLUTION; GATE; SPECT C1 [Buvat, Irene] UCL, London WC1E 6BT, England. [Buvat, Irene] NIH, Bethesda, MD 20892 USA. [Buvat, Irene] French Ctr Natl Rech Sci CNRS, Paris, France. RP Buvat, I (reprint author), Neurobiol & Cancerol CNRS Lab, Mol Imaging Team Imaging & Modelling, Quantificat, Orsay, France. NR 46 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-4110-5; 978-1-4398-4109-9 J9 SER MED PHYS BIOMED PY 2013 BP 273 EP 285 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BC7UC UT WOS:000355211800015 ER PT J AU Deeks, S Drosten, C Picker, L Subbarao, K Suzich, J AF Deeks, Steven Drosten, Christian Picker, Louis Subbarao, Kanta Suzich, Joann TI Roadblocks to translational challenges on viral pathogenesis SO NATURE MEDICINE LA English DT Article ID SYNCYTIAL VIRUS-INFECTION; INFLUENZA-VIRUSES; ENHANCED DISEASE; HIV-INFECTION; TRANSMISSION; VACCINE; STRATEGIES; ADULTS; PREVENTION; INFANTS C1 [Deeks, Steven] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Suzich, Joann] Medimmune Inc, Gaithersburg, MD 20878 USA. [Picker, Louis] Oregon Hlth & Sci Univ, Vaccine & Gene Therapy Inst, Beaverton, OR USA. [Drosten, Christian] Univ Bonn, Inst Virol, Bonn, Germany. [Subbarao, Kanta] NIAID, National Institutes Health, Bethesda, MD USA. RP Deeks, S (reprint author), Univ Calif San Francisco, Dept Med, San Francisco, CA USA. EM sdeeks@php.ucsf.edu; drosten@virologybonn.de; pickerl@ohsu.edu; ksubbarao@niaid.nih.gov; suzichj@medimmune.com NR 54 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 EI 1546-170X J9 NAT MED JI Nat. Med. PD JAN PY 2013 VL 19 IS 1 BP 30 EP 34 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 066OO UT WOS:000313230300022 ER PT J AU Hawe, RL Sukal-Moulton, T Dewald, JPA AF Hawe, Rachel L. Sukal-Moulton, Theresa Dewald, Julius P. A. TI The effect of injury timing on white matter changes in the corpus callosum following unilateral brain injury SO NEUROIMAGE-CLINICAL LA English DT Article DE Corpus callosum; Hemiplegia; Mirror movements; Diffusion tensor imaging AB Motor impairments following unilateral brain injuries may be related to changes in the corpus callosum. The purpose of this study was to determine if the corpus callosum is impacted differently in pediatric versus adult hemiplegia. Diffusion tensor imaging was completed on 41 participants (11 pediatric hemiplegia, 10 adult hemiplegia, 10 pediatric control and 10 adult control). Fractional anisotropy values and cross-sectional areas for five regions of the corpus callosum were compared between subject groups. Additionally, the amount of involuntary activity in the paretic elbow was quantified during non-paretic elbow flexion tasks for a subset of pediatric hemiplegia participants. Fractional anisotropy values were reduced in pediatric hemiplegia compared to pediatric control subjects in callosal regions corresponding to premotor and supplementary motor areas, primary sensory cortex, and parietal, temporal, and occipital cortices. Differences in fractional anisotropy between adult stroke and adult controls were only found in the region corresponding to parietal, temporal, and occipital cortices. Cross-sectional area was affected in all regions of the corpus callosum in pediatric hemiplegia, but only in the primary sensory region in adult hemiplegia. Additionally, changes in the cross-sectional areas were correlated with involuntary mirror movements in the pediatric hemiplegia group. In conclusion, the corpus callosum is affected to a greater extent in pediatric compared to adult hemiplegia, which may explain why unsuppressed mirror movements and difficulty with bimanual coordination are greater problems in this population. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Hawe, Rachel L.; Dewald, Julius P. A.] Northwestern Univ, Dept Phys Therapy & Human Movement Sci, Chicago, IL 60611 USA. [Hawe, Rachel L.; Dewald, Julius P. A.] Northwestern Univ, Dept Biomed Engn, Evanston, IL 60208 USA. [Sukal-Moulton, Theresa] NIH, Funct & Appl Biomech Sect, Ctr Clin, Bethesda, MD 20892 USA. [Dewald, Julius P. A.] Dept Phys Med & Rehabil, Chicago, IL 60611 USA. RP Dewald, JPA (reprint author), 645 N Michigan Ave,Suite 1100, Chicago, IL 60611 USA. EM j-dewald@northwestern.edu FU NIH [RO1 NS058667]; National Science Foundation Graduate Research Fellowship FX NIH Grant: RO1 NS058667 to Dr. Julius PA Dewald and National Science Foundation Graduate Research Fellowship to Dr. Rachel L. Hawe. NR 21 TC 2 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 115 EP 122 DI 10.1016/j.nicl.2013.08.002 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900013 PM 24179855 ER PT J AU Jones, BC Nair, G Shea, CD Crainiceanu, CM Cortese, ICM Reich, DS AF Jones, Blake C. Nair, Govind Shea, Colin D. Crainiceanu, Ciprian M. Cortese, Irene C. M. Reich, Daniel S. TI Quantification of multiple-sclerosis-related brain atrophy in two heterogeneous MRI datasets using mixed-effects modeling SO NEUROIMAGE-CLINICAL LA English DT Article DE Multiple sclerosis; MRI; Brain atrophy; Mixed-effects model; Heterogeneous data AB Brain atrophy, measured by MRI, has been proposed as a useful surrogate marker for disease progression in multiple sclerosis (MS). However, it is conventionally assumed that the accurate quantification of brain atrophy is made difficult, if not impossible, by changes in the parameters of the MRI acquisition, which are almost inevitable over the course of a longitudinal study since MRI technology changes rapidly. This state of affairs can negatively affect clinical trial design and limit the use of historical data. Here, we investigate whether we can coherently estimate brain atrophy rates in a heterogeneous MS sample via linear mixed-effects multivariable regression, incorporating three critical assumptions: (1) using age at time of scanning, rather than time since baseline, as the regressor of interest; (2) scanning individuals with a variety of techniques; and (3) introducing a simple additive correction for major differences in MRI protocol. We fit the model to several measures of brain volume as the outcome in two MS populations: 1123 scans from 195 cases acquired for over approximately 7 years in two natural history protocols (Cohort 1), and 1331 scans from 69 cases seen for over 11 years who were primarily treated with two specific MS disease-modifying therapies (Cohort 2). We compared the mixed-effects model with additive correction for MRI acquisition parameters to a model fit without this correction and performed sample-size calculations to provide an estimate of the number of participants in an MS clinical trial that might be required to see a therapeutic effect of treatment using the approach described here. The results show that without the additive correction for T1-weighted protocol parameters, atrophy was underestimated and subject-specific estimates were more narrowly distributed about the population mean. Ventricular CSF is the most consistently estimated brain volume, with a mean of 2.8%/year increase in Cohort 1 and 4.4%/year increase in Cohort 2. An interesting observation was that gray matter volume decreased and white matter volume remained essentially unchanged in both cohorts, suggesting that changes in ventricular CSF volume are a surrogate for changes in gray matter volume. In conclusion, the mixed-effects modeling framework presented here allows effective use of heterogeneously acquired and historical data in the study of brain atrophy in MS, potentially simplifying the design of future single- and multi-site clinical trials and natural history studies. c 2013 The Authors. Published by Elsevier Inc. C1 [Jones, Blake C.; Nair, Govind; Shea, Colin D.; Cortese, Irene C. M.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, NIH, Bethesda, MD 20892 USA. [Jones, Blake C.] Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. [Crainiceanu, Ciprian M.; Reich, Daniel S.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. RP Reich, DS (reprint author), NINDS, Translat Neuroradiol Unit, NIH, 10 Ctr Dr MSC 1400,Bldg 10 Room 5C103, Bethesda, MD 20892 USA. EM bcj20@case.edu; govind.bhagavatheeshwaran@nih.gov; sheacd@ninds.nih.gov; ccrainic@jhsph.edu; corteseir@ninds.nih.gov; daniel.reich@nih.gov RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program; NINDS Intramural Research Program FX The authors thank Henry McFarland and Bibiana Bielekova, who led the studies from which we drew many of the subjects included in this analysis. Subject follow-up and data acquisition could not have occurred without the clinicians, nurses, and staff of the Neuroimmunology Clinic; Roger Stone; John Ostuni; and the NIH FMRIF and Radiology and Imaging Sciences Department staff. BCJ was supported by the Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program. The NINDS Intramural Research Program supported this research. NR 42 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 171 EP 179 DI 10.1016/j.nicl.2013.08.001 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900019 PM 24179861 ER PT J AU Ceko, M Bushnell, MC Fitzcharles, MA Schweinhardt, P AF Ceko, Marta Bushnell, M. Catherine Fitzcharles, Mary-Ann Schweinhardt, Petra TI Fibromyalgia interacts with age to change the brain SO NEUROIMAGE-CLINICAL LA English DT Article DE Chronic pain; Age; MRI; Insula; Cingulate; VBM AB Although brain plasticity in the form of gray matter increases and decreases has been observed in chronic pain, factors determining the patterns of directionality are largely unknown. Here we tested the hypothesis that fibromyalgia interacts with age to produce distinct patterns of gray matter differences, specifically increases in younger and decreases in older patients, when compared to age-matched healthy controls. The relative contribution of pain duration was also investigated. Regional gray matter was measured in younger (n = 14, mean age 43, range 29-49) and older (n = 14; mean age 55, range 51-60) female fibromyalgia patients and matched controls using voxel-based morphometry and cortical thickness analysis of T1-weighted magnetic resonance images. To examine their functional significance, gray matter differences were compared with experimental pain sensitivity. Diffusion-tensor imaging was used to assess whether white matter changed in parallel with gray matter, and resting-state fMRI was acquired to examine whether pain-related gray matter changes are associated with altered functional connectivity. Older patients showed exclusively decreased gray matter, accompanied by compromised white matter integrity. In contrast, younger patients showed exclusively gray matter increases, namely in the basal ganglia and insula, which were independent of pain duration. Associated white matter changes in younger patients were compatible with gray matter hypertrophy. In both age groups, structural brain alterations were associated with experimental pain sensitivity, which was increased in older patients but normal in younger patients. Whereas more pronounced gray matter decreases in the posterior cingulate cortex were related to increased experimental pain sensitivity in older patients, insular gray matter increases in younger patients correlated with lower pain sensitivity, possibly indicating the recruitment of endogenous pain modulatory mechanisms. This is supported by the finding that the insula in younger patients showed functional decoupling from an important pain-processing region, the dorsal anterior cingulate cortex. These results suggest that brain structure and function shift from being adaptive in younger to being maladaptive in older patients, which might have important treatment implications. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-ND license. C1 [Ceko, Marta; Bushnell, M. Catherine; Schweinhardt, Petra] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ H3A O7C, Canada. [Ceko, Marta; Bushnell, M. Catherine; Schweinhardt, Petra] McGilll Univ, Integrated Program Neurosci, Montreal, PQ H3A 2B4, Canada. [Bushnell, M. Catherine; Schweinhardt, Petra] McGill Univ, Royal Victoria Hosp, Dept Anesthesia, Montreal, PQ H3A 1A1, Canada. [Bushnell, M. Catherine; Schweinhardt, Petra] McGill Univ, Fac Dent, Montreal, PQ H3A O7C, Canada. [Fitzcharles, Mary-Ann] MUHC Montreal Gen Hosp, Div Rheumatol, Montreal, PQ H3G 1A4, Canada. [Ceko, Marta; Bushnell, M. Catherine] NIH, NCCAM, Bethesda, MD 20892 USA. RP Schweinhardt, P (reprint author), McGill Univ, Fac Dent, Strathcona Anat & Dent Bldg Room M19,3640 Univ St, Montreal, PQ H3A O7C, Canada. OI CEKO, MARTA/0000-0001-8679-8145 FU American Fibromyalgia Syndrome Association (AFSA); Intramural Research Program of the NIH, National Center for Complementary and Alternative Medicine FX We acknowledge the American Fibromyalgia Syndrome Association (AFSA) for the financial support. This research was supported in part by the Intramural Research Program of the NIH, National Center for Complementary and Alternative Medicine. We thank the team at the McConnell Brain Imaging Centre of the Montreal Neurological Institute for the expert MRI data acquisition. We further thank Valerie Cotton, Marissa Lapedis, and Carl Frechette for the subject recruitment. Finally, we thank David Seminowicz, Brian Walitt, and Hakan Olausson for the valuable comments on the manuscript. NR 115 TC 24 Z9 26 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 249 EP 260 DI 10.1016/j.nicl.2013.08.015 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900028 PM 24273710 ER PT J AU Mueller-Pfeiffer, C Schick, M Schulte-Vels, T O'Gorman, R Michels, L Martin-Soelch, C Blair, JR Rufer, M Schnyder, U Zeffiro, T Hasler, G AF Mueller-Pfeiffer, Christoph Schick, Matthis Schulte-Vels, Thomas O'Gorman, Ruth Michels, Lars Martin-Soelch, Chantal Blair, James R. Rufer, Michael Schnyder, Ulrich Zeffiro, Thomas Hasler, Gregor TI Atypical visual processing in posttraumatic stress disorder SO NEUROIMAGE-CLINICAL LA English DT Article DE Visual system; Ventral stream; Dorsal stream; fMRI; International Affective Picture System; Sensory perception AB Background: Many patients with Posttraumatic Stress Disorder (PTSD) feel overwhelmed in situations with high levels of sensory input, as in crowded situations with complex sensory characteristics. These difficulties might be related to subtle sensory processing deficits similar to those that have been found for sounds in electrophysiological studies. Method: Visual processing was investigated with functional magnetic resonance imaging in trauma-exposed participants with (N = 18) and without PTSD (N = 21) employing a picture-viewing task. Results: Activity observed in response to visual scenes was lower in PTSD participants 1) in the ventral stream of the visual system, including striate and extrastriate, inferior temporal, and entorhinal cortices, and 2) in dorsal and ventral attention systems (P < 0.05, FWE-corrected). These effects could not be explained by the emotional salience of the pictures. Conclusions: Visual processing was substantially altered in PTSD in the ventral visual stream, a component of the visual system thought to be responsible for object property processing. Together with previous reports of subtle auditory deficits in PTSD, these findings provide strong support for potentially important sensory processing deficits, whose origins may be related to dysfunctional attention processes. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Mueller-Pfeiffer, Christoph; Schick, Matthis; Schulte-Vels, Thomas; Rufer, Michael; Schnyder, Ulrich] Univ Zurich Hosp, Dept Psychiat & Psychotherapy, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, Christoph] Psychiat Serv Cty St Gallen North, Ctr Educ & Res COEUR, Wil, Switzerland. [Mueller-Pfeiffer, Christoph] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Mueller-Pfeiffer, Christoph] Harvard Univ, Sch Med, Boston, MA USA. [O'Gorman, Ruth; Michels, Lars] Univ Childrens Hosp, Ctr MR Res, Zurich, Switzerland. [Michels, Lars] Univ Zurich Hosp, Inst Neuroradiol, CH-8091 Zurich, Switzerland. [Martin-Soelch, Chantal] Univ Fribourg, Dept Clin Psychol, CH-1700 Fribourg, Switzerland. [Blair, James R.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Zeffiro, Thomas] Massachusetts Gen Hosp, Neural Syst Grp, Boston, MA 02114 USA. [Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, Bern, Switzerland. RP Mueller-Pfeiffer, C (reprint author), Univ Zurich Hosp, Dept Psychiat & Psychotherapy, Culmannstr 8, CH-8091 Zurich, Switzerland. EM christoph.mueller-pfeiffer@access.uzh.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Rufer, Michael/0000-0003-4964-4213; O'Gorman, Ruth/0000-0001-5932-7786 FU "Stiftung fur wissenschaftliche Forschung" (University of Zurich); Stanley Thomas Johnson Foundation (Bern); "Helen Bieber-Fonds" (University of Zurich) FX The study was funded by the "Stiftung fur wissenschaftliche Forschung" (University of Zurich), Stanley Thomas Johnson Foundation (Bern), and the "Helen Bieber-Fonds" (University of Zurich). The authors report no competing interests. We are grateful to Dr Roger Pitman for helpful suggestions. NR 76 TC 8 Z9 8 U1 4 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 3 BP 531 EP 538 DI 10.1016/j.nicl.2013.08.009 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LI UT WOS:000209276900057 PM 24371791 ER PT J AU Raznahan, A Lenroot, R Thurm, A Gozzi, M Hanley, A Spence, SJ Swedo, SE Giedd, JN AF Raznahan, Armin Lenroot, Rhoshel Thurm, Audrey Gozzi, Marta Hanley, Allison Spence, Sarah J. Swedo, Susan E. Giedd, Jay N. TI Mapping cortical anatomy in preschool aged children with autism using surface-based morphometry SO NEUROIMAGE-CLINICAL LA English DT Article DE Cortical thickness; Surface area; Autism; Neuroimaging ID HUMAN CEREBRAL-CORTEX; PERVASIVE DEVELOPMENTAL DISORDERS; MIRROR-NEURON SYSTEM; SPECTRUM DISORDER; REPETITIVE BEHAVIOR; BRAIN-DEVELOPMENT; SPECIAL NEEDS; PROJECT SNAP; MRI; THICKNESS AB The challenges of gathering in-vivo measures of brain anatomy from young children have limited the number of independent studies examining neuroanatomical differences between children with autism and typically developing controls (TDCs) during early life, and almost all studies in this critical developmental window focus on global or lobar measures of brain volume. Using a novel cohort of young males with Autistic Disorder and TDCs aged 2 to 5 years, we (i) tested for group differences in traditional measures of global anatomy (total brain, total white, total gray and total cortical volume), and (ii) employed surface-based methods for cortical morphometry to directly measure the two biologically distinct sub-components of cortical volume (CV) at high spatial resolution-cortical thickness (CT) and surface area (SA). While measures of global brain anatomy did not show statistically significant group differences, children with autism showed focal, and CT-specific anatomical disruptions compared to TDCs, consisting of relative cortical thickening in regions with central roles in behavioral regulation, and the processing of language, biological movement and social information. Our findings demonstrate the focal nature of brain involvement in early autism, and provide more spatially and morphometrically specific anatomical phenotypes for subsequent translational study. (C) 2012 The Authors. Published by Elsevier Inc. Open access under CC BY-NC-SA license. C1 [Raznahan, Armin; Lenroot, Rhoshel; Hanley, Allison; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. [Thurm, Audrey; Gozzi, Marta; Spence, Sarah J.; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA. [Spence, Sarah J.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Neurol, Cambridge, MA 02138 USA. RP Raznahan, A (reprint author), Rm 4C108,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM raznahana@mail.nih.gov RI Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-2002-8978 NR 62 TC 11 Z9 11 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 111 EP 119 DI 10.1016/j.nicl.2012.10.005 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800013 ER PT J AU Kwan, JY Meoded, A Danielian, LE Wu, TX Floeter, MK AF Kwan, Justin Y. Meoded, Avner Danielian, Laura E. Wu, Tianxia Floeter, Mary Kay TI Structural imaging differences and longitudinal changes in primary lateral sclerosis and amyotrophic lateral sclerosis SO NEUROIMAGE-CLINICAL LA English DT Article DE Cortical thickness; Longitudinal studies; Motor neuron disease; Diffusion tensor imaging; FreeSurfer ID DIFFUSION TENSOR MRI; MOTOR-NEURON INVOLVEMENT; VOXEL-BASED MORPHOMETRY; SURFACE-BASED ANALYSIS; HUMAN CEREBRAL-CORTEX; WHITE-MATTER; CORTICOSPINAL TRACT; CORTICAL SURFACE; COGNITIVE IMPAIRMENT; DISEASE PROGRESSION AB Magnetic resonance imaging measures have been proposed as objective markers to study upper motor neuron loss in motor neuron disorders. Cross-sectional studies have identified imaging differences between groups of healthy controls and patients with amyotrophic lateral sclerosis (ALS) or primary lateral sclerosis (PLS) that correlate with disease severity, but it is not known whether imaging measures change as disease progresses. Additionally, whether imaging measures change in a similar fashion with disease progression in PLS and ALS is unclear. To address these questions, clinical and imaging evaluations were first carried out in a prospective cross-sectional study of 23 ALS and 22 PLS patients with similar motor impairment and 19 age-matched healthy controls. Clinical evaluations consisted of a neurological examination, the ALS Functional rating scale-revised, and measures of finger tapping, gait, and timed speech. Age and ALSFRS score were not different, but PLS patients had longer duration of symptoms. Imaging measures examined were cortical thickness, regional brain volumes, and diffusion tensor imaging of the corticospinal tract and callosum. Imaging measures that differed from controls in a cross-sectional vertex-wise analysis were used as regions of interest for longitudinal analysis, which was carried out in 9 of the ALS patients (interval 1.26 +/- 0.72 years) and 12 PLS patients (interval 2.08 +/- 0.93 years). In the cross-sectional study both groups had areas of cortical thinning, which was more extensive in motor regions in PLS patients. At follow-up, clinical measures declined more in ALS than PLS patients. Cortical thinning and grey matter volume loss of the precentral gyri progressed over