FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Dou, J AF Dou, J. TI Botanical New Drugs: From INDs to NDAs SO PLANTA MEDICA LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Pharmacognosy on Natural Products at a Crossroad - Current and Future Directions CY JUL 14-17, 2013 CL St Louis, MO SP Amer Soc Pharmacognosy C1 [Dou, J.] US FDA, Bot Review Team, ODE IV, CDER, Silver Spring, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0032-0943 EI 1439-0221 J9 PLANTA MED JI Planta Med. PD JUL PY 2013 VL 79 IS 10 MA PH4 BP 836 EP 836 PG 1 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA AK8RG UT WOS:000338695100117 ER PT J AU Yang, BW Qiao, LP Zhang, XL Cui, Y Xia, XD Cui, SH Wang, X Meng, XF Ge, WP Shi, XM Wang, DP Meng, JH AF Yang, Baowei Qiao, Liping Zhang, Xiuli Cui, Yue Xia, Xiaodong Cui, Shenghui Wang, Xin Meng, Xiaofeng Ge, Wupeng Shi, Xianming Wang, Dapeng Meng, Jianghong TI Serotyping, antimicrobial susceptibility, pulse field gel electrophoresis analysis of Salmonella isolates from retail foods in Henan Province, China SO FOOD CONTROL LA English DT Article DE Antimicrobial susceptibility; Pulse field gel electrophoresis; Salmonellae; Food safety ID RESISTANCE QNR GENES; QUINOLONE RESISTANCE; UNITED-STATES; FLUOROQUINOLONE RESISTANCE; ANTIBIOTIC-RESISTANCE; NONTYPHOIDAL SALMONELLA; REDUCED SUSCEPTIBILITY; CHICKEN CARCASSES; ESCHERICHIA-COLI; ENTERICA AB A total of 152 Salmonella isolates recovered from retail foods in Henan Province in China were characterized using serotyping and antimicrobial susceptibility testing. Nalidixic acid and/or ciprofloxacin-resistant isolates were further examined for amino acid substitution of gyrase and topoisomerase IV, and for the presence of qnr (qnrA, qnrB and qnrS) and aac(6')-Ib genes. Selected serovars were subtyped using pulse field gel electrophoresis (PFGE). Among all isolates tested, Salmonella Enteritidis (34.2%) was the most common serotype detected, followed by S. Indiana (9.9%), S. Derby (9.9%), S. Agona (6.6%), S. Typhimurium (5.3%) and S. Albany (4.6%). Twenty-eight percent of the isolates were resistant to 1-3 antimicrobials, 37% to 4-6 antimicrobials, 23% to 7-9 antimicrobials, and 12% to more than 10 antimicrobials. Resistance was most frequently detected to sulfamethoxazole (95.3%), followed by trimethoprim/sulfamethoxazole (80.5%), tetracycline (75.8%), nalidixic acid (75.8%), ampicillin (45.6%), chloramphenicol (35.6%), streptomycin (32.9%), kanamycin (24.8%), gentamicin (21.5%) and amoxicillin/clavulanic acid (14.8%). Resistance was also observed to ciprofloxacin (12.1%), cefoperazone (18.8%), ceftriaxone (6.0%) and cefoxitin (4.0%). A total of 45 amino acid substitutions were identified in quinolone resistant determination region (QRDR) of gyrA and parC of 19 ciprofloxacin-resistant isolates. The most common mutations in gyrA were Ser83Phe and Asp87Gly, in parC was Ser80Arg. QnrA, qnrB, qnrS and aac(6')-Ib genes were identified in 55 (46.6%), 15 (12.7%), 23 (19.5%) and 16 (13.6%) of 118 nalidixic acid resistant but ciprofloxacin susceptible or less resistant isolates, respectively. A total of 108 PFGE patterns were generated among 146 selected isolates. Our findings indicate that foodborne Salmonella isolates in Henan, China were phenotypically and genotypically diverse and many isolates demonstrated multidrug resistance. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Yang, Baowei; Qiao, Liping; Cui, Yue; Xia, Xiaodong; Wang, Xin; Meng, Xiaofeng; Ge, Wupeng; Meng, Jianghong] Northwest A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China. [Qiao, Liping] Zhejiang Univ, Sch Biosyst Engn & Food Sci, Dept Food Sci & Nutr, Hangzhou 310058, Zhejiang, Peoples R China. [Zhang, Xiuli] Henan Ctr Dis Control & Prevent, Zhengzhou 450016, Peoples R China. [Cui, Shenghui] Natl Inst Food & Drug Control, Beijing 100050, Peoples R China. [Shi, Xianming; Wang, Dapeng] Shanghai Jiao Tong Univ, Shanghai 200240, Peoples R China. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Xia, XD (reprint author), Northwest A&F Univ, Coll Food Sci & Engn, 28 Xinong Rd, Yangling 712100, Shaanxi, Peoples R China. EM foodscixiaodong@yahoo.com FU Chang Jiang Scholar Program of the Chinese Ministry of Education; Hou Ji Scholar Program of Northwest AF University; "National High Technology Research and Development Program of China" (863 Program) [2012AA101601] FX This research was supported in part by "Chang Jiang Scholar Program of the Chinese Ministry of Education", "Hou Ji Scholar Program of Northwest A&F University", and "the National High Technology Research and Development Program of China" (863 Program) (No. 2012AA101601). NR 51 TC 19 Z9 22 U1 2 U2 79 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD JUL PY 2013 VL 32 IS 1 BP 228 EP 235 DI 10.1016/j.foodcont.2012.11.022 PG 8 WC Food Science & Technology SC Food Science & Technology GA 106SC UT WOS:000316164000035 ER PT J AU Soon, GX Zhang, ZW Tsong, Y Nie, L AF Soon, Guoxing Zhang, Zhiwei Tsong, Yi Nie, Lei TI Assessing overall evidence from noninferiority trials with shared historical data SO STATISTICS IN MEDICINE LA English DT Article DE noninferiority; fixed margin approach; synthesis method; correlation; type I error; preservation ID NON-INFERIORITY TRIALS; ACTIVE-CONTROL TRIALS; CONTROLLED CLINICAL-TRIALS; PLACEBO-CONTROLLED TRIALS; STATISTICAL-METHODS; BAYESIAN-APPROACH; ERROR RATE; ISSUES; INFECTION; DESIGN AB For regulatory approval of a new drug, the United States Code of Federal Regulations (CFR) requires substantial evidence' from adequate and well-controlled investigations'. This requirement is interpreted in the Food and Drug Administration guidance as the need of at least two adequate and well-controlled studies, each convincing on its own to establish effectiveness'. The guidance also emphasizes the need of independent substantiation of experimental results from multiple studies'. However, several authors have noted the loss of independence between two noninferiority trials that use the same set of historical data to make inferences, raising questions about whether the CFR requirement is met in noninferiority trials through current practice. In this article, we first propose a statistical interpretation of the CFR requirement in terms of trial-level and overall type I error rates, which captures the essence of the requirement and can be operationalized for noninferiority trials. We next examine four typical regulatory settings in which the proposed requirement may or may not be fulfilled by existing methods of analysis (fixed margin and synthesis). In situations where the criteria are not met, we then propose adjustments to the existing methods. As illustrated with several examples, our results and findings can be helpful in designing and analyzing noninferiority trials in a way that is both compliant with the regulatory interpretation of the CFR requirement and reasonably powerful. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Soon, Guoxing; Nie, Lei] Off Biostat CDER FDA, Div Biometr 4, Silver Spring, MD 20993 USA. [Zhang, Zhiwei] Off Surveillance & Biometr CDRH FDA, Div Biostat, Silver Spring, MD 20993 USA. [Tsong, Yi] Off Biostat CDER FDA, Div Biometr 6, Silver Spring, MD 20993 USA. RP Nie, L (reprint author), OTS CDER FDA, Div Biometr 4, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lei.nie@fda.hhs.gov NR 38 TC 2 Z9 2 U1 2 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 2013 VL 32 IS 14 BP 2349 EP 2363 DI 10.1002/sim.5615 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 157FA UT WOS:000319880100002 PM 22987631 ER PT J AU Pogribny, IP Beland, FA AF Pogribny, Igor P. Beland, Frederick A. TI DNA methylome alterations in chemical carcinogenesis SO CANCER LETTERS LA English DT Review DE Carcinogenesis; DNA methylation; Genotoxic carcinogens; Non-genotoxic carcinogens ID RAT LUNG CARCINOGENESIS; GENE-PROMOTER HYPERMETHYLATION; CPG ISLAND HYPERMETHYLATION; HEPATOCELLULAR-CARCINOMA; METHYLATION PATTERNS; COLON-CANCER; EPIGENETIC CHANGES; COLORECTAL TUMORIGENESIS; CHROMOSOMAL INSTABILITY; ABERRANT METHYLATION AB Carcinogenesis, a complex multifactorial process of the transformation of normal cells into malignant cells, is characterized by many biologically significant and interdependent alterations triggered by the mutational and/or non-mutational (i.e., epigenetic) events. One of these events, specific to all types of cancer, is alterations in DNA methylation. This review summarizes the current knowledge of the role of DNA methylation changes induced by various genotoxic chemicals (carcinogenic agents that interact with DNA) and non-genotoxic carcinogens (chemicals causing tumor by mechanisms other than directly damaging DNA) in the lung, colorectal, liver, and hematologic carcinogenesis. It also emphasizes the potential role for epigenetic changes to serve as markers for carcinogen exposure and carcinogen risk assessment. Published by Elsevier Ireland Ltd. C1 [Pogribny, Igor P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; frederick.beland@fda.hhs.gov NR 141 TC 15 Z9 16 U1 2 U2 21 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JUN 28 PY 2013 VL 334 IS 1 SI SI BP 39 EP 45 DI 10.1016/j.canlet.2012.09.010 PG 7 WC Oncology SC Oncology GA 164MF UT WOS:000320413500008 PM 23010082 ER PT J AU Liao, HZ Shelor, CP Chen, YJ Sabaa-Srur, AUO Smith, RE Dasgupta, PK AF Liao, Hongzhu Shelor, C. Phillip Chen, Yongjing Sabaa-Srur, Armando U. O. Smith, Robert E. Dasgupta, Purnendu K. TI Anion Composition of Acai Extracts SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE ion chromatography; acai; malate; tartrate; phytic acid; inositol hexaphosphate ID EUTERPE-OLERACEA MART.; ORGANIC-ACID COMPOSITION; PERFORMANCE LIQUID-CHROMATOGRAPHY; ION CHROMATOGRAPHY; FRUIT JUICES; INOSITOL PHOSPHATES; ANTIOXIDANT ACTIVITY; GRAPE JUICE; PHYTIC ACID; HPLC METHOD AB Many products labeled acai are presently marketed as natural supplements with various claimed health benefits. Authentic acai is expensive; as a result, numerous products labeled as containing acai are being sold that actually contain little or no acai. Authentic acai samples from Brazil and Florida as well as several reputed acai products were analyzed by suppressed conductometric anion chromatography. Columns with different selectivities were used to obtain a complete separation of all anions. Tandem mass spectrometry was used for confirmation of the less common ions. Quinate, lactate, acetate, formate, galacturonate, chloride, sulfate, malate, oxalate, phosphate, citrate, isocitrate, and myo-inositol hexakisphosphate (phytate) were found. Only the Florida acai had detectable levels of hexanoate. No acai sample had any detectable levels of tartrate, which is present in abundance in grape juice, the most common adulterant. The highly characteristic anion profile and in particular the absence of tartrate can readily be used to identify authentic acai products. Acai from Florida had a 6 times greater level of phytate. The present analytical approach for phytate may be superior to extant methods. C1 [Liao, Hongzhu; Shelor, C. Phillip; Chen, Yongjing; Dasgupta, Purnendu K.] Univ Texas Arlington, Dept Chem & Biochem, Arlington, TX 76019 USA. [Sabaa-Srur, Armando U. O.] Univ Fed Rio de Janeiro, Inst Nutr, Dept Basic & Expt Nutr, BR-21841902 Rio De Janeiro, Brazil. [Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 West 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov; Dasgupta@uta.edu OI Shelor, Charles/0000-0002-2318-9411 FU Thermo Scientific/Dionex, Sunnyvale, CA, USA FX This work was supported in part by Thermo Scientific/Dionex, Sunnyvale, CA, USA. NR 57 TC 2 Z9 2 U1 1 U2 28 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 26 PY 2013 VL 61 IS 25 BP 5928 EP 5935 DI 10.1021/jf4014185 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 175NH UT WOS:000321236900002 PM 23772604 ER PT J AU Yewdell, JW Spiro, DJ Golding, H Quill, H Mittelman, A Nabel, GJ AF Yewdell, Jonathan W. Spiro, David J. Golding, Hana Quill, Helen Mittelman, Abraham Nabel, Gary J. TI Getting to the Heart of Influenza SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material C1 [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. [Mittelman, Abraham; Nabel, Gary J.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Spiro, David J.] NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. [Quill, Helen] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. [Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. EM gary.nabel@sanofi.com FU Intramural NIH HHS [ZIA AI001055-05] NR 4 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 26 PY 2013 VL 5 IS 191 AR 191ed8 DI 10.1126/scitranslmed.3006735 PG 2 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 171KX UT WOS:000320928000001 PM 23803701 ER PT J AU Banugaria, SG Prater, SN Patel, TT DeArmey, SM Milleson, C Sheets, KB Bali, DS Rehder, CW Raiman, JAJ Wang, RA Labarthe, F Charrow, J Harmatz, P Chakraborty, P Rosenberg, AS Kishnani, PS AF Banugaria, Suhrad G. Prater, Sean N. Patel, Trusha T. DeArmey, Stephanie M. Milleson, Christie Sheets, Kathryn B. Bali, Deeksha S. Rehder, Catherine W. Raiman, Julian A. J. Wang, Raymond A. Labarthe, Francois Charrow, Joel Harmatz, Paul Chakraborty, Pranesh Rosenberg, Amy S. Kishnani, Priya S. TI Algorithm for the Early Diagnosis and Treatment of Patients with Cross Reactive Immunologic Material-Negative Classic Infantile Pompe Disease: A Step towards Improving the Efficacy of ERT SO PLOS ONE LA English DT Article ID ENZYME REPLACEMENT THERAPY; ACID ALPHA-GLUCOSIDASE; ALGLUCOSIDASE ALPHA; CLINICAL-OUTCOMES; ANTIBODIES AB Objective: Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount a strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that immune tolerance induction (ITI) prevents or diminishes the development of antibody titers, resulting in a better clinical outcome compared to CN IPD patients treated with ERT monotherapy. Methods: We evaluated the safety, efficacy and feasibility of a clinical algorithm designed to accurately identify CN IPD patients and minimize delays between CRIM status determination and initiation of an ITI regimen (combination of rituximab, methotrexate and IVIG) concurrent with ERT. Clinical and laboratory data including measures of efficacy analysis for response to ERT were analyzed and compared to CN IPD patients treated with ERT monotherapy. Results: Seven CN IPD patients were identified and started on the ITI regimen concurrent with ERT. Median time from diagnosis of CN status to commencement of ERT and ITI was 0.5 months (range: 0.1-1.6 months). At baseline, all patients had significant cardiomyopathy and all but one required respiratory support. The ITI regimen was safely tolerated in all seven cases. Four patients never seroconverted and remained antibody-free. One patient died from respiratory failure. Two patients required another course of the ITI regimen. In addition to their clinical improvement, the antibody titers observed in these patients were much lower than those seen in ERT monotherapy treated CN patients. Conclusions: The ITI regimen appears safe and efficacious and holds promise in altering the natural history of CN IPD by increasing ERT efficacy. An algorithm such as this substantiates the benefits of accelerated diagnosis and management of CN IPD patients, thus, further supporting the importance of early identification and treatment initiation with newborn screening for IPD. C1 [Banugaria, Suhrad G.; Prater, Sean N.; Patel, Trusha T.; DeArmey, Stephanie M.; Milleson, Christie; Sheets, Kathryn B.; Bali, Deeksha S.; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Rehder, Catherine W.] Duke Univ Hlth Syst, Clin Mol Diagnost Labs, Durham, NC USA. [Raiman, Julian A. J.] Univ Toronto, Hosp Sick Children, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada. [Wang, Raymond A.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Labarthe, Francois] Univ Hosp, Hop Clocheville, Tours, France. [Charrow, Joel] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA. [Harmatz, Paul] Childrens Hosp & Res Ctr Oakland, Oakland, CA USA. [Chakraborty, Pranesh] Univ Ottawa, Dept Pediat, Ottawa, ON K1N 6N5, Canada. [Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kishnani, PS (reprint author), Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. EM priya.kishnani@duke.edu FU Lysosomal Disease Network, a part of National Institutes of Health Rare Diseases Clinical Research Network (RDCRN); NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS) [U54NS065768]; National Institute of Neurological Disorders and Stroke (NINDS) [U54NS065768]; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [U54NS065768] FX This research was funded in part by the Lysosomal Disease Network, a part of National Institutes of Health Rare Diseases Clinical Research Network (RDCRN). The Lysosomal Disease Network (U54NS065768) is a part of the National Institutes of Health (NIH) Rare Diseases Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), the National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the patients and their families who participated in this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 27 Z9 28 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 25 PY 2013 VL 8 IS 6 AR e67052 DI 10.1371/journal.pone.0067052 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 175IB UT WOS:000321223000068 PM 23825616 ER PT J AU Awotwe-Otoo, D Agarabi, C Read, EK Lute, S Brorson, KA Khan, MA Shah, RB AF Awotwe-Otoo, David Agarabi, Cyrus Read, Erik K. Lute, Scott Brorson, Kurt A. Khan, Mansoor A. Shah, Rakhi B. TI Impact of controlled ice nucleation on process performance and quality attributes of a lyophilized monoclonal antibody SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Freezing; Lyophilization; Controlled ice nucleation; Process performance; Monoclonal antibody ID MANOMETRIC TEMPERATURE-MEASUREMENT; PRIMARY DRYING RATE; PRODUCT TEMPERATURE; END-POINT; FORMULATION; DESIGN; PHARMACEUTICALS; STABILITY; MOISTURE; VIALS AB An efficient and potentially scalable technology was evaluated to control the ice nucleation step of the freezing process for a model monoclonal antibody formulation and the effect on process performance and quality attributes of the final lyophilized product was compared with the conventional shelf ramping method of freezing. Controlled ice nucleation resulted in uniform nucleation at temperatures between -2.3 and -3.2 degrees C while uncontrolled nucleation resulted in random nucleation at temperatures between -10 and -16.4 degrees C. The sublimation rate (dm/dt) during primary drying was higher in the controlled nucleation cycle (0.13 g/h/vial) than in the uncontrolled nucleation cycle (0.11 g/h/vial). This was due to the formation of larger ice crystals, leading to lower product resistance (R-p) and 19% reduction in the primary drying for the controlled nucleation cycle. Controlled ice nucleation resulted in lyophilized cakes with more acceptable appearance, no visible collapse or shrinkage and decreased reconstitution times compared with uncontrolled nucleation. There were no observed differences in the particle size, concentration (A(280) (nm)) and presence of aggregates (A(410) (nm)) between the two nucleation cycles when the lyophilized cakes were reconstituted. These were confirmed by SEC and protein A-HPLC analyses which showed similar peak shapes and retention times between the two cycles. However, uncontrolled nucleation resulted in cakes with larger specific surface area (0.90 m(2)/g) than controlled nucleation (0.46 m(2)/g). SEM images of the lyophilized cakes from uncontrolled nucleation revealed a sponge-like morphology with smaller pores while cakes from controlled nucleation cycle revealed plate-like structures with more open and larger pores. While controlled nucleation resulted in a final product with a higher residual moisture content (2.1 +/- 0.08%) than uncontrolled nucleation (1.62 +/- 0.11%), this was resolved by increasing the secondary drying temperature. Published by Elsevier B.V. C1 [Awotwe-Otoo, David; Agarabi, Cyrus; Khan, Mansoor A.; Shah, Rakhi B.] US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Rockville, MD 20857 USA. [Read, Erik K.; Lute, Scott; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, OPS,CDER, Rockville, MD 20857 USA. RP Shah, RB (reprint author), 7500 Standish Pl, Rockville, MD USA. EM rakhi.shah@fda.hhs.gov FU FDA/CDER's Regulatory Science and Review Enhancement (RSR) [12-22] FX This work was funded by FDA/CDER's Regulatory Science and Review Enhancement (RSR) grant (Project 12-22). NR 32 TC 14 Z9 14 U1 2 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD JUN 25 PY 2013 VL 450 IS 1-2 BP 70 EP 78 DI 10.1016/j.ijpharm.2013.04.041 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 151EU UT WOS:000319444300009 PM 23618961 ER PT J AU Ross, MM Jackson, L AF Ross, Mark M. Jackson, Lauren TI Summary of the ACS Symposium on Advances in Food Allergen Detection SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Editorial Material AB A symposium titled "Advances in Food Allergen Detection" was held at the 243rd National Meeting of the American Chemical Society (ACS) in March 2012 in San Diego, CA, and was sponsored by the ACS Division of Agricultural and Food Chemistry. The purpose of the symposium was to convene the leaders in the food allergen analysis field for presentations on, and discussions of, the state of the art, new developments, and critical challenges in the detection and quantitation of allergenic proteins in foods. Twenty-five presentations were delivered by speakers representing academic, government, and industrial institutions in 10 countries. The presentations covered all aspects of food allergens, including a historical progress review, regulatory policies, clinical practices, food-processing effects, food production equipment cross-contamination and cleaning, and the performance of several food allergen analytical strategies and technologies. This paper is intended to provide a brief summary of the presentations as well as a record of the proceedings of the symposium, which was deemed a great success in advancing food allergen analysis. C1 [Ross, Mark M.] Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Jackson, Lauren] Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Ross, MM (reprint author), US FDA, CFSAN, HFS 707,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM MarkM.Ross@fda.hhs.gov NR 5 TC 1 Z9 1 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5621 EP 5623 DI 10.1021/jf304327d PG 3 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600001 PM 23167825 ER PT J AU Gendel, SM AF Gendel, Steven M. TI The Regulatory Challenge of Food Allergens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE food allergy; food labeling; allergen labeling AB Food allergy is an important public health issue worldwide. Allergic consumers must avoid eating foods that could provoke potentially life-threatening reactions, and successful avoidance depends on having complete and accurate information on food labels. Regulatory agencies support allergic consumers by working with industry to ensure that all food allergens that are intended to be present in a food are declared on the label and that effective controls are used to prevent the presence of unintended allergens. These regulatory activities take place in a complex legal and policy environment both domestically and internationally. Protecting allergic consumers in this complex environment requires effective use of public health data and risk assessments. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gendel, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM steven.gendel@fda.hhs.gov NR 5 TC 9 Z9 9 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5634 EP 5637 DI 10.1021/jf302539a PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600003 PM 22866605 ER PT J AU Hebling, CM McFarland, MA Callahan, JH Ross, MM AF Hebling, Christine M. McFarland, Melinda A. Callahan, John H. Ross, Mark M. TI Global Proteomic Screening of Protein Allergens and Advanced Glycation Endproducts in Thermally Processed Peanuts SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE peanut allergens; roasted peanuts; Ara h; Maillard reaction; AGE; mass spectrometry ID TANDEM MASS-SPECTROMETRY; MAILLARD REACTION-PRODUCTS; IGE-BINDING EPITOPES; AMINO-ACIDS; FOOD; PEPTIDES; ELISA; CONFIRMATION; MS/MS; KITS AB Peanuts (Arachis hypogaea) are the cause of one of the most prevalent food allergies worldwide. Thermal processing (e.g., roasting) of peanuts and peanut-containing foods results in complex chemical reactions that alter structural conformations of peanut proteins, preventing accurate detection of allergens by most immunochemical and targeted screening methodologies. To improve food allergen detection and support more accurate food labeling, traditional methods for peanut protein extraction were modified to include protein denaturants and solubilization agents. Qualitative characterization by SDS-PAGE and Western blot analyses of raw and variably roasted peanut extracts confirmed improvements in total protein recovery and provided evidence for the incorporation of Ara h 1, Ara h 3, and, to a lesser extent, Ara h 2 into high molecular weight protein complexes upon roasting. Relative quantification of allergens in peanut lysates was accomplished by label-free spectral feature (MS 1) LC-MS/MS methodologies, by which peanut allergen peptides exhibiting a differential MS response in raw versus roasted peanuts were considered to be candidate targets of thermal modification. Identification of lysine-modified Mail lard advanced glycation endproducts (AGE) by LC-MS/MS confirmed the formation of (carboxymethyl)lysine (CML), (carboxyethyl)lysine (CEL), and pyrraline (Pyr) protein modifications on Ara h 1 and Ara h 3 tryptic peptides in roasted peanut varieties. These results suggest that complex processed food matrices require initial analysis by an untargeted LC-MS/MS approach to determine optimum analytes for subsequent targeted allergen analyses. C1 [Hebling, Christine M.; McFarland, Melinda A.; Callahan, John H.; Ross, Mark M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hebling, CM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Christine.Hebling@fda.hhs.gov NR 45 TC 21 Z9 21 U1 2 U2 42 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5638 EP 5648 DI 10.1021/jf303554t PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600004 PM 23039025 ER PT J AU Fu, TJ Maks, N AF Fu, Tong-Jen Maks, Nicole TI Impact of Thermal Processing on ELISA Detection of Peanut Allergens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE food allergen; peanut flours; ELISA test kits; thermal processing ID ARA H 1; TEST KITS; ANAPHYLACTIC REACTIONS; FOOD; PROTEINS; CHOCOLATE; ARA-H-1; FATALITIES; RESIDUES; HISTORY AB This study examined the effect of heat treatment on the solubility of peanut proteins and compared the performances of two commercial ELISA kits (Veratox Quantitative Peanut Allergen Test and BioKits Peanut Assay Kit) for quantitation of peanut residues as affected by different heat treatments (moist and dry heat) and detection targets (mixture of proteins vs specific protein). Both laboratory-prepared and commercial peanut flour preparations were used for the evaluation. The two ELISA kits tended to underestimate the levels of protein in samples that were subjected to elevated heat, respectively, by more than 60- or 400-fold lower for the autoclaved samples and by as much as 70- or 2000-fold lower for the dark-roast commercial flour samples. The BioKits test, which employs antibodies specific to a heat labile protein (Ara h 1), in general exhibited a greater degree of underestimation. These results suggest that commercial ELISA kits may not be able to accurately determine the amount of proteins present in thermally processed foods due to changes in the solubility and immunoreactivity of the target proteins. Users need to be aware of such limitations before applying ELISA kits for evaluation of food allergen control programs. C1 [Fu, Tong-Jen] US FDA, Div Food Proc Sci & Technol, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Maks, Nicole] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Fu, TJ (reprint author), US FDA, Div Food Proc Sci & Technol, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM tongjen.fu@fda.hhs.gov FU U.S. Food and Drug Administration [5U01FD003801]; Institute for Food Safety and Health [5U01FD003801] FX This work was supported by Cooperative Agreement 5U01FD003801 between the U.S. Food and Drug Administration and Institute for Food Safety and Health. NR 35 TC 12 Z9 12 U1 2 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5649 EP 5658 DI 10.1021/jf304920h PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600005 PM 23473340 ER PT J AU Newsome, GA Scholl, PF AF Newsome, G. Asher Scholl, Peter F. TI Quantification of Allergenic Bovine Milk alpha(S1)-Casein in Baked Goods Using an Intact N-15-Labeled Protein Internal Standard SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE baked; casein; food allergen; isotope dilution; mass spectrometry; milk; nonenzymatic glycation; quantification; regulatory enforcement; selected reaction monitoring ID CHROMATOGRAPHY-MASS SPECTROMETRY; LIQUID-CHROMATOGRAPHY; MAILLARD REACTION; AMINO-ACID; FOOD; PEPTIDES; PRODUCTS; ALPHA-S1-CASEIN; LACTOSYLATION; VALIDATION AB Intact bovine N-15-alpha(S1)-casein was used as an internal standard in a selected reaction monitoring (SRM) assay for milk protein in baked food samples containing fats, sugar, and gums. Effects on SRM results of sample matrix composition in two biscuit recipes containing nonfat dry milk (NFDM) were studied, including samples from a milk allergen ELISA proficiency trial. Following extraction of defatted samples with carbohydrate-degrading enzymes and acid precipitation of casein, the SRM assay exhibited an LOQ of <3 ppm NFDM with 60-80% recovery. NFDM levels measured by the SRM assay were 1.7-2.5 times greater than median levels determined by ELISA. Differences were observed in the alpha(S1)-casein interpeptide SRM ion abundance profile between recipes and after baking. N-15-alpha(S1)-Casein increases SRM analysis accuracy by correcting for extraction recovery but does not eliminate underestimation of allergen concentrations due to baking-related milk protein transformation (modifications). C1 [Newsome, G. Asher; Scholl, Peter F.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Scholl, PF (reprint author), 5100 Paint Branch Pkwy,HFS 707,Room BE-006, College Pk, MD 20740 USA. EM peter.scholl@fda.hhs.gov RI Newsome, G. Asher/J-8970-2012 OI Newsome, G. Asher/0000-0003-1683-2197 NR 60 TC 5 Z9 7 U1 3 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5659 EP 5668 DI 10.1021/jf3015238 PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600006 PM 22670623 ER PT J AU Eischeid, AC Kim, BH Kasko, SM AF Eischeid, Anne C. Kim, Bang-hyun Kasko, Sasha M. TI Two Quantitative Real-Time PCR Assays for the Detection of Penaeid Shrimp and Blue Crab, Crustacean Shellfish Allergens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE reaction efficiency; internal amplification control; thermal cycling; multiplex ID DNA; FOOD; RNA AB Food allergen detection methods must be able to specifically detect minute quantities of an allergenic food in a complex food matrix. One technique that can be used is real-time PCR For the work described here, real-time PCR assays were developed to detect penaeid shrimp and blue crab, crustacean shellfish allergens. The method was tested using shrimp meat and crab meat spiked into several types of foods, including canned soups, deli foods, meat, seafood, and prepared seafood products. Foods were spiked with either shrimp or crab at levels ranging from 0.1 to 10(6) parts per million (ppm) and analyzed either raw or cooked by a variety of methods. Real-time PCR data were used to generate linear standard curves, and assays were evaluated with respect to linear range and reaction efficiency. Results indicate that both assays performed well in a variety of food types. High reaction efficiencies were achieved across a linear range of 6-8 orders of magnitude. Limits of detection were generally between 0.1 and 1 ppm. Cooking methods used to simulate thermal processing of foods had little effect on assay performance. This work demonstrates that real-time PCR can be a valuable tool in the detection of crustacean shellfish. C1 [Eischeid, Anne C.; Kim, Bang-hyun; Kasko, Sasha M.] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Eischeid, AC (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Mailstop HFS 716, College Pk, MD 20740 USA. EM Anne.Eischeid@fda.hhs.gov FU Korean Government FX B.K. was supported through a Korean Government Long-term Fellowship for Overseas Studies. NR 11 TC 5 Z9 5 U1 4 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5669 EP 5674 DI 10.1021/jf3031524 PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600007 PM 23190158 ER PT J AU Toomer, OT Do, A Pereira, M Williams, K AF Toomer, Ondulla T. Do, Andrew Pereira, Marion Williams, Kristina TI Effect of Simulated Gastric and Intestinal Digestion on Temporal Stability and Immunoreactivity of Peanut, Almond, and Pine Nut Protein Allergens SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE food allergens; tree nuts; peanuts; digestibility; immunoreactivity ID IGE-BINDING PROTEINS; ARA H 1; FOOD ALLERGENS; CROSS-REACTIVITY; PRUNUS-AMYGDALUS; 2S ALBUMIN; IN-VITRO; POLLEN; IDENTIFICATION; ANAPHYLAXIS AB Current models of digestibility utilize pepsin stability to assess the safety of allergenic versus nonallergenic food proteins. Dietary protein digestion in vivo, however, requires acid denaturation and protease cleavage by pepsin, trypsin, and/or chymotrypsin. The ability of this approach to identify food protein stability in the mammalian gut may be limited. We determined the temporal stability and immunoreactivity of almond, pine nut, and peanut allergenic proteins under simulated physiologic gastric and intestinal digestive conditions in vitro. Gel electrophoresis and immunoblot analyses were used to determine protein stability and immunoreactivity, respectively. Peanut, almond, and pine nut proteins were pepsin- and pancreatin-stable and immunoreactive for up to 1 h after initiation of digestion. Moreover, successive acid denaturation and pepsin and pancreatin cleavage were necessary to hydrolyze these allergenic proteins and reduce their IgG- and IgE-binding capacity, which suggests that digestibility models must be improved for more accurate safety assessment of food allergens. C1 [Toomer, Ondulla T.; Do, Andrew; Pereira, Marion; Williams, Kristina] US FDA, Laurel, MD 20708 USA. RP Toomer, OT (reprint author), US Dept Food & Drug Adm, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl, Immunobiol Branch,Div Virulence Assessment, 8301 Muirkirk Rd,MOD 1,Room 2007, Laurel, MD 20708 USA. EM Ondulla.Toomer@fda.hhs.gov NR 37 TC 5 Z9 5 U1 4 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 19 PY 2013 VL 61 IS 24 BP 5903 EP 5913 DI 10.1021/jf400953q PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 171BA UT WOS:000320898600035 PM 23742710 ER PT J AU Keitel, WA Dai, ZD Awe, RW Atmar, RL Morris, S Schneerson, R Robbins, JB AF Keitel, Wendy A. Dai, ZhongDong Awe, Robert W. Atmar, Robert L. Morris, Sheldon Schneerson, Rachel Robbins, John B. TI Effects of infection and disease with Mycobacterium tuberculosis on serum antibody to glucan and arabinomannan: two surface polysaccharides of this pathogen SO BMC INFECTIOUS DISEASES LA English DT Article DE Mycobacterium tuberculosis; Capsular polysaccharides; Immune responses ID RICH OUTER LAYER; CELL-WALL; ANTIGENS; CHILDREN; RESPONSES AB Background: The role of the surface capsular polysaccharides (CPs) of Mycobacterium tuberculosis (Mtb) in the pathogenesis of infection and disease, as well their potential for use as diagnostic reagents and vaccine antigens, are unknown. Methods: Serum antibody to two CPs of Mtb, arabinomannan (AM) and glucan (Glu), were studied in samples from 52 18-74 year-old HIV seronegative, immunocompetent individuals in Houston Texas. The effects of Mtb exposure, infection and disease upon the levels of antibodies to these CPs were assessed. Subjects were grouped according to the standard international classification. Results: IgA anti-Glu levels were significantly higher in the active and treated TB compared to a group that was PPD-negative without TB exposure history (p<0.05). Antibodies against AM demonstrated a similar pattern, with the exception that IgG anti-AM was higher in groups who had active TB or previously documented active TB, and IgA anti-AM was higher in subjects with previously documented active TB compared to the level in an unexposed, PPD-negative group (p<0.05). Serum IgG anti-Glu levels were higher in subjects with active TB or previously documented active TB than in the unexposed PPD-negative group, but the differences were not significant. Conclusions: These data suggest that the evaluation of antibody responses to the CP of Mtb may have utility for TB serodiagnosis, and that vaccines designed to induce humoral responses to TB CPs should be tested for their capacity to evoke anti-tuberculosis protective immunity. C1 [Keitel, Wendy A.; Atmar, Robert L.] Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. [Keitel, Wendy A.; Atmar, Robert L.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA. [Dai, ZhongDong; Schneerson, Rachel; Robbins, John B.] Eunice Schriver Kennedy Inst Child Hlth & Human D, Program Dev Mol Immun, Rockville, MD 20852 USA. [Awe, Robert W.] Ben Taub Gen Hosp, Houston, TX 77030 USA. [Morris, Sheldon] Food & Drug Adm, CBER, Houston, TX USA. RP Keitel, WA (reprint author), Baylor Coll Med, Dept Mol Virol, Houston, TX 77030 USA. EM wkeitel@bcm.edu FU Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health; Food and Drug Administration/Center for Biologics Evaluation and Research internal funds FX This study was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health and Food and Drug Administration/Center for Biologics Evaluation and Research internal funds. NR 22 TC 3 Z9 4 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUN 19 PY 2013 VL 13 AR 276 DI 10.1186/1471-2334-13-276 PG 6 WC Infectious Diseases SC Infectious Diseases GA 188MU UT WOS:000322197900001 PM 23783070 ER PT J AU Rivers, K Bowen, LE Gao, J Yang, K Trombley, JE Bohannon, JK Eichelberger, MC AF Rivers, Katie Bowen, Larry E. Gao, Jin Yang, Kevin Trombley, John E. Bohannon, J. Kyle Eichelberger, Maryna C. TI Comparison of the effectiveness of antibody and cell-mediated immunity against inhaled and instilled influenza virus challenge SO VIROLOGY JOURNAL LA English DT Article DE Influenza; Aerosol; Inhalation; Instillation; Mouse; Antibody; CD8+T cell; Immunity ID NATURAL-KILLER-CELLS; A VIRUS; ANIMAL-MODELS; RESPIRATORY-TRACT; T-CELLS; MICE; PROTECTION; INFECTION; RESPONSES; VACCINES AB Background: To evaluate immunity against influenza, mouse challenge studies are typically performed by intranasal instillation of a virus suspension to anesthetized animals. This results in an unnatural environment in the lower respiratory tract during infection, and therefore there is some concern that immune mechanisms identified in this model may not reflect those that protect against infectious virus particles delivered directly to the lower respiratory tract as an aerosol. Method: To evaluate differences in protection against instilled and inhaled virus, mice were immunized with influenza antigens known to induce antibody or cell-mediated responses and then challenged with 100 LD50 A/PR/8/34 (PR8) in the form of aerosol (inhaled) or liquid suspension (instilled). Results: Mice immunized with recombinant adenovirus (Ad) expressing hemagglutinin were protected against weight loss and death in both challenge models, however immunization with Ad expressing nucleoprotein of influenza A (NPA) or M2 resulted in greater protection against inhaled aerosolized virus than virus instilled in liquid suspension. Ad-M2, but not Ad-NPA-immunized mice were protected against a lower instillation challenge dose. Conclusions: These results demonstrate differences in protection that are dependent on challenge method, and suggest that cell-mediated immunity may be more accurately demonstrated in mouse inhalation studies. Furthermore, the data suggest immune mechanisms generally characterized as incomplete or weak in mouse models C1 [Rivers, Katie; Gao, Jin; Yang, Kevin; Eichelberger, Maryna C.] US FDA, Div Viral Prod, OVRR, CBER, Bethesda, MD 20892 USA. [Bowen, Larry E.; Trombley, John E.; Bohannon, J. Kyle] Southern Res Inst, Birmingham, AL 35205 USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, OVRR, CBER, 8800 Rockville Pike,Bldg 29A 1D24, Bethesda, MD 20892 USA. EM Maryna.Eichelberger@fda.hhs.gov FU CBER [HHSF223201011220P] FX We thank the animal caretakers and facility management for excellent animal care at CBER and Southern Research. We also thank Jeremy Boydston, and Shixiong Li for excellent technical assistance, and Clement Meseda and Ewan Plant for critical reading of our manuscript. CBER PanFlu funds supported work done under contract HHSF223201011220P at Southern Research and all experiment performed at CBER. KY was supported by training funds administered by the Oak Ridge Institute for Science and Education. NR 37 TC 1 Z9 1 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD JUN 19 PY 2013 VL 10 AR 198 DI 10.1186/1743-422X-10-198 PG 9 WC Virology SC Virology GA 170BJ UT WOS:000320824200001 PM 23777453 ER PT J AU Fiedler, KL Cotter, RJ AF Fiedler, Katherine L. Cotter, Robert J. TI Using Glycinylation, a Chemical Derivatization Technique, for the Quantitation of Ubiquitinated Proteins SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; TRYPTIC PEPTIDES; HISTONE H2B; PROTEOMICS; QUANTIFICATION; ACETYLATION; IDENTIFICATION; UBIQUITYLATION; DEACETYLATION; STRATEGIES AB The quantitation of lysine post-translational modifications (PTMs) by bottom-up mass spectrometry is convoluted by the need for analogous derivatives and the production of different tryptic peptides from the unmodified and modified versions of a protein. Chemical derivatization of lysines prior to enzymatic digestion circumvents these problems and has proven to be a successful method for lysine PTM quantitation. The most notable example is the use of deuteroacetylation to quantitate lysine acetylation. In this work, levels of lysine ubiquitination were quantitated using a structurally homologous label that is chemically similar to the diglycine (GlyGly) tag, which is left at the ubiquitination site upon trypsinolysis. The LC-MS analysis of a chemically equivalent monoglycine (Gly) tag that is analogous to the corresponding GlyGly tag proved that the monoglycine tag can be used for the quantitation of ubiquitination. A glycinylation protocol was then established for the derivatization of proteins to label unmodified lysine residues with a single glycine tag. Ubiquitin multimers were used to show that after glycinylation and tryptic digestion, the mass spectrometric response from the corresponding analogous tagged peptides could be compared for relative quantitation. For a proof of principle regarding the applicability of this technique to the analysis of ubiquitination in biological samples, the glycinylation technique was used to quantitate the increase in monoubiquitinated histone H2B that is observed in yeast which lacks the enzyme responsible for deubiquitinating H2B-K123, compared to wild-type yeast. C1 [Fiedler, Katherine L.; Cotter, Robert J.] Johns Hopkins Univ, Sch Med, Middle Atlantic Mass Spectrometry Lab, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. RP Fiedler, KL (reprint author), US FDA, CFSAN, College Pk, MD USA. EM kstampe2@live.johnshopkins.edu FU NIH [U54 RR020839, S10 RR0023025] FX The authors would like to gratefully acknowledge Poonam Bheda for the preparation of the histone H2B samples and the alpha-ubiquitin Western blot, Jodie Franklin of the JHMI Synthesis and Sequencing Facility for the synthesis of the tagged K48-ubiquitin peptides, and David J. Meyers of the JHU SOM Synthetic Core Facility for the synthesis of the Boc-glycine anhydride. We would also like to thank the Mid-Atlantic Regional Office of Shimadzu Scientific Instruments, Inc. (Columbia, MD) for the use of the LCMS-IT-TOF. All analyses were carried out in the Middle Atlantic Mass Spectrometry Laboratory at JHU. This project was supported by grant U54 RR020839 (R. J. Cotter) from the NIH. The LTQ-Orbitrap used in this work was purchased with a high-end shared instrumentation grant S10 RR0023025 (R. J. Cotter) from the NIH. This paper is dedicated to the memory of the senior author (R. J. Cotter). NR 35 TC 0 Z9 0 U1 2 U2 26 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 18 PY 2013 VL 85 IS 12 BP 5827 EP 5834 DI 10.1021/ac400398s PG 8 WC Chemistry, Analytical SC Chemistry GA 169AL UT WOS:000320749200032 PM 23682733 ER PT J AU Chen, G Chen, JW Shi, CP Shi, LM Tong, WD Shi, TL AF Chen, Geng Chen, Jiwei Shi, Caiping Shi, Leming Tong, Weida Shi, Tieliu TI Dissecting the Characteristics and Dynamics of Human Protein Complexes at Transcriptome Cascade Using RNA-Seq Data SO PLOS ONE LA English DT Article ID MESSENGER-RNA; SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORK; HUMAN GENOME; EXPRESSION; CANCER; QUANTIFICATION; INTERACTOME; ANNOTATION; LANDSCAPE AB Human protein complexes play crucial roles in various biological processes as the functional module. However, the expression features of human protein complexes at the transcriptome cascade are poorly understood. Here, we used the RNA-Seq data from 16 disparate tissues and four types of human cancers to explore the characteristics and dynamics of human protein complexes. We observed that many individual components of human protein complexes can be generated by multiple distinct transcripts. Similar with yeast, the human protein complex constituents are inclined to co-express in diverse tissues. The dominant isoform of the genes involved in protein complexes tend to encode the complex constituents in each tissue. Our results indicate that the protein complex dynamics not only correlate with the presence or absence of complexes, but may also be related to the major isoform switching for complex subunits. Between any two cancers of breast, colon, lung and prostate, we found that only a few of the differentially expressed transcripts associated with complexes were identical, but 5-10 times more protein complexes involved in differentially expressed transcripts were common. Collectively, our study reveals novel properties and dynamics of human protein complexes at the transcriptome cascade in diverse normal tissues and different cancers. C1 [Chen, Geng; Chen, Jiwei; Shi, Caiping; Shi, Tieliu] E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Ctr Bioinformat & Computat Biol, Shanghai 200062, Peoples R China. [Chen, Geng; Chen, Jiwei; Shi, Caiping; Shi, Tieliu] E China Normal Univ, Sch Life Sci, Shanghai 200062, Peoples R China. [Shi, Leming; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, TL (reprint author), E China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Ctr Bioinformat & Computat Biol, Shanghai 200062, Peoples R China. EM tieliushi01@gmail.com FU National 973 Key Basic Research Program [2010CB945401, 2012CB910400]; National Natural Science Foundation of China [31240038, 31071162, 31000590]; Science and Technology Commission of Shanghai Municipality [11DZ2260300]; Graduate School of East China Normal University FX This work was supported by the National 973 Key Basic Research Program (Grant Nos. 2010CB945401 and 2012CB910400), the National Natural Science Foundation of China (Grant No. 31240038, 31071162, and 31000590), the Science and Technology Commission of Shanghai Municipality (11DZ2260300) and the Graduate School of East China Normal University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 2 Z9 2 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2013 VL 8 IS 6 AR e66521 DI 10.1371/journal.pone.0066521 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166SA UT WOS:000320576400121 PM 23824284 ER PT J AU Xie, T Sun, C Uslu, K Auth, RD Fang, H Ouyang, WM Frucht, DM AF Xie, Tao Sun, Chen Uslu, Kadriye Auth, Roger D. Fang, Hui Ouyang, Weiming Frucht, David M. TI A New Murine Model for Gastrointestinal Anthrax Infection SO PLOS ONE LA English DT Article ID INHALATIONAL ANTHRAX; BACILLUS-ANTHRACIS; LETHAL TOXIN; PATHOLOGY; HISTOPATHOLOGY; SUSCEPTIBILITY; DISSEMINATION AB The scientific community has been restricted by the lack of a practical and informative animal model of gastrointestinal infection with vegetative Bacillus anthracis. We herein report the development of a murine model of gastrointestinal anthrax infection by gavage of vegetative Sterne strain of Bacillus anthracis into the complement-deficient A/J mouse strain. Mice infected in this manner developed lethal infections in a dose-dependent manner and died 30 h-5 d following gavage. Histological findings were consistent with penetration and growth of the bacilli within the intestinal villi, with subsequent dissemination into major organs including the spleen, liver, kidney and lung. Blood cultures confirmed anthrax bacteremia in all moribund animals, with approximately 1/3 showing co-infection with commensal enteric organisms. However, no evidence of immune activation was observed during infection. Time-course experiments revealed early compromise of the intestinal epithelium, characterized by villus blunting and ulceration in the ileum and jejunum. A decrease in body temperature was most predictive of near-term lethality. Antibiotic treatment of infected animals 24 h following high-dose bacterial gavage protected all animals, demonstrating the utility of this animal model in evaluating potential therapeutics. C1 [Xie, Tao; Sun, Chen; Uslu, Kadriye; Auth, Roger D.; Fang, Hui; Ouyang, Weiming; Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Frucht, DM (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM david.frucht@fda.hhs.gov FU Federal Drug Administration Medical Countermeasures Initiative FX This project was supported by the Federal Drug Administration Medical Countermeasures Initiative. No external funding sources were used for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 6 Z9 6 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 18 PY 2013 VL 8 IS 6 AR e66943 DI 10.1371/journal.pone.0066943 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 166SA UT WOS:000320576400169 PM 23825096 ER PT J AU Cook, JA McCulloch, P Blazeby, JM Beard, DJ Marinac-Dabic, D Sedrakyan, A AF Cook, Jonathan A. McCulloch, Peter Blazeby, Jane M. Beard, David J. Marinac-Dabic, Danica Sedrakyan, Art CA IDEAL Grp TI IDEAL framework for surgical innovation 3: randomised controlled trials in the assessment stage and evaluations in the long term study stage SO BMJ-BRITISH MEDICAL JOURNAL LA English DT Article ID ABDOMINAL-AORTIC-ANEURYSM; OPEN REPAIR; SURGERY; HERNIA; KNEE AB The complexity of surgical procedures oft en poses challenges for conducting a rigorous and comprehensive evaluation. This paper considers the final two IDEAL stages of surgical innovation. Surgical randomised controlled trials are oft en challenging to undertake and require careful consideration of the intervention definition, who should deliver it, and the impact of surgeon and patient preferences. In the long term study stage, better monitoring of surgical procedures is needed, along with improved surveillance of devices. C1 [Cook, Jonathan A.] Univ Aberdeen, Hlth Serv Res Unit, Aberdeen AB25 2ZD, Scotland. [McCulloch, Peter] Univ Oxford, Nuffield Dept Surg Sci, Oxford, England. [Blazeby, Jane M.] Univ Bristol, Sch Social & Community Med, Surg Res Ctr, Bristol BS8 1TH, Avon, England. [Beard, David J.] Univ Oxford, Nuffield Dept Orthopaed Rheumatol & Musculoskelet, Oxford OX1 2JD, England. [Beard, David J.] Natl Inst Hlth Res, Oxford Musculoskeletal Biomed Res Unit, Oxford, England. [Marinac-Dabic, Danica] US FDA, Div Epidemiol, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Sedrakyan, Art] Cornell Univ, Weill Cornell Med Coll, New York, NY 10021 USA. [Sedrakyan, Art] New York Presbyterian Hosp, New York, NY USA. RP Cook, JA (reprint author), Univ Aberdeen, Hlth Serv Res Unit, Aberdeen AB25 2ZD, Scotland. EM j.a.cook@abdn.ac.uk RI Groves, Trish/A-9119-2009; Cook, Jonathan/D-3648-2015; OI Groves, Trish/0000-0001-7915-6419; Lyratzopoulos, Georgios/0000-0002-2873-7421; Cook, Jonathan/0000-0002-4156-6989 FU National Institute for Health Research's Health Technology Assessment programme; Johnson Johnson; Medtronic; Zimmer; Medical Research Council [G1002292]; Medical Research Council ConDuCT Hub for Trials Methodology Research; US Food and Drug Administration [HHSF22321110172C] FX PM received funding from the National Institute for Health Research's Health Technology Assessment programme, Johnson & Johnson, Medtronic, and Zimmer (all unrestricted grants) for the IDEAL workshop in December 2010. JAC holds a Medical Research Council Methodology Fellowship (G1002292). JMB is supported in part by the Medical Research Council ConDuCT Hub for Trials Methodology Research. AS is supported in part by the US Food and Drug Administration contract for MDEpiNet Science and Infrastructure Centre (HHSF22321110172C). NR 40 TC 43 Z9 43 U1 1 U2 12 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BMJ-BRIT MED J JI BMJ-British Medical Journal PD JUN 18 PY 2013 VL 346 AR f2820 DI 10.1136/bmj.f2820 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 171PQ UT WOS:000320941900001 PM 23778425 ER PT J AU Podskalny, D AF Podskalny, D. TI The registration process for botulinum neurotoxin drugs: The perspective of the regulatory authorities SO TOXICON LA English DT Meeting Abstract CT 7th International Conference on Basic and Therapeutic Aspects of Botulinum and Tetanus Toxins (TOXINS) CY OCT 02-05, 2011 CL Santa Fe, NM C1 [Podskalny, D.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUN 15 PY 2013 VL 68 BP 74 EP 74 DI 10.1016/j.toxicon.2012.07.054 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 159VN UT WOS:000320075500042 ER PT J AU Varada, JC Teferedegne, B Crim, RL Mdluli, T Audet, S Peden, K Beeler, J Murata, H AF Varada, Jan C. Teferedegne, Belete Crim, R. Lynne Mdluli, Thembi Audet, Susette Peden, Keith Beeler, Judy Murata, Haruhiko TI A neutralization assay for respiratory syncytial virus using a quantitative PCR-based endpoint assessment SO VIROLOGY JOURNAL LA English DT Article DE Respiratory syncytial virus; Neutralization; Antibody; Reverse transcription; RNA; Quantitative PCR; SYBR Green ID MICRONEUTRALIZATION ASSAY; MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; INFECTION; CHILDREN; INFANTS; IMMUNOPROPHYLAXIS; IMMUNOGENICITY; GLYCOPROTEIN; EXPRESSION AB Background: Few studies have used quantitative polymerase chain reaction (qPCR) as an approach to measure virus neutralization assay endpoints. Its lack of use may not be surprising considering that sample nucleic acid extraction and purification can be expensive, labor-intensive, and rate-limiting. Methods: Virus/antibody mixtures were incubated for one hour at 37 degrees C and then transferred to Vero cell monolayers in a 96-well plate format. At 24 (or 48) hours post-infection, we used a commercially available reagent to prepare cell lysates amenable to direct analysis by one-step SYBR Green quantitative reverse transcription PCR using primers specific for the RSV-N gene, thereby obviating the need for cumbersome RNA extraction and purification. The neutralization titer was defined as the reciprocal of the highest dilution needed to inhibit the PCR signal by 90% when compared with the mean value observed in virus control wells in the absence of neutralizing antibodies. Results: We have developed a qPCR-based neutralization assay for human respiratory syncytial virus. Due to the sensitivity of qPCR in detecting virus replication, endpoints may be assessed as early as 24 hours post-infection. In addition, the dynamic range of qPCR provides a basis for the assay to be relatively robust to perturbations in input virus dose (i.e., the assay is in compliance with the Percentage Law). Conclusions: This qPCR-based neutralization assay is suitable for automated high-throughput applications. In addition, our experimental approach may be generalizable for the rapid development of neutralization assays for other virus families. C1 [Varada, Jan C.; Teferedegne, Belete; Peden, Keith; Murata, Haruhiko] US FDA, Div Viral Prod, OVRR, Lab DNA Viruses,CBER, Bethesda, MD 20892 USA. [Varada, Jan C.; Crim, R. Lynne; Mdluli, Thembi; Audet, Susette; Beeler, Judy] US FDA, Lab Pediat & Resp Viral Dis, Div Viral Prod, OVRR,CBER, Bethesda, MD 20892 USA. RP Murata, H (reprint author), US FDA, Div Viral Prod, OVRR, Lab DNA Viruses,CBER, Bethesda, MD 20892 USA. EM haruhiko.murata@fda.hhs.gov FU Division of Microbiology and Infectious Diseases (DMID, NIAID, NIH, USA) [224-10-1018]; Oak Ridge Institute of Science and Education Fellowship; DMID FX This study was funded by a contract (Interagency Agreement Number 224-10-1018) from the Division of Microbiology and Infectious Diseases (DMID, NIAID, NIH, USA). We thank Sonnie Kim Grossman (DMID) for her support. J. V. was supported by an Oak Ridge Institute of Science and Education Fellowship through funds provided by DMID. We are grateful to Shuang Tang and Vladimir Lugovtsev for their critical review of this manuscript. NR 36 TC 7 Z9 7 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD JUN 15 PY 2013 VL 10 AR 195 DI 10.1186/1743-422X-10-195 PG 11 WC Virology SC Virology GA 167DY UT WOS:000320612100001 PM 23767960 ER PT J AU O'Brien, TJ Ding, H Suh, M Thompson, CM Parsons, BL Harris, MA Winkelman, WA Wolf, JC Hixon, JG Schwartz, AM Myers, MB Haws, LC Proctor, DM AF O'Brien, Travis J. Ding, Hao Suh, Mina Thompson, Chad M. Parsons, Barbara L. Harris, Mark A. Winkelman, William A. Wolf, Jeffrey C. Hixon, J. Gregory Schwartz, Arnold M. Myers, Meagan B. Haws, Laurie C. Proctor, Deborah M. TI Assessment of K-Ras mutant frequency and micronucleus incidence in the mouse duodenum following 90-days of exposure to Cr(VI) in drinking water SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Hexavalent chromium; K-Ras; Mutation; Micronucleus; Cancer risk assessment ID SMALL-BOWEL ADENOCARCINOMAS; HEXAVALENT CHROMIUM; ACTION FRAMEWORK; STEM-CELLS; MUTATIONS; CANCER; FRACTION; COLON; MODE; RATS AB Chronic exposure to high concentrations of hexavalent chromium [Cr(VI)] as sodium dichromate dihydrate (SDD) in drinking water induces duodenal tumors in mice, but the mode of action (MOA) for these tumors has been a subject of scientific debate. To evaluate the tumor-site-specific genotoxicity and cytotoxicity of SDD in the mouse small intestine, tissue pathology and cytogenetic damage were evaluated in duodenal crypt and villus enterocytes from B6C3F(1) mice exposed to 0.3-520 mg/L SOD in drinking water for 7 and 90 days. Allele-competitive blocker PCR (ACB-PCR) was used to investigate the induction of a sensitive, tumor-relevant mutation, specifically in vivo K-Ras codon 12 GAT mutation, in scraped duodenal epithelium following 90 days of drinking water exposure. Cytotoxicity was evident in the villus as disruption of cellular arrangement, desquamation, nuclear atypia and blunting. Following 90 days of treatment, aberrant nuclei, occurring primarily at villi tips, were significantly increased at >= 60 mg/L SDD. However, in the crypt compartment, there were no dose-related effects on mitotic and apoptotic indices or the formation of aberrant nuclei indicating that Cr(VI)-induced cytotoxicity was limited to the villi. Cr(VI) caused a dose-dependent proliferative response in the duodenal crypt as evidenced by an increase in crypt area and increased number of crypt enterocytes. Spontaneous K-Ras codon 12 GAT mutations in untreated mice were higher than expected, in the range of 10(-2) to 10(-3); however no treatment-related trend in the K-Ras codon 12 GAT mutation was observed. The high spontaneous background K-Ras mutant frequency and Cr(VI) dose-related increases in crypt enterocyte proliferation, without dose-related increase in K-Ras mutant frequency, micronuclei formation, or change in mitotic or apoptotic indices, are consistent with a lack of genotoxicity in the crypt compartment, and a MOA involving accumulation of mutations late in carcinogenesis as a consequence of sustained regenerative proliferation. Published by Elsevier B.V. C1 [O'Brien, Travis J.; Ding, Hao] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. [Suh, Mina; Proctor, Deborah M.] ToxStrategies Inc, Rancho Santa Margarita, CA 92688 USA. [Thompson, Chad M.; Harris, Mark A.] Tox Strategies Inc, Katy, TX 77494 USA. [Parsons, Barbara L.; Myers, Meagan B.] US FDA, NCTR, Jefferson, AR 72079 USA. [Winkelman, William A.; Wolf, Jeffrey C.] Expt Pathology Labs Inc, Sterling, VA 20166 USA. [Hixon, J. Gregory; Haws, Laurie C.] ToxStrategies Inc, Austin, TX 78759 USA. [Schwartz, Arnold M.] George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Proctor, DM (reprint author), ToxStrategies Inc, 23142 Arroyo Vista, Rancho Santa Margarita, CA 92688 USA. EM phmtjo@gwu.edu; dinghao@gwmail.gwu.edu; msuh@toxstrategies.com; cthompson@toxstrategies.com; barbara.parsons@fda.hhs.gov; mharris@toxstrategies.com; BWinkelman@epl-inc.com; jWolf@epl-inc.com; ghixon@toxstrategies.com; aschwartz@mfa.gwu.edu; meagan.myers@fda.hhs.gov; lhaws@toxstrategies.com; dproctor@toxstrategies.com FU Cr(VI) Panel of the American Chemistry Council FX This work was supported by the Cr(VI) Panel of the American Chemistry Council. NR 41 TC 12 Z9 12 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 EI 1879-3592 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 14 PY 2013 VL 754 IS 1-2 BP 15 EP 21 DI 10.1016/j.mrgentox.2013.03.008 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 165PG UT WOS:000320495200003 PM 23583686 ER PT J AU Meseda, CA Campbell, J Kumar, A Garcia, AD Merchlinsky, M Weir, JP AF Meseda, Clement A. Campbell, Joseph Kumar, Arunima Garcia, Alonzo D. Merchlinsky, Michael Weir, Jerry P. TI Effect of the Deletion of Genes Encoding Proteins of the Extracellular Virion Form of Vaccinia Virus on Vaccine Immunogenicity and Protective Effectiveness in the Mouse Model SO PLOS ONE LA English DT Article ID HUMORAL IMMUNE-RESPONSE; OUTER-MEMBRANE PROTEINS; 2 INFECTIOUS FORMS; SMALLPOX VACCINE; DNA VACCINE; NEUTRALIZING ANTIBODY; ENVELOPE PROTEIN; MONKEYPOX; MICE; ANTIGENS AB Antibodies to both infectious forms of vaccinia virus, the mature virion (MV) and the enveloped virion (EV), as well as cell-mediated immune response appear to be important for protection against smallpox. EV virus particles, although more labile and less numerous than MV, are important for dissemination and spread of virus in infected hosts and thus important in virus pathogenesis. The importance of the EV A33 and B5 proteins for vaccine induced immunity and protection in a murine intranasal challenge model was evaluated by deletion of both the A33R and B5R genes in a vaccine-derived strain of vaccinia virus. Deletion of either A33R or B5R resulted in viruses with a small plaque phenotype and reduced virus yields, as reported previously, whereas deletion of both EV proteinen-coding genes resulted in a virus that formed small infection foci that were detectable and quantifiable only by immunostaining and an even more dramatic decrease in total virus yield in cell culture. Deletion of B5R, either as a single gene knockout or in the double EV gene knockout virus, resulted in a loss of EV neutralizing activity, but all EV gene knockout viruses still induced a robust neutralizing activity against the vaccinia MV form of the virus. The effect of elimination of A33 and/or B5 on the protection afforded by vaccination was evaluated by intranasal challenge with a lethal dose of either vaccinia virus WR or IHD-J, a strain of vaccinia virus that produces relatively higher amounts of EV virus. The results from multiple experiments, using a range of vaccination doses and virus challenge doses, and using mortality, morbidity, and virus dissemination as endpoints, indicate that the absence of A33 and B5 have little effect on the ability of a vaccinia vaccine virus to provide protection against a lethal intranasal challenge in a mouse model. C1 [Meseda, Clement A.; Campbell, Joseph; Kumar, Arunima; Garcia, Alonzo D.; Merchlinsky, Michael; Weir, Jerry P.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Meseda, CA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Clement.Meseda@fda.hhs.gov FU US Food and Drug Administration [Y1-AI-6153-01]; National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIAID) [Y1-AI-6153-01] FX Funding for this work was partly provided by an Inter- Agency Agreement between the US Food and Drug Administration and the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIAID Agreement number Y1-AI-6153-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 7 Z9 7 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 13 PY 2013 VL 8 IS 6 AR e67984 DI 10.1371/journal.pone.0067984 PG 21 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 172XB UT WOS:000321038800001 PM 23785523 ER PT J AU Zhou, ZH Kumari, N Nekhai, S Clouse, KA Wahl, LM Yamada, KM Dhawan, S AF Zhou, Zhao-Hua Kumari, Namita Nekhai, Sergei Clouse, Kathleen A. Wahl, Larry M. Yamada, Kenneth M. Dhawan, Subhash TI Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE HIV-1; Heme oxygenase-1; Macrophages; CCR-5; Chemokines ID MONOCYTE-DERIVED MACROPHAGES; HIV-1 INFECTION; CARBON-MONOXIDE; EXPRESSION; REPLICATION; SECRETION; MALARIA; CELLS AB We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1 alpha and MIP1 beta) by LPS-activated MDM, significantly decreased-surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1 alpha, MIP1 beta, and LD78 beta chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM. Published by Elsevier Inc. C1 [Zhou, Zhao-Hua; Clouse, Kathleen A.] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. [Kumari, Namita; Nekhai, Sergei] Howard Univ, Dept Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Wahl, Larry M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. [Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD USA. [Dhawan, Subhash] US FDA, Ctr Biol Evaluat & Res, Viral Immunol Sect, Lab Mol Virol,Div Emerging & Transfus Transmitted, Bethesda, MD USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Viral Immunol Sect, Lab Mol Virol,Div Emerging & Transfus Transmitted, Bethesda, MD USA. EM subhash.dhawan@fda.hhs.gov FU FDA; NIDCR FX We thank Dr. Krishnakumar Devadas, Dr. Viswanath Ragupathy, Dr. Indira Hewlett and Dr. Robin Biswas for helpful suggestions and critical review of the manuscript. The findings and conclusions in this paper have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy. Supported by FDA and NIDCR Intramural Research Programs. NR 20 TC 11 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 7 PY 2013 VL 435 IS 3 BP 373 EP 377 DI 10.1016/j.bbrc.2013.04.095 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 171DI UT WOS:000320904900009 PM 23665328 ER PT J AU Jha, KN Coleman, AR Wong, L Salicioni, AM Howcroft, E Johnson, GR AF Jha, Kula N. Coleman, Alyssa R. Wong, Lily Salicioni, Ana M. Howcroft, Elizabeth Johnson, Gibbes R. TI Heat Shock Protein 90 Functions to Stabilize and Activate the Testis-specific Serine/Threonine Kinases, a Family of Kinases Essential for Male Fertility SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHAPERONE MACHINERY; HSP90 FUNCTION; GERM-CELLS; IN-VIVO; DEGRADATION; MOUSE; GELDANAMYCIN; EXPRESSION; PROTEASOME; INHIBITOR AB Spermiogenesis is characterized by a profound morphological differentiation of the haploid spermatid into spermatozoa. The testis-specific serine/ threonine kinases (TSSKs) comprise a family of post-meiotic kinases expressed in spermatids, are critical to spermiogenesis, and are required for male fertility in mammals. To explore the role of heat shock protein 90 (HSP90) in regulation of TSSKs, the stability and catalytic activity of epitope-tagged murine TSSKs were assessed in 293T and COS-7 cells. TSSK1, -2, -4, and -6 (small serine/threonine kinase) were all found to associate with HSP90, and pharmacological inhibition of HSP90 function using the highly specific drugs 17-AAG, SNX-5422, or NVP-AUY922 reduced TSSK protein levels in cells. The attenuation of HSP90 function abolished the catalytic activities of TSSK4 and -6 but did not significantly alter the specific activities of TSSK1 and -2. Inhibition of HSP90 resulted in increased TSSK ubiquitination and proteasomal degradation, indicating that HSP90 acts to control ubiquitin-mediated catabolism of the TSSKs. To study HSP90 and TSSKs in germ cells, a mouse primary spermatid culture model was developed and characterized. Using specific antibodies against murine TSSK2 and -6, it was demonstrated that HSP90 inhibition resulted in a marked decrease of the endogenous kinases in spermatids. Together, our findings demonstrate that HSP90 plays a broad and critical role in stabilization and activation of the TSSK family of protein kinases. C1 [Jha, Kula N.; Coleman, Alyssa R.; Wong, Lily; Howcroft, Elizabeth; Johnson, Gibbes R.