the follow-up interval. Fractional anisotropy of the corticospinal tracts remained stable, but the cross-sectional area declined in ALS patients. Changes in clinical measures correlated with changes in precentral cortical thickness and grey matter volume. The rate of cortical thinning was greater in ALS patients with shorter disease durations, suggesting that thickness decreases in a non-linear fashion. Thus, cortical thickness changes are a potential imaging marker for disease progression in individual patients, but the magnitude of change likely depends on disease duration and progression rate. Differences between PLS and ALS patients in the magnitude of thinning in cross-sectional studies are likely to reflect longer disease duration. We conclude that there is an evolution of structural imaging changes with disease progression in motor neuron disorders. Some changes, such as diffusion properties of the corticospinal tract, occur early while cortical thinning and volume loss occur later. (C) 2012 The Authors. Published by Elsevier Inc. C1 [Kwan, Justin Y.; Meoded, Avner; Danielian, Laura E.; Wu, Tianxia; Floeter, Mary Kay] NINDS, NIH, Bethesda, MD 20892 USA. RP Floeter, MK (reprint author), 10 Ctr Dr MSC 1404,Bldg 10 CRC Room 7-5680, Bethesda, MD 20892 USA. EM floeterm@ninds.nih.gov FU Intramural Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health [Z01 NS002976] FX This work was supported by the Intramural Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (Z01 NS002976). NR 76 TC 9 Z9 9 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 151 EP 160 DI 10.1016/j.nicl.2012.12.003 PG 10 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800017 ER PT J AU Blumenthal, JD Baker, EH Lee, NR Wade, B Clasen, LS Lenroot, RK Giedd, JN AF Blumenthal, Jonathan D. Baker, Eva H. Lee, Nancy Raitano Wade, Benjamin Clasen, Liv S. Lenroot, Rhoshel K. Giedd, Jay N. TI Brain morphological abnormalities in 49,XXXXY syndrome: A pediatric magnetic resonance imaging study SO NEUROIMAGE-CLINICAL LA English DT Article DE Sex chromosome aneuploidy; MRI; Children; Adolescents; X chromosome ID SEX-CHROMOSOME ANEUPLOIDIES; KLINEFELTER-SYNDROME; CORPUS-CALLOSUM; XXXXY SYNDROME; MRI DATA; 48,XXXY AB As a group, people with the sex chromosome aneuploidy 49,XXXXY have characteristic physical and cognitive/behavioral tendencies, although there is high individual variation. In this study we use magnetic resonance imaging (MRI) to examine brain morphometry in 14 youth with 49, XXXXY compared to 42 age-matched healthy controls. Total brain size was significantly smaller (t=9.0, p<.001), and rates of brain abnormalities such as colpocephaly, plagiocephaly, periventricular cysts, and minor craniofacial abnormalities were significantly increased. White matter lesions were identified in 50% of subjects, supporting the inclusion of 49, XXXXY in the differential diagnosis of small multifocal white matter lesions. Further evidence of abnormal development of white matter was provided by the smaller cross sectional area of the corpus callosum. These results suggest that increased dosage of genes on the X chromosome has adverse effects on white matter development. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Blumenthal, Jonathan D.; Lee, Nancy Raitano; Wade, Benjamin; Clasen, Liv S.; Giedd, Jay N.] NIMH, Child Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. [Baker, Eva H.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, DHHS, Bethesda, MD 20892 USA. [Lenroot, Rhoshel K.] Univ New S Wales, Sydney, NSW, Australia. [Lenroot, Rhoshel K.] Neurosci Res Australia, Sydney, NSW, Australia. RP Blumenthal, JD (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Room 4C110,MSC 1367,10 Ctr Dr, Bethesda, MD 20892 USA. EM jb364e@nih.gov RI Giedd, Jay/J-9644-2015; Lee, Nancy/M-7492-2016 OI Giedd, Jay/0000-0003-2002-8978; Lee, Nancy/0000-0002-6663-0713 FU Intramural Research Program of the NIMH FX The Intramural Research Program of the NIMH supported this research. NR 38 TC 8 Z9 8 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 197 EP 203 DI 10.1016/j.nicl.2013.01.003 PG 7 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800022 PM 23667827 ER PT J AU Savitz, J Nugent, AC Bellgowan, PSF Wright, N Tinsley, R Zarate, CA Herscovitch, P Drevets, WC AF Savitz, Jonathan Nugent, Allison C. Bellgowan, Patrick S. F. Wright, Niara Tinsley, Ruth Zarate, Carlos A., Jr. Herscovitch, Peter Drevets, Wayne C. TI Catecholamine depletion in first-degree relatives of individuals with mood disorders: An [F-18]fluorodeoxyglucose positron emission tomography study SO NEUROIMAGE-CLINICAL LA English DT Article DE Catecholamine depletion; Endophenotype; Positron emission tomography; Major depressive disorder; Bipolar disorder; Ventral striatum ID MAJOR DEPRESSIVE DISORDER; STRIATAL DOPAMINE TRANSPORTER; ACUTE TRYPTOPHAN DEPLETION; LOCUS-COERULEUS; SEROTONIN TRANSPORTER; MONOAMINE DEPLETION; PREFRONTAL CORTEX; GENETIC-VARIATION; BIPOLAR DISORDER; HEALTHY-SUBJECTS AB Catecholamine depletion with alpha-methylparatyrosine (AMPT) has previously been shown to induce depressive symptoms in currently remitted patients with major depressive disorder (MDD) but not healthy controls. Thus sensitivity to catecholamine depletion has been hypothesized to be an endophenotype of MDD. Here we tested this hypothesis in the context of a randomized, double-blinded, placebo-controlled design by measuring changes in mood in a group of psychiatrically-healthy individuals at risk of mood disorders by virtue of family history (high-risk subjects, HRs). In addition, we tested whether HRs differed from healthy controls with no family-history of mood disorders (low-risk controls, LRs) in their cerebral metabolic response when undergoing catecholamine depletion. Eight healthy LRs (6 males, mean age = 34.1 +/- 7.1) and 6 healthy HRs (3 males, mean age = 29.3 +/- 4.6) participated in two, 3-day-long identical sessions during which they completed standardized measures of depression, anxiety and fatigue and an [F-18] fluorodeoxyglucose (FDG) positron emission tomography (PET) scan. On one occasion participants received 4 weight-adjusted doses of AMPT and on the other occasion participants received 4 doses of placebo. The LR and HR groups did not differ from each other in their mood during sham depletion. However, during the period of peak catecholamine depletion, the HR group reported significantly more depression, anxiety and fatigue than the LR group. A region-of-interest analysis showed that during catecholamine depletion versus placebo the combined LR and HR groups displayed a significant increase in cerebral metabolic rate in the left and right ventral striata, left and right amygdalae, and left and right hippocampi (FWE-corrected p < 0.05). Whole brain voxel-wise analyses indicated significantly increased glucose metabolism in the left and right putamina (FWE-corrected p < 0.05) in the combined LR and HR groups in the AMPT versus the placebo session. In the LR group, alone, no significant elevation in glucose metabolism was observed in the regions-of-interest in the catecholamine depletion versus placebo condition. In the HR group, alone, the region-of-interest analysis showed a significant increase in cerebral metabolic rate in the left and right ventral striata (FWE-corrected p < 0.05). No regions-of-interest showed significantly different metabolism in the HR group versus the LR group in the placebo condition, however compared with the LR group, the HR group displayed nominally increased glucose metabolism in the left amygdala during catecholamine depletion (SVC-corrected p = 0.05). A region-of-interest analysis for the interaction contrast confirmed that catecholamine depletion had differential effects on HR and LR participants. Compared with the LR group, the HR group displayed significantly increased glucose metabolism in the left ventral striatum, left amygdala, and left lateral orbitofrontal cortex (OFC) (FWE-corrected p < 0.05). Our results suggest that sensitivity to catecholamine depletion may be a phenotypic marker of vulnerability to mood disorders that is characterized at the neurophysiological level by disinhibition of the striatum and its efferent projections comprising the limbic-cortical-striatal-pallidal-thalamic circuitry. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Savitz, Jonathan; Bellgowan, Patrick S. F.; Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA. [Savitz, Jonathan; Bellgowan, Patrick S. F.] Univ Tulsa, Tulsa Sch Community Med, Dept Med, Tulsa, OK 74104 USA. [Savitz, Jonathan; Wright, Niara; Tinsley, Ruth; Drevets, Wayne C.] NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Nugent, Allison C.; Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA. [Herscovitch, Peter] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Drevets, Wayne C.] Janssen Pharmaceut Johnson & Johnson Inc, Titusville, NJ 08560 USA. RP Savitz, J (reprint author), Laureate Inst Brain Res, 6655 S Yale Ave, Tulsa, OK 74136 USA. EM jsavitz@laureateinstitute.org OI Nugent, Allison/0000-0003-2569-2480 FU NIMH; Hope for Depression Research Foundation (HDRF) [RGA 8-015] FX This study was funded by the intramural program of the NIMH and a Hope for Depression Research Foundation (HDRF) grant (RGA 8-015) awarded to JS and WCD. NR 62 TC 2 Z9 2 U1 4 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 341 EP 355 DI 10.1016/j.nicl.2013.02.004 PG 15 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800039 PM 24179788 ER PT J AU Sweeney, EM Shinohara, RT Shiee, N Mateen, FJ Chudgar, AA Cuzzocreo, JL Calabresi, PA Pham, DL Reich, DS Crainiceanu, CM AF Sweeney, Elizabeth M. Shinohara, Russell T. Shiee, Navid Mateen, Farrah J. Chudgar, Avni A. Cuzzocreo, Jennifer L. Calabresi, Peter A. Pham, Dzung L. Reich, Daniel S. Crainiceanu, Ciprian M. TI OASIS is Automated Statistical Inference for Segmentation, with applications to multiple sclerosis lesion segmentation in MRI SO NEUROIMAGE-CLINICAL LA English DT Article DE Multiple sclerosis; MRI; Brain; Lesion segmentation; Statistical modeling; Logistic regression ID BLOOD-BRAIN-BARRIER; PROBABILISTIC SEGMENTATION; INTENSITY NONUNIFORMITY; IMAGES; QUANTIFICATION; DIAGNOSIS; TISSUE AB Magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients and is essential for diagnosing the disease and monitoring its progression. In practice, lesion load is often quantified by either manual or semi-automated segmentation of MRI, which is time-consuming, costly, and associated with large inter-and intra-observer variability. We propose OASIS is Automated Statistical Inference for Segmentation (OASIS), an automated statistical method for segmenting MS lesions in MRI studies. We use logistic regression models incorporating multiple MRI modalities to estimate voxel-level probabilities of lesion presence. Intensity-normalized T1-weighted, T2-weighted, fluid-attenuated inversion recovery and proton density volumes from 131 MRI studies (98 MS subjects, 33 healthy subjects) with manual lesion segmentations were used to train and validate our model. Within this set, OASIS detected lesions with a partial area under the receiver operating characteristic curve for clinically relevant false positive rates of 1% and below of 0.59% (95% CI; [0.50%, 0.67%]) at the voxel level. An experienced MS neuroradiologist compared these segmentations to those produced by LesionTOADS, an image segmentation software that provides segmentation of both lesions and normal brain structures. For lesions, OASIS out-performed LesionTOADS in 74% (95% CI: [65%, 82%]) of cases for the 98 MS subjects. To further validate the method, we applied OASIS to 169 MRI studies acquired at a separate center. The neuroradiologist again compared the OASIS segmentations to those from LesionTOADS. For lesions, OASIS ranked higher than LesionTOADS in 77% (95% CI: [71%, 83%]) of cases. For a randomly selected subset of 50 of these studies, one additional radiologist and one neurologist also scored the images. Within this set, the neuroradiologist ranked OASIS higher than LesionTOADS in 76% (95% CI: [64%, 88%]) of cases, the neurologist 66% (95% CI: [52%, 78%]) and the radiologist 52% (95% CI: [38%, 66%]). OASIS obtains the estimated probability for each voxel to be part of a lesion by weighting each imaging modality with coefficient weights. These coefficients are explicit, obtained using standard model fitting techniques, and can be reused in other imaging studies. This fully automated method allows sensitive and specific detection of lesion presence and may be rapidly applied to large collections of images. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Sweeney, Elizabeth M.; Reich, Daniel S.; Crainiceanu, Ciprian M.] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. [Sweeney, Elizabeth M.; Shinohara, Russell T.; Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. [Shinohara, Russell T.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Shiee, Navid; Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Mateen, Farrah J.] Johns Hopkins Univ, Dept Int Hlth, Baltimore, MD 21205 USA. [Chudgar, Avni A.] Brigham & Womens Hosp, Div Emergency Radiol, Dept Radiol, Boston, MA 02115 USA. [Chudgar, Avni A.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Cuzzocreo, Jennifer L.; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol, Sch Med, Baltimore, MD 21287 USA. [Calabresi, Peter A.; Reich, Daniel S.] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. RP Sweeney, EM (reprint author), Johns Hopkins Univ, Dept Biostat, 615 N Wolfe St,E3518, Baltimore, MD 21205 USA. EM emsweene@jhsph.edu RI Reich, Daniel/E-5701-2010 OI Reich, Daniel/0000-0002-2628-4334 FU Intramural Research Program of NINDS [NINDS R01 NS070906, NINDS R01 NS060910]; NIBIB [R01 EB012547] FX The authors would like to thank Colin Shea, the Neuroimmunology Branch clinical group and the technicians at the NIH and Kirby Center who were instrumental in helping to collect and process the study data. This research was partially supported by the Intramural Research Program of NINDS, NINDS R01 NS070906, NINDS R01 NS060910, and NIBIB R01 EB012547. NR 42 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 402 EP 413 DI 10.1016/j.nicl.2013.03.002 PG 12 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800045 PM 24179794 ER PT J AU Grodin, EN Lin, H Durkee, CA Hommer, DW Momenan, R AF Grodin, Erica N. Lin, Henry Durkee, Caitlin A. Hommer, Daniel W. Momenan, Reza TI Deficits in cortical, diencephalic and midbrain gray matter in alcoholism measured by VBM: Effects of co-morbid substance abuse SO NEUROIMAGE-CLINICAL LA English DT Article DE Voxel-based morphometry; Alcoholism; Polysubstance use; Gray matter structure ID VOXEL-BASED MORPHOMETRY; POSTTRAUMATIC-STRESS-DISORDER; DEPENDENT INDIVIDUALS; ORBITOFRONTAL CORTEX; HIPPOCAMPAL VOLUME; INTELLIGENCE SCALE; KORSAKOFF-SYNDROME; MAJOR DEPRESSION; BRAIN ATROPHY; MR-IMAGES AB Objective: Alcoholism has been associated with a widespread pattern of gray matter atrophy. This study sought to investigate the spectrum of volume alterations in a population of alcoholics with only alcohol dependence, polysubstance abusing alcoholics, and a comparison population of healthy controls. Method: Thirty-seven 'pure' alcoholics, 93 polysubstance abusing alcoholics, and 69 healthy controls underwent structural T1 MRI scans. Voxel-based morphometry was performed to investigate gray matter alterations. Results: Alcoholic dependent inpatients (both with and without a history of DSM-IV substance abuse/dependence diagnosis) displayed significant gray matter differences in the mesial region of the frontal lobe and right temporal lobe. 'Pure' alcoholics exhibited a pattern of subcortical changes similar to that seen in Wernicke-Korsakoff Syndrome when compared to polysubstance abusing alcoholics. 'Pure' alcoholics and polysubstance abusing alcoholics did not differ significantly in measures of cortical gray matter, liver function, or nutrition. Conclusions: These findings reinforce the accepted literature in regards to frontal lobe gray matter atrophy in alcohol dependence. This study calls for additional research in order to investigate the spectrum from uncomplicated alcoholism to Wernicke-Korsakoff Syndrome. Further research is needed to elucidate the exact cause of this pattern of differences and to determine what factors are responsible for the patterns of gray matter reduction or difference in 'pure' and polysubstance abusing alcoholics. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Grodin, Erica N.; Lin, Henry; Durkee, Caitlin A.; Hommer, Daniel W.; Momenan, Reza] NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Momenan, R (reprint author), NIAAA, Sect Brain Electrophysiol & Imaging, LCTS, NIH, 10 Ctr Dr,Room 10 CRC 1E-5435, Bethesda, MD 20892 USA. EM rezam@nih.gov RI Grodin, Erica/G-1054-2015; OI Grodin, Erica/0000-0001-5528-4918 FU National Institute on Alcohol Abuse and Alcoholism FX This research was sponsored by the intramural research funds from the National Institute on Alcohol Abuse and Alcoholism. NR 52 TC 17 Z9 17 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 469 EP 476 DI 10.1016/j.nicl.2013.03.013 PG 8 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800052 PM 24179800 ER PT J AU Thomas, LA Kim, P Bones, BL Hinton, KE Milch, HS Reynolds, RC Adleman, NE Marsh, AA Blair, RJR Pine, DS Leibenluft, E AF Thomas, Laura A. Kim, Pilyoung Bones, Brian L. Hinton, Kendra E. Milch, Hannah S. Reynolds, Richard C. Adleman, Nancy E. Marsh, Abigail A. Blair, R. J. R. Pine, Daniel S. Leibenluft, Ellen TI Elevated amygdala responses to emotional faces in youths with chronic irritability or bipolar disorder SO NEUROIMAGE-CLINICAL LA English DT Article DE Severe mood dysregulation; Bipolar disorder; Amygdala; Face; Emotion ID SEVERE MOOD DYSREGULATION; FACIAL EXPRESSIONS; LONGITUDINAL COURSE; SPECTRUM DISORDERS; LABELING DEFICITS; NEURAL RESPONSES; RATING-SCALE; CHILDREN; ADOLESCENTS; DEPRESSION AB A major controversy in child psychiatry is whether bipolar disorder (BD) presents in children as severe, non-episodic irritability (operationalized here as severe mood dysregulation, SMD), rather than with manic episodes as in adults. Both classic, episodic BD and SMD are severe mood disorders characterized by deficits in processing emotional stimuli. Neuroimaging techniques can be used to test whether the pathophysiology mediating these deficits are similar across the two phenotypes. Amygdala dysfunction during face emotion processing is well-documented in BD, but little is known about amygdala dysfunction in chronically irritable youth. We compared neural activation in SMD (n = 19), BD (n = 19), and healthy volunteer (HV; n = 15) youths during an implicit face-emotion processing task with angry, fearful and neutral expressions. In the right amygdala, both SMD and BD exhibited greater activity across all expressions than HV. However, SMD and BD differed from each other and HV in posterior cingulate cortex, posterior insula, and inferior parietal lobe. In these regions, only SMD showed deactivation in response to fearful expressions, whereas only BD showed deactivation in response to angry expressions. Thus, during implicit face emotion processing, youth with BD and those with SMD exhibit similar amygdala dysfunction but different abnormalities in regions involved in information monitoring and integration. (C) 2013 The Authors. Published by Elsevier Inc. Open access under CC BY license. C1 [Thomas, Laura A.; Kim, Pilyoung; Bones, Brian L.; Hinton, Kendra E.; Adleman, Nancy E.; Blair, R. J. R.; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Emot & Dev Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Thomas, Laura A.] NIDA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Kim, Pilyoung] Univ Denver, Dept Psychol, Denver, CO 80208 USA. [Milch, Hannah S.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Reynolds, Richard C.] NIMH, Sci & Stat Comp Core, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Marsh, Abigail A.] Georgetown Univ, Dept Psychol, Washington, DC 20057 USA. RP Thomas, LA (reprint author), NIDA, Off Director, 6001 Execut Blvd MSC 9581, Bethesda, MD 20892 USA. EM tlaura@mail.nih.gov OI Thomas, Laura/0000-0002-4106-1358 FU Intramural Research Program of the National Institute of Mental Health, National Institutes of Health FX Funding for this study was provided exclusively by the Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. The authors have no conflicts to disclose. We would like to thank the staff of the Emotion and Development Branch at NIMH and the children and families for their participation. NR 47 TC 18 Z9 18 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 637 EP 645 DI 10.1016/j.nicl.2013.04.007 PG 9 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800070 PM 23977455 ER PT J AU Maccotta, L He, BJ Snyder, AZ Eisenman, LN Benzinger, TL Ances, BM Corbetta, M Hogan, RE AF Maccotta, Luigi He, Biyu J. Snyder, Abraham Z. Eisenman, Lawrence N. Benzinger, Tammie L. Ances, Beau M. Corbetta, Maurizio Hogan, R. Edward TI Impaired and facilitated functional networks in temporal lobe epilepsy SO NEUROIMAGE-CLINICAL LA English DT Article DE Epilepsy; Temporal lobe; Hippocampus; Insula; fMRI; Functional connectivity ID RESTING HUMAN BRAIN; RESONANCE-IMAGING CONNECTIVITY; DEFAULT-MODE NETWORK; NEURONAL-ACTIVITY; STATE NETWORKS; BASAL GANGLIA; WHITE-MATTER; NORMAL MRI; FMRI; SCLEROSIS AB How epilepsy affects brain functional networks remains poorly understood. Here we investigated resting state functional connectivity of the temporal region in temporal lobe epilepsy. Thirty-two patients with unilateral temporal lobe epilepsy underwent resting state blood-oxygenation level dependent functional magnetic resonance imaging. We defined regions of interest a priori focusing on structures involved, either structurally or metabolically, in temporal lobe epilepsy. These structures were identified in each patient based on their individual anatomy. Our principal findings are decreased local and inter-hemispheric functional connectivity and increased intra-hemispheric functional connectivity ipsilateral to the seizure focus compared to normal controls. Specifically, several regions in the affected temporal lobe showed increased functional coupling with the ipsilateral insula and immediately