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Salicioni, Ana M.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. RP Jha, KN (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,HFD 122, Bethesda, MD 20892 USA. EM kula.jha@fda.hhs.gov; gibbes.johnson@fda.hhs.gov FU A.R.C FX This work was supported in part by an appointment of A.R.C. to the ORISE Research Participation Program at the Center for Drug Evaluation and Research (CDER) administered by the Oak Ridge Institute for Science and Education through an agreement between the United States Department of Energy and CDER. NR 46 TC 9 Z9 9 U1 3 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 2013 VL 288 IS 23 BP 16308 EP 16320 DI 10.1074/jbc.M112.400978 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 163ZU UT WOS:000320378900010 PM 23599433 ER PT J AU Fan, YX Wong, L Marino, MP Ou, W Shen, Y Wu, WJ Wong, KK Reiser, J Johnson, GR AF Fan, Ying-Xin Wong, Lily Marino, Michael P. Ou, Wu Shen, Yi Wu, Wen Jin Wong, Kwok-Kin Reiser, Jakob Johnson, Gibbes R. TI Acquired Substrate Preference for GAB1 Protein Bestows Transforming Activity to ERBB2 Kinase Lung Cancer Mutants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; FACTOR RECEPTOR; PHOSPHORYLATION SITES; SIGNAL-TRANSDUCTION; ADAPTER PROTEINS; TYROSINE KINASES; EGFR MUTATIONS; BREAST-CANCER; MET RECEPTOR; IN-VITRO AB Activating mutations in the alpha C-beta 4 loop of the ERBB2 kinase domain, such as ERBB2(YVMA) and ERBB2(G776VC), have been identified in human lung cancers and found to drive tumor formation. Here we observe that the docking protein GAB1 is hyper-phosphorylated in carcinomas from transgenic mice and in cell lines expressing these ERBB2 cancer mutants. Using dominant negative GAB1 mutants lacking canonical tyrosine residues for SHP2 and PI3K interactions or lentiviral shRNA that targets GAB1, we demonstrate that GAB1 phosphorylation is required for ERBB2 mutant-induced cell signaling, cell transformation, and tumorigenesis. An enzyme kinetic analysis comparing ERBB2(YVMA) to wild type using physiologically relevant peptide substrates reveals that ERBB2(YVMA) kinase adopts a striking preference for GAB1 phosphorylation sites as evidenced by similar to 150-fold increases in the specificity constants (k(cat)/K-m) for several GAB1 peptides, and this change in substrate selectivity was predominantly attributed to the peptide binding affinities as reflected by the apparent K-m values. Furthermore, we demonstrate that ERBB2(YVMA) phosphorylates GAB1 protein similar to 70-fold faster than wild type ERBB2 in vitro. Notably, the mutation does not significantly alter the K-m for ATP or sensitivity to lapatinib, suggesting that, unlike EGFR lung cancer mutants, the ATP binding cleft of the kinase is not significantly changed. Taken together, our results indicate that the acquired substrate preference for GAB1 is critical for the ERBB2 mutant-induced oncogenesis. C1 [Fan, Ying-Xin; Wong, Lily; Johnson, Gibbes R.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Marino, Michael P.; Ou, Wu; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Shen, Yi; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Wong, Kwok-Kin] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Fan, YX (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Rm 3B-20,8800 Rockville Pike, Bethesda, MD 20892 USA. EM ying-xin.fan@fda.hhs.gov; gibbes.johnson@fda.hhs.gov OI wong, kwok kin/0000-0001-6323-235X FU NCI NIH HHS [R01 CA140594, R01 CA122794, P01 CA154303] NR 51 TC 3 Z9 5 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 2013 VL 288 IS 23 BP 16895 EP 16904 DI 10.1074/jbc.M112.434217 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 163ZU UT WOS:000320378900062 PM 23612964 ER PT J AU Mitkus, RJ Hess, MA Schwartz, SL AF Mitkus, Robert J. Hess, Maureen A. Schwartz, Sorell L. TI Pharmacokinetic modeling as an approach to assessing the safety of residual formaldehyde in infant vaccines SO VACCINE LA English DT Article DE Formaldehyde; Inactivating agent; Safety; Pharmacokinetics; Modeling ID ALCOHOL-DEHYDROGENASE; HYPERSENSITIVITY REACTIONS; SYSTEMIC DISTRIBUTION; PULPOTOMY TREATMENT; HUMAN-TISSUES; DNA-DAMAGE; BLOOD-FLOW; TOXICITY; RAT; EXPOSURE AB Formaldehyde is a one-carbon, highly water-soluble aldehyde that is used in certain vaccines to inactivate viruses and to detoxify bacterial toxins. As part of the manufacturing process, some residual formaldehyde can remain behind in vaccines at levels less than or equal to 0.02%. Environmental and occupational exposure, principally by inhalation, is a continuing risk assessment focus for formaldehyde. However, exposure to formaldehyde via vaccine administration is qualitatively and quantitatively different from environmental or occupational settings and calls for a different perspective and approach to risk assessment. As part of a rigorous and ongoing process of evaluating the safety of biological products throughout their lifecycle at the FDA, we performed an assessment of formaldehyde in infant vaccines, in which estimates of the concentrations of formaldehyde in blood and total body water following exposure to formaldehyde-containing vaccines at a single medical visit were compared with endogenous background levels of formaldehyde in a model 2-month-old infant. Formaldehyde levels were estimated using a physiologically-based pharmacokinetic (PBPK) model of formaldehyde disposition following intramuscular (IM) injection. Model results indicated that following a single dose of 200 mu g, formaldehyde is essentially completely removed from the site of injection within 30 min. Assuming metabolism at the site of injection only, peak concentrations of formaldehyde in blood/total body water were estimated to be 22 mu g/L, which is equivalent to a body burden of 66 mu g or <1% of the endogenous level of formaldehyde. Predicted levels in the lymphatics were even lower. Assuming no adverse effects from endogenous formaldehyde, which exists in blood and extravascular water at background concentrations of 0.1 mM, we conclude that residual, exogenously applied formaldehyde continues to be safe following incidental exposures from infant vaccines. Published by Elsevier Ltd. C1 [Mitkus, Robert J.; Schwartz, Sorell L.] USFDA Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20852 USA. [Hess, Maureen A.] USFDA Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20852 USA. [Schwartz, Sorell L.] Georgetown Univ, Med Ctr, Dept Physiol & Pharmacol, Washington, DC 20057 USA. RP Mitkus, RJ (reprint author), USFDA Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, 1401 Rockville Pike,HFM 210, Rockville, MD 20852 USA. EM Robert.Mitkus@fda.hhs.gov NR 62 TC 5 Z9 5 U1 0 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JUN 7 PY 2013 VL 31 IS 25 BP 2738 EP 2743 DI 10.1016/j.vaccine.2013.03.071 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 167MC UT WOS:000320635100003 PM 23583892 ER PT J AU Racoosin, JA Roberson, DW Pacanowski, MA Nielsen, DR AF Racoosin, Judith A. Roberson, David W. Pacanowski, Michael A. Nielsen, David R. TI New Evidence about an Old Drug - Risk with Codeine after Adenotonsillectomy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHILDREN; TONSILLECTOMY C1 [Racoosin, Judith A.; Pacanowski, Michael A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Roberson, David W.; Nielsen, David R.] Amer Acad Otolaryngol Head & Neck Surg, Alexandria, VA USA. [Roberson, David W.] Boston Childrens Hosp, Dept Otolaryngol, Boston, MA USA. [Roberson, David W.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Racoosin, JA (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 29 Z9 31 U1 1 U2 8 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 2013 VL 368 IS 23 BP 2155 EP 2157 DI 10.1056/NEJMp1302454 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 158DN UT WOS:000319948900003 PM 23614474 ER PT J AU Papafragkou, E Hewitt, J Park, GW Greening, G Vinje, J AF Papafragkou, Efstathia Hewitt, Joanne Park, Geun Woo Greening, Gail Vinje, Jan TI Challenges of Culturing Human Norovirus in Three-Dimensional Organoid Intestinal Cell Culture Models SO PLOS ONE LA English DT Article ID REVERSE TRANSCRIPTION-PCR; NORWALK VIRUS-INFECTION; BLOOD GROUP ANTIGENS; UNITED-STATES; CLINICAL SPECIMENS; MAMMALIAN-CELLS; DENDRITIC CELLS; CACO-2 CELLS; BINDING; TISSUE AB Human noroviruses are the most common cause of acute gastroenteritis worldwide. Recently, cell culture systems have been described using either human embryonic intestinal epithelial cells (Int-407) or human epithelial colorectal adenocarcinoma cells (Caco-2) growing on collagen-I porous micro carrier beads in a rotating bioreactor under conditions of physiological fluid shear. Here, we describe the efforts from two independent laboratories to implement this three dimensional (3D) cell culture system for the replication of norovirus. Int-407 and Caco-2 were grown in a rotating bioreactor for up to 28 days. Prior to infection, cells were screened for the presence of microvilli by electron microscopy and stained for junction proteins (zonula occludens-1, claudin-1, and b-catenin). Differentiated 3D cells were transferred to 24-well plates and infected with bacteria-free filtrates of various norovirus genotypes (GI. 1, GI. 3, GI. 8, GII. 2, GII. 4, GII. 7, and GII. 8). At 12 h, 24 h, and 48 h post inoculation, viral RNA from both cells and supernatants were collected and analyzed for norovirus RNA by real-time reverse transcription PCR. Despite observations of high expression of junction proteins and microvilli development in stained thin sections, our data suggest no significant increase in viral titer based on norovirus RNA copy number during the first 48 h after inoculation for the different samples and virus culture conditions tested. Our combined efforts demonstrate that 3D cell culture models using Int-407 or Caco-2 cells do not support norovirus replication and highlight the complexity and difficulty of developing a reproducible in vitro cell culture system for human norovirus. C1 [Papafragkou, Efstathia; Park, Geun Woo; Vinje, Jan] Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA. [Papafragkou, Efstathia] US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Laurel, MD USA. [Hewitt, Joanne; Greening, Gail] Inst Environm Sci & Res Ltd, Kenepuru Sci Ctr, Porirua, New Zealand. RP Vinje, J (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Atlanta, GA 30333 USA. EM jvinje@cdc.gov OI Vinje, Jan/0000-0002-1530-3675 FU ASM/CDC Fellowship Program in Infectious Disease and Public Health Microbiology; ESR Capability Fund FX This research was funded in part by the ASM/CDC Fellowship Program in Infectious Disease and Public Health Microbiology for EP. The New Zealand study was funded by the ESR Capability Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 26 Z9 27 U1 4 U2 30 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 3 PY 2013 VL 8 IS 6 AR e63485 DI 10.1371/journal.pone.0063485 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157CD UT WOS:000319872300010 ER PT J AU Tournas, VH Calo, JR Sapp, C AF Tournas, V. H. Calo, J. Rivera Sapp, C. TI Fungal profiles in various milk thistle botanicals from US retail SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Milk thistle botanicals; Fungal contaminants; Enumeration; Identification ID MEDICINAL-PLANTS; LIQUID-CHROMATOGRAPHY; FUMONISINS B-1; CONTAMINATION; MYCOTOXINS; AFLATOXINS; TEA; PROGRESSION; SUPPLEMENTS; SILYMARIN AB Milk thistle (MT) dietary supplements are widely consumed due to their possible beneficial effect on liver health. As botanicals, they can be contaminated with a variety of fungi and their secondary metabolites, mycotoxins. This study was conducted in an effort to determine the mycological quality of various MT botanical supplements from the US market. Conventional plating methods were used for the isolation and enumeration of fungi, while conventional microscopy as well as molecular methods were employed for the speciation of the isolated strains. Results showed that a high percentage of the MT samples tested were contaminated with fungi. Total counts ranged between <2.00 and 5.60 log10 colony forming units per gram (cfu/g). MT whole seeds carried the highest fungal levels followed by MT cut herb. No live fungi were recovered from MT seed tea bags, liquid extracts, capsules or soft gels. Potentially toxigenic molds from the Aspergillus sections Flavi and Nigri as well as Eurotium, Penicillium, Fusarium and Alternaria species were isolated from MT supplements. The predominant molds were Eurotia (E. repens, E. amstelodami and E. rubrum), A. flavus, A. tubingensis, A. niger and A. candidus. To our knowledge, this is the first study reporting on fungal contamination profiles of MT botanicals. Published by Elsevier B.V. C1 [Tournas, V. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Calo, J. Rivera] Univ Arkansas, Fayetteville, AR 72701 USA. [Sapp, C.] Johns Hopkins Sch Med, Baltimore, MD USA. RP Tournas, VH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM valerie.tournas@fda.hhs.gov NR 40 TC 4 Z9 4 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 EI 1879-3460 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 3 PY 2013 VL 164 IS 1 BP 87 EP 91 DI 10.1016/j.ijfoodmicro.2013.03.026 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 152PF UT WOS:000319542900014 PM 23624536 ER PT J AU Mezal, EH Stefanova, R Khan, AA AF Mezal, Ezat H. Stefanova, Rossina Khan, Ashraf A. TI Isolation and molecular characterization of Salmonella enterica serovar Javiana from food, environmental and clinical samples SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella Javiana; Pulsed-field gel electrophoresis fingerprinting; Antibiotic susceptibility; Virulence genes; Plasmids ID FIELD GEL-ELECTROPHORESIS; IMPORTED SEAFOOD; ANTIMICROBIAL RESISTANCE; ESCHERICHIA-COLI; OUTBREAK; IDENTIFICATION; ANIMALS; HEALTH; BORNE; SPP. AB A total of 50 Salmonella enterica serovar Javiana isolates, isolated from food, environmental and clinical samples, were analyzed for antibiotic resistance, presence of virulence genes, plasmids and plasmid replicon types. To assess the genetic diversity, pulsed-field gel electrophoresis (PFGE) fingerprinting and plasmid profiles were performed. All of the isolates were sensitive to chloramphenicol, nalidixic acid, and sulfisoxazole, and four isolates showed intermediate resistance to gentamicin or kanamycin. Eleven isolates, including representatives from each of the source types, were resistant to ampicillin. Four isolates from either clinical or environmental sources were resistant to tetracycline, while an additional 20 isolates showed intermediate resistance to this drug. Fourteen isolates, primarily from food sources, showed intermediate resistance to streptomycin. The S. Javiana isolates were screened by PCR for 17 virulence genes (spvB, spiA, pagC, msgA, invA, sipB, prgH, spaN, orgA, tolC, iroN, sitC, lpfC, sifA, sopB, cdtB, and pefA). All isolates were positive for nine to fourteen of these genes, but none were positive for. pefA, spvB and lpfC, which are typically present on the Salmonella virulence plasmid. Seven of the virulence genes including cdtB were found in all 50 isolates, suggesting that S. Javiana from food and environmental sources had virulence similar to clinical isolates. Four clinical isolates and two food isolates carried one or more plasmids of approximately 30, 38, and 58 kb, with the 58 kb plasmids belonging to incompatibility group IncFIIA. Two clinical isolates carried Inch l type mega plasmid (80 kb), and one clinical isolate carried plasmids of 4.5 and 7 kb. The PFGE profiles resulted 34 patterns in five clusters at a 90% similarity threshold. Our results indicate that S. Javiana isolates have a diverse clonal population among the clinical, food and environmental samples and this serotype possesses several virulent genes and plasmids that can contribute to the development of salmonellosis in human. This study provides data that support the potential transmission of S. Javiana virulence factors from food and environmental sources to cause infections in humans. Published by Elsevier B.V. C1 [Mezal, Ezat H.; Khan, Ashraf A.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mezal, Ezat H.] Univ Arkansas, Little Rock, AR 72205 USA. [Mezal, Ezat H.] Univ Thi Qar, Coll Sci, Dept Biol, Thi Qar, Iraq. [Stefanova, Rossina] Arkansas Dept Hlth, Little Rock, AR 72205 USA. RP Khan, AA (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Ashraf.khan@fda.hhs.gov RI Khan, Ashraf/E-8133-2013 NR 33 TC 10 Z9 10 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD JUN 3 PY 2013 VL 164 IS 1 BP 113 EP 118 DI 10.1016/j.ijfoodmicro.2013.03.021 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 152PF UT WOS:000319542900018 PM 23628778 ER PT J AU Rouse, RL Stewart, SR Thompson, KL Zhang, J AF Rouse, Rodney L. Stewart, Sharron R. Thompson, Karol L. Zhang, Jun TI Kidney Injury Biomarkers in Hypertensive, Diabetic, and Nephropathy Rat Models Treated with Contrast Media SO TOXICOLOGIC PATHOLOGY LA English DT Article DE contrast nephropathy; acute kidney injury; contrast media; risk factors; kidney injury biomarkers ID GELATINASE-ASSOCIATED LIPOCALIN; SALT-SENSITIVE RATS; ADVERSE EVENTS CAUSE; RENAL DAMAGE; VASCULAR INJURY; BLOOD-PRESSURE; CYSTATIN C; IN-VITRO; NEPHROTOXICITY; MARKERS AB Contrast-induced nephropathy (CIN) refers to a decline in renal function following exposure to iodinated contrast media (CM). The present study was initiated to explore the role of known human risk factors (spontaneous hypertension, diabetes, protein-losing nephropathy) on CIN development in rodent models and to determine the effect of CM administration on kidney injury biomarkers in the face of preexisting kidney injury. Spontaneously hypertensive rats (hypertension), streptozotocin-treated Sprague Dawley rats (diabetes), and Dahl salt-sensitive rats (protein-losing nephropathy) were given single intravenous injections of the nonionic, low osmolar contrast medium, iohexol. Blood urea nitrogen (BUN), serum creatinine (sCr), and urinary biomarkers; albumin, lipocalin 2 (Lcn-2), osteopontin (Opn), kidney injury molecule 1 (Kim-1), renal papillary antigen 1 (Rpa-1), alpha-glutathione S-transferase (alpha-Gst), mu-glutathione S-transferase (mu-Gst), and beta-2 microglobulin (beta 2m) were measured in disease models and appropriate controls to determine the response of these biomarkers to CM administration. Each disease model produced elevated biomarkers of kidney injury without CM. Preexisting histopathology was exacerbated by CM but little or no significant increases in biomarkers were observed. When 1.5-fold or greater sCr increases from pre-CM were used to define true positives, receiver-operating characteristic curve analysis of biomarker performance showed sCr was the best predictor of CIN across disease models. beta 2m, Lcn-2, and BUN were the best predictors of histopathology defined kidney injury. C1 [Rouse, Rodney L.; Stewart, Sharron R.; Thompson, Karol L.] US FDA, Div Drug Safety Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Zhang, Jun] US FDA, Silver Spring, MD USA. RP Rouse, RL (reprint author), US Food & Drug Adm HFD 910, Div Drug Safety Res, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rodney.rouse@fda.hhs.gov FU Division of Drug Safety Research [operating budget], Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration FX This work was supported by the Division of Drug Safety Research [operating budget], Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, U.S. Food and Drug Administration. The authors would like to acknowledge P. Scott Pine for his assistance in creating relevant figures from the complex data sets. NR 56 TC 5 Z9 6 U1 0 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 EI 1533-1601 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JUN PY 2013 VL 41 IS 4 BP 662 EP 680 DI 10.1177/0192623312464122 PG 19 WC Pathology; Toxicology SC Pathology; Toxicology GA AB0EL UT WOS:000331464500006 PM 23085980 ER PT J AU Zhou, WL Wang, PG Ogunsola, OA Kraeling, MEK AF Zhou, Wanlong Wang, Perry G. Ogunsola, Oluwatosin A. Kraeling, Margaret E. K. TI Rapid determination of hexapeptides by hydrophilic interaction LC-MS/MS for in vitro skin-penetration studies SO BIOANALYSIS LA English DT Article ID TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; PERCUTANEOUS-ABSORPTION; COSMETIC FORMULATIONS; HPLC; VALIDATION; PERMEATION; ANTAGONIST; PEPTIDES; SAMPLES AB Background: A sensitive analytical method is needed for assessing penetration of topically applied peptides for in vitro skin-penetration studies. Results: A rapid hydrophilic interaction LC (HILIC)-MS/MS method for analyzing the polar peptides Ac-EEMQRR-amide and H2N-EEMQRR-amide in various skin layers and matrices has been developed and evaluated. The matrices included emulsion, receptor fluids, cotton-tipped applicators, stratum corneum tape strips, epidermis and dermis of the skin. Stable isotopically labeled analogues were used as internal standards to correct for recovery and matrix effects. A HILIC-SPE procedure was optimized to minimize significant ion suppression in the more complex matrices. Conclusion: This HILIC-MS/MS method is applicable to the determination of Ac-EEMQRR-amide and H2N-EEMQRR-amide in complex skin samples and other matrices generated during in vitro skin-penetration studies. C1 [Zhou, Wanlong; Wang, Perry G.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Ogunsola, Oluwatosin A.; Kraeling, Margaret E. K.] Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Wang, PG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM perry.wang@fda.hhs.gov FU US FDA FX Part of this work was supported by the appointment of W Zhou to the research fellowship program of the US FDA administrated by the Oak Ridge Institute for Science and Education. The authors wish to thank JI Rader, AJ Krynitsky, JJ Yourick, RL Sprando, WG Wamer, H Chou, R Bronaugh, J Callahan, J Wong and P Scholl (FDA, Center for Food Safety and Applied Nutrition) for helpful discussions. NR 24 TC 9 Z9 9 U1 2 U2 10 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 EI 1757-6199 J9 BIOANALYSIS JI Bioanalysis PD JUN PY 2013 VL 5 IS 11 BP 1353 EP 1362 DI 10.4155/BIO.13.60 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA AA2UG UT WOS:000330949000014 PM 23742305 ER PT J AU Pontone, GM Williams, JR Anderson, KE Chase, G Goldstein, SR Grill, S Hirsch, ES Lehmann, S Little, JT Margolis, RL Palanci, J Rabins, PV Weiss, HD Marsh, L AF Pontone, Gregory M. Williams, James R. Anderson, Karen E. Chase, Gary Goldstein, Susanne R. Grill, Stephen Hirsch, Elaina S. Lehmann, Susan Little, John T. Margolis, Russell L. Palanci, Justin Rabins, Peter V. Weiss, Howard D. Marsh, Laura TI Pharmacologic Treatment of Anxiety Disorders in Parkinson Disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Parkinson disease; non-motor symptoms; anxiety; anxiety disorders; psychiatric disorders; treatment ID QUALITY-OF-LIFE; OLDER-ADULTS; FOLLOW-UP; DEPRESSION; FLUCTUATIONS; COMORBIDITY; PREVALENCE; DISABILITY; BLIND AB Objective: Neither best practices nor an evidence base for the pharmacologic treatment of anxiety in Parkinson disease (PD) has been established. This study investigated pharmacologic treatment of anxiety disorders in idiopathic PD and the associated clinical features. Design: Cross-sectional. Setting: Three community-based movement disorder neurology practices. Participants: 250 subjects with PD. Measurements: Anxiety disorder diagnoses were established by consensus using a panel of six psychiatrists with expertise in geriatric psychiatry and movement disorders. Current medications were provided by the treating neurologists at the time of interview. Results: Among subjects with anxiety disorders only, 53% were untreated with medications. When anxious subjects with comorbid depressive disorders were included, 70.8% were on medications effective for treatment of anxiety. Subjects with anxiety and comorbid depressive disorders were more likely to be treated for their psychiatric disturbances than subjects with anxiety disorders alone (odds ratio: 8.33), as were subjects with comorbid motor fluctuations (odds ratio: 3.65). There were no differences in the types of anti-anxiety medications used in regard to the presence of depression or motor fluctuations. Conclusions: These findings suggest that over half of nondepressed PD patients with clinically significant anxiety are untreated with medication. A better understanding of the role of clinical features associated with anxiety in PD, such as depression and motor fluctuations, may improve the recognition and treatment of anxiety disorders in this population. C1 [Pontone, Gregory M.; Williams, James R.; Hirsch, Elaina S.; Lehmann, Susan; Margolis, Russell L.; Palanci, Justin; Rabins, Peter V.; Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Williams, James R.] Biogen Idec Inc, Cambridge, MA USA. [Anderson, Karen E.] Univ Maryland, Med Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Anderson, Karen E.] Univ Maryland, Med Ctr, Dept Neurol, Baltimore, MD 21201 USA. [Chase, Gary] Penn State Univ, Dept Hlth Evaluat Sci, Hershey, PA USA. [Goldstein, Susanne R.] US FDA, Silver Spring, MD USA. [Grill, Stephen] Parkinsons & Movement Disorders Ctr Maryland, Elkridge, MD USA. [Grill, Stephen; Weiss, Howard D.; Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Neurol & Neurol Sci, Baltimore, MD 21287 USA. [Little, John T.] Vet Affairs Med Ctr, Washington, DC 20422 USA. [Little, John T.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Little, John T.] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC USA. [Weiss, Howard D.] Sinai Hosp, Dept Neurol, Baltimore, MD 21215 USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Pontone, GM (reprint author), Johns Hopkins Univ, Sch Med, 600 N Wolfe St Phipps 300, Baltimore, MD 21287 USA. EM gponton1@jhmi.edu FU NIH [R01-MH069666, NIH-P50-NS-38377, NIH-5T32-AG-027668-02]; Parkinson's Disease Foundation/Parkinson Study Group Mentored Clinical Research Award; Donna Jeanne Gault Baumann Fund FX This study was supported by NIH grants (R01-MH069666 to L. Marsh; the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins [NIH-P50-NS-38377] and the Age-Related Cognitive Disorders training grant [NIH-5T32-AG-027668-02] to J. R. Williams); the Parkinson's Disease Foundation/Parkinson Study Group Mentored Clinical Research Award (Gregory M. Pontone); and the Donna Jeanne Gault Baumann Fund. The views expressed in this article do not necessarily represent the views of the Food and Drug Administration or the United States. The work presented was completed prior to James R. Williams's employment at Biogen Idec. NR 34 TC 9 Z9 9 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 EI 1545-7214 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD JUN PY 2013 VL 21 IS 6 BP 520 EP 528 DI 10.1016/j.jagp.2012.10.023 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 298XV UT WOS:000330358900004 PM 23567419 ER PT J AU Gamalo, MA Muthukumarana, S Ghosh, P Tiwari, RC AF Gamalo, Mark A. Muthukumarana, Saman Ghosh, Pulak Tiwari, Ram C. TI A generalized p-value approach for assessing noninferiority in a three-arm trial SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article DE Behrens-Fisher problem; coverage probability; Dirichlet distribution; generalized test function; noninferiority; Type-I error ID ASSESSING NON-INFERIORITY; BEHRENS-FISHER PROBLEM; THERAPEUTIC EQUIVALENCE; VARIANCE-COMPONENTS; ISSUES; STATISTICS; INTERVALS; PLACEBO; DESIGN AB The existing generalized p-value approach, from statistical literature, is applied to assess noninferiority of an experimental treatment in a three-arm clinical trial including a placebo. Two generalized test functions (GTFs) are constructed and Monte Carlo simulations are used to compute the p-value. The GTFs perform well in terms of maintaining the Type-I error probabilities, and the power of the tests are shown to increase to 1 as both the sample size and the parameter denoting the fraction of the effect of the reference drug with respect to placebo increase. The generalized confidence intervals are shown to retain the coverage probabilities. A published dataset is re-analysed using the proposed test and the results are in agreement with earlier findings. C1 [Gamalo, Mark A.; Tiwari, Ram C.] Ctr Drug Evaluat & Res Food & Drug Adm, Off Biostat, Silver Spring, MD 20993 USA. [Muthukumarana, Saman] Univ Manitoba, Dept Stat, Winnipeg, MB R3T 2N2, Canada. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Sci, Bangalore, Karnataka, India. RP Gamalo, MA (reprint author), Ctr Drug Evaluat & Res Food & Drug Adm, Off Biostat, Silver Spring, MD 20993 USA. EM Mark.Gamalo@fda.hhs.gov NR 27 TC 5 Z9 5 U1 1 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD JUN PY 2013 VL 22 IS 3 BP 261 EP 277 DI 10.1177/0962280210395739 PG 17 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 296ZI UT WOS:000330224000002 PM 21300626 ER PT J AU Cooper-DeHoff, RM Bird, ST Nichols, GA Delaney, JA Winterstein, AG AF Cooper-DeHoff, Rhonda M. Bird, Steven T. Nichols, Gregory A. Delaney, Joseph A. Winterstein, Almut G. TI Antihypertensive Drug Class Interactions and Risk for Incident Diabetes: A Nested Case-Control Study SO JOURNAL OF THE AMERICAN HEART ASSOCIATION LA English DT Article DE beta blockers; diabetes; diabetogenic; drug interactions; hypertension; RAS blockers; thiazide diuretics ID UNITED-STATES; HYPERTENSION; PREVALENCE; METAANALYSIS; MELLITUS; OUTCOMES; ADULTS; ALLHAT; US AB Background-We aimed to determine how single and combination antihypertensive therapy alters risk for diabetes mellitus (DM). Thiazide diuretics (TD), beta blockers (BB), and renin-angiotensin system blockers (RASB) impact DM risk while calcium channel blockers (CCB) are neutral. DM risk associated with combinations is unclear. Methods and Results-We enrolled nondiabetic patients from Kaiser Permanente Northwest with a fasting plasma glucose (FPG) <126 mg/dL between 1997 and 2010. DM cases were defined by a FPG >= 126 mg/dL, random plasma glucose >= 200 mg/dL, HbA(1c) >= 7.0%, or new DM prescription (index date). We used incidence density sampling to match 10 controls per case on the date of follow-up glucose test (to reduce detection bias), in addition to age and date of cohort entry. Exposure to antihypertensive class was assessed during the 30 days prior to index date. Our cohort contained 134 967 patients and had 412 604 glucose tests eligible for matching. A total of 9097 DM cases were matched to 90 495 controls (median age 51 years). Exposure to TD (OR 1.54, 95% CI 1.41 to 1.68) or BB (OR 1.19, 95% CI 1.11 to 1.28) was associated with an increased DM risk, while CCB and RASB exposure was not. TD+BB combination resulted in the fully combined diabetogenic risk of both agents (OR 1.99, 95% CI 1.80 to 2.20; interaction OR 1.09, 95% CI 0.97 to 1.22). In contrast, combination of RASB with either TD or BB showed significant negative interactions, resulting in a smaller DM risk than TD or BB monotherapy. Conclusions-Diabetogenic potential of combination therapy should be considered when prescribing antihypertensive therapy. C1 [Cooper-DeHoff, Rhonda M.] Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL 32611 USA. [Bird, Steven T.; Delaney, Joseph A.; Winterstein, Almut G.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32611 USA. [Cooper-DeHoff, Rhonda M.] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL 32611 USA. [Bird, Steven T.] US Dept HHS, Food & Drug Adm, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol,Dept Epidemiol, Silver Spring, MD USA. [Nichols, Gregory A.] Kaiser Permanente Ctr Hlth Res, Portland, OR USA. [Delaney, Joseph A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Winterstein, Almut G.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol, Gainesville, FL 32611 USA. [Winterstein, Almut G.] Univ Florida, Coll Med, Gainesville, FL 32611 USA. RP Cooper-DeHoff, RM (reprint author), Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, 1600 SW Archer Rd,POB 100486, Gainesville, FL 32611 USA. EM dehoff@cop.ufl.edu RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 FU NIH National Heart Lung and Blood institute [K23HL086558]; NIH National Institute of General Medicine Sciences [2U01 GM074492] FX This study was supported, in part, by the NIH National Heart Lung and Blood institute (K23HL086558) and NIH National Institute of General Medicine Sciences (2U01 GM074492) (Dr. Cooper-DeHoff). NR 25 TC 8 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 2047-9980 J9 J AM HEART ASSOC JI J. Am. Heart Assoc. PD JUN PY 2013 VL 2 IS 3 AR UNSP e000125 DI 10.1161/JAHA.113.000125 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 243TH UT WOS:000326340100010 PM 23752710 ER PT J AU Vesnovsky, O Casamento, JP AF Vesnovsky, Oleg Casamento, Jon P. TI Development of a Coring Test for Non-Coring Huber Needles SO JOURNAL OF MEDICAL DEVICES-TRANSACTIONS OF THE ASME LA English DT Article; Proceedings Paper CT University-of-Minnesota's Design of Medical Devices (DMD) Conference CY APR 09-11, 2013 CL Minneapolis, MN C1 [Vesnovsky, Oleg; Casamento, Jon P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Vesnovsky, O (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 1 TC 0 Z9 0 U1 0 U2 4 PU ASME PI NEW YORK PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA SN 1932-6181 EI 1932-619X J9 J MED DEVICES JI J. Med. Devices PD JUN PY 2013 VL 7 IS 2 AR UNSP 020930 PG 2 WC Engineering, Biomedical SC Engineering GA 240SP UT WOS:000326117600031 ER PT J AU Keller, SE Shazer, AG Fleischman, GJ Chirtel, S Anderson, N Larkin, J AF Keller, Susanne E. Shazer, Arlette G. Fleischman, Gregory J. Chirtel, Stuart Anderson, Nathan Larkin, John TI "Thermal Inactivation of Campylobacter jejuni in Broth,'' A Comment on: J. Food Prot. 75(6): 1029-1035 (2012) SO JOURNAL OF FOOD PROTECTION LA English DT Letter C1 [Keller, Susanne E.; Shazer, Arlette G.; Fleischman, Gregory J.; Chirtel, Stuart; Anderson, Nathan; Larkin, John] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. RP Keller, SE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. NR 2 TC 0 Z9 0 U1 0 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2013 VL 76 IS 6 BP 928 EP 928 DI 10.4315/0362-028X.76.6.928 PG 1 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FR UT WOS:000326080900001 PM 23726185 ER PT J AU Dey, M Mayo, JA Saville, D Wolyniak, C Klontz, KC AF Dey, Manashi Mayo, Jonathan A. Saville, Deborah Wolyniak, Cecilia Klontz, Karl C. TI Recalls of Foods due to Microbiological Contamination Classified by the US Food and Drug Administration, Fiscal Years 2003 through 2011 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; MULTISTATE OUTBREAK; SALMONELLA-TYPHIMURIUM; FOODBORNE ILLNESS; INFECTIONS; LISTERIOSIS; PATHOGENS; COSMETICS; PRODUCE AB Recalls of foods contaminated with pathogens help reduce the transmission of infectious diseases. Here, we summarize the number and nature of foods recalled as a result of microbiological contamination, classified by the U. S. Food and Drug Administration for the period 1 October 2002 through 30 September 2011. Microbiological contamination accounted for 1,395 (42%) of 3,360 recalls of food during this period. Nuts and edible seeds, followed by fishery-seafood products and spices, were the types of products most commonly recalled for microbiological contamination. Salmonella contamination accounted for the greatest number of food products recalled due to microbiological contamination, and was the pathogen most often linked to reported outbreaks involving recalled food products. C1 [Dey, Manashi; Saville, Deborah; Wolyniak, Cecilia; Klontz, Karl C.] US FDA, College Pk, MD 20740 USA. [Mayo, Jonathan A.] George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC 20007 USA. RP Klontz, KC (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM karl.klontz@fda.hhs.gov NR 21 TC 4 Z9 4 U1 2 U2 14 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2013 VL 76 IS 6 BP 932 EP 938 DI 10.4315/0362-028X.JFP-12-464 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FR UT WOS:000326080900003 PM 23726186 ER PT J AU Hoelzer, K Fanaselle, W Pouillot, R Van Doren, JM Dennis, S AF Hoelzer, K. Fanaselle, W. Pouillot, R. Van Doren, J. M. Dennis, S. TI Virus Inactivation on Hard Surfaces or in Suspension by Chemical Disinfectants: Systematic Review and Meta-Analysis of Norovirus Surrogates SO JOURNAL OF FOOD PROTECTION LA English DT Review ID HEPATITIS-A VIRUS; FELINE CALICIVIRUS; MURINE NOROVIRUS; GERMICIDAL ACTIVITY; VIRAL SURROGATES; GII.4 NOROVIRUS; ENTERIC VIRUSES; HEALTH-CARE; CHITOSAN; EFFICACY AB Norovirus (NoV) infections are the leading cause of foodborne illness in the United States. Effective disinfection is important for controlling outbreaks caused by this highly infectious virus but can be difficult to achieve because NoV is very resistant to many common disinfection protocols. The inability of human NoV to replicate in tissue culture complicates NoV research, generally necessitating genome copy quantification, the use of surrogate viruses, or the use of other substitutes such as virus-like particles. To date, comprehensive comparisons among NoV surrogates and between surrogates and human NoV are missing, and it is not clear how best to extrapolate information from surrogate data. We conducted a systematic review and meta-analysis of comparisons of NoV surrogates with regard to their susceptibility to disinfection on hard surfaces or in suspension. Restricting our analysis to those studies in which two or more virus surrogates were compared allowed us to improve the signal-to-noise ratio in our analysis, similar to the epidemiological concept of matching. Using meta-analysis methods, our results indicate that hepatitis A virus, murine norovirus 1, and phage MS2 are significantly more resistant to disinfection than is feline calicivirus, but average differences in viral titer reduction appeared to be modest, 1.5 log PFU or less in all cases. None of the studies that compared surrogates and human NoV met our inclusion criteria, precluding a direct comparison between human NoV and NoV surrogates in this study. For all surrogates with sufficient data available to permit subgroup analyses, we detected strong evidence that the type of disinfectant impacted the relative susceptibility of the surrogates. Therefore, extrapolation of results between surrogates or from surrogates to human NoV must consider the type of disinfectant studied. C1 [Hoelzer, K.; Fanaselle, W.; Pouillot, R.; Van Doren, J. M.; Dennis, S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hoelzer, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM karin.hoelzer@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU FDA; appointments to the Research Participation Program at the Center for Food Safety and Applied Nutrition FX This work was supported by the FDA and in part by appointments to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the FDA. NR 55 TC 12 Z9 12 U1 2 U2 31 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2013 VL 76 IS 6 BP 1006 EP 1016 DI 10.4315/0362-028X.JFP-12-438 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FR UT WOS:000326080900013 PM 23726196 ER PT J AU Tournas, VH Kohn, JS Johny, A AF Tournas, V. H. Kohn, J. S. Johny, A. TI Fungal contaminants recovered from selected tree nuts and dried fruits SO PHYTOPATHOLOGY LA English DT Meeting Abstract CT Joint Meeting of the American-Phytopathological-Society (APS) and the Mycological-Society-of-America (MSA) CY AUG 10-14, 2013 CL Austin, TX SP Amer Phytopathol Soc (APS), Mycol Soc Amer (MSA) C1 [Tournas, V. H.] US FDA, CFSAN, College Pk, MD USA. [Kohn, J. S.] US FDA, ORA, NERL, Jamaica, NY USA. [Johny, A.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2013 VL 103 IS 6 SU 2 BP 147 EP 147 PG 1 WC Plant Sciences SC Plant Sciences GA 196TM UT WOS:000322799500810 ER PT J AU Tournas, VH Niazi, NS Katsoudas, EJ AF Tournas, V. H. Niazi, N. S. Katsoudas, E. J. TI Use of PCR technology for the speciation of fungi recovered from dried fruits and tree nuts SO PHYTOPATHOLOGY LA English DT Meeting Abstract CT Joint Meeting of the American-Phytopathological-Society (APS) and the Mycological-Society-of-America (MSA) CY AUG 10-14, 2013 CL Austin, TX SP Amer Phytopathol Soc (APS), Mycol Soc Amer (MSA) C1 [Tournas, V. H.] US FDA, CFSAN, College Pk, MD USA. [Niazi, N. S.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. [Katsoudas, E. J.] US FDA, ORA, NERL, Jamaica, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2013 VL 103 IS 6 SU 2 BP 147 EP 147 PG 1 WC Plant Sciences SC Plant Sciences GA 196TM UT WOS:000322799500809 ER PT J AU Schaer, DJ Buehler, PW AF Schaer, Dominik J. Buehler, Paul W. TI Cell-Free Hemoglobin and Its Scavenger Proteins: New Disease Models Leading the Way to Targeted Therapies SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE LA English DT Article ID EXPERIMENTAL CEREBRAL MALARIA; NITRIC-OXIDE BIOAVAILABILITY; INDUCED RENAL-FAILURE; RED-BLOOD-CELLS; PULMONARY-HYPERTENSION; EXTRACELLULAR HEMOGLOBIN; INTRAPLAQUE HEMORRHAGE; ANTIOXIDANT CAPACITY; HEME OXYGENASE-1; STORAGE LESION AB Hemoglobin (Hb) has multiple pathophysiologic effects when released into the intravascular space during hemolysis. The extracellular effects of Hb have resulted in novel models of toxicity, which help to explain endothelial dysfunction and cardiovascular complications that accompany genetic hemolytic anemias, malaria, blood transfusion, and atherosclerosis. The majority of models focus on nitric oxide (NO) depletion; however, in local tissue environments, Hb can also act as a pro-oxidant and inflammatory agent. This can alter cellular differentiation with the potential to deviate immune responses. The understanding of these mechanisms set in the context of natural scavenger and detoxification systems may accelerate the development of novel treatment strategies. C1 [Schaer, Dominik J.] Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. [Schaer, Dominik J.] Univ Zurich, Ctr Integrat Human Physiol, CH-8057 Zurich, Switzerland. [Schaer, Dominik J.] Univ Zurich, Ctr Evolutionary Med, CH-8057 Zurich, Switzerland. [Buehler, Paul W.] Food & Drug Adm, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. RP Schaer, DJ (reprint author), Univ Zurich Hosp, Div Internal Med, CH-8091 Zurich, Switzerland. EM dominik.schaer@usz.ch; paul.buehler@fda.hhs.gov FU Swiss National Science Foundation [310030/120658, 31003A/138500]; University of Zurich Research Priority Program "Integrative Human Physiology"; Swiss Federal Commission for Technology and Innovation (CTI); FDA Internal Funding FX This work is supported by the Swiss National Science Foundation (grants 310030/120658 and 31003A/138500), the University of Zurich Research Priority Program "Integrative Human Physiology," the Swiss Federal Commission for Technology and Innovation (CTI), and FDA Internal Funding. NR 79 TC 9 Z9 9 U1 0 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 2157-1422 J9 CSH PERSPECT MED JI Cold Spring Harb. Perspect. Med. PD JUN PY 2013 VL 3 IS 6 AR a013433 DI 10.1101/cshperspect.a013433 PG 18 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187ZU UT WOS:000322161600009 ER PT J AU Bird, ST Delaney, JAC Etminan, M Brophy, JM Hartzema, AG AF Bird, S. T. Delaney, J. A. C. Etminan, M. Brophy, J. M. Hartzema, A. G. TI Drospirenone and non-fatal venous thromboembolism: is there a risk difference by dosage of ethinyl-estradiol? SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE comparative study; contraception; drospirenone; Levonorgestrel; venous thromboembolism ID POLYCYSTIC-OVARY-SYNDROME; ORAL-CONTRACEPTIVES; HORMONAL CONTRACEPTIVES; ALDOSTERONE SYSTEM; COHORT ANALYSIS; WOMEN; PROGESTOGEN; EFFICACY AB BackgroundPrevious studies concluded that there was an increased risk of non-fatal venous thromboembolism (VTE) with drospirenone. It is unknown whether the risk is differential by ethinyl-estradiol dosage. ObjectivesTo assess the risk of VTE with drospirenone and to determine whether drospirenone and ethinyl-estradiol 20g (DRSP/EE20) has a lower VTE risk than drospirenone and ethinyl-estradiol 30g (DRSP/EE30). MethodsOur cohort included women aged 18-46years taking drospirenone or levonorgestrel (LNG)-containing combined oral contraceptives (COCs) in the IMS claims database between 2001 and 2009. VTE was defined using ICD-9-CM coding and anticoagulation. The hazard ratio (HR) from Cox proportional hazards models was used to assess the VTE relative risk (RR) with drospirenone compared with levonorgestrel, adjusted by a propensity score used to control for baseline co-morbidity and stratified by EE dosage and user-type (new/current). ResultsThe study included 238683 drospirenone and 193495 levonorgestrel users. Among new and current users, a 1.90-fold (95% CI, 1.51-2.39) increased VTE relative risk was observed for drospirenone (18.0 VTE/10000 women-years) vs. levonorgestrel (8.9 VTE/10000 women-years). In analysis of new users, DRSP/EE20 had a 2.35-fold (95% CI, 1.44-3.82) VTE RR versus LNG/EE20. New users of DRSP/EE30 observed an increased RR versus LNG/EE30 among women starting to use COCs between 2001 and 2006 (2.51, 95% CI, 1.12-5.64) but not between 2007 and 2009 (0.76, 95% CI, 0.42-1.39), attributable to an increased incidence rate with LNG/EE30 from 2007 to 2009. In direct comparison, DRSP/EE20 had an elevated risk of VTE compared with DRSP/EE30 (RR, 1.55; 95% CI, 0.99-2.41). ConclusionsWe observed a modestly elevated risk of VTE with drospirenone, compared with levonorgestrel. The larger VTE incidence rate observed in DRSP/EE20 than in DRSP/EE30 and the increasing VTE incidence rate with levonorgestrel between 2007 and 2009 were unexpected. C1 [Bird, S. T.; Hartzema, A. G.] Univ Florida, Coll Pharm & Epidemiol, Gainesville, FL 32611 USA. [Bird, S. T.] US FDA, Dept Hlth & Human Serv, CDER, Off Management,Acad Collaborat Program, Silver Spring, MD USA. [Delaney, J. A. C.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Etminan, M.] Univ British Columbia, Pharmaceut Outcomes Programme, Vancouver, BC V5Z 1M9, Canada. [Bird, S. T.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32611 USA. RP Bird, ST (reprint author), Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, 101 S Newell Dr HPNP,POB 1 00496, Gainesville, FL 32611 USA. EM bird.steven@gmail.com FU McGill University Health Center; Fonds de la Recherche en Sante du Quebec; Ministere de la Sante et des Services Sociaux; le Fonds de la Recherche en Sante du Quebec; AHRQ; National Institute of Health FX This work was supported by an unrestricted operating grant funded in part by the McGill University Health Center, Fonds de la Recherche en Sante du Quebec, and the Ministere de la Sante et des Services Sociaux. J. M. Brophy is a physician scientist who receives peer review financial support from le Fonds de la Recherche en Sante du Quebec. J. A. C. Delaney receives peer review financial support from AHRQ. A. G. Hartzema holds a grant from the National Institute of Health and is the PI for the Observational Medical Outcomes Partnership (OMOP), a private-public partnership designed to help improve drug safety monitoring. The authors have no other conflicts of interest to declare. NR 34 TC 8 Z9 8 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUN PY 2013 VL 11 IS 6 BP 1059 EP 1068 DI 10.1111/jth.12224 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 175UR UT WOS:000321259600008 PM 23574590 ER PT J AU Xiong, HS Yu, LX Qu, HB AF Xiong, Haoshu Yu, Lawrence X. Qu, Haibin TI Batch-to-Batch Quality Consistency Evaluation of Botanical Drug Products Using Multivariate Statistical Analysis of the Chromatographic Fingerprint SO AAPS PHARMSCITECH LA English DT Article DE botanical drug products; chromatographic fingerprint; manufacturing process; multivariate statistical analysis; quality consistency ID TRADITIONAL CHINESE MEDICINES; HERBAL MEDICINE; LIQUID; SIMILARITY; CHEMOMETRICS; RADIX AB Botanical drug products have batch-to-batch quality variability due to botanical raw materials and the current manufacturing process. The rational evaluation and control of product quality consistency are essential to ensure the efficacy and safety. Chromatographic fingerprinting is an important and widely used tool to characterize the chemical composition of botanical drug products. Multivariate statistical analysis has showed its efficacy and applicability in the quality evaluation of many kinds of industrial products. In this paper, the combined use of multivariate statistical analysis and chromatographic fingerprinting is presented here to evaluate batch-to-batch quality consistency of botanical drug products. A typical botanical drug product in China, Shenmai injection, was selected as the example to demonstrate the feasibility of this approach. The high-performance liquid chromatographic fingerprint data of historical batches were collected from a traditional Chinese medicine manufacturing factory. Characteristic peaks were weighted by their variability among production batches. A principal component analysis model was established after outliers were modified or removed. Multivariate (Hotelling T-2 and DModX) control charts were finally successfully applied to evaluate the quality consistency. The results suggest useful applications for a combination of multivariate statistical analysis with chromatographic fingerprinting in batch-to-batch quality consistency evaluation for the manufacture of botanical drug products. C1 [Xiong, Haoshu; Qu, Haibin] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Zhejiang, Peoples R China. [Xiong, Haoshu] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Qu, HB (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310058, Zhejiang, Peoples R China. EM quhb@zju.edu.cn RI Yu, Lawrence/L-6280-2016 FU China International Science and Technology Cooperation Project [2010DFB33630] FX This work was financially supported by the China International Science and Technology Cooperation Project (no. 2010DFB33630). NR 47 TC 4 Z9 6 U1 1 U2 28 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2013 VL 14 IS 2 BP 802 EP 810 DI 10.1208/s12249-013-9966-9 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156CU UT WOS:000319799100036 PM 23636818 ER PT J AU Sha, J Rosenzweig, JA Kozlova, EV Wang, SF Erova, TE Kirtley, ML van Lier, CJ Chopra, AK AF Sha, Jian Rosenzweig, Jason A. Kozlova, Elena V. Wang, Shaofei Erova, Tatiana E. Kirtley, Michelle L. van Lier, Christina J. Chopra, Ashok K. TI Evaluation of the roles played by Hcp and VgrG type 6 secretion system effectors in Aeromonas hydrophila SSU pathogenesis SO MICROBIOLOGY-SGM LA English DT Article ID VI-SECRETION; CLINICAL ISOLATE; VIBRIO-CHOLERAE; BIOFILM FORMATION; VIRULENCE; PROTEIN; CELLS; GENE; GASTROENTERITIS; IDENTIFICATION AB Aeromonas hydrophila, a Gram-negative bacterium, is an emerging human pathogen equipped with both a type 3 and a type 6 secretion system (T6SS). In this study, we evaluated the roles played by paralogous T6SS effector proteins, hemolysin co-regulated proteins (Hop-1 and -2) and valine glycine repeat G (VgrG-1, -2 and -3) protein family members in A. hydrophila SSU pathogenesis by generating various combinations of deletion mutants of the their genes. In addition to their predicted roles as structural components and effector proteins of the T6SS, our data clearly demonstrated that paralogues of Hop and VgrG also influenced bacterial motility, protease production and biofilm formation. Surprisingly, there was limited to no observed functional redundancy among and/or between the aforementioned T6SS effector paralogues in multiple assays. Our data indicated that Hcp and VgrG paralogues located within the T6SS cluster were more involved in forming T6SS structures, while the primary roles of Hop-1 and VgrG-1, located outside of the T6SS cluster, were as T6SS effectors. In terms of influence on bacterial physiology, Hcp-1, but not Hcp-2, influenced bacterial motility and protease production, and in its absence, increases in both of the aforementioned activities were observed. Likewise, VgrG-1 played a major role in regulating bacterial protease production, while VgrG-2 and VgrG-3 were critical in regulating bacterial motility and biofilm formation. In an intraperitoneal murine model of infection, all Hcp and VgrG paralogues were required for optimal bacterial virulence and dissemination to mouse peripheral organs. Importantly, the observed phenotypic alterations of the T6SS mutants could be fully complemented. Taking these results together, we have further established the roles played by the two known T6SS effectors of A. hydrophila by defining their contributions to T6SS function and virulence in both in vitro and in vivo models of infection. C1 [Sha, Jian; Kozlova, Elena V.; Wang, Shaofei; Erova, Tatiana E.; Kirtley, Michelle L.; van Lier, Christina J.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Rosenzweig, Jason A.] Texas So Univ, CBER, Dept Biol, Houston, TX 77004 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. RP Chopra, AK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. EM achopra@utmb.edu FU National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) [AI041611]; Environmental Protection Agency (EPA); National Aeronautics and Space Administration (NASA) [NNX08B4A47A] FX Studies conducted for this manuscript were supported by the National Institutes of Health/National Institute of Allergy and Infectious Diseases (NIH/NIAID) AI041611 and Environmental Protection Agency (EPA) grants (A. K. C). J. A. R. was supported by the National Aeronautics and Space Administration (NASA) cooperative agreement NNX08B4A47A. C. J. v. L. was supported by the NIH/NIAID T32 predoctoral training grant. NR 49 TC 12 Z9 12 U1 2 U2 20 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2013 VL 159 BP 1120 EP 1135 DI 10.1099/mic.0.063495-0 PN 6 PG 16 WC Microbiology SC Microbiology GA 181PT UT WOS:000321681700013 PM 23519162 ER PT J AU Chen, JJ Lin, WJ Chen, HC AF Chen, James J. Lin, Wei-Jiun Chen, Hung-Chia TI Pharmacogenomic biomarkers for personalized medicine SO PHARMACOGENOMICS LA English DT Review DE biomarker identification; biomarkers of susceptibility; prognostic and predictive biomarkers; subgroup identification; survival risk prediction ID CELL-LUNG-CANCER; GENE-EXPRESSION DATA; ACUTE LYMPHOBLASTIC-LEUKEMIA; CLINICAL-TRIAL DESIGNS; NEGATIVE BREAST-CANCER; MOLECULAR CLASSIFICATION; ADJUVANT CHEMOTHERAPY; RISK STRATIFICATION; SURVIVAL PREDICTION; DRUG DEVELOPMENT AB Pharmacogenomics examines how the benefits and adverse effects of a drug vary among patients in a target population by analyzing genomic profiles of individual patients. Personalized medicine prescribes specific therapeutics that best suit an individual patient. Much current research focuses on developing genomic biomarkers to identify patients, to identify which patients would benefit from a treatment, have an adverse response, or no response at all, prior to treatment according to relevant differences in risk factors, disease types and/or responses to therapy. This review describes the use of the two personalized medicine biomarkers, prognostic and predictive, to classify patients into subgroups for treatment recommendation. C1 [Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Chen, James J.; Chen, Hung-Chia] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.; Chen, Hung-Chia] China Med Univ, Ctr Biostat, Taichung, Taiwan. [Lin, Wei-Jiun] Feng Chia Univ, Dept Appl Math, Taichung 40724, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, 3900 NCTR Rd,HFT-20, Jefferson, AR 72079 USA. EM James.chen@fda.hhs.gov NR 98 TC 3 Z9 3 U1 0 U2 18 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUN PY 2013 VL 14 IS 8 BP 969 EP 980 DI 10.2217/PGS.13.75 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 164SL UT WOS:000320429700020 PM 23746190 ER PT J AU Matza, LS Patrick, DL Riley, AW Alexander, JJ Rajmil, L Pleil, AM Bullinger, M AF Matza, Louis S. Patrick, Donald L. Riley, Anne W. Alexander, John J. Rajmil, Luis Pleil, Andreas M. Bullinger, Monika TI Pediatric Patient-Reported Outcome Instruments for Research to Support Medical Product Labeling: Report of the ISPOR PRO Good Research Practices for the Assessment of Children and Adolescents Task Force SO VALUE IN HEALTH LA English DT Article DE adolescents; children; ISPOR; medical product labeling; patient-reported outcomes; pediatrics; PRO; task force ID QUALITY-OF-LIFE; GENERIC CORE SCALES; EVALUATING CONTENT VALIDITY; COST-UTILITY ANALYSES; SELF-REPORT MEASURES; PARENT-PROXY; HEALTH-STATUS; METHODOLOGICAL CONSIDERATIONS; CULTURAL-ADAPTATION; ECONOMIC-EVALUATION AB Background: Patient-reported outcome (PRO) instruments for children and adolescents are often included in clinical trials with the intention of collecting data to support claims in a medical product label. Objective: The purpose of the current task force report is to recommend good practices for pediatric PRO research that is conducted to inform regulatory decision making and support claims made in medical product labeling. The recommendations are based on the consensus of an interdisciplinary group of researchers who were assembled for a task force associated with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR). In those areas in which supporting evidence is limited or in which general principles may not apply to every situation, this task force report identifies factors to consider when making decisions about the design and use of pediatric PRO instruments, while highlighting issues that require further research. Good Research Practices: Five good research practices are discussed: 1) Consider developmental differences and determine age-based criteria for PRO administration: Four age groups are discussed on the basis of previous research (<5 years old, 5-7 years, 8-11 years, and 12-18 years). These age groups are recommended as a starting point when making decisions, but they will not fit all PRO instruments or the developmental stage of every child. Specific age ranges should be determined individually for each population and PRO instrument. 2) Establish content validity of pediatric PRO instruments: This section discusses the advantages of using children as content experts, as well as strategies for concept elicitation and cognitive interviews with children. 3) Determine whether an informant-reported outcome instrument is necessary: The distinction between two types of informant-reported measures (proxy vs. observational) is discussed, and recommendations are provided. 4) Ensure that the instrument is designed and formatted appropriately for the target age group. Factors to consider include health-related vocabulary, reading level, response scales, recall period, length of instrument, pictorial representations, formatting details, administration approaches, and electronic data collection (ePRO). 5) Consider cross-cultural issues. Conclusions: Additional research is needed to provide methodological guidance for future studies, especially for studies involving young children and parents' observational reports. As PRO data are increasingly used to support pediatric labeling claims, there will be more information regarding the standards by which these instruments will be judged. The use of PRO instruments in clinical trials and regulatory submissions will help ensure that children's experience of disease and treatment are accurately represented and considered in regulatory decisions. C1 [Matza, Louis S.] United BioSource Corp, Outcomes Res, Bethesda, MD 20814 USA. [Patrick, Donald L.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [Riley, Anne W.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Alexander, John J.] US FDA, Div Antiinfect Prod, Silver Spring, MD USA. [Rajmil, Luis] IMIM Hosp del Mar, Med Res Inst, Barcelona, Spain. [Rajmil, Luis] Catalan Agcy Hlth Informat Assessment & Qual, Barcelona, Spain. [Pleil, Andreas M.] Pfizer Inc, Pfizer Global Pharmaceut, San Diego, CA USA. [Bullinger, Monika] Univ Med Ctr Hamburg Eppendorf, Dept Med Psychol, Hamburg, Germany. RP Matza, LS (reprint author), United BioSource Corp, 7101 Wisconsin Ave,Suite 600, Bethesda, MD 20814 USA. EM louis.matza@unitedbiosource.com OI Rajmil, Luis/0000-0002-6625-0649 NR 147 TC 44 Z9 44 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD JUN PY 2013 VL 16 IS 4 BP 461 EP 479 DI 10.1016/j.jval.2013.04.004 PG 19 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 178IK UT WOS:000321440900005 PM 23796280 ER PT J AU Choudhary, A Galvin, TA Williams, DK Beren, J Bryant, MA Khan, AS AF Choudhary, Anil Galvin, Teresa A. Williams, Dhanya K. Beren, Joel Bryant, Mark A. Khan, Arifa S. TI Influence of Naturally Occurring Simian Foamy Viruses (SFVs) on SIV Disease Progression in the Rhesus Macaque (Macaca mulatta) Model SO VIRUSES-BASEL LA English DT Article DE Indian rhesus macaques; simian immunodeficiency virus; simian foamy virus; SIV pathogenesis; preclinical AIDS model; dual retrovirus infections ID CLASS-I ALLELES; IMMUNODEFICIENCY-VIRUS; PERSISTENT INFECTION; NONHUMAN-PRIMATES; VIRAL LOAD; REPLICATION; EXPRESSION; MONKEYS; NEUTRALIZATION; RETROVIRUSES AB We have investigated the influence of naturally occurring simian foamy viruses (SFVs) on simian immunodeficiency virus (SIV) infection and disease in Indian rhesus macaques. Animals were divided into two groups based upon presence or absence of SFV; in each group, eight monkeys were injected with SIVmac239 virus obtained from a molecular clone and four were injected with medium. Blood was collected every two weeks for evaluation of SIV infection based upon T cell-subsets, plasma viral load, development and persistence of virus-specific antibodies, and clinical changes by physical examination and hematology. Comparative analysis of SFV+/SIV+ and SFV-/SIV+ monkey groups indicated statistically significant differences in the plasma viral load between 6-28 weeks, particularly after reaching plateau at 20-28 weeks, in the CD4(+) and CD8(+) T-cell numbers over the entire study period (2-43 weeks), and in the survival rates evaluated at 49 weeks. There was an increase in the plasma viral load, a decreasing trend in the CD4(+) T cells, and a greater number of animal deaths in the SFV+/SIV+ group. The results, although based upon a small number of animals, indicated that pre-existing SFV infection can influence SIV infection and disease outcome in the rhesus macaque model. The study highlights consideration of the SFV status in evaluating results from SIV pathogenesis and vaccine challenge studies in monkeys and indicates the potential use of the SFV/SIV monkey model to study the dynamics of SFV and HIV-1 dual infections, recently reported in humans. C1 [Choudhary, Anil; Galvin, Teresa A.; Williams, Dhanya K.; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Beren, Joel] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Bryant, Mark A.] NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM anil.choudhary@fda.hhs.gov; teresa.galvin@fda.hhs.gov; dhanya.williams@fda.hhs.gov; joel.beren@fda.hhs.gov; bryantm@ors.od.nih.gov; arifa.khan@fda.hhs.gov FU Biomedical Advanced Research and Development Authority (BARDA) FX We thank the assistance of Ernest Madison, Shelly Lower, Lewis Shankle, and Brianna Skinner-Harris with animal bleeds and care, and David C. Montefiori for providing the SIV neutralizing antibody data. The study was initiated by funding from Biomedical Advanced Research and Development Authority (BARDA; previously ORDC/OPHEMC). The following reagent was obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: 174xCEM from Peter Cresswell. We are grateful to Ronald Desrosiers and Eliosa Yuste for the cloned SIVmac239 DNA, protocols for virus preparation, and to Ronald Desrosiers and Mark Lewis for discussions regarding the SIV study. NR 41 TC 12 Z9 12 U1 1 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1999-4915 J9 VIRUSES-BASEL JI Viruses-Basel PD JUN PY 2013 VL 5 IS 6 BP 1414 EP 1430 DI 10.3390/v5061414 PG 17 WC Virology SC Virology GA 169HE UT WOS:000320769900003 PM 23744104 ER PT J AU Zhang, ZW Kotz, RM Wang, CG Ruan, SL Ho, M AF Zhang, Zhiwei Kotz, Richard M. Wang, Chenguang Ruan, Shiling Ho, Martin TI A Causal Model for Joint Evaluation of Placebo and Treatment-Specific Effects in Clinical Trials SO BIOMETRICS LA English DT Article DE Blinding; Causal inference; Confounding; Counterfactual; Placebo effect; Potential outcome ID DOUBLY ROBUST ESTIMATION; PROPENSITY SCORE; MISSING DATA; INFERENCE; SENSITIVITY; DISULFIRAM AB Evaluation of medical treatments is frequently complicated by the presence of substantial placebo effects, especially on relatively subjective endpoints, and the standard solution to this problem is a randomized, double-blinded, placebo-controlled clinical trial. However, effective blinding does not guarantee that all patients have the same belief or mentality about which treatment they have received (or treatmentality, for brevity), making it difficult to interpret the usual intent-to-treat effect as a causal effect. We discuss the causal relationships among treatment, treatmentality and the clinical outcome of interest, and propose a causal model for joint evaluation of placebo and treatment-specific effects. The model highlights the importance of measuring and incorporating patient treatmentality and suggests that each treatment group should be considered a separate observational study with a patient's treatmentality playing the role of an uncontrolled exposure. This perspective allows us to adapt existing methods for dealing with confounding to joint estimation of placebo and treatment-specific effects using measured treatmentality data, commonly known as blinding assessment data. We first apply this approach to the most common type of blinding assessment data, which is categorical, and illustrate the methods using an example from asthma. We then propose that blinding assessment data can be collected as a continuous variable, specifically when a patient's treatmentality is measured as a subjective probability, and describe analytic methods for that case. C1 [Zhang, Zhiwei; Kotz, Richard M.; Ruan, Shiling; Ho, Martin] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Wang, Chenguang] Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Div Biostat & Bioinformat, Baltimore, MD 21287 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM zhiwei.zhang@fda.hhs.gov FU NCI NIH HHS [P30 CA006973] NR 28 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2013 VL 69 IS 2 BP 318 EP 327 DI 10.1111/biom.12005 PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 171LV UT WOS:000320931300005 PM 23432119 ER PT J AU Krumholz, A Ting, TY Jiang, W Barry, E Polli, JE AF Krumholz, A. Ting, T. Y. Jiang, W. Barry, E. Polli, J. E. TI DESIGN OF A PROTOTYPIC TEST MODEL TO ASSESS STANDARDS OF GENERIC AND BRAND ANTIEPILEPTIC DRUG BIOEQUIVALENCE SO EPILEPSIA LA English DT Meeting Abstract CT 30th International Epilepsy Congress CY JUN 23-27, 2013 CL Montreal, CANADA SP Int Bur Epilepsy (IBE), Int League Against Epilepsy (ILAE) C1 [Krumholz, A.; Ting, T. Y.; Barry, E.