neighboring subcortical regions. Additionally there was significantly decreased functional connectivity between regions in the affected temporal lobe and their contralateral homologous counterparts. Intriguingly, decreased local and inter-hemispheric connectivity was not limited or even maximal for the hippocampus or medial temporal region, which is the typical seizure onset region. Rather it also involved several regions in temporal neo-cortex, while also retaining specificity, with neighboring regions such as the amygdala remaining unaffected. These findings support a view of temporal lobe epilepsy as a disease of a complex functional network, with alterations that extend well beyond the seizure onset area, and the specificity of the observed connectivity changes suggests the possibility of a functional imaging biomarker for temporal lobe epilepsy. (C) 2013 The Authors. Published by Elsevier Inc. C1 [Maccotta, Luigi; Snyder, Abraham Z.; Eisenman, Lawrence N.; Ances, Beau M.; Corbetta, Maurizio; Hogan, R. Edward] Washington Univ, Dept Neurol, St Louis, MO 63110 USA. [He, Biyu J.] NINDS, NIH, Bethesda, MD 20892 USA. [Snyder, Abraham Z.; Benzinger, Tammie L.; Corbetta, Maurizio] Washington Univ, Dept Radiol, St Louis, MO 63110 USA. [Benzinger, Tammie L.] Washington Univ, Dept Neurol Surg, St Louis, MO 63110 USA. [Corbetta, Maurizio] Washington Univ, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Maccotta, L (reprint author), Washington Univ, Dept Neurol, 660 South Euclid Ave,Campus Box 8111, St Louis, MO 63110 USA. EM maccottal@neuro.wustl.edu; biyu.jade.he@gmail.com; avi@npg.wustl.edu; eisenmanl@neuro.wustl.edu; benzingert@mir.wustl.edu; ancesb@neuro.wustl.edu; mau@npg.wustl.edu; hogane@neuro.wustl.edu OI Ances, Beau/0000-0003-3862-7397; He, Biyu/0000-0003-1549-1351 FU National Center for Advancing Translational Sciences [UL1TR000448, KL2TR000450]; National Institutes of Health [P50AG05681, 5P01AG026276, AG00399127, 5P30NS04805608]; Institute of Clinical and Translational Sciences at Washington University [UL1RR024992] FX This work was supported by the National Center for Advancing Translational Sciences [UL1TR000448, sub award KL2TR000450], the National Institutes of Health [P50AG05681, 5P01AG026276, AG00399127, 5P30NS04805608], and the Institute of Clinical and Translational Sciences at Washington University [UL1RR024992]. NR 76 TC 40 Z9 41 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1582 J9 NEUROIMAGE-CLIN JI NeuroImage-Clin. PY 2013 VL 2 BP 862 EP 872 DI 10.1016/j.nicl.2013.06.011 PG 11 WC Neuroimaging SC Neurosciences & Neurology GA V37LH UT WOS:000209276800095 PM 24073391 ER PT S AU Resnik, DB AF Resnik, David B. BE Rappert, B Selgelid, MJ TI Scientific Control Over Dual-Use Research: Prospects for Self-Regulation SO ON THE DUAL USES OF SCIENCE AND ETHICS: PRINCIPLES, PRACTICES, AND PROSPECTS SE Practical Ethics and Public Policy Monograph LA English DT Proceedings Paper CT Workshop on Promoting Dual Use Ethics CY JAN, 2010 CL Australian Natl Univ, Ctr Appl Philosophy & Publ Eth, Canberra, AUSTRALIA SP Wellcome Trust HO Australian Natl Univ, Ctr Appl Philosophy & Publ Eth ID CONFLICTS-OF-INTEREST; RESPONSIBLE CONDUCT; BIOMEDICAL-RESEARCH; NATIONAL-SURVEY; LIFE SCIENCES; USE DILEMMA; POLICIES; VIRUS; BIOSECURITY; ETHICS C1 [Resnik, David B.] NIEHS, NIH, Bethesda, MD USA. NR 52 TC 0 Z9 1 U1 0 U2 0 PU AUSTRALIAN NATL UNIV PI CANBERRA ACT PA P O BOX 4, 2600 CANBERRA ACT, AUSTRALIA SN 2202-4816 BN 978-1-925021-33-2; 978-1-925021-34-9 J9 PRACT ETHIC PUB POL PY 2013 IS 4 BP 237 EP 253 PG 17 WC Ethics; Social Issues SC Social Sciences - Other Topics; Social Issues GA BB7SW UT WOS:000345978000015 ER PT J AU Mannisto, T Karumanchi, SA Pouta, A Vaarasmaki, M Mendola, P Miettola, S Surcel, HM Bloigu, A Ruokonen, A Jarvelin, MR Hartikainen, AL Suvanto, E AF Maennistoe, Tuija Karumanchi, S. Ananth Pouta, Anneli Vaarasmaki, Marja Mendola, Pauline Miettola, Satu Surcel, Helja-Marja Bloigu, Aini Ruokonen, Aimo Jarvelin, Marjo-Riitta Hartikainen, Anna-Liisa Suvanto, Eila TI Preeclampsia, gestational hypertension and subsequent hypothyroidism SO PREGNANCY HYPERTENSION-AN INTERNATIONAL JOURNAL OF WOMENS CARDIOVASCULAR HEALTH LA English DT Article DE Preeclampsia; Gestational hypertension; Thyroid; Hypothyroidism AB Objectives: To evaluate the effect of preeclampsia (PE) and gestational hypertension (GH) on subsequent hypothyroidism. Recent studies suggest that women with PE have increased risk for reduced thyroid function, but the association between PE and GH with overt hypothyroidism has not been examined. Study design: Two prospective population-based cohort studies, the Northern Finland Birth Cohorts 1966 and 1986, followed women who had PE (N = 955), GH (N = 1449) or were normotensive (N = 13531) during pregnancy. Finnish national registers were used to confirm subsequent hypothyroidism. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) estimated hypothyroidism risk when comparing women with PE or GH with normotensive women. Main outcome measures: Primary hypothyroidism during follow-up of 20-40 years. Results: The subsequent prevalence of hypothyroidism was higher among women with PE (4.0%) and GH (4.5%) compared with normotensive women (3.5%), but the risk increase was not significant (aHR for PE 1.13, 95% CI 0.80-1.59 and aHR for GH 1.11, 95% CI 0.85-1.45). Subgroup analysis among nulliparous women revealed a significant association between late PE and subsequent hypothyroidism (aHR 1.82, 95% CI 1.04-3.19). Early or recurrent PE was not associated with hypothyroidism (aHR 0.93, 95% CI 0.46-1.81 and aHR 1.35, 95% CI 0.63-2.88, respectively). Conclusions: Overall, PE or GH during pregnancy was not significantly associated with subsequent hypothyroidism in Finnish women after 20-40 years of follow-up. However, late PE in nulliparous women was associated with a 1.8-fold increased risk of subsequent hypothyroidism, a finding that merits further study in other populations. Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. C1 [Maennistoe, Tuija; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Dept Epidemiol Stat & Prevent Res, NIH, Rockville, MD 20852 USA. [Maennistoe, Tuija; Ruokonen, Aimo] Univ Oulu, Dept Clin Chem, Oulu 90014, Finland. [Karumanchi, S. Ananth] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Boston, MA 02115 USA. [Pouta, Anneli; Miettola, Satu; Surcel, Helja-Marja; Bloigu, Aini; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Dept Children Young People & Families, Oulu 90101, Finland. [Pouta, Anneli; Vaarasmaki, Marja; Miettola, Satu; Hartikainen, Anna-Liisa; Suvanto, Eila] Univ Oulu, Dept Obstet & Gynecol, Oulu 90014, Finland. [Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu 90014, Finland. [Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London SW7 2AZ, England. RP Mannisto, T (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Dept Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B05, Rockville, MD 20852 USA. EM mannistoTI@mail.nih.gov OI Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Mannisto, Tuija/0000-0002-6382-9153; Mendola, Pauline/0000-0001-5330-2844 FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development; Alma and K.A. Snellman Foundation (Oulu, Finland); Jalmari and Rauha Ahokas Foundation (Finland); Northern Ostrobothnia Hospital District (Finland); Academy of Finland FX This work was supported in part by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development, the Alma and K.A. Snellman Foundation (Oulu, Finland), the Jalmari and Rauha Ahokas Foundation (Finland), the Northern Ostrobothnia Hospital District (Finland) and the Academy of Finland. The sponsors had no role in study design, data collection, analysis and interpretation of data, in writing the report or in the decision to submit the paper for publication. NR 31 TC 2 Z9 6 U1 2 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2210-7789 J9 PREGNANCY HYPERTENS JI Pregnancy Hypertens. PD JAN PY 2013 VL 3 IS 1 BP 21 EP 27 DI 10.1016/j.preghy.2012.09.001 PG 7 WC Obstetrics & Gynecology; Peripheral Vascular Disease SC Obstetrics & Gynecology; Cardiovascular System & Cardiology GA V39YK UT WOS:000209446100005 PM 23439671 ER PT J AU Maciag, AE Holland, RJ Cheng, YSR Rodriguez, LG Saavedra, JE Anderson, LM Keefer, LK AF Maciag, Anna E. Holland, Ryan J. Cheng, Y. -S. Robert Rodriguez, Luis G. Saavedra, Joseph E. Anderson, Lucy M. Keefer, Larry K. TI Nitric oxide-releasing prodrug triggers cancer cell death through deregulation of cellular redox balance SO REDOX BIOLOGY LA English DT Article DE Glutathione; Nitric oxide; Arylated diazeniumdiolate; Leukemia AB JS-K is a nitric oxide (NO) releasing prodrug of the O-2-arylated diazeniumdiolate family that has demonstrated pronounced cytotoxicity and antitumor properties in a variety of cancer models both in vitro and in vivo. The current study of the metabolic actions of JS-K was undertaken to investigate mechanisms of its cytotoxicity. Consistent with model chemical reactions, the activating step in the metabolism of JS-K in the cell is the clearylation of the diazeniurndiolate by glutathione (GSH) via a nucleophilic aromatic substitution reaction. The resulting product (CEP/NO anion) spontaneously hydrolyzes, releasing two equivalents of NO The GSH/GSSG reclox couple is considered to be the major redox buffer of the cell, helping maintain a reducing environment under basal conditions. We have quantified the effects of JS-K on cellular GSH content, and show that JS -K markedly depletes GSH, due to JS-K's rapid uptake and cascading release of NO and reactive nitrogen species. The depletion of GSH results in alterations in the redox potential of the cellular environment, initiating MARK stress signaling pathways, and inducing apoptosis. Microarray analysis confirmed signaling gene changes at the transcriptional level and revealed alteration in the expression of several genes crucial for maintenance of cellular redox homeostasis, as well as cell proliferation and survival, including MYC. Pre-treating cells with the known GSH precursor and nucleophilic reducing agent N-acetylcysteine prevented the signaling events that lead to apoptosis. These data indicate that multiplicative depletion of the reduced glutathione pool and deregulation of intracellular redox balance are important initial steps in the mechanism of JS-K's cytotoxic action. (C) 2013 The Authors. Published by Elsevier By. Open access under CC BY-NC-ND license. C1 [Maciag, Anna E.; Saavedra, Joseph E.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. [Holland, Ryan J.; Anderson, Lucy M.; Keefer, Larry K.] Frederick Natl Lab Canc Res, Biol Chem Lab, Frederick, MD USA. [Cheng, Y. -S. Robert] NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Rodriguez, Luis G.] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Lab Prote & Analyt Technol, Adv Technol Program, Frederick, MD 21702 USA. RP Maciag, AE (reprint author), SAIC Frederick Inc, Frederick Natl Lab Canc Res, Bldg 538,Rm 206, Frederick, MD 21702 USA. EM maciaga@mail.nih.gov FU Intramural Research Program of the National Institutes of Health, National Cancer Institute; National Cancer Institute [HHSN261200800001E] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and with Federal funds from the National Cancer Institute under Contract HHSN261200800001E. NR 34 TC 15 Z9 16 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 2213-2317 J9 REDOX BIOL JI Redox Biol. PY 2013 VL 1 IS 1 BP 115 EP 124 DI 10.1016/j.redox.2012.12.002 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V38BC UT WOS:000209317900019 PM 24024144 ER PT B AU Holmgren, M Rosenthal, JJC AF Holmgren, Miguel Rosenthal, Joshua J. C. BE Maas, S TI Regulation of Ion Channel and Transporter Function Through RNA Editing SO RNA EDITING: CURRENT RESEARCH AND FUTURE TRENDS LA English DT Article; Book Chapter ID CURRENT-VOLTAGE RELATIONSHIP; GLUTAMATE-OPERATED CHANNELS; SHAKER POTASSIUM CHANNELS; PIG VENTRICULAR MYOCYTES; RECEPTOR SUBUNITS GLUR5; DEPENDENT K+ CHANNELS; MEMBRANE FATTY-ACIDS; AUDITORY HAIR-CELLS; PRE-MESSENGER-RNAS; NA/K PUMP CURRENT AB A large proportion of the recoding events mediated by RNA editing are in mRNAs that encode ion channels and transporters. The effects of these events on protein function have been characterized in only a few cases. In even fewer instances are the mechanistic underpinnings of these effects understood. This chapter focuses on how RNA editing affects protein function and higher order physiology. In mammals, particular attention is given to the GluA2, an ionotropic glutamate receptor subunit, and K(v)1.1, a voltage-dependent K+ channel, because they are particularly well understood. In addition, work on cephalopod K+ channels and Na+/K+-ATPases has also provided important clues on the rules used by RNA editing to regulate excitability. Finally, we discuss some of the emerging targets for editing and how this process may be used to regulate nervous function in response to a variable environment. C1 [Holmgren, Miguel] NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. [Rosenthal, Joshua J. C.] Univ Puerto Rico, Inst Neurobiol, San Juan, PR 00901 USA. [Rosenthal, Joshua J. C.] Univ Puerto Rico, Dept Biochem, San Juan, PR 00936 USA. RP Holmgren, M (reprint author), NINDS, Mol Neurophysiol Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM holmgren@ninds.nih.gov; rosenthal.joshua@gmail.com NR 101 TC 0 Z9 0 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-88-1; 978-1-908230-23-2 PY 2013 BP 1 EP 16 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF6XK UT WOS:000383756900002 ER PT B AU Maas, S AF Maas, Stefan BE Maas, S TI RNA Editing Current Research and Future Trends Preface SO RNA EDITING: CURRENT RESEARCH AND FUTURE TRENDS LA English DT Editorial Material; Book Chapter C1 [Maas, Stefan] NIGMS, Div Genet & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Maas, S (reprint author), NIGMS, Div Genet & Dev Biol, NIH, Bethesda, MD 20892 USA. EM stefan.maas@nih.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-908230-88-1; 978-1-908230-23-2 PY 2013 BP VII EP VII PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BF6XK UT WOS:000383756900001 ER PT J AU Kikuchi, K Taniguchi, E Chen, HIH Svalina, MN Abraham, J Huang, ET Nishijo, K Davis, S Louden, C Zarzabal, LA Recht, O Bajwa, A Berlow, N Suelves, M Perkins, SL Meltzer, PS Mansoor, A Michalek, JE Chen, YD Rubin, BP Keller, C AF Kikuchi, Ken Taniguchi, Eri Chen, Hung-I Harry Svalina, Matthew N. Abraham, Jinu Huang, Elaine T. Nishijo, Koichi Davis, Sean Louden, Christopher Zarzabal, Lee Ann Recht, Olivia Bajwa, Ayeza Berlow, Noah Suelves, Monica Perkins, Sherrie L. Meltzer, Paul S. Mansoor, Atiya Michalek, Joel E. Chen, Yidong Rubin, Brian P. Keller, Charles TI Rb1 loss modifies but does not initiate alveolar rhabdomyosarcoma SO SKELETAL MUSCLE LA English DT Article DE Alveolar rhabdomyosarcoma; Disease modifier; Sarcoma; Rb1; Spindle cell; Retinoblastoma AB Background: Alveolar rhabdomyosarcoma (aRMS) is a myogenic childhood sarcoma frequently associated with a translocation-mediated fusion gene, Pax3:Foxo1a. Methods: We investigated the complementary role of Rb1 loss in aRMS tumor initiation and progression using conditional mouse models. Results: Rb1 loss was not a necessary and sufficient mutational event for rhabdomyosarcomagenesis, nor a strong cooperative initiating mutation. Instead, Rb1 loss was a modifier of progression and increased anaplasia and pleomorphism. Whereas Pax3: Foxo1a expression was unaltered, biomarkers of aRMS versus embryonal rhabdomyosarcoma were both increased, questioning whether these diagnostic markers are reliable in the context of Rb1 loss. Genome-wide gene expression in Pax3: Foxo1a, Rb1 tumors more closely approximated aRMS than embryonal rhabdomyosarcoma. Intrinsic loss of pRb function in aRMS was evidenced by insensitivity to a Cdk4/6 inhibitor regardless of whether Rb1 was intact or null. This loss of function could be attributed to low baseline Rb1, pRb and phospho-pRb expression in aRMS tumors for which the Rb1 locus was intact. Pax3: Foxo1a RNA interference did not increase pRb or improve Cdk inhibitor sensitivity. Human aRMS shared the feature of low and/or heterogeneous tumor cell pRb expression. Conclusions: Rb1 loss from an already low pRb baseline is a significant disease modifier, raising the possibility that some cases of pleomorphic rhabdomyosarcoma may in fact be Pax3: Foxo1a-expressing aRMS with Rb1 or pRb loss of function. C1 [Kikuchi, Ken; Svalina, Matthew N.; Abraham, Jinu; Huang, Elaine T.; Recht, Olivia; Berlow, Noah; Keller, Charles] Pape Family Pediat Res Inst, Pediat Canc Biol Program, Dept Pediat, Portland, OR 97239 USA. [Taniguchi, Eri; Chen, Hung-I Harry; Nishijo, Koichi; Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Taniguchi, Eri; Chen, Hung-I Harry; Nishijo, Koichi; Chen, Yidong] Univ Texas Hlth Sci Ctr San Antonio, Dept Biostat, Greehey Childrens Canc Res Inst, San Antonio, TX 78229 USA. [Davis, Sean; Louden, Christopher; Zarzabal, Lee Ann; Meltzer, Paul S.; Michalek, Joel E.; Chen, Yidong] NCI, Oncogen Sect, Pediat Oncol Branch, Adv Technol Ctr, Gaithersburg, MD 20877 USA. [Bajwa, Ayeza; Mansoor, Atiya] Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. [Suelves, Monica] Inst Med Predict & Personalitzada Canc, Barcelona 08916, Spain. [Perkins, Sherrie L.] Univ Utah, ARUP Labs, Salt Lake City, UT 84112 USA. [Perkins, Sherrie L.] Univ Utah, Dept Pathol, Salt Lake City, UT 84112 USA. [Rubin, Brian P.] Cleveland Clin Fdn, Taussig Canc Ctr, Dept Anat Pathol, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin Fdn, Taussig Canc Ctr, Dept Mol Genet, Cleveland, OH 44195 USA. [Rubin, Brian P.] Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH 44195 USA. RP Keller, C (reprint author), Pape Family Pediat Res Inst, Pediat Canc Biol Program, Dept Pediat, Portland, OR 97239 USA. EM keller@ohsu.edu OI Kikuchi, Ken/0000-0003-3097-7480; Davis, Sean/0000-0002-8991-6458 FU Nylund estate; Scott Carter Foundation; [NIH1R01CA133229] FX Primary funding sources were NIH1R01CA133229 and a gift from the Nylund estate. KN and JA were supported by a training award from the Scott Carter Foundation. The Developmental Studies Hybridoma Bank is developed under the auspices of the NICHD and maintained by The University of Iowa, Iowa City, IA, USA. De-identified human tumor samples were provided by the Nationwide Children's Hospital Biopathology Center or the Children's Oncology Group Biorepository. The authors thank Amy Paul for assistance with studies, Dennis Duran for slide scanning and Hajime Hosoi for reagents. NR 42 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 2044-5040 J9 SKELET MUSCLE JI Skeletal Muscle PY 2013 VL 3 AR 27 DI 10.1186/2044-5040-3-27 PG 15 WC Cell Biology SC Cell Biology GA V39PN UT WOS:000209423000027 PM 24274149 ER PT S AU Blanchard, RC Tolson, RH Lugo, RA Huh, L AF Blanchard, Robert C. Tolson, Robert H. Lugo, Rafael A. Huh, Lynn BE Tanygin, S Park, RS Starchville, TF Newman, LK TI INERTIAL NAVIGATION ENTRY, DESCENT, AND LANDING RECONSTRUCTION USING MONTE CARLO TECHNIQUES SO SPACEFLIGHT MECHANICS 2013, PTS I-IV SE Advances in the Astronautical Sciences LA English DT Proceedings Paper CT 23rd AAS/AIAA Space Flight Mechanics Meeting CY FEB 10-14, 2013 CL Kauai, HI SP Amer Astronaut Soc, Space Flight Mech Tech Comm, Amer Inst Aeronaut & Astronaut, Astrodynam Tech Comm, Anal Graph Inc AB A new method for performing entry, descent, and landing trajectory reconstruction is presented as an extension of the standard inertial navigation approach of integrating inertial navigation unit data. The method, Inertial Navigation Statistical Trajectory and Atmosphere Reconstruction (INSTAR), provides statistical uncertainties for the reconstructed trajectory parameters by incorporating inertial navigation and Monte Carlo dispersion techniques. It also permits the inclusion of redundant data by refining the dispersed trajectories with those that satisfy the redundant observations to within specified tolerances. The primary advantage of inertial navigation over typical existing filtering techniques is the independence from aerodynamic and atmospheric models. The INSTAR concept along with a demonstration using flight data from the recent Mars Science Laboratory mission is presented. Initial conditions and acceleration biases are dispersed from nominal using Monte Carlo techniques, and the subset of trajectories that land near the reference landing site are used to update initial conditions and acceleration biases and to obtain trajectory statistics. These biases are then compared to the acceleration biases observed in the flight data. Eventually, the process will extend to other redundant data types and to atmosphere reconstruction, a process that relies on trajectory parameters and their uncertainties. C1 [Blanchard, Robert C.; Tolson, Robert H.; Huh, Lynn] NIA, 100 Explorat Way, Hampton, VA 23666 USA. [Lugo, Rafael A.] N Carolina State Univ, Dept Mech & Aerosp Engn, NIA, 100 Explorat Way, Hampton, VA 23666 USA. RP Blanchard, RC (reprint author), NIA, 100 Explorat Way, Hampton, VA 23666 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU UNIVELT INC PI SAN DIEGO PA PO BOX 28130, SAN DIEGO, CA 92128 USA SN 1081-6003 BN 978-0-87703-597-8 J9 ADV ASTRONAUT SCI PY 2013 VL 148 BP 1575 EP 1594 PN I-IV PG 20 WC Engineering, Aerospace SC Engineering GA BE9KW UT WOS:000377723700092 ER PT J AU Duggan, C Ballard-Barbash, R Baumgartner, RN Baumgartner, KB Bernstein, L McTiernan, A AF Duggan, Catherine Ballard-Barbash, Rachel Baumgartner, Richard N. Baumgartner, Kathy B. Bernstein, Leslie McTiernan, Anne TI Associations between null mutations in GSTT1 and GSTM1, the GSTP1 Ile (105)Val polymorphism, and mortality in breast cancer survivors SO SPRINGERPLUS LA English DT Article DE Glutathione-S-transferases; GSTT1; GSTM1; GSTP1; Polymorphisms; Breast cancer survival; Mortality AB Purpose: Here we assessed associations between null mutations in glutathione-S-transferase (GST)T1 and GSTM1 genes, and the rs1695 polymorphism in GSTP1 (Ile (105)Val), and risk of breast cancer-specific (n=45) and all-cause (n=99) mortality in a multiethnic, prospective cohort of 533 women diagnosed with stage I-IIIA breast cancer in 1995-1999, enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. Methods: We measured the presence of the null mutation in GSTT1 and GSTM1, and the rs1695 polymorphism in GSTP1 by polymerase chain reaction. We assessed associations between breast-cancer specific and all-cause mortality using Cox proportional hazards models. Results: Participants with ER-negative tumors were more likely to be GSTT1 null (X-2=4.52; P=0.03), and African American women were more likely to be GSTM1 null (X-2=34.36; P<0.0001). Neither GSTM1 nor GSTT1 null mutations were associated with breast cancer-specific or all-cause mortality. In a model adjusted for body mass index, race/ethnicity, tumor stage and treatment received at diagnosis, the variant Val allele of rs1695 was associated with increased risk of all-cause (HR=1.81, 95% CI 1.16-2.82, P=0.008), but not breast cancer-specific mortality. The GSTT1 null mutation was associated with significantly higher levels of C-reactive protein. Conclusions: GSTM1 and GSTT1 null genotypes had no effect on outcome; however the variant allele of rs1695 appears to confer increased risk for all-cause mortality in breast-cancer survivors. Given the limited sample size of most studies examining associations between GST polymorphisms with breast cancer survival, and the lack of women undergoing more contemporary treatment protocols (treated prior to 1999), it may be helpful to re-examine this issue among larger samples of women diagnosed after the late 1990s, who all received some form of chemotherapy or radiotherapy. C1 [Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci, Seattle, WA 98104 USA. [Ballard-Barbash, Rachel] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Baumgartner, Richard N.; Baumgartner, Kathy B.] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Epidemiol & Populat Hlth, Louisville, KY 40292 USA. [Bernstein, Leslie] City Hope Natl Med Ctr, Div Populat Sci, Duarte, CA 91010 USA. RP Duggan, C (reprint author), Fred Hutchinson Canc Res Ctr, Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA. EM cduggan@fhcrc.org OI Duggan, Catherine/0000-0001-7369-4021 FU National Cancer Institute [N01-CN-75036-20, N01-CN-05228, N01-PC-67010, R25-CA94880]; National Institutes of Health [M01-RR-00037]; University of New Mexico [NCRR M01-RR-0997]; National Institute of Child Health and Human Development [N01-HD-3-3175]; California Department of Health Services [050Q-8709-S1528] FX National Cancer Institute (N01-CN-75036-20, N01-CN-05228, N01-PC-67010, R25-CA94880); National Institutes of Health (M01-RR-00037); University of New Mexico (NCRR M01-RR-0997); National Institute of Child Health and Human Development (N01-HD-3-3175); California Department of Health Services (050Q-8709-S1528). NR 24 TC 11 Z9 12 U1 0 U2 4 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PY 2013 VL 2 AR 450 DI 10.1186/2193-1801-2-450 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V40FS UT WOS:000209465100022 PM 24083102 ER PT J AU Hirko, KA Soliman, AS Banerjee, M Ruterbusch, J Harford, JB Chamberlain, RM Graff, JJ Merajver, SD Schwartz, K AF Hirko, Kelly A. Soliman, Amr S. Banerjee, Mousumi Ruterbusch, Julie Harford, Joe B. Chamberlain, Robert M. Graff, John J. Merajver, Sofia D. Schwartz, Kendra TI Characterizing inflammatory breast cancer among Arab Americans in the California, Detroit and New Jersey Surveillance, Epidemiology and End Results (SEER) registries (1988-2008) SO SPRINGERPLUS LA English DT Article DE Inflammatory breast cancer; Arab; Race; Hierarchical logistic regression AB Introduction: Inflammatory breast cancer (IBC) is characterized by an apparent geographical distribution in incidence, being more common in North Africa than other parts of the world. Despite the rapid growth of immigrants to the United States from Arab nations, little is known about disease patterns among Arab Americans because a racial category is rarely considered for this group. The aim of this study was to advance our understanding of the burden of IBC in Arab ethnic populations by describing the proportion of IBC among different racial groups, including Arab Americans from the Detroit, New Jersey and California Surveillance, Epidemiology and End Results (SEER) registries. Methods: We utilized a validated Arab surname algorithm to identify women of Arab descent from the SEER registries. Differences in the proportion of IBC out of all breast cancer and IBC characteristics by race and menopausal status were evaluated using chi-square tests for categorical variables, t-tests and ANOVA tests for continuous variables, and log-rank tests for survival data. We modeled the association between race and IBC among all women with breast cancer using hierarchical logistic regression models, adjusting for individual and census tract-level variables. Results: Statistically significant differences in the proportion of IBC out of all breast cancers by race were evident. In a hierarchical model, adjusting for age, estrogen and progesterone receptor, human epidermal growth receptor 2, registry and census-tract level education, Arab-Americans (OR = 1.5, 95% CI = 1.2,1.9), Hispanics (OR= 1.2, 95% CI = 1.1,1.3), Non-Hispanic Blacks (OR = 1.3, 95% CI = 1.2, 1.4), and American Indians/Alaskans (OR= 1.9, 95% CI = 1.1, 3.4) had increased odds of IBC, while Asians (OR = 0.6, 95% CI = 0.6, 0.7) had decreased odds of IBC as compared to Non-Hispanic Whites. Conclusions: IBC may be more common among certain minority groups, including Arab American women. Understanding the descriptive epidemiology of IBC by race may generate hypotheses about risk factors for this aggressive disease. Future research should focus on etiologic factors that may explain these differences. C1 [Hirko, Kelly A.; Chamberlain, Robert M.; Merajver, Sofia D.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hirko, Kelly A.; Merajver, Sofia D.] Univ Michigan, Ctr Global Hlth, Ann Arbor, MI 48104 USA. [Soliman, Amr S.] Univ Nebraska Med Ctr, Dept Epidemiol, Omaha, NE 68198 USA. [Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Ruterbusch, Julie] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI USA. [Harford, Joe B.] NCI, Dept Hlth & Human Serv, Ctr Global Hlth, NIH, Bethesda, MD 20892 USA. [Chamberlain, Robert M.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Graff, John J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Radiat Oncol, New Brunswick, NJ 08901 USA. [Merajver, Sofia D.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. [Schwartz, Kendra] Wayne State Univ, Sch Med, Dept Family Med & Publ Hlth Sci, Detroit, MI USA. RP Hirko, KA (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. EM kellyannelamb@gmail.com FU Avon Foundation; Breast Cancer Research Foundation; University of Michigan Center for Global Health and Rackham School of Graduate studies; Cancer Epidemiology Education in Special Populations Program of the University of Michigan [CA R25 112383] FX We would like to thank Xiaoling Niu from the New Jersey SEER Cancer Registry and Allyn Fernandez-Ami and Dr. Cyllene Morris from the California Cancer Registry for their efforts in compiling the datasets for our analysis. The authors also would like to thank Kirsten Herold for her review and comments on the manuscript. This work supported in part by the Avon Foundation (AS,SDM), the Breast Cancer Research Foundation (SDM), The University of Michigan Center for Global Health and Rackham School of Graduate studies (KH) and the Cancer Epidemiology Education in Special Populations Program of the University of Michigan (CA R25 112383). NR 42 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 2193-1801 J9 SPRINGERPLUS JI SpringerPlus PY 2013 VL 2 AR 3 DI 10.1186/2193-1801-2-3 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V40EM UT WOS:000209461900003 PM 23420611 ER PT J AU Zhang, Y Thomas, GL Swat, M Shirinifard, A Glazier, JA AF Zhang, Ying Thomas, Gilberto L. Swat, Maciej Shirinifard, Abbas Glazier, James A. BE Kraikivski, P TI Differential Adhesion and Cell Sorting SO TRENDS IN BIOPHYSICS: FROM CELL DYNAMICS TOWARD MULTICELLULAR GROWTH PHENOMENA LA English DT Article; Book Chapter DE Adhesion Energy; Cadherin; Cell Clusters; Cell-Sorting; Molecular Level ID HOMOPHILIC CADHERIN ADHESION; N-CADHERIN; ACTIN CYTOSKELETON; FORCE MEASUREMENTS; MEDIATED ADHESION; STRUCTURAL BASIS; WOUND CLOSURE; CHICK LIMB; MORPHOGENESIS; SPECIFICITY C1 [Zhang, Ying] NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. [Thomas, Gilberto L.] Univ Fed Rio Grande do Sul, Inst Fis, Porto Alegre, RS, Brazil. [Swat, Maciej; Shirinifard, Abbas; Glazier, James A.] Indiana Univ, Biocomplex Inst, Bloomington, IN USA. [Swat, Maciej; Shirinifard, Abbas; Glazier, James A.] Indiana Univ, Dept Phys, Bloomington, IN 47405 USA. RP Zhang, Y (reprint author), NCI, Canc & Dev Biol Lab, Frederick, MD 21701 USA. NR 55 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4665-8410-5 PY 2013 BP 237 EP 262 D2 10.1201/b14602 PG 26 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA BF7RB UT WOS:000384331900013 ER PT S AU Reis, JP Lutsey, PL AF Reis, Jared P. Lutsey, Pamela L. BE Gombart, AF TI Vitamin D and Cardiovascular Disease SO VITAMIN D: OXIDATIVE STRESS, IMMUNITY, AND AGING SE Oxidative Stress and Disease LA English DT Article; Book Chapter ID CHRONIC KIDNEY-DISEASE; PERIPHERAL ARTERIAL-DISEASE; 25-HYDROXYVITAMIN D LEVELS; NUTRITION EXAMINATION SURVEY; RANDOMIZED CONTROLLED-TRIAL; CONGESTIVE-HEART-FAILURE; DEPENDENT-DIABETES-MELLITUS; BEAM COMPUTED-TOMOGRAPHY; CLINICAL-RESEARCH CENTER; INTIMA-MEDIA THICKNESS C1 [Reis, Jared P.] NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. [Lutsey, Pamela L.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 136 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA SN 2155-0255 BN 978-1-4398-5021-3; 978-1-4398-5020-6 J9 OXIDAT STRESS DIS PY 2013 VL 31 BP 363 EP 384 PG 22 WC Biochemistry & Molecular Biology; Immunology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Immunology; Nutrition & Dietetics GA BF0KW UT WOS:000379007600017 ER PT J AU Olivera, A Allende, ML Proia, RL AF Olivera, Ana Allende, Maria Laura Proia, Richard L. TI Shaping the landscape: Metabolic regulation of S1P gradients SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE Sphingosine-1-phosphate; Sphingolipid; Signaling; Gradient; Receptor; Metabolism ID EXTRACELLULAR SPHINGOSINE 1-PHOSPHATE; INTEGRAL MEMBRANE-PROTEIN; ENDOTHELIAL-CELLS; SPHINGOSINE-1-PHOSPHATE PHOSPHOHYDROLASE; NEUTRAL CERAMIDASE; LYMPHOCYTE EGRESS; ATOPIC-DERMATITIS; PLASMA-MEMBRANE; ANTIINFLAMMATORY PHENOTYPE; LYSOPHOSPHATIDIC ACID AB Sphingosine-1-phosphate (S1P) is a lipid that functions as a metabolic intermediate and a cellular signaling molecule. These roles are integrated when compartments with differing extracellular S1P concentrations are formed that serve to regulate functions within the immune and vascular systems, as well as during pathologic conditions. Gradients of S1P concentration are achieved by the organization of cells with specialized expression of S1P metabolic pathways within tissues. S1P concentration gradients underpin the ability of S1P signaling to regulate in vivo physiology. This review will discuss the mechanisms that are necessary for the formation and maintenance of S1P gradients, with the aim of understanding how a simple lipid controls complex physiology. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. Published by Elsevier B.V. C1 [Allende, Maria Laura; Proia, Richard L.] NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. [Olivera, Ana] NIAMSD, Immunogenet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDK, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. EM oliveraa@mail.nih.gov; mariaa@intra.niddk.nih.gov; proia@nih.gov FU Intramural Research Programs of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Arthritis and Musculoskeletal and Skin Diseases FX This research was supported by the Intramural Research Programs of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. NR 139 TC 21 Z9 21 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JAN PY 2013 VL 1831 IS 1 SI SI BP 193 EP 202 DI 10.1016/j.bbalip.2012.06.007 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 044CI UT WOS:000311596600023 PM 22735358 ER PT J AU Deng, Q Zheng, TZ Lan, Q Lan, YJ Holford, T Chen, YT Dai, M Leaderer, B Boyle, P Chanock, SJ Rothman, N Zhang, YW AF Deng, Qian Zheng, Tongzhang Lan, Qing Lan, Yajia Holford, Theodore Chen, Yingtai Dai, Min Leaderer, Brian Boyle, Peter Chanock, Stephen J. Rothman, Nathaniel Zhang, Yawei TI Occupational solvent exposure, genetic variation in immune genes, and the risk for non-Hodgkin lymphoma SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE immune genes; non-Hodgkin lymphoma; occupational exposure; single nucleotide polymorphism; solvents ID B-CELL LYMPHOMA; INTERLYMPH-CONSORTIUM; ORGANIC-SOLVENTS; BENZENE EXPOSURE; POLYMORPHISMS; INTERLEUKIN-10; WORKERS; TNF; METAANALYSIS; CONNECTICUT AB Solvent exposure has been inconsistently linked to the risk for non-Hodgkin lymphoma (NHL). The aim of this study was to determine whether the association is modified by genetic variation in immune genes. A population-based case-control study involving 601 incident cases of NHL and 717 controls was carried out in 1996-2000 among women from Connecticut. Thirty single nucleotide polymorphisms in 17 immune genes were examined in relation to the associations between exposure to various solvents and the risk for NHL. The study found that polymorphism in interleukin 10 (IL10; rs1800890) modified the association between occupational exposure to organic solvents and the risk for diffuse large B-cell lymphoma (P-for interaction=0.0058). The results remained statistically significant after adjustment for false discovery rate. Compared with women who were never occupationally exposed to any organic solvents, women who were exposed to organic solvents at least once had a significantly increased risk for diffuse large B-cell lymphoma if they carried the IL10 (rs1800890) TT genotype (odds ratio=3.31, 95% confidence interval: 1.80-6.08), but not if they carried the AT/AA genotype (odds ratio=1.14, 95% confidence interval: 0.72-1.79). No significant interactions were observed for other immune gene single nucleotide polymorphisms and various solvents in relation to NHL overall and its major subtypes. The study provided preliminary evidence supporting a role of immune gene variations in modifying the association between occupational solvent exposure and the risk for NHL. European Journal of Cancer Prevention 22:77-82 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. European Journal of Cancer Prevention 2013, 22:77-82 C1 [Deng, Qian; Zheng, Tongzhang; Holford, Theodore; Leaderer, Brian; Rothman, Nathaniel; Zhang, Yawei] Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. [Deng, Qian; Lan, Yajia] Sichuan Univ, Dept Occupat & Environm Hlth, W China Sch Publ Hlth, Chengdu 610064, Peoples R China. [Chen, Yingtai; Dai, Min] Chinese Acad Med Sci, Canc Inst Hosp, Beijing 100730, Peoples R China. [Lan, Qing; Chanock, Stephen J.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. [Chanock, Stephen J.] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,DHHS, Gaithersburg, MD USA. [Boyle, Peter] Int Prevent Res Inst, Lyon, France. RP Zhang, YW (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, 60 Coll St,LEPH 440, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU NIH [CA62006, CA165923]; National Institutes of Health (NIH); National Cancer Institute; National Institutes of Health [1D43TW008323-01, 1D43TW007864-01, HD70324-01] FX This research was supported by the NIH grants CA62006 and CA165923, the Intramural Research Program of the National Institutes of Health (NIH), the National Cancer Institute, and the National Institutes of Health training grants 1D43TW008323-01, 1D43TW007864-01, and HD70324-01. NR 40 TC 1 Z9 1 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD JAN PY 2013 VL 22 IS 1 BP 77 EP 82 DI 10.1097/CEJ.0b013e328354d2c1 PG 6 WC Oncology SC Oncology GA 048HL UT WOS:000311901900011 PM 22609637 ER PT J AU Dutton, SB Makinson, CD Papale, LA Shankar, A Balakrishnan, B Nakazawa, K Escayg, A AF Dutton, Stacey B. Makinson, Christopher D. Papale, Ligia A. Shankar, Anupama Balakrishnan, Bindu Nakazawa, Kazu Escayg, Andrew TI Preferential inactivation of Scn1a in parvalbumin interneurons increases seizure susceptibility SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Epilepsy; SCN1A; Ion channels; Interneurons; Pyramidal neurons ID SEVERE MYOCLONIC EPILEPSY; SODIUM-CHANNEL SCN1A; DE-NOVO MUTATIONS; MOUSE MODEL; INHIBITORY INTERNEURONS; MICROARRAY ANALYSIS; STATUS EPILEPTICUS; PREFRONTAL CORTEX; GENE-EXPRESSION; DRAVET SYNDROME AB Voltage-gated sodium channels (VGSCs) are essential for the generation and propagation of action potentials in electrically excitable cells. Dominant mutations in SCN1A, which encodes the Na(v)1.1 VGSC alpha-subunit, underlie several forms of epilepsy, including Dravet syndrome (DS) and genetic epilepsy with febrile seizures plus (GEFS+). Electrophysiological analyses of DS and GEFS+ mouse models have led to the hypothesis that SCN1A mutations reduce the excitability of inhibitory cortical and hippocampal interneurons. To more directly examine the relative contribution of inhibitory interneurons and excitatory pyramidal cells to SCN1A-derived epilepsy, we first compared the expression of Na(v)1.1 in inhibitory parvalbumin (PV) interneurons and excitatory neurons from P22 mice using fluorescent immunohistochemistry. In the hippocampus and neocortex, 69% of Na(v)1.1 immunoreactive neurons were also positive for PV. In contrast, 13% and 5% of Na(v)1.1 positive cells in the hippocampus and neocortex, respectively, were found to co-localize with excitatory cells identified by CaMK2 alpha immunoreactivity. Next, we reduced the expression of Scn1a in either a subset of interneurons (mainly PV interneurons) or excitatory cells by crossing mice heterozygous for a foxed Scn1a allele to either the Ppp1r2-Cre or EMX1-Cre transgenic lines, respectively. The inactivation of one Scn1a allele in interneurons of the neocortex and hippocampus was sufficient to reduce thresholds to flurothyl- and hyperthermia-induced seizures, whereas thresholds were unaltered following inactivation in excitatory cells. Reduced interneuron Scn1a expression also resulted in the generation of spontaneous seizures. These findings provide direct evidence for an important role of PV interneurons in the pathogenesis of Scn1a-derived epilepsies. (C) 2012 Elsevier Inc. All rights reserved. C1 [Dutton, Stacey B.; Makinson, Christopher D.; Papale, Ligia A.; Shankar, Anupama; Balakrishnan, Bindu; Escayg, Andrew] Emory Univ, Dept Human Genet, Atlanta, GA 30022 USA. [Nakazawa, Kazu] NIMH, Unit Genet Cognit & Behav, Bethesda, MD 20892 USA. RP Escayg, A (reprint author), Emory Univ, Dept Human Genet, 615 Michael St,Whitehead Bldg,Suite 301, Atlanta, GA 30322 USA. EM aescayg@emory.edu RI Nakazawa, Kazutoshi/J-6195-2015 OI Nakazawa, Kazutoshi/0000-0001-5699-9093 FU NIH [R01 NS072221, 1F31 NS065694]; Epilepsy Foundation; NINDS [P30N5055077] FX We would like to thank the laboratory of Dr. William Catterall for assistance with the hyperthermia seizure induction paradigm and guidance with immunohistochemistry. We are grateful to Cheryl Strauss for editorial assistance. This study was supported by grants from the NIH (R01 NS072221 to A.E., and 1F31 NS065694 to S.B.D.) and by a predoctoral fellowship from the Epilepsy Foundation (S.B.D.). This research was also supported in part by the NINDS core facilities grant P30N5055077 to the Emory University Microscopy Core. NR 41 TC 17 Z9 19 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JAN PY 2013 VL 49 BP 211 EP 220 DI 10.1016/j.nbd.2012.08.012 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 044BO UT WOS:000311594600023 PM 22926190 ER PT J AU DiMichele, DM AF DiMichele, Donna M. TI Inhibitors in childhood hemophilia A: Genetic and treatment-related risk factors for development and eradication SO PEDIATRIC BLOOD & CANCER LA English DT Review DE eradication; hemophilia A; genetic risk factors; inhibitors; treatment ID FACTOR-VIII INHIBITORS; IMMUNE TOLERANCE INDUCTION; PREVIOUSLY UNTREATED PATIENTS; UNITED-KINGDOM; CANAL COHORT; CHILDREN; MILD; POLYMORPHISMS; ANTIBODIES; PRODUCTS AB The development of neutralizing antibodies remains a serious complication of hemophilia replacement therapy. Factor VIII inhibiting antibodies (inhibitors) occur commonly following replacement therapy in hemophilia A, creating a significant burden of clinical disease. This article will review our current understanding of risk factors and their known impact on inhibitor development in previously untreated or minimally treated children with severe and mild hemophilia A. It will also explore how the most recently elucidated immunology of inhibitor development might hold important clues to more effective inhibitor eradication and prevention in this heavily impacted patient population. Pediatr Blood Cancer 2012; 60: S30S33. (C) 2012 Wiley Periodicals, Inc. C1 NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP DiMichele, DM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,Room 9132, Bethesda, MD 20892 USA. EM dimicheledm@nhlbi.nih.gov FU Hospital for Sick Children in Toronto FX Wiley has published this supplement with financial support from the Hospital for Sick Children in Toronto [non-commercial entity]. NR 47 TC 6 Z9 6 U1 0 U2 7 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PY 2013 VL 60 IS 1 SU 1 BP S30 EP S33 DI 10.1002/pbc.24338 PG 4 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 038HU UT WOS:000311166600009 PM 23109404 ER PT J AU Insel, T Krystal, J Ehlers, M AF Insel, Thomas Krystal, John Ehlers, Michael TI New drug development for cognitive enhancement in mental health: Challenges and opportunities SO NEUROPHARMACOLOGY LA English DT Editorial Material C1 [Insel, Thomas] NIMH, NIH, Bethesda, MD 20892 USA. [Krystal, John] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06520 USA. [Krystal, John] Yale New Haven Med Ctr, New Haven, CT USA. RP Insel, T (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 19 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JAN PY 2013 VL 64 SI SI BP 2 EP 7 DI 10.1016/j.neuropharm.2012.07.041 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 039MN UT WOS:000311250300002 PM 23145450 ER EF