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. [Jiang, W.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Polli, J. E.] Univ Maryland, Sch Med, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2013 VL 54 SU 3 SI SI BP 68 EP 68 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 165GS UT WOS:000320472000199 ER PT J AU Sona, I Zheng, J Keys, CE Zhao, SH Meng, JH Brown, EW AF Sona, Insook Zheng, Jie Keys, Christine E. Zhao, Shaohua Meng, Jianghong Brown, Eric W. TI Analysis of pulsed field gel electrophoresis profiles using multiple enzymes for predicting potential source reservoirs for strains of Salmonella Enteritidis and Salmonella Typhimurium isolated from humans SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Salmonella enterica; PFGE; Phylogenetic analysis; Human isolates; Congruence ID ENTERICA SEROTYPE ENTERITIDIS; ESCHERICHIA-COLI O157-H7; UNITED-STATES; SURVEILLANCE AB We reported previously on a highly discriminatory pulsed field gel electrophoresis-based (PFGE) subtyping scheme for Salmonella enterica serovar Enteritidis (SE) and Salmonella Typhimurium (ST) that relies on combined cluster analysis of up to six restriction enzymes. This approach allowed for the high-resolution separation of numerous poultry-derived SE and ST isolates into several distinct clusters that sorted along several geographical and host-linked boundaries. In this study, 101 SE and 151 ST strains isolated from poultry, swine, beef, mouse, and produce origins were combined with 62 human SE and ST isolates of unknown sources. PFGE profiles were generated across six restriction enzymes (XbaI, BlnI, SpeI, SfiI, PacI, and NotI) for human SE and ST isolates. The combined six-enzyme UPGMA trees of SE and ST revealed six separate origins of North American human SE isolates including one association with a "cosmopolitan" cluster of SEs from poultry originating in Scotland, Mexico, and China. In the case of ST, human isolates assorted readily along host lines rather than geographical partitions with the majority of human STs clustering in a larger group of STs of potential porcine origin. Such observations may underscore the ecological importance of poultry and pork reservoirs for SE and ST transmission to humans, respectively. In an examination of the relationship between enzyme diversity and congruence among enzymes, pairwise genetic diversity ranged from 6.5% to 9.7% for SE isolates and, more widely, from 17.5% to 27.4% for ST isolates. Phylogenetic congruence measures singled out XbaI, BlnI, and SfiI as most concordant for SE while XbaI and SfiI were most concordant among ST strains. Thus, these data provide the first proof of principal for concatenated PFGE, when coupled with sufficient enzyme numbers and combinations, as one effective means for predicting geographical and food source reservoirs for human isolates of these two highly prevalent Salmonella serovars. (C) 2013 Published by Elsevier B.V. C1 [Sona, Insook; Zheng, Jie; Keys, Christine E.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Brown, EW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol, 5100 Paint Branch Pkwy,Mailstop HFS-712, College Pk, MD 20740 USA. EM eric.brown@fda.hhs.gov NR 19 TC 0 Z9 0 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUN PY 2013 VL 16 BP 226 EP 233 DI 10.1016/j.meegid.2013.01.020 PG 8 WC Infectious Diseases SC Infectious Diseases GA 166PM UT WOS:000320569500030 ER PT J AU Samp, RA Andrews, CL AF Samp, Richard A. Andrews, Cory L. TI Comments of the Washington Legal Foundation to the Food and Drug Administration Concerning Citizen Petition by Abbott Laboratories Regarding Biosimilar Applications That Cite Biological Products for Which the BLA Was Submitted to FDA Before March 23, 2010 SO BIOTECHNOLOGY LAW REPORT LA English DT Letter C1 [Samp, Richard A.; Andrews, Cory L.] Washington Legal Fdn, Washington, DC 20036 USA. US FDA, Div Dockets Management HFA 305, Rockville, MD 20852 USA. RP Samp, RA (reprint author), Washington Legal Fdn, 2009 Massachusetts Ave NW, Washington, DC 20036 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0730-031X J9 BIOTECHNOL LAW REP JI Biotechnol. Law Rep. PD JUN PY 2013 VL 32 IS 3 BP 186 EP 195 DI 10.1089/blr.2013.9926 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 164AB UT WOS:000320380000007 ER PT J AU Chen, JM Florian, J Carter, W Fleischer, RD Hammerstrom, TS Jadhav, PR Zeng, W Murray, J Birnkrant, D AF Chen, Jianmeng Florian, Jeffry Carter, Wendy Fleischer, Russell D. Hammerstrom, Thomas S. Jadhav, Pravin R. Zeng, Wen Murray, Jeffrey Birnkrant, Debra TI Earlier Sustained Virologic Response End Points for Regulatory Approval and Dose Selection of Hepatitis C Therapies SO GASTROENTEROLOGY LA English DT Article DE Therapy; Outcome; Effectiveness; Quantification. ID GENOTYPE 1 INFECTION; INTERFERON-ALPHA; VIRUS-INFECTION; HCV INFECTION; FOLLOW-UP; RIBAVIRIN; BOCEPREVIR; TELAPREVIR; RNA; MANAGEMENT AB BACKGROUND & AIMS: Trials of therapies for chronic hepatitis C have used detection of hepatitis C virus (HCV) at week 24 of follow-up (sustained virologic response [SVR] 24) as a primary end point. However, there is increasing evidence that most patients who have an SVR at earlier time points (such as SVR12) maintain it until week 24. Use of earlier time points for key regulatory decisions (SVR12) and dose selection (SVR4) could facilitate HCV drug development. METHODS: We assessed data from 15 phase II and III trials, 3 pediatric studies, and 5 drug-development programs to determine the concordance between SVR24 and SVR12 or SVR4. Data were analyzed from groups of subjects who received various combinations and regimens with interferon, pegylatedinterferon, ribavirin, and direct-acting antivirals. RESULTS: The positive predictive value (PPV) of SVR12 was 98% and the negative predictive value (NPV) was 99% for SVR24 among subjects with genotype 1 HCV infection. A similar level of concordance was observed for subjects with HCV genotype 2 or 3 infections, as well as in pediatric studies. About 2% of subjects who achieved an SVR12 subsequently relapsed by week 24 (did not achieve an SVR24). Furthermore, the treatment effect size (difference between treatment and active control arms) was similar for subjects with SVR12 and SVR24. The PPV of SVR4 was 91% and the NPV was 98% for SVR24 in subjects with genotype 1 HCV infection. CONCLUSIONS: SVR12 and SVR24 measurements were concordant in a large population of subjects with HCV infection who participated in clinical trials with various treatment regimens and durations. SVR12 is suitable as a primary end point for regulatory approval. SVR4 might be used to guide dose and treatment strategies in trials. C1 [Chen, Jianmeng; Florian, Jeffry; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Chen, Jianmeng] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Carter, Wendy; Fleischer, Russell D.; Murray, Jeffrey; Birnkrant, Debra] US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hammerstrom, Thomas S.; Zeng, Wen] US FDA, Div Biometr, Silver Spring, MD 20993 USA. RP Florian, J (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Room 3180,Bldg 51, Silver Spring, MD 20993 USA. EM jeffry.florian@fda.hhs.gov FU ORISE Research Participation Program at the Center for Drug Evaluation and Research FX This project was supported by funding through a critical path grant and in part by an appointment to the ORISE Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an agreement between the US Department of Energy and Center for Drug Evaluation and Research. NR 26 TC 81 Z9 83 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUN PY 2013 VL 144 IS 7 BP 1450 EP U218 DI 10.1053/j.gastro.2013.02.039 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 151ZI UT WOS:000319498500028 PM 23470616 ER PT J AU Wang, CC Wang, SG Xia, QS He, WW Yin, JJ Fu, PP Li, JH AF Wang, Chia-Chi Wang, Shuguang Xia, Qingsu He, Weiwei Yin, Jun-Jie Fu, Peter P. Li, Jih-Heng TI Phototoxicity of Zinc Oxide Nanoparticles in HaCaT Keratinocytes-Generation of Oxidative DNA Damage During UVA and Visible Light Irradiation SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article DE Zinc Oxide; Nanomaterials; ROS; 8-OHdG; Human Keratinocytes; UVA; Lipid Peroxidation ID NEMATODE CAENORHABDITIS-ELEGANS; LIPID-PEROXIDATION; RETINYL PALMITATE; PARTICLE-SIZE; STRESS; OXYGEN; CELLS; ZNO; NANOMATERIALS; TOXICITY AB Zinc oxide nanoparticles (nano-ZnO) are one of the most commonly used nanomaterials in industrial products including paints, cosmetics, and medical materials. Since ZnO is a well-known photocatalyst, it is important to further study if nano-ZnO cause phototoxic effect on skin cells under UVA-irradiation and visible light illumination. Human-derived keratinocytes (HaCaT) were treated with 1-20 mu g/mL of nano-ZnO (<50 nm) and then exposed to UVA (0.5-2 J/cm(2)). Twenty four hours later, cell viability, membrane integrity, and oxidative DNA damage were determined by MTS assay, lactate dehydrogenase (LDH) release, and the formation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) adduct, respectively. High concentration of nano-ZnO (10-20 mu g/mL) significantly induced cytotoxicity, whereas 0.5-2 J/cm(2) of UVA irradiation dose-dependently aggravated nano-ZnO-induced cell death via induction of LDH release and DNA damage. The level of photocytotoxicity is mainly dependent on the level of reactive oxygen species (ROS) production. UVA irradiation of nano-ZnO in methanol induced lipid peroxidation in a light dose and substrate dose response manner. Electron spin resonance (ESR) spin trapping studies confirmed that both hydroxyl radical and superoxide anion radical were formed during photoirradiation, while nano-ZnO-induced hydroxyl radical formation is not evolved from superoxide. In addition, nano-ZnO dose-dependently induced single strand DNA break in supercoiled Phi x 174 plasmid DNA. Under visible light illumination, nano-ZnO induced the LDH leakage, hydroxyl radical generation, and 8-OHdG formation in a dose-dependent manner. Collectively, these results suggest the photocytotoxic and photogenotoxic effects of nano-ZnO on human skin keratinocytes. C1 [Wang, Chia-Chi; Li, Jih-Heng] Kaohsiung Med Univ, Sch Pharm, Kaohsiung 80708, Taiwan. [Wang, Shuguang; Xia, Qingsu; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [He, Weiwei; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wang, CC (reprint author), Kaohsiung Med Univ, Sch Pharm, 100 Shih Chuan 1st Rd, Kaohsiung 80708, Taiwan. RI Yin, Jun Jie /E-5619-2014 FU National Science Council, Executive Yuan (Taipei, Taiwan) [NSC101-2320-B-037-001]; Kaohsiung Medical University Research Foundation (Kaohsiung City, Taiwan) [KMUCOP-102-02, KMU-Q110004, KMU-EU-R013] FX This work was supported by grants NSC101-2320-B-037-001 from the National Science Council, Executive Yuan (Taipei, Taiwan) and KMUCOP-102-02, KMU-Q110004 and KMU-EU-R013 from Kaohsiung Medical University Research Foundation (Kaohsiung City, Taiwan). NR 36 TC 26 Z9 26 U1 1 U2 41 PU AMER SCIENTIFIC PUBLISHERS PI VALENCIA PA 26650 THE OLD RD, STE 208, VALENCIA, CA 91381-0751 USA SN 1533-4880 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD JUN PY 2013 VL 13 IS 6 BP 3880 EP 3888 DI 10.1166/jnn.2013.7177 PG 9 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 161PI UT WOS:000320205400018 PM 23862422 ER PT J AU Olumee-Shabon, Z Boehmer, JL AF Olumee-Shabon, Zohra Boehmer, Jamie L. TI Detection of Casein Phosphopeptides in Goat Milk SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE casein; phosphotylation; phosphoproteome; post-translational modification; milk; mastitis ID DIFFERENTIALLY EXPRESSED PROTEINS; TANDEM MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; PHOSPHORYLATED PEPTIDES; LIQUID-CHROMATOGRAPHY; BOVINE-MILK; IDENTIFICATION; MASTITIS; ENRICHMENT; PHOSPHOPROTEOME AB The aims of this study were to profile casein phosphopeptides in goat milk, to accurately determine the site of phosphorylation, and to evaluate whether or not any of the casein phosphorylation patterns were specific to a given physiological condition. Goat milk, collected before and after experimental induction of endotoxin mastitis, was separated by SDSPAGE. Casein bands were digested with trypsin and the resulting peptides were analyzed by nLC MS/MS. Eight out of nine predicted tryptic phosphopeptides corresponding to 18 different phosphorylation sites were detected in alpha(s1)-, a(s2)-, and beta-casein. Characterization of the phosphorylation sites illustrated the capability of tandem MS to accurately localize phosphorylated residues among a number of other putative sites. Despite an apparent lower abundance, almost all of the phosphopeptides were also detected in milk samples obtained from the goats following experimental induction of endotoxin mastitis. However, a tetraphosphopeptide in alpha(s2)-casein was only observed in the milk samples obtained from healthy animals. The absence of this multiphosphopeptide in the mastitic goat milk samples could indicate changes in phosphorylation as a result of disease and potentially be used as a marker for milk quality. This study represents the first comprehensive analysis of casein phosphoproteome and reveals a much higher level of phosphorylation than previously demonstrated in goat milk. C1 [Olumee-Shabon, Zohra; Boehmer, Jamie L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Olumee-Shabon, Z (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Zohra.olumee-shabon@fda.hhs.gov NR 38 TC 1 Z9 1 U1 5 U2 42 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD JUN PY 2013 VL 12 IS 6 BP 3034 EP 3041 DI 10.1021/pr3010666 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 162XF UT WOS:000320298600061 PM 23586903 ER PT J AU Mossoba, MM Azizian, H Tyburczy, C Kramer, JKG Delmonte, P Kia, ARF Rader, JI AF Mossoba, Magdi M. Azizian, Hormoz Tyburczy, Cynthia Kramer, John K. G. Delmonte, Pierluigi Kia, Ali-Reza Fardin Rader, Jeanne I. TI Rapid FT-NIR Analysis of Edible Oils for Total SFA, MUFA, PUFA, and Trans FA with Comparison to GC SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE Fats and oils; Spectroscopy; Lipid Chemistry/Lipid Analysis ID NEAR-INFRARED SPECTROSCOPY; FATTY-ACID DETERMINATION; CHROMATOGRAPHIC-SEPARATION; OLIVE OIL; MILK-FAT; MODELS; CIS AB Declarations of the total content of trans fatty acids (FA) and saturated FA (SFA) are mandatory on food labels in the US and Canada. Gas chromatography (GC) has been the method of choice for the determination of FA composition. However, GC is time consuming and requires conversion of fats and oils to their FA methyl esters. In the present study, a recently published Fourier transform near-infrared (FT-NIR) spectroscopic procedure was applied to the rapid (<5 min) determination of total SFA, monounsaturated FA (MUFA), polyunsaturated FA (PUFA), and trans FA contents of 30 commercially available edible fats and oils. Good agreement was obtained between the GC and FT-NIR methods for the determination of total SFA, MUFA, and PUFA contents. Differences between the two methods were apparent for the determination of trans fat at trans fat levels <2 % of total fat. The analytical determinations of total SFA, MUFA, and PUFA contents for many of the oils examined differed from the respective values declared on the product labels. Our findings demonstrate that the FT-NIR procedure serves as a suitable alternative method for the rapid determination of total SFA, MUFA, PUFA and trans FA contents of neat vegetable oils. C1 [Mossoba, Magdi M.; Tyburczy, Cynthia; Delmonte, Pierluigi; Kia, Ali-Reza Fardin; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Azizian, Hormoz] NIR Technol Inc, Oakville, ON, Canada. [Kramer, John K. G.] Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 32 TC 4 Z9 4 U1 4 U2 61 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD JUN PY 2013 VL 90 IS 6 BP 757 EP 770 DI 10.1007/s11746-013-2234-z PG 14 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 164UC UT WOS:000320434500001 ER PT J AU Xu, F Gelderman, MP Farrell, J Vostal, JG AF Xu, Fei Gelderman, Monique P. Farrell, John Vostal, Jaroslav G. TI Temperature cycling improves in vivo recovery of cold-stored human platelets in a mouse model of transfusion SO TRANSFUSION LA English DT Article ID CHILLED BLOOD-PLATELETS; APHERESIS PLATELETS; BACTERIAL-CONTAMINATION; CLEARANCE; SURVIVAL; STORAGE; MICE; GLYCOSYLATION; 4-DEGREES-C; RECEPTORS AB BACKGROUND: Platelet (PLT) storage at room temperature (RT) is limited to 5 days to prevent growth of bacteria, if present, to high levels. Storage in cold temperatures would reduce bacterial proliferation, but cold-exposed PLTs are rapidly cleared from circulation by the hepatic Ashwell-Morell (AM) receptor, which recognizes PLT surface carbohydrates terminated by -galactose. We cycled storage temperature between 4 and 37 degrees C to preserve PLT function and reduce bacterial growth. STUDY DESIGN AND METHODS: Temperature-cycled (TC) human PLTs were stored at 4 degrees C for 12 hours and then incubated at 37 degrees C for 30 minutes before returning back to cold storage. PLTs stored at RT or at 4 degrees C (COLD) or TC for 2, 5, and 7 days were infused into SCID mice and the in vivo recovery was determined at 5, 20, and 60 minutes after transfusion. RESULTS: PLTs stored for 2 days in COLD had significantly lower in vivo recoveries than RT PLTs. TC PLTs had improved recoveries over COLD and comparable to RT PLTs. After 5- and 7-day storage, TC PLTs had better recoveries than RT and COLD PLTs. PLT surface -galactose was increased significantly for both COLD and TC PLTs compared to RT. Blocking of the AM receptor by asialofetuin increased COLD but not TC PLT recovery. CONCLUSION: TC cold storage may be an effective method to store PLTs without loss of in vivo recovery. The increased -galactose exposure in TC PLTs suggests that mechanisms in addition to AM receptors may mediate clearance of cold-stored PLTs. C1 [Xu, Fei; Gelderman, Monique P.; Farrell, John; Vostal, Jaroslav G.] US FDA, Lab Cellular Hematol, CBER, Bethesda, MD 20014 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Off Blood Res & Review, CBER, 1401 Rockville Pike,HFM 335, Rockville, MD 20852 USA. EM jaroslav.vostal@fda.hhs.gov NR 28 TC 6 Z9 6 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUN PY 2013 VL 53 IS 6 BP 1178 EP 1186 DI 10.1111/j.1537-2995.2012.03896.x PG 9 WC Hematology SC Hematology GA 161HI UT WOS:000320183000007 PM 22998069 ER PT J AU Kuhn, JH Bao, YM Bavari, S Becker, S Bradfute, S Brister, JR Bukreyev, AA Cai, YY Chandran, K Davey, RA Dolnik, O Dye, JM Enterlein, S Gonzalez, JP Formenty, P Freiberg, AN Hensley, LE Honko, AN Ignatyev, GM Jahrling, PB Johnson, KM Klenk, HD Kobinger, G Lackemeyer, MG Leroy, EM Lever, MS Lofts, LL Muhlberger, E Netesov, SV Olinger, GG Palacios, G Patterson, JL Paweska, JT Pitt, L Radoshitzky, SR Ryabchikova, EI Saphire, EO Shestopalov, AM Smither, SJ Sullivan, NJ Swanepoel, R Takada, A Towner, JS van der Groen, G Volchkov, VE Wahl-Jensen, V Warren, TK Warfield, KL Weidmann, M Nichol, ST AF Kuhn, Jens H. Bao, Yiming Bavari, Sina Becker, Stephan Bradfute, Steven Brister, J. Rodney Bukreyev, Alexander A. Cai, Yingyun Chandran, Kartik Davey, Robert A. Dolnik, Olga Dye, John M. Enterlein, Sven Gonzalez, Jean-Paul Formenty, Pierre Freiberg, Alexander N. Hensley, Lisa E. Honko, Anna N. Ignatyev, Georgy M. Jahrling, Peter B. Johnson, Karl M. Klenk, Hans-Dieter Kobinger, Gary Lackemeyer, Matthew G. Leroy, Eric M. Lever, Mark S. Lofts, Loreen L. Muehlberger, Elke Netesov, Sergey V. Olinger, Gene G. Palacios, Gustavo Patterson, Jean L. Paweska, Janusz T. Pitt, Louise Radoshitzky, Sheli R. Ryabchikova, Elena I. Saphire, Erica Ollmann Shestopalov, Aleksandr M. Smither, Sophie J. Sullivan, Nancy J. Swanepoel, Robert Takada, Ayato Towner, Jonathan S. van der Groen, Guido Volchkov, Viktor E. Wahl-Jensen, Victoria Warren, Travis K. Warfield, Kelly L. Weidmann, Manfred Nichol, Stuart T. TI Virus nomenclature below the species level: a standardized nomenclature for laboratory animal-adapted strains and variants of viruses assigned to the family Filoviridae SO ARCHIVES OF VIROLOGY LA English DT Article ID VERVET MONKEY DISEASE; MARBURG VIRUS; EBOLA-VIRUS; RHABDOVIRUS-SIMIAE; HEMORRHAGIC-FEVER; MOUSE MODEL; GUINEA-PIGS; VERO CELLS; INFECTION; AGENT AB The International Committee on Taxonomy of Viruses (ICTV) organizes the classification of viruses into taxa, but is not responsible for the nomenclature for taxa members. International experts groups, such as the ICTV Study Groups, recommend the classification and naming of viruses and their strains, variants, and isolates. The ICTV Filoviridae Study Group has recently introduced an updated classification and nomenclature for filoviruses. Subsequently, and together with numerous other filovirus experts, a consistent nomenclature for their natural genetic variants and isolates was developed that aims at simplifying the retrieval of sequence data from electronic databases. This is a first important step toward a viral genome annotation standard as sought by the US National Center for Biotechnology Information (NCBI). Here, this work is extended to include filoviruses obtained in the laboratory by artificial selection through passage in laboratory hosts. The previously developed template for natural filovirus genetic variant naming (< virus name > < isolation host-suffix >/< country of sampling >/< year of sampling >/< genetic variant designation >-< isolate designation >) is retained, but it is proposed to adapt the type of information added to each field for laboratory animal-adapted variants. For instance, the full-length designation of an Ebola virus Mayinga variant adapted at the State Research Center for Virology and Biotechnology "Vector" to cause disease in guinea pigs after seven passages would be akin to "Ebola virus VECTOR/C.porcellus-lab/COD/1976/Mayinga-GPA-P7". As was proposed for the names of natural filovirus variants, we suggest using the full-length designation in databases, as well as in the method section of publications. Shortened designations (such as "EBOV VECTOR/C.por/COD/76/May-GPA-P7") and abbreviations (such as "EBOV/May-GPA-P7") could be used in the remainder of the text depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed. C1 [Kuhn, Jens H.; Cai, Yingyun; Jahrling, Peter B.; Lackemeyer, Matthew G.; Wahl-Jensen, Victoria] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Frederick, MD 21702 USA. [Bao, Yiming; Brister, J. Rodney] Natl Lib Med, Informat Engn Branch, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Bavari, Sina; Dye, John M.; Honko, Anna N.; Lofts, Loreen L.; Olinger, Gene G.; Palacios, Gustavo; Pitt, Louise; Radoshitzky, Sheli R.; Warren, Travis K.] USA, Med Res Inst Infect Dis, Frederick, MD USA. [Becker, Stephan; Dolnik, Olga; Klenk, Hans-Dieter] Univ Marburg, Inst Virol, D-35032 Marburg, Germany. [Bradfute, Steven] Univ New Mexico, Albuquerque, NM 87131 USA. [Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Bukreyev, Alexander A.; Freiberg, Alexander N.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Chandran, Kartik] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Davey, Robert A.; Patterson, Jean L.] Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA. [Enterlein, Sven; Warfield, Kelly L.] Integrated BioTherapeut Inc, Gaithersburg, MD USA. [Gonzalez, Jean-Paul] Inst Rech Dev, Dept Hlth, Marseille, France. [Gonzalez, Jean-Paul] Metabiota Inc, San Francisco, CA USA. [Formenty, Pierre] World Hlth Org, Geneva, Switzerland. [Hensley, Lisa E.] US FDA, Med Countermeasure Initiat, Silver Spring, MD USA. [Ignatyev, Georgy M.] Fed State Unitary Co Microgen Sci Ind Co Immunobi, Minist Hlth & Social Dept Russian Federat, Moscow, Russia. [Kobinger, Gary] Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB, Canada. [Leroy, Eric M.] Ctr Int Rech Med Franceville, Franceville, Gabon. [Lever, Mark S.; Smither, Sophie J.] Dstl, Dept Biomed Sci, Salisbury, Wilts, England. [Muehlberger, Elke] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. [Muehlberger, Elke] Boston Univ, Sch Med, Natl Emerging Infect Dis Lab, Boston, MA 02118 USA. [Netesov, Sergey V.; Shestopalov, Aleksandr M.] Novosibirsk State Univ, Novosibirsk, Novosibirsk Obl, Russia. [Paweska, Janusz T.] Natl Hlth Lab Serv, Ctr Emerging & Zoonot Dis, Natl Inst Communicable Dis, Sandringham Johannesburg, Gauteng, South Africa. [Ryabchikova, Elena I.] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Novosibirsk Obl, Russia. [Saphire, Erica Ollmann] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Saphire, Erica Ollmann] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Shestopalov, Aleksandr M.] State Res Ctr Virol & Biotechnol Vector, Koltsov, Novosibirsk Obl, Russia. [Sullivan, Nancy J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Swanepoel, Robert] Univ Pretoria, Zoonoses Res Unit, ZA-0002 Pretoria, South Africa. [Takada, Ayato] Hokkaido Univ, Div Global Epidemiol, Res Ctr Zoonosis Control, Sapporo, Hokkaido, Japan. [Towner, Jonathan S.; Nichol, Stuart T.] Ctr Dis Control & Prevent CDC, VSPB, DHCPP, NCEZID, Atlanta, GA 30333 USA. [van der Groen, Guido] Prins Leopold Inst Trop Geneeskunde, Antwerp, Belgium. [Volchkov, Viktor E.] Univ Lyon, Lab Filovirus, Inserm U758, UCB Lyon 1,Ecole Normale Super Lyon, Lyon, France. [Weidmann, Manfred] Univ Med Gottingen, Abt Virol, Gottingen, Germany. RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Frederick, MD 21702 USA. EM kuhnjens@mail.nih.gov; stn1@cdc.gov RI LEROY, Eric/I-4347-2016; Ryabchikova, Elena /G-3089-2013; Netesov, Sergey/A-3751-2013; Volchkov, Viktor/M-7846-2014; Kuhn, Jens H./B-7615-2011; Becker, Stephan/A-1065-2010; Palacios, Gustavo/I-7773-2015; Weidmann, Manfred/G-1817-2015; OI Gonzalez, Jean-Paul/0000-0003-3063-1770; Muhlberger, Elke/0000-0003-3547-9376; Honko, Anna/0000-0001-9165-148X; LEROY, Eric/0000-0003-0022-0890; Ryabchikova, Elena /0000-0003-4714-1524; Netesov, Sergey/0000-0002-7786-2464; Volchkov, Viktor/0000-0001-7896-8706; Kuhn, Jens H./0000-0002-7800-6045; Becker, Stephan/0000-0002-2794-5659; Palacios, Gustavo/0000-0001-5062-1938; Weidmann, Manfred/0000-0002-7063-7491; Shestopalov, Alexander/0000-0002-9734-0620; Olinger, Gene/0000-0001-7338-0292 FU Joint Science and Technology Office for Chem Bio Defense [TMTI0048_09_RD_T]; NIAID [HHSN272200200016I]; Intramural Research Program of the NIH, National Library of Medicine FX The content of this publication does not necessarily reflect the views or policies of the US Department of the Army, the US Department of Defense or the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. This work was funded in part by the Joint Science and Technology Office for Chem Bio Defense (proposal #TMTI0048_09_RD_T to SB). YC, JHK, and VWJ performed this work as employees of Tunnell Consulting, Inc., and MGL as an employee of Lovelace Respiratory Research Institute, both subcontractors to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN272200200016I. This research was also supported in part by the Intramural Research Program of the NIH, National Library of Medicine (YB and JRB). NR 42 TC 21 Z9 22 U1 1 U2 24 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 EI 1432-8798 J9 ARCH VIROL JI Arch. Virol. PD JUN PY 2013 VL 158 IS 6 BP 1425 EP 1432 DI 10.1007/s00705-012-1594-2 PG 8 WC Virology SC Virology GA 155QK UT WOS:000319762800035 PM 23358612 ER PT J AU Chen, YL Reese, DH AF Chen, Yanling Reese, David H. TI A Screen for Disruptors of the Retinol (Vitamin A) Signaling Pathway SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE Tox21; development; stem cells; retinoids; xenoestrogens; phthalate esters; teratogens ID IN-UTERO EXPOSURE; GENE-EXPRESSION; ACID SYNTHESIS; REPRODUCTIVE DEVELOPMENT; ALDEHYDE DEHYDROGENASE; PROSTATIC EPITHELIUM; POTENTIAL MECHANISM; RAT TESTES; CELLS; PHTHALATE AB The pathway through which retinol (vitamin A) is converted to its active metabolite, all-trans-retinoic acid (atRA), and subsequent receptor-mediated regulation of gene transcription by atRA is essential for all mammal life stages. This pathway is required for normal embryonic development and maintenance of cellular phenotype in adult organisms; chemicals that cause even minor interference with its normal function are potential developmental and adult toxicants. A short-term (24 h) in vitro mode-of-action screen for detecting chemicals that disrupt this essential pathway is described. It uses the mouse pluripotent P19 stem cell in a 96-well format, RT-qPCR gene-expression assay that does not require RNA purification to detect chemicals that interfere with retinol-induced Hoxa1 gene expression, a target of retinol signaling in mammals. A total of 21 chemicals were screened at a single 45 M concentration. Four chemicals known to disrupt the pathway in the rodent embryo (citral, disulfiram, and two rodent teratogens, nitrofen and bisdiamine) all significantly inhibited Hoxa1 upregulation by retinol. An additional four of seven chemicals with varying degrees of structural similarity to known disruptors or to the retinoid side chain, but not previously known to disrupt the pathway, were positive in the screen. The xenoestrogens, diethylstilbestrol, bisphenol A, 4-n-nonylphenol, and genistein and the phthalate esters, dibutyl phthalate and dipentyl phthalate, but not diethylhexyl phthalate, also significantly disrupted the pathway. Of the 21 chemicals tested, diethylstilbestrol was the only chemical that showed evidence in the MTT assay that cytotoxicity may have contributed to disruption of the pathway. Birth Defects Res (Part B) 98:276-282, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Chen, Yanling; Reese, David H.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Laurel, MD 20708 USA. RP Reese, DH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM david.reese@fda.hhs.gov FU Center for Food Safety and Applied Nutrition; U.S. Department of Energy; U.S. Food and Drug Administration FX The authors thank Christopher Elkins for reviewing this manuscript and helpful comments. The authors thank Martine Ferguson for providing statistical advice for data analyses in this work. This project was supported in part by the appointment of Yanling Chen to the Research Participation Program at the Center for Food Safety and Applied Nutrition administrated by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 43 TC 6 Z9 6 U1 5 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2013 VL 98 IS 3 BP 276 EP 282 DI 10.1002/bdrb.21062 PG 7 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 160NL UT WOS:000320126300008 PM 23696197 ER PT J AU Wilson, WH Schenkein, DP Jernigan, CL Woodcock, J Schilsky, RL AF Wilson, Wyndham H. Schenkein, David P. Jernigan, Cheryl L. Woodcock, Janet Schilsky, Richard L. TI Reevaluating the Accelerated Approval Process for Oncology Drugs SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; HODGKIN-LYMPHOMA; TRASTUZUMAB; LAPATINIB; PROGRESS; PATIENT AB For a new therapy to qualify for the accelerated approval pathway, it must treat a serious disease for which there is "unmet medical need"-defined as providing a therapy where none exists or providing a therapy that may be potentially superior to existing therapy. The increasing number of available therapies, coupled with the lack of accepted endpoints considered "reasonably likely to predict clinical benefit" and the lack of clarity early in development about circumstances in which a new product will qualify for accelerated approval, is pushing developers to pursue accelerated approval in heavily pretreated patients to fulfill an unmet need. To optimize the accelerated approval pathway, we propose here a reevaluation of what constitutes "unmet medical need" and "available therapy" in oncology. We also discuss ways for new endpoints to become qualified for use in supporting accelerated approval, and propose a structured process for pursuing accelerated approval. (C) 2013 AACR. C1 [Wilson, Wyndham H.] NCI, Lymphoma Therapeut Sect, Bethesda, MD 20892 USA. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Schenkein, David P.] Agios Pharmaceut, Cambridge, MA USA. [Jernigan, Cheryl L.] Susan G Komen Cure, Kansas City, MO USA. [Schilsky, Richard L.] Amer Soc Clin Oncol, Alexandria, VA 22314 USA. RP Schilsky, RL (reprint author), Amer Soc Clin Oncol, 2318 Mill Rd,Suite 800, Alexandria, VA 22314 USA. EM Richard.Schilsky@asco.org NR 30 TC 8 Z9 8 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 JUN 1 PY 2013 VL 19 IS 11 BP 2804 EP 2809 DI 10.1158/1078-0432.CCR-13-0315 PG 6 WC Oncology SC Oncology GA 155FF UT WOS:000319732000004 PM 23553847 ER PT J AU Funk, JA Abley, MJ Bowman, AS Gebreyes, WA Morrow, WEM Tadesse, DA AF Funk, Julie A. Abley, Melanie J. Bowman, Andrew S. Gebreyes, Wondwossen A. Morrow, William E. Morgan Tadesse, Daniel A. TI Prevalence of Yersinia enterocolitica in Antimicrobial-Free and Conventional Antimicrobial Use Swine Production SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; PIGS; SLAUGHTER; VIRULENCE; FARMS; FECES AB Swine are the primary reservoir for foodborne illness associated with Yersinia enterocolitica. The use of antimicrobials in animal agriculture has been hypothesized as having a potential role in the increase in prevalence of zoonotic pathogens. The objective of this study was to compare the frequency of Y. enterocolitica fecal shedding in swine reared on farms with conventional antimicrobial use policies to farms that were antimicrobial free (ABF). Swine farms were selected from three regions in the United States. In each region, farms were categorized based on antimicrobial use policy. Fecal samples were collected from pigs on-farm within 48 h of harvest. The overall proportion of Y. enterocolitica and ail-harboring Y. enterocolitica-positive pigs was 10.9% and 4.0%, respectively. There were increased odds (odds ratio [OR] 6.8, 95% confidence interval [CI] 3.46-13.28) for a pig to be Y. enterocolitica positive if it was reared on an ABF farm as compared to a conventional farm. There was no significant association between farm antimicrobial use policy and isolation of an ail-harboring Y. enterocolitica from an individual pig (OR 1.8, 95% CI 0.90-3.61). The association of antimicrobial use policy with Y. enterocolitica shedding in feces should be interpreted cautiously, as antimicrobial use cannot be separated from other management factors (e.g., confinement or outdoor housing), which may be associated with risk of Y. enterocolitica in swine. C1 [Funk, Julie A.] Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. [Abley, Melanie J.; Bowman, Andrew S.; Gebreyes, Wondwossen A.] Ohio State Univ, Coll Vet Med, Dept Vet Prevent Med, Columbus, OH 43210 USA. [Morrow, William E. Morgan] N Carolina State Univ, Coll Agr & Life Sci, Dept Anim Sci, Raleigh, NC 27695 USA. [Tadesse, Daniel A.] US FDA, Ctr Vet Med, Res Off, Laurel, MD USA. RP Funk, JA (reprint author), Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, 1129 Farm Lane,Room B51A, E Lansing, MI 48824 USA. EM funkj@cvm.msu.edu RI Bowman, Andrew/B-4321-2012 OI Bowman, Andrew/0000-0002-0738-8453 FU United States Department of Agriculture [2002-51110-01508] FX This work was supported by a research grant funded by the United States Department of Agriculture (2002-51110-01508). We thank the producers who participated in this research. NR 28 TC 0 Z9 0 U1 1 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD JUN PY 2013 VL 10 IS 6 BP 514 EP 519 DI 10.1089/fpd.2012.1354 PG 6 WC Food Science & Technology SC Food Science & Technology GA 164AC UT WOS:000320380100005 PM 23614802 ER PT J AU Liefer, JD Robertson, A MacIntyre, HL Smith, WL Dorsey, CP AF Liefer, Justin D. Robertson, Alison MacIntyre, Hugh L. Smith, William L. Dorsey, Carol P. TI Characterization of a toxic Pseudo-nitzschia spp. bloom in the Northern Gulf of Mexico associated with domoic acid accumulation in fish SO HARMFUL ALGAE LA English DT Article DE Pseudo-nitzschia subfradulenta; Domoic acid; Submarine groundwater discharge; Trophic transfer; Fish; Gulf of Mexico ID HARMFUL ALGAL BLOOMS; PRINCE-EDWARD-ISLAND; SPECIES BACILLARIOPHYCEAE; COASTAL WATERS; MONTEREY BAY; SEA LIONS; FOOD WEBS; AUSTRALIS BACILLARIOPHYCEAE; PSEUDONITZSCHIA-AUSTRALIS; SILICATE LIMITATION AB A toxic bloom of Pseudo-nitzschia spp. was observed in the Alabama coastal waters of the northern Gulf of Mexico (NGOM) in June 2009 that resulted in the accumulation of domoic acid (DA) in fish. The bloom initiated following a large storm event that likely caused increased groundwater discharge 16-20 days prior to peak densities. Eleven sites, located in littoral shoreline waters and inshore embayments spanning the entire Alabama NGOM coastline, were sampled during peak densities to assess Pseudo-nitzschia species composition and toxicity, and associated water-quality parameters. Small fish (0.27-11.9 g body weight) were collected at six of these sites for analysis of DA content. High Pseudo-nitzschia spp. densities (8.27 x 10(4)-5.05 x 10(6) cell l(-1)) were detected at eight sites located in the littoral shoreline and particulate DA was detected at six of these littoral sites (48.0-540 pg ml(-1)). The bloom consisted primarily (>90%) of Pseudo-nitzschia subfraudulenta, a species previously characterized as forming only a minor component of Pseudo-nitzschia assemblages and not known to produce DA. Pseudo-nitzschia spp. were at low densities or not detected at the inshore sites and DA was detected at these sites. Pseudo-nitzschia spp. density varied along an estuarine gradient, with greater densities occurring in the most saline, clear, and nutrient-poor waters. Cell density was strongly and negatively correlated with silicate (Si) concentrations and the ratios of silicate to dissolved inorganic nitrogen and phosphate (Si:DIN and Si:PO4). Cell toxin quota was negatively correlated with phosphate, and strongly and positively correlated with the ratio of total nitrogen to total phosphorus (TN:TP). These relationships are consistent with previous observations that indicate Pseudo-nitzschia spp. density and toxicity are likely to be greater in high salinity, high irradiance, and nutrient-poor waters. DA was detected in 128 of 131 (98%) of the fish collected, which included seven primary and secondary consumer species. This is the first demonstration of trophic transfer of DA in this region of the NGOM, indicating that toxic blooms of Pseudo-nitzschia spp. in Alabama coastal waters have the potential to transfer DA to recreationally and commercially important fish species. (c) 2013 Elsevier B.V. All rights reserved. C1 [Liefer, Justin D.; MacIntyre, Hugh L.] Dauphin Isl Sea Lab, Dauphin Isl, AL 36528 USA. [Liefer, Justin D.] Univ S Alabama, Dept Marine Sci, Mobile, AL 36688 USA. [Robertson, Alison] FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Smith, William L.; Dorsey, Carol P.] Alabama Dept Publ Hlth, Mobile Branch Lab, Mobile, AL 36608 USA. RP Liefer, JD (reprint author), Dauphin Isl Sea Lab, 101 Bienville Blvd, Dauphin Isl, AL 36528 USA. EM jliefer@disl.org RI MacIntyre, Hugh/B-4555-2011 OI MacIntyre, Hugh/0000-0002-8852-6984 FU Alabama Department of Conservation and Natural Resources, State Lands Division [DISL-CZM-306-10-1]; National Oceanic and Atmospheric Administration [R/CEH-32]; National Science Foundation [OCE-0961994]; US Food and Drug Administration; DISL-FDA Cooperative Fellowship program FX We thank personnel at the Baldwin County Health Department and the Alabama Department of Environmental Management, particularly Camilla English, Suzie Rice, and Byron Webb, for sample collection. We thank Emily Goldman for assistance with field-work and sample processing, and Claire Pabody, Nicholas Bawden and Kevan Gregalis for assistance with fish identification. A special thanks goes to Dr. Michael Parsons for assistance with electron microscopy and Pseudo-nitzschia identification and to the staff at the Florida FWC Fish and Wildlife Research Institute, particularly Dr. Earnest Truby, for use of and assistance with SEM and TEM. This work was supported by grants from the Alabama Department of Conservation and Natural Resources, State Lands Division (DISL-CZM-306-10-1), the National Oceanic and Atmospheric Administration (R/CEH-32) and the National Science Foundation (OCE-0961994) to HLM; and by an award from the US Food and Drug Administration, administered through the DISL-FDA Cooperative Fellowship program, to JDL.[SS] NR 84 TC 6 Z9 6 U1 6 U2 44 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-9883 J9 HARMFUL ALGAE JI Harmful Algae PD JUN PY 2013 VL 26 BP 20 EP 32 DI 10.1016/j.hal.2013.03.002 PG 13 WC Marine & Freshwater Biology SC Marine & Freshwater Biology GA 164OF UT WOS:000320418700003 ER PT J AU Glasgow, RE Doria-Rose, VP Khoury, MJ Elzarrad, M Brown, ML Stange, KC AF Glasgow, Russell E. Doria-Rose, V. Paul Khoury, Muin J. Elzarrad, Mohammed Brown, Martin L. Stange, Kurt C. TI Comparative Effectiveness Research in Cancer: What Has Been Funded and What Knowledge Gaps Remain? SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PRACTICAL CLINICAL-TRIALS; MULTIMETHOD RESEARCH; HEALTH-CARE; UNINTENDED CONSEQUENCES; PARTICIPATORY RESEARCH; MULTISITE MULTIMETHOD; POPULATION HEALTH; DECISION-MAKING; PUBLIC-HEALTH; MEDICINE C1 [Glasgow, Russell E.; Doria-Rose, V. Paul; Khoury, Muin J.; Elzarrad, Mohammed; Brown, Martin L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Elzarrad, Mohammed] NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. [Khoury, Muin J.] Ctr Dis Control & Prevent, Off Publ Hlth Genom, Atlanta, GA USA. [Elzarrad, Mohammed] US FDA, Interagency Oncol Task Force Joint Fellowship Pro, Silver Spring, MD USA. [Stange, Kurt C.] Case Western Reserve Univ, Cleveland Clin & Translat Sci Collaborat, Case Comprehens Canc Ctr, Dept Family Med & Community Hlth,Dept Epidemiol &, Cleveland, OH 44106 USA. [Stange, Kurt C.] Case Western Reserve Univ, Cleveland Clin & Translat Sci Collaborat, Case Comprehens Canc Ctr, Dept Sociol, Cleveland, OH 44106 USA. RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, NIH, 6130 Execut Blvd, Rockville, MD 20852 USA. EM glasgowre@mail.nih.gov OI Doria-Rose, Vincent/0000-0002-8802-5143 NR 64 TC 8 Z9 8 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD JUN PY 2013 VL 105 IS 11 BP 766 EP 773 DI 10.1093/jnci/djt066 PG 8 WC Oncology SC Oncology GA 160QK UT WOS:000320134100007 PM 23578853 ER PT J AU Franco, A Damdinsuren, B Ise, T Dement-Brown, J Li, HF Nagata, S Tolnay, M AF Franco, Andrea Damdinsuren, Bazarragchaa Ise, Tomoko Dement-Brown, Jessica Li, Huifang Nagata, Satoshi Tolnay, Mate TI Human Fc Receptor-Like 5 Binds Intact IgG via Mechanisms Distinct from Those of Fc Receptors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCLONAL-ANTIBODIES; GAMMA RECEPTORS; B-CELLS; ANTIINFLAMMATORY ACTIVITY; MULTIPLE-MYELOMA; IMMUNE-RESPONSES; EXPRESSION; AFFINITY; PROTEIN AB Fc receptor-like (FCRL) 5 regulates B cell Ag receptor signaling and has been reported to bind aggregated IgG. Using surface plasmon resonance, we analyzed the interaction of native IgG samples with FCRL5, revealing a complex binding mechanism, where isotype is just one factor. FCRL5 bound IgG1 and IgG4 with similar to 1 mu M K-D, whereas the interaction with IgG3 was a magnitude weaker. However, IgG2 samples displayed a wide range of affinities, indicating that additional factors affect binding. We used a panel of 19 anti-FCRL5 mAbs with defined reactivity to identify domains involved in ligand binding. Six mAbs blocked IgG binding, indicating critical roles of FCRL5 domains 1 and 3, as well as epitopes at the domain 1/2 and domain 2/3 boundaries. We found that only glycosylated IgG containing both Fab arms and the Fc region bound with high affinity. Furthermore, the presence of sialic acid in the IgG carbohydrate altered FCRL5 binding. The interaction of IgG and FCRL5 consisted of two kinetic components, suggesting a complex binding mechanism. We established that the IgG-Fc and IgG-F(ab ')(2) fragments bind FCRL5 independently but with low affinity, revealing the mechanism behind the two-step binding of whole IgG. This complex binding mechanism is distinct from that of Fc receptors, which bind through the Fc. We propose that FCRL5 is a new type of receptor that recognizes intact IgG, possibly enabling B cells to sense Ig quality. Recognition of undamaged IgG molecules by FCRL5 could allow B cells to engage recently produced Abs. C1 [Franco, Andrea; Damdinsuren, Bazarragchaa; Dement-Brown, Jessica; Li, Huifang; Tolnay, Mate] Ctr Drug Evaluat & Res, Food & Drug Admin, Div Monoclonal Antibodies, Silver Spring, MD 20993 USA. [Ise, Tomoko; Nagata, Satoshi] Sanford Research USD, Cancer Biol Res Ctr, Sioux Falls, SD 57105 USA. RP Tolnay, M (reprint author), Ctr Drug Evaluat & Res, Food & Drug Admin, Div Monoclonal Antibodies, HFD-123,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mate.tolnay@fda.hhs.gov FU Intramural Research Program of the Center for Drug Evaluation and Research/Food and Drug Administration; Research Fellowship Program for the Center for Drug Evaluation and Research; Food and Drug Administration Commissioner's Fellowship Program; Leukemia Research Foundation; Chronic Lymphocytic Leukemia Global Research Foundation; National Institutes of Health Centers of Biomedical Research Excellence [1P20RR024219-01A2] FX This work was supported by the Intramural Research Program of the Center for Drug Evaluation and Research/Food and Drug Administration. AR and H.L. were supported through the Research Fellowship Program for the Center for Drug Evaluation and Research administered by the Oak Ridge Associated Universities. BD. was supported by the Food and Drug Administration Commissioner's Fellowship Program. S.N. and T.I. were supported by the Leukemia Research Foundation, the Chronic Lymphocytic Leukemia Global Research Foundation, and National Institutes of Health Centers of Biomedical Research Excellence Grant 1P20RR024219-01A2. NR 45 TC 16 Z9 16 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2013 VL 190 IS 11 BP 5739 EP 5746 DI 10.4049/jimmunol.1202860 PG 8 WC Immunology SC Immunology GA 147XY UT WOS:000319205900044 PM 23616577 ER PT J AU Wang, PG Zhou, WL AF Wang, Perry G. Zhou, Wanlong TI Rapid determination of parabens in personal care products by stable isotope GC-MS/MS with dynamic selected reaction monitoring SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Dynamic selected reaction monitoring; GC-MS; MS; Parabens ID CHROMATOGRAPHY-MASS SPECTROMETRY; SOLID-PHASE DISPERSION; COSMETIC PRODUCTS; GAS-CHROMATOGRAPHY; LIQUID-CHROMATOGRAPHY; EXTRACTION AB In this study, a rapid and sensitive analytical method for the determination of methyl-, ethyl-, propyl-, and butyl esters of para-hydroxy benzoic acid (parabens) in personal care products was developed and fully validated. Test portions were extracted with methanol followed by vortexing, sonication, centrifugation, and filtration without derivatization. The four parabens were quantified by GC-MS/MS in the electron ionization mode. Four corresponding isotopically labeled parabens were selected as internal standards, which were added at the beginning of the sample preparation and used to correct for recovery and matrix effects. Sensitivity, extraction efficiency, and recovery of the respective analytes were evaluated. The coefficients of determination (r2) were all greater than 0.995 for the four parabens investigated. The recoveries ranged from 97 to 107% at three spiked levels and a one-time (single) extraction efficiency greater than 97% was obtained. This method has been applied to screen 26 personal care products. This is the first time that a unique GC-MS/MS method with dynamic selected reaction monitoring and confirmation of analytes has been used to determine these parabens in cosmetic personal care products. C1 [Wang, Perry G.; Zhou, Wanlong] US FDA, College Pk, MD 20740 USA. RP Wang, PG (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM perry.wang@fda.hhs.gov NR 19 TC 12 Z9 12 U1 1 U2 36 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD JUN PY 2013 VL 36 IS 11 BP 1781 EP 1787 DI 10.1002/jssc.201201098 PG 7 WC Chemistry, Analytical SC Chemistry GA 157SR UT WOS:000319919900013 PM 23494853 ER PT J AU Senior, JR AF Senior, John R. TI Why the threshold criteria should not be modified for detection of possibly serious drug-induced hepatotoxicity in special groups of trial subjects SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID INDUCED LIVER-INJURY; HYS LAW C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Senior, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM John.Senior@fda.hhs.gov NR 21 TC 2 Z9 2 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2013 VL 22 IS 6 BP 579 EP 582 DI 10.1002/pds.3435 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 157DG UT WOS:000319875400003 PM 23512228 ER PT J AU Shaheen, BW Nayak, R Boothe, DM AF Shaheen, Bashar W. Nayak, Rajesh Boothe, Dawn M. TI Emergence of a New Delhi Metallo-beta-Lactamase (NDM-1)-Encoding Gene in Clinical Escherichia coli Isolates Recovered from Companion Animals in the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Letter ID MOLECULAR CHARACTERIZATION; CARBAPENEMASE C1 [Shaheen, Bashar W.; Nayak, Rajesh] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Boothe, Dawn M.] Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. RP Nayak, R (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM Rajesh.Nayak@fda.hhs.gov NR 11 TC 18 Z9 18 U1 0 U2 10 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 JUN PY 2013 VL 57 IS 6 BP 2902 EP 2903 DI 10.1128/AAC.02028-12 PG 2 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 148UC UT WOS:000319272100071 PM 23587948 ER PT J AU Praveen, C Dancho, BA Kingsley, DH Calci, KR Meade, GK Mena, KD Pillai, SD AF Praveen, Chandni Dancho, Brooke A. Kingsley, David H. Calci, Kevin R. Meade, Gloria K. Mena, Kristina D. Pillai, Suresh D. TI Susceptibility of Murine Norovirus and Hepatitis A Virus to Electron Beam Irradiation in Oysters and Quantifying the Reduction in Potential Infection Risks SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID UNITED-STATES; VIBRIO-PARAHAEMOLYTICUS; SHELLFISH CONSUMPTION; BIVALVE SHELLFISH; FOODBORNE ILLNESS; INACTIVATION; RADIATION; ROTAVIRUS; PATHOGENS; GAMMA AB Consumption of raw oysters is an exposure route for human norovirus (NoV) and hepatitis A virus (HAV). Therefore, efficient postharvest oyster treatment technology is needed to reduce public health risks. This study evaluated the inactivation of HAV and the NoV research surrogate, murine norovirus-1 (MNV-1), in oysters (Crassostrea virginica) by electron beam (E-beam) irradiation. The reduction of potential infection risks was quantified for E-beam irradiation technology employed on raw oysters at various virus contamination levels. The E-beam dose required to reduce the MNV and HAV titer by 90% (D-10 value) in whole oysters was 4.05 (standard deviations [SD], +/- 0.63) and 4.83 (SD, +/- 0.08) kGy, respectively. Microbial risk assessment suggests that if a typical serving of 12 raw oysters was contaminated with 105 PFU, a 5-kGy treatment would achieve a 12% reduction (from 4.49 out of 10 persons to 3.95 out of 10 persons) in NoV infection and a 16% reduction (from 9.21 out of 10 persons to 7.76 out of 10 persons) in HAV infections. If the serving size contained only 102 PFU of viruses, a 5-kGy treatment would achieve a 26% reduction (2.74 out of 10 persons to 2.03 out of 10 persons) of NoV and 91% reduction (2.1 out of 10 persons to 1.93 out of 100 persons) of HAV infection risks. This study shows that although E-beam processing cannot completely eliminate the risk of viral illness, infection risks can be reduced. C1 [Praveen, Chandni] Texas A&M Univ, Natl Ctr Electron Beam Res, College Stn, TX USA. [Dancho, Brooke A.; Kingsley, David H.; Meade, Gloria K.; Pillai, Suresh D.] Delaware State Univ, James WW Baker Ctr, Food Safety & Intervent Technol Res Unit, Dept Agr,Agr Res Serv, Dover, DE USA. [Calci, Kevin R.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. [Mena, Kristina D.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, El Paso, TX USA. RP Pillai, SD (reprint author), Delaware State Univ, James WW Baker Ctr, Food Safety & Intervent Technol Res Unit, Dept Agr,Agr Res Serv, Dover, DE USA. EM s-pillai@tamu.edu FU Texas AgriLife Hatch program [H 8708]; USDA-NIFA FX Funding from the Texas AgriLife Hatch program H 8708 and USDA-NIFA are acknowledged. NR 36 TC 18 Z9 18 U1 4 U2 24 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 2013 VL 79 IS 12 BP 3796 EP 3801 DI 10.1128/AEM.00347-13 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 152CO UT WOS:000319507700029 PM 23584781 ER PT J AU Reynolds, KS AF Reynolds, K. S. TI Acceleration of Drug Development: A Collaboration of Many Stakeholders SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Modern drugs are used to treat and prevent diseases that previously led to morbidity and mortality.There is a high cost to this achievement-investment for each successful drug can exceed $1.8 billion. Late-phase drug candidate failure decreases efficiency of drug development because each failure represents lost or delayed opportunity to develop successful drugs. Collaboration of stakeholders and the use of new science and knowledge management can reduce late-phase failure and accelerate drug development. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Reynolds, KS (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. EM kellie.reynolds@fda.hhs.gov NR 10 TC 1 Z9 2 U1 0 U2 6 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 JUN PY 2013 VL 93 IS 6 BP 455 EP 459 DI 10.1038/clpt.2013.63 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149FQ UT WOS:000319304800001 PM 23689207 ER PT J AU Owen, RP Jain, L Zhang, L Zineh, I AF Owen, R. P. Jain, L. Zhang, L. Zineh, I. TI Office of Clinical Pharmacology Science Day: A Forum to Stimulate Innovation in Clinical Pharmacology SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The Office of Clinical Pharmacology (OCP) of the US Food and Drug Administration (FDA) has hosted an office-wide event called Science Day (SD) since 1999. SD 2012 included presentations on physiologically based pharmacokinetic models, exposure-response analyses, and other research projects. SD provides a forum for showcasing clinical pharmacology (CP) research within the OCP and provides an opportunity for professional development. This article discusses the evolution of Science Day and then focuses on SD 2012 as an example platform for promotion of regulatory research. C1 [Owen, R. P.; Jain, L.; Zhang, L.; Zineh, I.] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. RP Owen, RP (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. EM ryan.owen@fda.hhs.gov NR 1 TC 2 Z9 2 U1 0 U2 1 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 JUN PY 2013 VL 93 IS 6 BP 471 EP 473 DI 10.1038/clpt.2013.33 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149FQ UT WOS:000319304800015 PM 23689212 ER PT J AU Zineh, I Woodcock, J AF Zineh, I. Woodcock, J. TI Clinical Pharmacology and the Catalysis of Regulatory Science: Opportunities for the Advancement of Drug Development and Evaluation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID QUANTITATIVE DISEASE; SAFETY ASSESSMENT; TRIAL MODELS; APPROVAL; IMPACT; PHARMACOGENOMICS; INNOVATION; RISKS AB The"regulatory paradox"is a tension between aversion to uncertainty and willingness to accept unknowns about a drug before its approval. Finding the right balance may mean the difference between fostering and stifling innovation. Clinical pharmacology applied in the drug development and regulatory contexts can bridge mechanistic reasoning and empiricism to help reconcile the regulatory paradox. Here, we propose that the discipline of clinical pharmacology, in the regulatory setting, is well positioned to build on its past successes in the advancement and acceleration of drug development. C1 [Zineh, I.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Woodcock, J.] US FDA, Off Ctr Director, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zineh, I (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM issam.zineh@fda.hhs.gov NR 35 TC 16 Z9 17 U1 0 U2 13 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 JUN PY 2013 VL 93 IS 6 BP 515 EP 525 DI 10.1638/clpt.2013.32 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149FQ UT WOS:000319304800022 PM 23571772 ER PT J AU Bough, KJ Lerman, C Rose, JE McClernon, FJ Kenny, PJ Tyndale, RF David, SP Stein, EA Uhl, GR Conti, DV Green, C Amur, S AF Bough, K. J. Lerman, C. Rose, J. E. McClernon, F. J. Kenny, P. J. Tyndale, R. F. David, S. P. Stein, E. A. Uhl, G. R. Conti, D. V. Green, C. Amur, S. TI Biomarkers for Smoking Cessation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NICOTINE METABOLITE RATIO; GENOME-WIDE ASSOCIATION; TRANSDERMAL NICOTINE; CYP2A6 GENOTYPE; CANDIDATE GENE; CLINICAL-TRIALS; LUNG-CANCER; SMOKERS; PREDICTS; BEHAVIOR AB One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development. Promising biomarkers are presented across a range of approaches including metabolism, genetics, and neuroimaging. A preclinical viewpoint is also offered, as are analytical considerations and a regulatory perspective summarizing a pathway toward biomarker qualification. C1 [Bough, K. J.] NIDA, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA. [Lerman, C.] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Rose, J. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [McClernon, F. J.] Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. [Kenny, P. J.] Scripps Res Inst Florida, Dept Mol Therapeut, Jupiter, FL USA. [Kenny, P. J.] Scripps Res Inst Florida, Dept Neurosci, Jupiter, FL USA. [Tyndale, R. F.] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada. [David, S. P.] Stanford Univ, Dept Family & Community Med, Stanford, CA 94305 USA. [Stein, E. A.; Uhl, G. R.] NIDA, Intramural Res Program, Bethesda, MD 20892 USA. [Conti, D. V.] Univ So Calif, Dept Prevent Med, Los Angeles, CA 90089 USA. [Green, C.] Univ Texas Houston, Sch Med, Dept Pediat, Houston, TX USA. [Amur, S.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Bough, KJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences, Bethesda, MD 20892 USA. EM boughk@mail.nih.gov OI David, Sean/0000-0002-4922-2603 FU NIH (Pharmacogenomics Research Network) [U01 DA020830, P50 CA143187, P50 DA027840, P50 DA009262, R01DA025983, R01 DA017441, R01 DA025876, R01 CA140561, R01 ES019876, R21DA027331]; NIDA Intramural Research Program; Canadian Institutes of Health Research [MOP-86471, TMH-109787]; Centre for Addiction and Mental Health; GlaxoSmithKline; Pfizer; AstraZeneca FX This work was supported in part through grants funded by the NIH (Pharmacogenomics Research Network U01 DA020830, P50 CA143187, P50 DA027840, P50 DA009262, R01DA025983, R01 DA017441, R01 DA025876, R01 CA140561, R01 ES019876, and R21DA027331), the NIDA Intramural Research Program, Canadian Institutes of Health Research grants (MOP-86471 and TMH-109787), and the Centre for Addiction and Mental Health. All listed authors contributed to the composition of this review.The views expressed in this presentation are those of the authors and may not necessarily reflect the position of the FDA (S.A.) or NIH (K.J.B.).; C.L. has received funding and/or served as a consultant to GlaxoSmithKline, Pfizer, and AstraZeneca. R.F.T. has participated in 1-day advisory meetings for Novartis and McNeil. Associate Editor R.F.T. was not involved in the review or decision process for this article. F.J.M. has received research funding from Pfizer (primary investigator: Munafo).J.E.R. and G.R.U. are listed as co-inventors on a patent application filed by Duke University based on genomic markers that distinguish successful quitters from unsuccessful quitters. S.P.D. has consulted for a 1-day Pfizer-sponsored conference on behavioral treatments for smoking cessation and is a scientific advisor to Genophen. D.V.C. has served as a consultant to Pfizer.The other authors declared no conflict of interest. NR 73 TC 24 Z9 24 U1 1 U2 19 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 JUN PY 2013 VL 93 IS 6 BP 526 EP 538 DI 10.1038/clpt.2013.57 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149FQ UT WOS:000319304800023 PM 23588313 ER PT J AU Hammad, TA Neyarapally, GA Pinheiro, SP Iyasu, S Rochester, G Dal Pan, G AF Hammad, Tarek A. Neyarapally, George A. Pinheiro, Simone P. Iyasu, Solomon Rochester, George Dal Pan, Gerald TI Reporting of meta-analyses of randomized controlled trials with a focus on drug safety: An empirical assessment SO CLINICAL TRIALS LA English DT Article ID INHALED CORTICOSTEROIDS; CLINICAL-TRIALS; POOLED ANALYSIS; WEIGHT-LOSS; RISK; EFFICACY; INHIBITORS; STATEMENT; THERAPY; INTERVENTIONS AB Background Due to the sparse nature of serious drug-related adverse events (AEs), meta-analyses combining data from several randomized controlled trials (RCTs) to evaluate drug safety issues are increasingly being conducted and published, influencing clinical and regulatory decision making. Evaluation of meta-analyses involves the assessment of both the individual constituent trials and the approaches used to combine them. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting framework is designed to enhance the reporting of systematic reviews and meta-analyses. However, PRISMA may not cover all critical elements useful in the evaluation of meta-analyses with a focus on drug safety particularly in the regulatory-public health setting. Purpose This work was conducted to (1) evaluate the adherence of a sample of published drug safety-focused meta-analyses to the PRISMA reporting framework, (2) identify gaps in this framework based on key aspects pertinent to drug safety, and (3) stimulate the development and validation of a more comprehensive reporting tool that incorporates elements unique to drug safety evaluation. Methods We selected a sample of meta-analyses of RCTs based on review of abstracts from high-impact journals as well as top medical specialty journals between 2009 and 2011. We developed a preliminary reporting framework based on PRISMA with specific additional reporting elements critical for the evaluation of drug safety meta-analyses of RCTs. The reporting of pertinent elements in each meta-analysis was reviewed independently by two authors; discrepancies in the independent evaluations were resolved through discussions between the two authors. Results A total of 27 meta-analyses, 12 from highest impact journals, 13 from specialty medical journals, and 2 from Cochrane reviews, were identified and evaluated. The great majority (>85%) of PRISMA elements were addressed in more than half of the meta-analyses reviewed. However, the majority of meta-analyses (>60%) did not address most (>80%) of the additional reporting elements critical for the evaluation of drug safety. Some of these elements were not addressed in any of the reviewed meta-analyses. Limitations This review included a sample of meta-analyses, with a focus on drug safety, recently published in high-impact journals; therefore, we may have underestimated the extent of the reporting problem across all meta-analyses of drug safety. Furthermore, temporal trends in reporting could not be evaluated in this review because of the short time interval selected. Conclusions While the majority of PRISMA elements were addressed by most studies reviewed, the majority of studies did not address most of the additional safety-related elements. These findings highlight the need for the development and validation of a drug safety reporting framework and the importance of the current initiative by the Council for International Organizations of Medical Sciences (CIOMS) to create a guidance document for drug safety information synthesis/meta-analysis, which may improve reporting, conduct, and evaluation of meta-analyses of drug safety and inform clinical and regulatory decision making. C1 [Hammad, Tarek A.; Neyarapally, George A.; Pinheiro, Simone P.; Iyasu, Solomon; Rochester, George; Dal Pan, Gerald] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hammad, TA (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 22,Room 24, Silver Spring, MD 20993 USA. EM tarek.hammad@fda.hhs.gov NR 47 TC 10 Z9 10 U1 0 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD JUN PY 2013 VL 10 IS 3 BP 389 EP 397 DI 10.1177/1740774513479467 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 148FI UT WOS:000319228200004 PM 23508987 ER PT J AU Zhang, J Dang, QY Malik, M AF Zhang, Joanne Dang, Qianyu Malik, Marek TI Baseline Correction in Parallel Thorough QT Studies SO DRUG SAFETY LA English DT Article ID DIURNAL-VARIATION; POSITIVE CONTROL; INTERVAL; QT/QTC; VARIABILITY; STABILITY AB Background In parallel thorough QT (TQT) studies, it has been speculated that either baseline correction should be omitted, under the assumption that it only adds noise to the data, or a time-averaged baseline instead of a time-matched baseline correction should be considered in order to reduce the study variability. Objective This study characterized the assumptions and implications of different baseline correction approaches in parallel TQT studies submitted for regulatory review. Data and methods 57 parallel TQT studies conducted between 2002 and 2009 in 5591 healthy volunteers were evaluated. Only moxifloxacin and placebo arms, including their baselines, were considered. The options of using no baseline correction, time-averaged baseline correction, and time-matched baseline correction were examined and compared. Results QTc values exhibited a diurnal pattern, with longer QTc intervals during sleep preserved when correcting for a time-averaged baseline. Post-dose and baseline QTc values were highly correlated (mean rho = 0.80, range 0.56-0.98 and mean rho = 0.79, range 0.50-0.96 in the placebo and moxifloxacin groups, respectively). The variability of raw QTc values was substantially larger than that of baseline-adjusted QTc values. The difference in the point estimate of QTc differences between moxifloxacin and placebo differed by up to +/- 4 ms between the time-averaged and the time-matched baseline corrections. Statistical tests indicate that assumptions of time-averaged baseline and no baseline correction are not appropriate. Conclusions Baseline correction in parallel TQT studies leads to more precise QTc estimates. Because of possible inaccuracy introduced by time-averaged baseline correction, the time-matched baseline correction appears to be preferable for a parallel TQT study to both reduce the intrinsic variability due to circadian patterns and obtain more accurate point estimates. C1 [Zhang, Joanne; Dang, Qianyu] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Malik, Marek] St Pauls Cardiac Electrophysiol, London CR8 3NQ, England. [Malik, Marek] Univ London, London CR8 3NQ, England. RP Zhang, J (reprint author), US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21 Room 4668, Silver Spring, MD 20993 USA. EM Joanne.Zhang@fda.hhs.gov; Marek.Malik@btinternet.com NR 19 TC 1 Z9 1 U1 0 U2 6 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD JUN PY 2013 VL 36 IS 6 BP 441 EP 453 DI 10.1007/s40264-013-0040-z PG 13 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 151RB UT WOS:000319476800006 PM 23620166 ER PT J AU Pogribny, IP Kutanzi, K Melnyk, S de Conti, A Tryndyak, V Montgomery, B Pogribna, M Muskhelishvili, L Latendresse, JR James, SJ Beland, FA Rusyn, I AF Pogribny, Igor P. Kutanzi, Kristy Melnyk, Stepan de Conti, Aline Tryndyak, Volodymyr Montgomery, Beverly Pogribna, Marta Muskhelishvili, Levan Latendresse, John R. James, S. Jill Beland, Frederick A. Rusyn, Ivan TI Strain-dependent dysregulation of one-carbon metabolism in male mice is associated with choline- and folate-deficient diet-induced liver injury SO FASEB JOURNAL LA English DT Article DE strain differences; methyl donor deficiency; gene expression; homocysteinemia; NAFLD ID ENDOPLASMIC-RETICULUM STRESS; COULOMETRIC ELECTROCHEMICAL DETECTION; ALCOHOL-FED MICE; FATTY LIVER; GENE-EXPRESSION; INTERSTRAIN DIFFERENCES; COLLABORATIVE CROSS; DISEASE; METHIONINE; HYPERHOMOCYSTEINEMIA AB Dysregulation of one-carbon metabolism-related metabolic processes is a major contributor to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). It is well established that genetic and gender-specific variations in one-carbon metabolism contribute to the vulnerability to NAFLD in humans. To examine the role of one-carbon metabolism dysregulation in the pathogenesis and individual susceptibility to NAFLD, we used a "population-based" mouse model where male mice from 7 inbred were fed a choline-and folate-deficient (CFD) diet for 12 wk. Strain-dependent down-regulation of several key one-carbon metabolism genes, including methionine adenosyltransferase 1 alpha (Mat1a), cystathionine-beta-synthase (Cbs), methylenetetrahydrofolate reductase (Mthfr), adenosyl-homocysteinase (Ahcy), and methylenetetrahydrofolate dehydrogenase 1 (Mthfd1), was observed. These changes were strongly associated with interstrain variability in liver injury (steatosis, necrosis, inflammation, and activation of fibrogenesis) and hyperhomocysteinemia. Mechanistically, the decreased expression of Mat1a, Ahcy, and Mthfd1 was linked to a reduced level and promoter binding of transcription factor CCAAT/enhancer binding protein beta (CEBP beta), which directly regulates their transcription. The strain specificity of diet-induced dysregulation of one-carbon metabolism suggests that interstrain variation in the regulation of one-carbon metabolism may contribute to the differential vulnerability to NFLD and that correcting the imbalance may be considered as preventive and treatment strategies for NAFLD.-Pogribny, I. P., Kutanzi, K., Melnyk, S., de Conti, A., Tryndyak, V., Montgomery, B., Pogribna, M., Muskhelishvili, L., Latendresse, J. R., James, S. J., Beland, F. A., Rusyn, I. Strain-dependent dysregulation of one-carbon metabolism in male mice is associated with choline- and folate-deficient diet-induced liver injury. C1 [Pogribny, Igor P.; Kutanzi, Kristy; de Conti, Aline; Tryndyak, Volodymyr; Montgomery, Beverly; Pogribna, Marta; Beland, Frederick A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Muskhelishvili, Levan; Latendresse, John R.] US FDA, Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Melnyk, Stepan; James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. RP Pogribny, IP (reprint author), NCTR, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov RI de Conti, Aline/I-1666-2013; Rusyn, Ivan/S-2426-2016 NR 55 TC 7 Z9 7 U1 0 U2 7 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 JUN PY 2013 VL 27 IS 6 BP 2233 EP 2243 DI 10.1096/fj.12-227116 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 154II UT WOS:000319667600014 PM 23439872 ER PT J AU Sun, W Laughren, TP Zhu, H Hochhaus, G Wang, YN AF Sun, Wan Laughren, Thomas P. Zhu, Hao Hochhaus, Guenther Wang, Yaning TI Development of a placebo effect model combined with a dropout model for bipolar disorder SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE Bipolar disorder; Placebo model; Dropout; Clinical trial simulation ID MAJOR DEPRESSIVE DISORDER; PHARMACODYNAMIC MODEL; EXPLORATORY ANALYSES; STRUCTURAL MODELS; DRUG APPLICATIONS; CLINICAL-TRIALS; EFFICACY DATA; TIME-COURSE; SCHIZOPHRENIA; SIMULATION AB The aim of this study was to develop a placebo model for bipolar disorder to help optimize clinical trial designs for studies targeting manic episodes in bipolar disorder. A bipolar disease database was built based on individual longitudinal data collected from over 3,000 patients in 11 clinical trials for 5 approved bipolar drugs. An empirical placebo effect model with an exponential decay process plus a linear progression process was developed to quantify the time course of the Young Mania Rating Scale total score based on only placebo data from the database. In order to describe the dropout pattern during the trials, a parametric survival model was developed and the Weibull distribution was identified to be the best distribution to describe the data. Based on the likelihood ratio test, it was found that patients with higher baseline score, slower disease improvement and more rapid disease progression tended to dropout earlier, and the trial features such as trial starting year and trial site were also significant covariates for dropout. A combination of the placebo effect model and the dropout model was applied to simulate new clinical trials through Monte-Carlo simulation. Both the placebo effect model and dropout model described the observed data reasonably well based on various diagnostic plots. The joint placebo response and dropout models can serve as a tool to simulate the most likely level of placebo response with the expected dropout pattern to help design a new clinical trial. C1 [Sun, Wan; Wang, Yaning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Laughren, Thomas P.] US FDA, Div Psychiat Prod, Silver Spring, MD 20993 USA. [Zhu, Hao] US FDA, Div Clin Pharmacol, Off Clin Pharmacol 1, Silver Spring, MD 20993 USA. [Hochhaus, Guenther] Univ Florida, Dept Pharmaceut, Gainesville, FL 32610 USA. RP Wang, YN (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yaning.wang@fda.hhs.gov NR 31 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD JUN PY 2013 VL 40 IS 3 SI SI BP 359 EP 368 DI 10.1007/s10928-013-9305-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 150WG UT WOS:000319421600009 PM 23456101 ER PT J AU Calvert, RJ Gupta, M Maciag, A Shiao, YH Anderson, LM AF Calvert, Richard J. Gupta, Meghana Maciag, Anna Shiao, Yih-Horng Anderson, Lucy M. TI K-ras 4A and 4B mRNA levels correlate with superoxide in lung adenocarcinoma cells, while at the protein level, only mutant K-ras 4A protein correlates with superoxide SO LUNG CANCER LA English DT Article DE K-ras 4A; Lung; Adenocarcinoma; Superoxide; Mutant K-ras; Cell lines; siRNA ID DNA-DAMAGE; IONIZING-RADIATION; EXON 4A; CANCER; TRANSFORMATION; EXPRESSION; TISSUES; GROWTH; OXYGEN; LINES AB The K-ras gene is frequently mutated in lung and other cancers. K-ras protein includes two splice variants, K-ras 4A and 4B. While K-ras 4B is more widely expressed, recent evidence implicates K-ras 4A in lung tumorigenesis. We found that K-ras 4A protein has a wide range of expression in a large panel of human lung adenocarcinoma cell lines. In cell lines with mutant K-ras, but not those with wildtype K-ras, the K-ras 4A protein had a strong positive correlation with levels of cellular superoxide. We investigated whether K-ras 4A protein was involved in superoxide production, or alternatively was modulated by elevated superoxide. Experiments with small interfering RNA targeting K-ras 4A did not confirm its role in superoxide generation. However, decreasing cellular superoxide with the scavenger Tiron tended to reduce levels of K-ras 4A protein. K-ras 4A and 4B mRNA were also quantified in a number of NSCLC cell lines. 4A mRNA correlated with 4A protein only in K-ras-mutant cells. K-ras 4A mRNA also correlated with superoxide, but with no difference between cell lines with mutant or wildtype K-ras. K-ras 4B mRNA correlated with 4A mRNA and with superoxide, in both K-ras mutant and wildtype cells. The results are consistent with superoxide directly or indirectly up-regulating expression of all K-ras genes, and also increasing the stability of K-ras 4A mutant protein selectively. Published by Elsevier Ireland Ltd. C1 [Calvert, Richard J.] US FDA, MOD Lab 1, Laurel, MD 20708 USA. [Gupta, Meghana; Shiao, Yih-Horng; Anderson, Lucy M.] Frederick Natl Lab Canc Res, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. [Maciag, Anna] SAIC Frederick Inc, Frederick Natl Lab Canc Res, Basic Sci Program, Frederick, MD 21702 USA. RP Calvert, RJ (reprint author), US FDA, MOD Lab 1, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM richard.calvert@fda.hhs.gov FU National Institutes of Health, National Cancer Institute; National Cancer Institute [HHSN261200800001E] FX We wish to thank Drs. A. Masuda and T. Takahashi for providing the HPL cells on a collaborative basis. The authors also wish to recognize the technical assistance of William T. Calvert. 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. Any opinions, findings, conclusions, or recommendations in this publication are those of the authors and do not necessarily reflect the views of the Department of Health and Human Services. NR 29 TC 2 Z9 2 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER JI Lung Cancer PD JUN PY 2013 VL 80 IS 3 BP 263 EP 269 DI 10.1016/j.lungcan.2013.01.022 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 153XX UT WOS:000319637200005 PM 23474128 ER PT J AU Gubrij, IB Pangle, AK Pang, L Johnson, LG AF Gubrij, Igor B. Pangle, Amanda K. Pang, Li Johnson, Larry G. TI MicroRNAs as Potential Targets for Therapy of Pulmonary Hypertension SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Gubrij, Igor B.; Pangle, Amanda K.; Johnson, Larry G.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. [Gubrij, Igor B.; Johnson, Larry G.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Pang, Li] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 439 BP S169 EP S169 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400438 ER PT J AU Ou, W Li, PJ Reiser, J AF Ou, Wu Li, Pingjuan Reiser, Jakob TI Engineering of Safety Control Switches for Human Induced Pluripotent Stem Cells SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Ou, Wu; Li, Pingjuan; Reiser, Jakob] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 467 BP S179 EP S179 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400466 ER PT J AU Tian, J Xu, ZL Byrnes, AP AF Tian, Jie Xu, Zhili Byrnes, Andrew P. TI Adenovirus Serotypes Differ in Their Susceptibility to Neutralization by Mouse Serum: Role of Coagulation Factor X SO MOLECULAR THERAPY LA English DT Meeting Abstract CT 16th Annual Meeting of the American-Society-of-Gene-and-Cell-Therapy (ASGCT) CY MAY 15-18, 2013 CL Salt Lake City, UT SP Amer Soc Gene & Cell Therapy (ASGCT) C1 [Tian, Jie; Xu, Zhili; Byrnes, Andrew P.] FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2013 VL 21 SU 1 MA 133 BP S54 EP S54 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 156XY UT WOS:000319858400134 ER PT J AU Lumen, A Mattie, DR Fisher, JW AF Lumen, Annie Mattie, David R. Fisher, Jeffrey W. TI Evaluation of Perturbations in Serum Thyroid Hormones During Human Pregnancy Due to Dietary Iodide and Perchlorate Exposure Using a Biologically Based Dose-Response Model SO TOXICOLOGICAL SCIENCES LA English DT Article DE BBDR-HPT axis model; thyroid hormones; perchlorate; iodide; fetus; human pregnancy ID FETAL-BRAIN-DEVELOPMENT; MATERNAL HYPOTHYROXINEMIA; UNITED-STATES; DRINKING-WATER; NEUROPSYCHOLOGICAL DEVELOPMENT; TRIIODOTHYRONINE DISTRIBUTION; CONGENITAL HYPOTHYROIDISM; STIMULATING HORMONE; REFERENCE INTERVALS; THYROXINE TURNOVER AB A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 g/day and an environmentally relevant exposure of perchlorate (similar to 0.1 g/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 g/day, the dose of perchlorate required to reduce maternal fT(4) levels to a hypothyroxinemic state was estimated at 32.2 g/kg/day. As iodide intake was lowered to 75 g/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 g/kg/day for daily iodide intake of 25075 g/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment. C1 [Lumen, Annie] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA. [Lumen, Annie; Fisher, Jeffrey W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Lumen, A (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT 110, Jefferson, AR 72079 USA. EM Annie.Lumen@fda.hhs.gov FU Air Force Center for Engineering & the Environment through the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc.; 711 Human Performance Wing/RHDJ; Food and Drug Administration, National Center for Toxicological Research FX Air Force Center for Engineering & the Environment through the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., and the 711 Human Performance Wing/RHDJ; and the Food and Drug Administration, National Center for Toxicological Research. NR 116 TC 11 Z9 11 U1 3 U2 20 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2013 VL 133 IS 2 BP 320 EP 341 DI 10.1093/toxsci/kft078 PG 22 WC Toxicology SC Toxicology GA 151AA UT WOS:000319431800012 PM 23535361 ER PT J AU Boudreau, MD AF Boudreau, Mary D. TI Nondecolorized Qualifier Is a Misnomer for the Aloe Vera Whole Leaf Extract Test Material SO TOXICOLOGICAL SCIENCES LA English DT Letter C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Boudreau, MD (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 110, Jefferson, AR 72079 USA. EM mary.boudreau@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2013 VL 133 IS 2 BP 343 EP 343 DI 10.1093/toxsci/kft073 PG 1 WC Toxicology SC Toxicology GA 151AA UT WOS:000319431800014 PM 23515465 ER PT J AU Andersson, LG Wu, KC Wieslander, B Loring, Z Frank, TF Maynard, C Gerstenblith, G Tomaselli, GF Weiss, RG Wagner, GS Ugander, M Strauss, DG AF Andersson, Linus G. Wu, Katherine C. Wieslander, Bjorn Loring, Zak Frank, Terry F. Maynard, Charles Gerstenblith, Gary Tomaselli, Gordon F. Weiss, Robert G. Wagner, Galen S. Ugander, Martin Strauss, David G. TI Left ventricular mechanical dyssynchrony by cardiac magnetic resonance is greater in patients with strict vs nonstrict electrocardiogram criteria for left bundle-branch block SO AMERICAN HEART JOURNAL LA English DT Article ID INTRAVENTRICULAR-CONDUCTION DISTURBANCES; AMERICAN-HEART-ASSOCIATION; RESYNCHRONIZATION THERAPY; CLINICAL CARDIOLOGY; MYOCARDIAL SCAR; FAILURE; CARDIOMYOPATHY; ACTIVATION; STATEMENT; COMMITTEE AB Background Left bundle-branch block (LBBB) is a marker of increased delay between septal and left ventricular (LV) lateral wall electrical activation and is a predictor of which patients will benefit from cardiac resynchronization therapy. Recent analysis has suggested that one-third of patients meeting the conventional electrocardiogram criteria for LBBB are misdiagnosed, and new strict LBBB criteria have been proposed. We tested the hypothesis that patients with strict LBBB have greater LV mechanical dyssynchrony than do patients meeting the nonstrict LBBB criteria, whereas there is no difference between patients with nonstrict LBBB and LV conduction delay with a QRS duration of 110 to 119 ms. Methods Sixty-four patients referred for primary prevention implantable cardioverter-defibrillators underwent 12-lead electrocardiogram and cardiac magnetic resonance myocardial tagging. The patients were classified as strict LBBB, nonstrict LBBB, or non-LBBB (nonspecific LV conduction delay with a QRS duration of 110-119 ms). The time delay between septal and lateral LV wall peak circumferential strain (septal-to-lateral wall delay) was measured by cardiac magnetic resonance. Results Patients with strict LBBB (n = 31) had a greater septal-to-lateral wall delay compared with patients with nonstrict LBBB (n = 19) (210 +/- 137 ms vs 122 +/- 102 ms, P = .045). There was no significant difference between nonstrict LBBB and non-LBBB (n = 14) septal-to-lateral wall delay (122 +/- 102 ms vs 100 +/- 86 ms, P = .51). Conclusions Strict LBBB criteria identify patients with greater mechanical dyssynchrony compared with patients only meeting the nonstrict LBBB criteria, whereas there was no significant difference between patients with nonstrict LBBB and nonLBBB. The greater observed LV dyssynchrony may explain why patients with strict LBBB have a better response to cardiac resynchronization therapy. C1 [Andersson, Linus G.; Wieslander, Bjorn; Ugander, Martin; Strauss, David G.] Karolinska Inst, Dept Clin Physiol, Cardiac MR Grp, S-10401 Stockholm, Sweden. [Andersson, Linus G.; Wieslander, Bjorn; Ugander, Martin; Strauss, David G.] Karolinska Univ Hosp, Stockholm, Sweden. [Andersson, Linus G.; Wieslander, Bjorn; Wagner, Galen S.] Duke Clin Res Inst, Durham, MD USA. [Wu, Katherine C.; Frank, Terry F.; Gerstenblith, Gary; Tomaselli, Gordon F.; Weiss, Robert G.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Loring, Zak; Strauss, David G.] US FDA, Office Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Loring, Zak] Duke Univ, Sch Med, Durham, NC USA. [Maynard, Charles] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Strauss, DG (reprint author), 10903 New Hampshire Ave,62-1126, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov RI Maynard, Charles/N-3906-2015; OI Maynard, Charles/0000-0002-1644-7814; Ugander, Martin/0000-0003-3665-2038 FU National Heart, Lung, and Blood Institute; National Institutes of Health [HL103812, HL91062, HL61912]; DW Reynolds Foundation; Food and Drug Administration Critical Path Initiative FX The study was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (HL103812 to K.C.W., HL91062 to G.F.T., and HL61912 to R.G.W.), the DW Reynolds Foundation and the Food and Drug Administration Critical Path Initiative. NR 25 TC 15 Z9 17 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2013 VL 165 IS 6 BP 956 EP 963 DI 10.1016/j.ahj.2013.03.013 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 151DD UT WOS:000319439900018 PM 23708167 ER PT J AU Ahmad, H Soldani, F AF Ahmad, H. Soldani, F. TI Risk-benefit & decision analyses of electroconvulsive therapy (ECT) in treatment refractory depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 10th International Conference on Bipolar Disorder of the International-Society-for-Bipolar-Disorders CY JUN 13-16, 2013 CL Miami Beach, FL SP Int Soc Bipolar Disorders DE electroconvulsive therapy; ECT; refractory depression; treatment resistant depression C1 [Ahmad, H.; Soldani, F.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2013 VL 15 SU 1 SI SI BP 102 EP 103 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156MR UT WOS:000319826800234 ER PT J AU Wang, C Liu, F Patterson, TA Paul, MG Slikker, W AF Wang, Cheng Liu, Fang Patterson, Tucker A. Paul, Merle G. Slikker, William, Jr. TI Preclinical Assessment of Ketamine SO CNS NEUROSCIENCE & THERAPEUTICS LA English DT Review DE Antioxidants; Development; Ketamine; Neurodegeneration; Neuroprotection; NMDA receptor; Reactive oxygen species ID DEVELOPING RAT-BRAIN; D-ASPARTATE RECEPTOR; INDUCED APOPTOTIC NEURODEGENERATION; CYTOCHROME-C-OXIDASE; SCHOOL-AGED CHILDREN; OPERANT TEST BATTERY; NEURONAL CELL-DEATH; NMDA RECEPTORS; CARDIOPULMONARY BYPASS; FOREBRAIN CULTURE AB Ketamine is used as a general anesthetic, and recent data suggest that anesthetics can cause neurodegeneration and/or neuroprotection. The precise mechanisms are not completely understood. This review is to examine the work on ketamine and to address how developmental biology may be utilized when combined with biochemical, pathological, and pharmacokinetic assessments to produce a bridging model that may decrease the uncertainty in extrapolating preclinical data to human conditions. Advantages of using preclinical models to study critical issues related to ketamine anesthesia have been described. These include the relationships between ketamine-induced neurotoxicity/protection and the preclinical models/approaches in elucidating mechanisms associated with ketamine exposure. The discussions focus on the following: (1) the doses and time-course over which ketamine is associated with damage to, or protection of, neural cells, (2) how ketamine directs or signals neural cells to undergo apoptosis or necrosis, (3) how such exposures can trigger mitochondrial dysfunction, (4) how antioxidants and knockdowns of specific transcription modulators or receptors affect neurotoxicity induced by ketamine, and (5) whether the potential neural damage can be monitored after ketamine exposure in living animals using positron emission tomography. C1 [Wang, Cheng; Liu, Fang; Patterson, Tucker A.; Paul, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Slikker, William, Jr.] US FDA, Off Director, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, HFT 132, Jefferson, AR 72079 USA. EM Cheng.Wang@fda.hhs.gov NR 78 TC 14 Z9 15 U1 2 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1755-5930 J9 CNS NEUROSCI THER JI CNS Neurosci. Ther. PD JUN PY 2013 VL 19 IS 6 SI SI BP 448 EP 453 DI 10.1111/cns.12079 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 149US UT WOS:000319347500010 PM 23462308 ER PT J AU Zhang, YH Raymick, J Sarkar, S Lahiri, DK Ray, B Holtzman, D Dumas, M Schmued, LC AF Zhang, Yi-Hong Raymick, James Sarkar, Sumit Lahiri, Debomoy K. Ray, Balmiki Holtzman, David Dumas, Melanie Schmued, Larry C. TI Efficacy and Toxicity of Clioquinol Treatment and A-beta(42) Inoculation in the APP/PSI Mouse Model of Alzheimer's Disease SO CURRENT ALZHEIMER RESEARCH LA English DT Article DE Alzheimer's disease; amyloid plaque; transgenic mice; clioquinol; amyloid-beta(42) vaccine; myelinopathy; astrocytes ID AMYLOID PRECURSOR PROTEIN; A-BETA-IMMUNOTHERAPY; MYELO-OPTICO-NEUROPATHY; LOW-DENSITY-LIPOPROTEIN; TRANSGENIC MICE; MICROGLIAL ACTIVATION; ANTIBODY-RESPONSE; NERVOUS-SYSTEM; SENILE PLAQUES; HUMAN CD68 AB Alzheimer's disease (AD), the most common human neurodegenerative disease, is characterized pathologically by numerous deposits of amyloid plaques in the brain. Systemic administration of clioquinol (CQ) and inoculation with amyloid-beta(42) (A beta(42)) vaccines have been demonstrated to significantly inhibit deposits of amyloid in AD brains. However, each of these treatments has also been reported to be neurotoxic. The generation of transgenic mice models of AD has made it possible to study aspects of this disease employing experimental animals. In the present study, we investigated the efficacy and toxicity of CQ and A beta(42) vaccine in a transgenic AD (APP/PS1) mouse model. Our results confirmed that both CQ and A beta(42) vaccine were effective in significantly reducing the deposits of amyloid in the brains of transgenic AD mice. We also report here that systemic CQ induces myelinopathies in the dorsal lateral geniculate nucleus (DLG), which was almost devoid of amyloid plaques and is the primary site of retinal efferent projections via the optic nerve. This is the first report that systemic administration of CQ causes myelinopathies in the central nervous system (CNS) of a transgenic AD mouse model as well as wild-type mice. Inoculation with an A beta(42) vaccine was also found, for the first time, to result in a significant increase in plaque-independent astrocytic hyperplasia in the dorsal part of the lateral septal nucleus (LSD) which was also devoid of plaques, reflecting potential brain inflammatory processes. C1 [Zhang, Yi-Hong; Sarkar, Sumit; Schmued, Larry C.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res NCTR, Jefferson, AR 72079 USA. [Raymick, James] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Lahiri, Debomoy K.; Ray, Balmiki] Indiana Univ Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [Lahiri, Debomoy K.] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. [Holtzman, David] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. RP Schmued, LC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res NCTR, Jefferson, AR 72079 USA. EM larry.schmued@fda.hhs.gov FU FDA/NCTR [E7273]; Alzheimer's Association IIRG; National Institutes of Health [AG18379, AG1888,4] FX The contents of this manuscript do not necessarily reflect the views and policies of the U.S. Food and Drug Administration, nor does the mention of trade names or commercial products constitute endorsement or a recommendation for use. This work was supported by FDA/NCTR protocol E7273, and in part by an appointment (YZ) to the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. It was also partly supported by Alzheimer's Association IIRG, and National Institutes of Health grants, AG18379 and AG1888,4 to DKL. NR 81 TC 9 Z9 11 U1 0 U2 16 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD JUN PY 2013 VL 10 IS 5 BP 494 EP 506 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 147TS UT WOS:000319190900005 PM 23627708 ER PT J AU Allen, CE Burgos, JM Schmitt, MP AF Allen, Courtni E. Burgos, Jonathan M. Schmitt, Michael P. TI Analysis of Novel Iron-Regulated, Surface-Anchored Hemin-Binding Proteins in Corynebacterium diphtheriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCUS; STAPHYLOCOCCUS-AUREUS; TRANSPORT-SYSTEM; BROAD-SPECTRUM; DTXR; ACQUISITION; TOXIN; SIDEROPHORE; HEMOGLOBIN; GENE AB Corynebacterium diphtheriae utilizes hemin and hemoglobin (Hb) as iron sources during growth in iron-depleted environments, and recent studies have shown that the surface-exposed HtaA protein binds both hemin and Hb and also contributes to the utilization of hemin iron. Conserved (CR) domains within HtaA and in the associated hemin-binding protein, HtaB, are required for the ability to bind hemin and Hb. In this study, we identified and characterized two novel genetic loci in C. diphtheriae that encode factors that bind hemin and Hb. Both genetic systems contain two-gene operons that are transcriptionally regulated by DtxR and iron. The gene products of these operons are ChtA-ChtB and ChtC-CirA (previously DIP0522-DIP0523). The chtA and chtB genes are carried on a putative composite transposon associated with C. diphtheriae isolates that dominated the diphtheria outbreak in the former Soviet Union in the 1990s. ChtA and ChtC each contain a single N-terminal CR domain and exhibit significant sequence similarity to each other but only limited similarity with HtaA. The chtB and htaB gene products exhibited a high level of sequence similarity throughout their sequences, and both proteins contain a single CR domain. Whole-cell binding studies as well as protease analysis indicated that all four of the proteins encoded by these two operons are surface exposed, which is consistent with the presence of a transmembrane segment in their C-terminal regions. ChtA, ChtB, and ChtC are able to bind hemin and Hb, with ChtA showing the highest affinity. Site-directed mutagenesis showed that specific tyrosine residues within the ChtA CR domain were critical for hemin and Hb binding. Hemin iron utilization assays using various C. diphtheriae mutants indicate that deletion of the chtA-chtB region and the chtC gene has no affect on the ability of C. diphtheriae to use hemin or Hb as iron sources; however, a chtB htaB double mutant exhibits a significant decrease in hemin iron use, indicating a role in hemin transport for HtaB and ChtB. C1 [Allen, Courtni E.; Burgos, Jonathan M.; Schmitt, Michael P.] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Schmitt, MP (reprint author), US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM michael.schmitt@fda.hhs.gov FU Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by the intramural research program at the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 40 TC 9 Z9 9 U1 3 U2 12 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2013 VL 195 IS 12 BP 2852 EP 2863 DI 10.1128/JB.00244-13 PG 12 WC Microbiology SC Microbiology GA 151HG UT WOS:000319450700015 PM 23585541 ER PT J AU Glenn, LM Lindsey, RL Folster, JP Pecic, G Boerlin, P Gilmour, MW Harbottle, H Zhao, SH McDermott, PF Fedorka-Cray, PJ Frye, JG AF Glenn, LaShanda M. Lindsey, Rebecca L. Folster, Jason P. Pecic, Gary Boerlin, Patrick Gilmour, Mathew W. Harbottle, Heather Zhao, Shaohua McDermott, Patrick F. Fedorka-Cray, Paula J. Frye, Jonathan G. TI Antimicrobial Resistance Genes in Multidrug-Resistant Salmonella enterica Isolated from Animals, Retail Meats, and Humans in the United States and Canada SO MICROBIAL DRUG RESISTANCE LA English DT Article ID PATHOGENIC ESCHERICHIA-COLI; SEROVAR TYPHIMURIUM; FOOD ANIMALS; PLASMIDS; MICROARRAY; STRAINS; SEQUENCE; IDENTIFICATION; POPULATIONS; HEIDELBERG AB Salmonella enterica is a prevalent foodborne pathogen that can carry multidrug resistance (MDR) and pose a threat to human health. Identifying the genetics associated with MDR in Salmonella isolated from animals, foods, and humans can help determine sources of MDR in food animals and their impact on humans. S. enterica serovars most frequently carrying MDR from healthy animals, retail meats, and human infections in the United States and Canada were identified and isolates resistant to the largest number of antimicrobials were chosen. Isolates were from U. S. slaughter (n = 12), retail (9), and humans (9), and Canadian slaughter (9), retail (9), and humans (8; total n = 56). These isolates were assayed by microarray for antimicrobial resistance and MDR plasmid genes. Genes detected encoded resistance to aminoglycosides (alleles of aac, aad, aph, strA/B); betalactams (blaTEM, blaCMY, blaPSE-1); chloramphenicol (cat, flo, cmlA); sulfamethoxazole (sulI); tetracycline (tet(A, B, C, D) and tetR); and trimethoprim (dfrA). Hybridization with IncA/C plasmid gene probes indicated that 27/56 isolates carried one of these plasmids; however, they differed in several variable regions. Cluster analysis based on genes detected separated most of the isolates into two groups, one with IncA/C plasmids and one without IncA/C plasmids. Other plasmid replicons were detected in all but one isolate, and included I1 (25/56), N (23/56), and FIB (10/56). The presence of different mobile elements along with similar resistance genes suggest that these genetic elements may acquire similar resistance cassettes, and serve as multiple sources for MDR in Salmonella from food animals, retail meats, and human infections. C1 [Glenn, LaShanda M.; Lindsey, Rebecca L.; Fedorka-Cray, Paula J.; Frye, Jonathan G.] USDA, Bacterial Epidemiol & Antimicrobial Resistance Re, Richard B Russell Res Ctr, ARS, Athens, GA 30605 USA. [Folster, Jason P.; Pecic, Gary] Ctr Dis Control & Prevent, Atlanta, GA USA. [Boerlin, Patrick] Ontario Vet Coll, Guelph, ON, Canada. [Gilmour, Mathew W.] Publ Hlth Agcy Canada, Winnipeg, MB, Canada. [Harbottle, Heather; Zhao, Shaohua; McDermott, Patrick F.] US FDA, Ctr Vet Med, Laurel, MD USA. RP Frye, JG (reprint author), USDA, Bacterial Epidemiol & Antimicrobial Resistance Re, Richard B Russell Res Ctr, ARS, 950 Coll Stn Rd, Athens, GA 30605 USA. EM jonathan.frye@ars.usda.gov RI Frye, Jonathan/I-6382-2013 OI Frye, Jonathan/0000-0002-8500-3395 FU USDA [6612-32000-006-00] FX The authors thank Jennifer Turpin, Georgina Hidalgo, Jovita Haro, Benny Barrett, and Takiyah Ball at USDA for technical assistance. From CDC we thank Jean Whichard for helpful conversations and editing the manuscript. From CIPARS we thank Lucie Dutil for isolate selection, and Laura Martin and Emily Weir for DNA isolation. We would also like to dedicate this article in memory of our colleague, Lucie Dutil, whom we had the privilege to know and work with through NARMS and CIPARS collaborations. This work was supported by USDA project number 6612-32000-006-00. NR 43 TC 14 Z9 14 U1 3 U2 25 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist. PD JUN PY 2013 VL 19 IS 3 BP 175 EP 184 DI 10.1089/mdr.2012.0177 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 150OG UT WOS:000319399900004 PM 23350745 ER PT J AU Sjolund-Karlsson, M Howie, RL Blickenstaff, K Boerlin, P Ball, T Chalmers, G Duval, B Haro, J Rickert, R Zhao, SH Fedorka-Cray, PJ Whichard, JM AF Sjolund-Karlsson, Maria Howie, Rebecca L. Blickenstaff, Karen Boerlin, Patrick Ball, Takiyah Chalmers, Gabhan Duval, Brea Haro, Jovita Rickert, Regan Zhao, Shaohua Fedorka-Cray, Paula J. Whichard, Jean M. TI Occurrence of beta-Lactamase Genes Among Non-Typhi Salmonella enterica Isolated from Humans, Food Animals, and Retail Meats in the United States and Canada SO MICROBIAL DRUG RESISTANCE LA English DT Article ID CEFTRIAXONE-RESISTANT SALMONELLA; EXTENDED-SPECTRUM CEPHALOSPORINS; MULTIDRUG-RESISTANT; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; SEROTYPE; CMY-2; PREVALENCE; EMERGENCE; INFECTION AB Non-Typhi Salmonella cause over 1.7 million cases of gastroenteritis in North America each year, and food-animal products are commonly implicated in human infections. For invasive infections, antimicrobial therapy is indicated. In North America, the antimicrobial susceptibility of Salmonella is monitored by the U. S. National Antimicrobial Resistance Monitoring System (NARMS) and The Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS). In this study, we determined the susceptibility to cephalosporins by broth microdilution among 5,041 non-Typhi Salmonella enterica isolated from food animals, retail meats, and humans. In the United States, 109 (4.6%) of isolates collected from humans, 77 (15.7%) from retail meat, and 140 (10.6%) from food animals displayed decreased susceptibility to cephalosporins (DSC). Among the Canadian retail meat and food animal isolates, 52 (13.0%) and 42 (9.4%) displayed DSC. All isolates displaying DSC were screened for beta-lactamase genes (bla(TEM), bla(SHV), bla(CMY), bla(CTX-M), and bla(OXA-1)) by polymerase chain reaction. At least one beta-lactamase gene was detected in 74/109 (67.9%) isolates collected from humans, and the blaCMY genes were most prevalent (69/109; 63.3%). Similarly, the blaCMY genes predominated among the beta-lactamase-producing isolates collected from retail meats and food animals. Three isolates from humans harbored a bla(CTX-M-15) gene. No animal or retail meat isolates harbored a bla(CTX-M) or bla(OXA-1) gene. A bla(TEM) gene was found in 5 human, 9 retail meat, and 17 animal isolates. Although serotype distributions varied among human, retail meat, and animal sources, overlap in bla(CMY)-positive serotypes across sample sources supports meat and food-animal sources as reservoirs for human infection. C1 [Sjolund-Karlsson, Maria; Rickert, Regan; Whichard, Jean M.] Ctr Dis Control & Prevent, Natl Antimicrobial Resistance Monitoring Syst, Atlanta, GA 30329 USA. [Howie, Rebecca L.] IHRC Inc, Atlanta, GA USA. [Blickenstaff, Karen; Zhao, Shaohua] US FDA, Laurel, MD USA. [Boerlin, Patrick; Chalmers, Gabhan] Ontario Vet Coll, Guelph, ON, Canada. [Ball, Takiyah; Duval, Brea; Haro, Jovita; Fedorka-Cray, Paula J.] USDA, Athens, GA USA. RP Sjolund-Karlsson, M (reprint author), Ctr Dis Control & Prevent, Natl Antimicrobial Resistance Monitoring Syst, OID NCEZID DFWED EDLB, 1600 Clifton Rd,Mail Stop G29, Atlanta, GA 30329 USA. EM fwt4@cdc.gov FU CDC; FDA-CVM; Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, Ontario, Canada FX We thank the NARMS-participating public health laboratories, the Retail Foods Survey Working Group, and the FSIS laboratories for submitting the isolates. We also thank the CO, MO, and NY Divisions of Public Health for providing patient interviews. This work was supported by an interagency agreement between CDC and FDA-CVM. Regarding CIPARS abattoir isolates, we thank the abattoir industry personnel and the Canadian Food Inspection Agency regional directors, inspection managers, and onsite staff for their extensive voluntary participation. The CIPARS farm surveillance component thanks all participating veterinarians and producers, the CIPARS Farm Swine Surveillance Advisory Committee as well as Agriculture and Agri-Food Canada, the provincial ministries of agriculture in BC, SK, AB, and QC, and the USDA, CAHFSE Program. The CIPARS retail component thanks the field technicians as well as the University of Prince Edward Island. Lastly, CIPARS thanks all laboratory technicians and data management staff for their contributions to the overall program. The molecular characterization of Canadian isolates was financially supported by the Laboratory for Foodborne Zoonoses, Public Health Agency of Canada, Guelph, Ontario, Canada. NR 52 TC 8 Z9 8 U1 0 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist. PD JUN PY 2013 VL 19 IS 3 BP 191 EP 197 DI 10.1089/mdr.2012.0178 PG 7 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 150OG UT WOS:000319399900006 PM 23289438 ER PT J AU Rios, M Anez, G Heisey, D Espina, LM Stramer, SL AF Rios, M. Anez, G. Heisey, D. Espina, L. M. Stramer, S. L. TI MOLECULAR, VIROLOGICAL AND PHYLOGENETIC CHARACTERIZATION OF DENGUE VIRUS TYPES 1 AND 4 INFECTING BLOOD DONORS FROM PUERTO RICO, 2012 SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Rios, M.; Anez, G.; Heisey, D.; Espina, L. M.] US FDA, Bethesda, MD 20014 USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUN PY 2013 VL 105 SU 1 SI SI BP 57 EP 58 PG 2 WC Hematology SC Hematology GA 148FH UT WOS:000319228100146 ER PT J AU Stramer, L Boucher, B Foster, A Krysztof, E Winton, S Merced, L Miller, D Dickson, S Brodsky, P Munoz-Jordan, L Hunsperger, A Lanteri, C Anez, J Heisey, AR Rios, J Cory, E Innen, J AF Stramer, L. Boucher, B. Foster, A. Krysztof, E. Winton, S. Merced, L. Miller, D. Dickson, S. Brodsky, P. Munoz-Jordan, L. Hunsperger, A. Lanteri, C. Anez, J. Heisey, A. R. Rios, J. Cory, E. Innen, J. TI INVESTIGATIONAL DENGUE TESTING YIELDS HIGH RATES OF RNA-POSITIVE DONORS IN PUERTO RICO SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Stramer, L.] Amer Red Cross, Gaithersburg, MD USA. [Boucher, B.; Foster, A.; Krysztof, E.; Winton, S.] Amer Red Cross, Sceintif Support Off, Gaithersburg, MD USA. [Merced, L.] Amer Red Cross Blood Serv, San Juan, PR USA. [Miller, D.] Amer Red Cross, Biomed Serv Testing Support, Charlotte, NC USA. [Dickson, S.] Amer Red Cross, Natl Testing Lab, Charlotte, NC USA. [Brodsky, P.] Quality Analyt Inc, Riverwoods, IL USA. [Munoz-Jordan, L.; Hunsperger, A.] Ctr Dis Control & Prevent, San Juan, PR USA. [Lanteri, C.] Blood Syst Res Inst, San Francisco, CA USA. [Anez, J.; Heisey, A. R.; Rios, J.] US FDA, DETTD, OBRR, CBER, Bethesda, MD 20014 USA. [Cory, E.; Innen, J.] Hologicgen Probe, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUN PY 2013 VL 105 SU 1 SI SI BP 195 EP 195 PG 1 WC Hematology SC Hematology GA 148FH UT WOS:000319228100514 ER PT J AU Anderson, A Gregori, L Asher, DM Piccardo, P Yang, H AF Anderson, A. Gregori, L. Asher, D. M. Piccardo, P. Yang, H. TI RISK ASSESSMENT MODELS FOR VARIANT CREUTZFELDT-JAKOB DISEASE (VCJD) TRANSMISSION VIA RED BLOOD CELLS SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Anderson, A.; Gregori, L.; Asher, D. M.; Piccardo, P.; Yang, H.] US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUN PY 2013 VL 105 SU 1 SI SI BP 197 EP 197 PG 1 WC Hematology SC Hematology GA 148FH UT WOS:000319228100519 ER PT J AU Mintz, P Menis, M McKean, S Izurieta, HS Ovanesov, MV Liang, Y Gondalia, R Warnock, R Johnson, C Worrall, CM MaCurdy, TE Kelman, J AF Mintz, P. Menis, M. McKean, S. Izurieta, H. S. Ovanesov, M., V Liang, Y. Gondalia, R. Warnock, R. Johnson, C. Worrall, C. M. MaCurdy, T. E. Kelman, J. TI THROMBOTIC EVENT OCCURRENCE AMONG THE ELDERLY US MEDICARE BENEFICIARIES TRANSFUSED IN THE INPATIENT SETTING, AS RECORDED IN LARGE ADMINISTRATIVE DATABASES DURING 2007-2011 SO VOX SANGUINIS LA English DT Meeting Abstract C1 [Mintz, P.; Menis, M.; Izurieta, H. S.; Ovanesov, M., V; Liang, Y.] US FDA, Rockville, MD 20857 USA. [McKean, S.; Gondalia, R.; Warnock, R.; Johnson, C.; MaCurdy, T. E.] Acumen LLC, Burlingame, CA USA. [Worrall, C. M.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUN PY 2013 VL 105 SU 1 SI SI BP 275 EP 275 PG 1 WC Hematology SC Hematology GA 148FH UT WOS:000319228100746 ER PT J AU Pogribny, IP Beland, FA AF Pogribny, Igor P. Beland, Frederick A. TI Role of microRNAs in the regulation of drug metabolism and disposition genes in diabetes and liver disease SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE drug metabolism; metabolic syndrome; microRNAs; regulation of gene expression ID FARNESOID X RECEPTOR; ARYL-HYDROCARBON RECEPTOR; BREAST-CANCER CELLS; FATTY-ACID TRANSLOCASE/CD36; NONALCOHOLIC STEATOHEPATITIS; HEPATIC STEATOSIS; INSULIN-RESISTANCE; NUCLEAR RECEPTOR; INCREASED EXPRESSION; CHOLESTEROL EFFLUX AB Introduction: The pathogenesis of diabetes mellitus and nonalcoholic fatty liver disease (NAFLD) is complex, and the underlying molecular mechanisms are only partially understood. Areas covered: This review summarizes current knowledge of the role of microRNAs (miRNAs) in the regulation of drug absorption, distribution, metabolism, and excretion genes in the pathogenesis of diabetes and NAFLD. The literature search was performed using the PubMed database (up to February 2013). Expert opinion: miRNAs play a fundamental role in diabetes and NAFLD. This review focuses on the dysregulation of miRNAs involved in the regulation of drug metabolism and disposition in the pathogenesis of these metabolic syndromes. The evidence presented indicates that better understanding of the underlying molecular mechanisms associated with dysregulation of miRNAs controlling the cellular drug metabolizing system is of great importance not only from a scientific, but also from a clinical perspective. More importantly, an association between these metabolic disorders and miRNA dysregulation suggests that correcting miRNA expression by either their up-regulation or inhibition holds a promise for treating these metabolic syndrome and alleviating disease progression. C1 [Pogribny, Igor P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 140 TC 5 Z9 6 U1 0 U2 24 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD JUN PY 2013 VL 9 IS 6 BP 713 EP 724 DI 10.1517/17425255.2013.783817 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 143QY UT WOS:000318883500004 PM 23565851 ER PT J AU Li, X Li, Y Wang, B Ji, K Liang, ZW Guo, BF Hu, JD Yin, D Du, YW Kopecko, DJ Kalvakolanu, DV Zhao, XJ Xu, DQ Zhang, L AF Li, Xin Li, Yang Wang, Bo Ji, Kun Liang, Zuowen Guo, Baofeng Hu, Jiadi Yin, Di Du, Yanwei Kopecko, Dennis J. Kalvakolanu, Dhananjaya V. Zhao, Xuejian Xu, Deqi Zhang, Ling TI Delivery of the co-expression plasmid pEndo-Si-Stat3 by attenuated Salmonella serovar typhimurium for prostate cancer treatment SO JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY LA English DT Article DE Prostate cancer; Stat3; Endostatin; Attenuated Salmonella typhimurium ID METASTATIC MOUSE MODELS; SMALL INTERFERING RNAS; IN-VIVO; TUMOR-GROWTH; BREAST-CANCER; NUDE-MICE; TARGETED THERAPY; DOWN-REGULATION; GENE-TRANSFER; ENDOSTATIN AB To investigate the therapeutic utility of an attenuated bacterium carrying a plasmid that co-expresses Endostatin, an inhibitor of tumor neovasculogenesis, and a shRNA that targets Stat3 to suppress prostate cancer growth. Plasmid pEndo-Si-Stat3 was constructed and introduced into an attenuated strain of Salmonella enterica serovar typhimurium. The resultant recombinant bacterium was used as a vector to deliver the plasmid to tumor cells growing in vivo. Tumor-associated gene and protein expression changes were measured by using RT-PCR and Western blot analyses. Expression of Endostatin in tumor tissue was detected by ELISA. The presence of vector bacteria in tissues was monitored and tumor destruction was assessed by using TUNEL and H&E staining assays. Bacterially delivered pEndo-Si-Stat3 decreased Stat3 levels and increased Endostatin expression in mouse tumors, resulting in a significant suppression of tumor growth (P < 0.01). Expression of Bcl-2 and PCNA was down-regulated and Caspase3 expression was up-regulated to promote apoptosis of tumor cells. Successful delivery by attenuated Salmonella of the combination therapeutic plasmid simultaneously knocked down the expression of Stat3 and resulted in over-expression of Endostatin, which synergistically inhibited prostate cancer growth. C1 [Li, Xin; Li, Yang; Wang, Bo; Ji, Kun; Liang, Zuowen; Guo, Baofeng; Yin, Di; Du, Yanwei; Zhao, Xuejian; Zhang, Ling] Jilin Univ, Dept Pathophysiol, Prostate Dis Prevent & Treatment Res Ctr, Norman Bethune Med Sch, Changchun 130021, Peoples R China. [Hu, Jiadi] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Kalvakolanu, Dhananjaya V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Mol Biol Program,Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Xu, Deqi] New Vaccine Natl Engn Res Ctr, Beijing 100024, Peoples R China. RP Zhang, L (reprint author), Jilin Univ, Dept Pathophysiol, Prostate Dis Prevent & Treatment Res Ctr, Norman Bethune Med Sch, Xinmin St, Changchun 130021, Peoples R China. EM dqxujl@gmail.com; zhangling3@jlu.edu.cn FU National Natural Science Foundation of China [30801354, 30970791, 81201188]; Jilin Provincial Science and Technology Department [20080154]; United States National Institutes of Health [CA105005, CA78282] FX This work was funded by the National Natural Science Foundation of China (No. 30801354, No. 30970791 and No. 81201188) and the Jilin Provincial Science and Technology Department (Nos. 20080154). DVK is supported by the United States National Institutes of Health grants CA105005 and CA78282. NR 46 TC 5 Z9 7 U1 1 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-5216 J9 J CANCER RES CLIN JI J. Cancer Res. Clin. Oncol. PD JUN PY 2013 VL 139 IS 6 BP 971 EP 980 DI 10.1007/s00432-013-1398-0 PG 10 WC Oncology SC Oncology GA 143WM UT WOS:000318899600009 PM 23463096 ER PT J AU Matyi, SA Dupre, JM Johnson, WL Hoyt, PR White, DG Brody, T Odenwald, WF Gustafson, JE AF Matyi, S. A. Dupre, J. M. Johnson, W. L. Hoyt, P. R. White, D. G. Brody, T. Odenwald, W. F. Gustafson, J. E. TI Isolation and characterization of Staphylococcus aureus strains from a Paso del Norte dairy SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE Staphylococcus aureus; methicillin-resistant; mastitis; genomics ID CASSETTE CHROMOSOME MEC; FIELD GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; METHICILLIN-RESISTANT; GENETIC ELEMENT; IN-VIVO; IDENTIFICATION; HOSPITALS; EVOLUTION; HUMANS AB The primary purpose of this study was to determine if methicillin-resistant Staphylococcus aureus (MRSA) strains could be identified in the milk of dairy cattle in a Paso del Norte region dairy of the United States. Using physiological and PCR-based identification schemes, a total of 40 Staph. aureus strains were isolated from 29 raw milk samples of 133 total samples analyzed. Pulsed-field gel electrophoresis after digestion with the SmaI enzyme revealed that the 40 confirmed strains were represented by 5 pulsed-field types, which each contained 3 or more strains. Of 7 hospital strains isolated from cows undergoing antibiotic therapy, 3 demonstrated resistance to 3 or more antimicrobial classes and displayed similar pulsed-field gel electrophoresis patterns. A secondary purpose of this study was to elucidate the evolutionary relationships of strains isolated in this study to genomically characterized Staph. aureus strains. Therefore, Roche 454 GS (Roche Diagnostics Corp., Dallas, TX) pyrosequencing was used to produce draft genome sequences of an MRSA raw milk isolate (H29) and a methicillin-susceptible Staph. aureus (PB32). Analysis using the BLASTn database (http://blast.ncbi.nlm.nih.gov/) demonstrated that the H29 draft genome was highly homologous to the human MRSA strain JH1, yet the beta-lactamase plasmid carried by H29 was different from that carried by JH1. Genomic analysis of H29 also clearly explained the multidrug resistance phenotype of this raw milk isolate. Analysis of the PB32 draft genome (using BLASTn) demonstrated that this raw milk isolate was most related to human MRSA strain 04-02981. Although PB32 is not a MRSA, the PB32 draft genome did reveal the presence of a unique staphylococcal cassette mec (SCCmec) remnant In addition, the PB32 draft genome revealed the presence of a novel bovine staphylococcal pathogenicity island, SaPIbovPB32. This study demonstrates the presence of clones closely related to human and (or) bovine Staph. aureus strains circulating in a dairy herd. C1 [Matyi, S. A.; Dupre, J. M.; Johnson, W. L.; Hoyt, P. R.; Gustafson, J. E.] New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. [Matyi, S. A.; Hoyt, P. R.; Gustafson, J. E.] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. [White, D. G.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Brody, T.; Odenwald, W. F.] NIH, Neural Cell Fate Determinants Sect, Bethesda, MD 20892 USA. RP Gustafson, JE (reprint author), New Mexico State Univ, Dept Biol, Las Cruces, NM 88003 USA. EM john.gustafson@okstate.edu FU NSF [DBI-0821806]; National Institutes of Health [R25 GM07667-30, S06-GM61222-05]; National Institute of General Medical Sciences [8P20GM103451] FX All authors acknowledge the participation of the Roadrunner Genomics Facility at New Mexico State University (NMSU; Las Cruces) and NSF award no. DBI-0821806. All authors also acknowledge prior support from the National Institutes of Health: SC-1GM083882-01 (J. E. Gustafson), R25 GM07667-30 [NMSU Minority Access to Research Careers (MARC) program], S06-GM61222-05 [NMSU Minority Biomedical Research Support-Research Initiative for Scientific Enhancement (MBRS-RISE) program], the National Center for Research Resources (5P20RR016480-12), and the National Institute of General Medical Sciences [8P20GM103451; New Mexico Idea Network of Biomedical Research Excellence (INBRE) program]. NR 48 TC 1 Z9 1 U1 2 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD JUN PY 2013 VL 96 IS 6 BP 3535 EP 3542 DI 10.3168/jds.2013-6590 PG 8 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 145OX UT WOS:000319027600014 PM 23608491 ER PT J AU Self, RL AF Self, Randy L. TI Direct analysis in real time-mass spectrometry (DART-MS) for rapid qualitative screening of toxic glycols in glycerin-containing products SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Direct analysis in real time; Orbitrap; Diethylene glycol; Ethylene glycol; Glycerin ID DIETHYLENE GLYCOL; INTOXICATION; CHILDREN AB In 2007, the United States Food and Drug Administration released guidance recommending testing of glycerin used in regulated consumer products, such as cough syrup preparations, toothpaste, and other pharmaceutical and food products, for the toxic compounds ethylene glycol and diethylene glycol. Regulatory laboratories routinely test glycerin, and products containing glycerin or related compounds for these toxic glycols, using an official gas chromatographic method, to ensure the safety of these products. The current work describes a companion technique to compliment this GC-FID method utilizing Orbitrap mass spectrometry with direct analysis in real time ionization to rapidly screen these samples qualitatively, with results in as little as five seconds, with no sample preparation required. This allows the more time and resource intensive method to be reserved for those rare cases when these compounds are detected, potentially greatly improving laboratory efficiency. The technique was evaluated for qualitative sensitivity and repeatability, and compared against the GC-FID method. The method appears to perform well against these metrics. Published by Elsevier B.V. C1 US FDA, Off Regulatory Affairs, Pacific Reg Lab Northwest, Appl Technol Ctr, Bothell, WA 98021 USA. RP Self, RL (reprint author), US FDA, Off Regulatory Affairs, Pacific Reg Lab Northwest, Appl Technol Ctr, 22201 23rd DR SE, Bothell, WA 98021 USA. EM randy.self@fda.hhs.gov NR 18 TC 9 Z9 9 U1 5 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUN PY 2013 VL 80 BP 155 EP 158 DI 10.1016/j.jpba.2013.02.037 PG 4 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 141TH UT WOS:000318748900019 PM 23584076 ER PT J AU Siddiqui, A Shah, RB Khan, MA AF Siddiqui, Akhtar Shah, Rakhi B. Khan, Mansoor A. TI Oseltamivir phosphate-amberlite (TM) IRP 64 ionic complex for taste masking: Preparation and chemometric evaluation SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE oseltamivir; ionpair complex; taste masking; AmberliteTM; resins; Multivariate Analysis; Principal component Analysis; Complexation; Near Infrared Spectroscopy; FTIR ID FORMULATION DEVELOPMENT; IN-VITRO; ELECTRONIC TONGUE; TANNATE COMPLEXES; BETA-CYCLODEXTRIN; DISSOLUTION; RISPERIDONE; RESIN; IMPROVEMENT; INFLUENZA AB The objective of the present work was to evaluate and characterize a pediatric-friendly formulation of a bitter tasting drug, oseltamivir phosphate (drug). Amberlite IRP64 (resin) was used to make ionic complexes for masking its bitterness. Complexes of four drug-to-resin ratios, 1:1, 1:2, 1:4, and 1:6 (w/w), were prepared and characterized. At buccal pH of 6.8, drugresin complexes of 1:1, 1:2, 1:4, and 1:6 ratios released 42.13%, 23.26%, 4.13%, and 14.94%, respectively, of loaded drug after 20 s. However, at stomach pH of 1.2 (0.1 N HCl), 61.96%, 70.18%, 85.88%, and 91.42% of drug was released from the same complexes in 6 min. Near-infrared (NIR) chemical imaging of the complexes showed homogeneous distribution of drug in the resin. Chemometric partial least squares model using NIR data of the drug showed a high correlation between calibration and predicted data (R2 > 0.998). Overall, these results indicated the complex formation between drug and resin. The pH dependence of drug release from these complexes could minimize drug release in the mouth, whereas immediately releasing it in the stomach. Electronic tongue used to evaluate taste indicated that conductivity taste signals were different from control, suggesting taste masking of the drug. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:18001812, 2013 C1 [Siddiqui, Akhtar; Shah, Rakhi B.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Silver Spring, MD USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, OPS,CDER, Silver Spring, MD USA. EM Mansoor.Khan@fda.hhs.gov FU NIH; Medical Counter Measure initiative; Oak Ridge Institute for Science and Education FX This work was supported by funding from the NIH and the Medical Counter Measure initiative. The authors would like to thank Oak Ridge Institute for Science and Education for supporting postdoctoral research program. The authors would like to thank to colleagues at Division of Product Quality Research for sharing their working experiences on instruments and would also like to thank Dr. David Awotwe-Otoo for conducting SEM studies. NR 33 TC 4 Z9 6 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUN PY 2013 VL 102 IS 6 BP 1800 EP 1812 DI 10.1002/jps.23518 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 146EC UT WOS:000319071200014 PM 23559456 ER PT J AU Guo, J Saylor, DM Glaser, EP Patwardhan, DV AF Guo, Ji Saylor, David M. Glaser, Ethan P. Patwardhan, Dinesh V. TI Impact of artificial plaque composition on drug transport SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE drug transport; drug eluting stents; drug uptake; diffusion coefficient; drug distribution ID PERCUTANEOUS CORONARY INTERVENTION; HUMAN ATHEROSCLEROTIC PLAQUES; CHOLESTERYL ESTERS; RAMAN-SPECTROSCOPY; ELUTING STENTS; FATTY STREAKS; PACLITAXEL; HYDROGELS; DELIVERY; WOMEN AB Drug-eluting stent (DES) implantation is a common treatment for atherosclerosis. The safety and efficacy of these devices will depend on the uptake and distribution of drug into the vessel wall. It is established that the composition of atherosclerotic vessels can vary dramatically with patients' age and gender. However, studies focused on elucidating and quantifying the impact of these variations on important drug transport properties, such as diffusion (D) and partition (k) coefficients, are limited. We have developed an improved tissue mimic or artificial plaque to probe the effect of varying concentrations of plaque constituents on drug transport in vitro. Based on these artificial plaques, we have quantified the impact of gelatin (hydrolyzed collagen) and lipid (cholesterol) concentration on D and k using two model drugs, tetracycline and fluvastatin. We found that for tetracycline, increasing the collagen concentration from 0.025 to 0.100 (w/w) resulted in a fivefold decrease in diffusivity, whereas there was no discernible impact on solubility. Increasing the lipid concentration up to 0.034 (w/w) resulted in only minor changes to transport properties of tetracycline. However, fluvastatin exhibited nearly a fivefold increase in k and 10-fold decrease in D with increased lipid concentration. These results were in reasonable agreement with existing models and exhibited behavior consistent with previous observations on drugs commonly used in DES applications. These observations suggest that variations in the chemical characteristics of atherosclerotic plaque can significantly alter the release rate and distribution of drug following DES implantation. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:19051914, 2013 C1 [Guo, Ji; Saylor, David M.; Patwardhan, Dinesh V.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Glaser, Ethan P.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. RP Guo, J (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM ji.guo@fda.hhs.gov FU FDA Office of Women's Health FX This research was supported by the FDA Office of Women's Health. The authors are indebted Benita J. Dair, Martin K. McDermott, and Nicholas Benetatos (FDA) for their critical review of the manuscript. NR 50 TC 5 Z9 5 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUN PY 2013 VL 102 IS 6 BP 1905 EP 1914 DI 10.1002/jps.23537 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 146EC UT WOS:000319071200023 PM 23568279 ER PT J AU Ju, WT Shen, JL Toro, M Zhao, SH Meng, JH AF Ju, Wenting Shen, Jinling Toro, Magaly Zhao, Shaohua Meng, Jianghong TI Distribution of Pathogenicity Islands OI-122, OI-43/48, and OI-57 and a High-Pathogenicity Island in Shiga Toxin-Producing Escherichia coli SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID GENOMIC ISLAND; ENTEROCYTE EFFACEMENT; CITROBACTER-RODENTIUM; EPITHELIAL-CELLS; IN-VITRO; IDENTIFICATION; STRAINS; LOCUS; SEROPATHOTYPES; UREASE AB Pathogenicity islands (PAIs) play an important role in Shiga toxin-producing Escherichia coli (STEC) pathogenicity. The distribution of PAIs OI-122, OI-43/48, and OI-57 and a high-pathogenicity island (HPI) were determined among 98 STEC strains assigned to seropathotypes (SPTs) A to E. PCR and PCR-restriction fragment length polymorphism assays were used to identify 14 virulence genes that belonged to the four PAIs and to subtype eae and stx genes, respectively. Phylogenetic trees were constructed based on the sequences of pagC among 34 STEC strains and iha among 67 diverse pathogenic E. coli, respectively. Statistical analysis demonstrated that the prevalences of OI-122 (55.82%) and OI-57 (82.35%) were significantly greater in SPTs (i.e., SPTs A, B, and C) that are frequently associated with severe disease than in other SPTs. terC (62.5%) and ureC (62.5%) in OI-43/48 were also significantly more prevalent in SPTs A, B, and C than in SPTs D and E. In addition, OI-122, OI-57, and OI-43/48 and their associated virulence genes (except iha) were found to be primarily associated with eae-positive STEC, whereas HPI occurred independently of the eae presence. The strong association of OI-122, OI-43/48, and OI-57 with eae-positive STEC suggests in part that different pathogenic mechanisms exist between eae-positive and eae-negative STEC strains. Virulence genes in PAIs that are associated with severe diseases can be used as potential markers to aid in identifying highly virulent STEC. C1 [Ju, Wenting; Shen, Jinling; Toro, Magaly; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Shen, Jinling] Northwest A&F Univ, Coll Food Sci & Engn, Yangling, Shaanxi Provinc, Peoples R China. [Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu RI Toro, Magaly/F-6525-2011 OI Toro, Magaly/0000-0002-6280-2215 FU Joint Institute for Food Safety and Applied Nutrition, University of Maryland, College Park, MD FX The study was supported in part by the Joint Institute for Food Safety and Applied Nutrition, University of Maryland, College Park, MD. NR 44 TC 11 Z9 12 U1 0 U2 21 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 2013 VL 79 IS 11 BP 3406 EP 3412 DI 10.1128/AEM.03661-12 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 139UZ UT WOS:000318611800011 PM 23524679 ER PT J AU Colmenares, LU Coelho, S Miller, SA Boomer, KB Beer, JZ AF Colmenares, Leticia U. Coelho, Sergio Miller, Sharon A. Boomer, K. B. Beer, Janusz Z. TI UV responses in Native Hawaiians and Pacific Islanders, and, Asians residing in Hawai'i and in Maryland SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE erythema; pigmentation; race/ethnicity; ultraviolet radiation ID DIFFUSE-REFLECTANCE SPECTROSCOPY; INDUCED DNA-DAMAGE; ULTRAVIOLET-RADIATION; HUMAN SKIN; INDUCED ERYTHEMA; PIGMENTATION; MELANIN; CANCER; APOPTOSIS; COLOR AB Background UV exposure causes a wide range of skin damage including cutaneous melanoma. The mechanisms of cellular and molecular damage, as well as those of erythemal and pigmentation responses to UV exposure, have largely been studied in the White population. Methods This study systematically investigates responses to UV exposure in the Native Hawaiian and Pacific Islander (NHPI) and Asian populations living in Hawai'i (A/HI) as well as in Asians living in Maryland (A/MD). Results Our analyses indicate that the NHPI population is less sensitive to UV exposure than the A/HI population. Comparisons between the two Asian groups suggest that, despite slightly but not statistically different baseline constitutive pigmentation (pre-UV exposure), the A/HI and A/MD had similar UV sensitivity, measured as minimal erythemal dose (MED). However, the A/MD population had higher levels of oxyhemoglobin at doses of 2.0, 2.8 and 4.0 MED. Unexpectedly, the A/MD subjects retained higher levels of pigmentation 2 weeks post-UV exposure. Conclusion This study provides insight into UV responses of the inhabitants of Hawai'i and shows that such responses are statistically significant for relatively small samples of NHPI and for A/HI and A/MD. C1 [Colmenares, Leticia U.] Univ Hawaii Windward, Dept Nat Sci, Kaneohe, HI USA. [Coelho, Sergio; Miller, Sharon A.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Boomer, K. B.] Bucknell Univ, Dept Math, Lewisburg, PA 17837 USA. RP Colmenares, LU (reprint author), 45-720 Keaahala Rd, Kaneohe, HI 96744 USA. EM Leticia@hawaii.edu FU National Institute of Health through BRIN [P20 RR1646703] FX The authors are grateful to the volunteers in this study. We thank Dr Allan Izumi, MD, Professor at the University of Hawai'i John A. Burns School of Medicine, project dermatologist, and Jennifer White and Clinton Nishida for their assistance in the conduct of the clinical study in Hawai'i. This study was funded by the National Institute of Health through BRIN Grant Number P20 RR1646703. NR 37 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD JUN PY 2013 VL 29 IS 3 BP 121 EP 131 DI 10.1111/phpp.12035 PG 11 WC Dermatology SC Dermatology GA 140CV UT WOS:000318632800003 PM 23651272 ER PT J AU Swain, MD Orzechowski, KL Swaim, HL Jones, YL Robl, MG Tinaza, CA Myers, MJ Jhingory, MV Buckely, LE Lancaster, VA Yancy, HF AF Swain, M. D. Orzechowski, K. L. Swaim, H. L. Jones, Y. L. Robl, M. G. Tinaza, C. A. Myers, M. J. Jhingory, M. V. Buckely, L. E. Lancaster, V. A. Yancy, H. F. TI P-gp substrate-induced neurotoxicity in an Abcb1a knock-in/Abcb1b knock-out mouse model with a mutated canine ABCB1 targeted insertion SO RESEARCH IN VETERINARY SCIENCE LA English DT Article DE P-glycoprotein; Collie; ABCB1-1 Delta; Mouse; Moxidectin; Doramectin; Digoxin ID MULTIDRUG-RESISTANCE GENE; BLOOD-BRAIN-BARRIER; IVERMECTIN TOXICITY; DIAGNOSTIC-TEST; MDR1 MUTATION; GLYCOPROTEIN; DOGS; COLLIES; SENSITIVITY; MDR1-1-DELTA AB Certain dog breeds, especially Collies, are observed to exhibit neurotoxicity to avermectin drugs, which are P-glycoprotein (P-gp) substrates. This neurotoxicity is due to an ABCB1 gene mutation (ABCB1-1 Delta) that results in non-functional P-gp expression. A developed Abcb1 a knock-in/Abcb1b knock-out mouse model expressing the ABCB1-1 Delta canine gene was previously reported and mice exhibited sensitivity upon ivermectin administration. Here, model and wild-type mice were administered P-gp substrates doramectin, moxidectin, and digoxin. While knock-in/knock-out mice exhibited ataxia, lethargy and tremor, wild-type mice remained unaffected. In addition, no neurotoxic clinical signs were observed in either mouse type administered domperidone, a P-gp substrate with no reported neurotoxicity in ABCB1-1 Delta Collies. Overall, neurotoxic signs displayed by model mice closely paralleled those observed in ivermectin-sensitive Collies. This model can be used to identify toxic P-gp substrates with altered safety in dog populations and may reduce dog use in safety studies that are part of the drug approval process. Published by Elsevier Ltd. C1 [Swain, M. D.; Orzechowski, K. L.; Swaim, H. L.; Jones, Y. L.; Myers, M. J.; Jhingory, M. V.; Buckely, L. E.; Yancy, H. F.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Robl, M. G.; Tinaza, C. A.] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessments, Laurel, MD 20708 USA. [Lancaster, V. A.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Swain, MD (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM marla.swain@fda.hhs.gov NR 26 TC 2 Z9 3 U1 0 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD JUN PY 2013 VL 94 IS 3 BP 656 EP 661 DI 10.1016/j.rvsc.2012.10.025 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 136RH UT WOS:000318380600049 PM 23186803 ER PT J AU Gieraltowski, L Julian, E Pringle, J Macdonald, K Quilliam, D Marsden-Haug, N Saathoff-Huber, L Von Stein, D Kissler, B Parish, M Elder, D Howard-King, V Besser, J Sodha, S Loharikar, A Dalton, S Williams, I Behravesh, CB AF Gieraltowski, L. Julian, E. Pringle, J. Macdonald, K. Quilliam, D. Marsden-Haug, N. Saathoff-Huber, L. Von Stein, D. Kissler, B. Parish, M. Elder, D. Howard-King, V. Besser, J. Sodha, S. Loharikar, A. Dalton, S. Williams, I. Behravesh, C. Barton TI Nationwide outbreak of Salmonella Montevideo infections associated with contaminated imported black and red pepper: warehouse membership cards provide critical clues to identify the source SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Enteric bacteria; epidemiology; outbreaks; Salmonella ID TYPHIMURIUM; SEROTYPE; CANADA; SALAMI AB In November 2009, we initiated a multistate investigation of Salmonella Montevideo infections with pulsed-field gel electrophoresis pattern JIXX01.0011. We identified 272 cases in 44 states with illness onset dates ranging from 1 July 2009 to 14 April 2010. To help generate hypotheses, warehouse store membership card information was collected to identify products consumed by cases. These records identified 19 ill persons who purchased company A salami products before onset of illness. A case-control study was conducted. Ready-to-eat salami consumption was significantly associated with illness (matched odds ratio 8.5, 95% confidence interval 2.1-75.9). The outbreak strain was isolated from company A salami products from an environmental sample from one manufacturing plant, and sealed containers of black and red pepper at the facility. This outbreak illustrates the importance of using membership card information to assist in identifying suspect vehicles, the potential for spices to contaminate ready-to-eat products, and preventing raw ingredient contamination of these products. C1 [Gieraltowski, L.; Loharikar, A.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Epidem Intelligence Serv, Atlanta, GA USA. [Julian, E.; Quilliam, D.] Rhode Isl Dept Hlth, Providence, RI 02908 USA. [Pringle, J.; Besser, J.; Sodha, S.; Dalton, S.; Williams, I.; Behravesh, C. Barton] Ctr Dis Control & Prevent, Atlanta, GA USA. [Macdonald, K.; Marsden-Haug, N.] Washington State Dept Hlth, Olympia, WA USA. [Saathoff-Huber, L.] Illinois Dept Publ Hlth, Springfield, IL 62761 USA. [Von Stein, D.] Iowa Dept Hlth, De Moines, IA USA. [Kissler, B.] US Food Safety & Inspect Serv, USDA, Atlanta, GA USA. [Parish, M.; Elder, D.; Howard-King, V.] US FDA, Rockville, MD 20857 USA. RP Gieraltowski, L (reprint author), 1600 Clifton Rd NE,MS A38, Atlanta, GA 30329 USA. EM lax2@cdc.gov NR 23 TC 18 Z9 18 U1 1 U2 21 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 2013 VL 141 IS 6 BP 1244 EP 1252 DI 10.1017/S0950268812001859 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 135SS UT WOS:000318309400014 PM 23200262 ER PT J AU Choi, SS Kim, JS Valerio, LG Sadrieh, N AF Choi, Sydney S. Kim, Jae S. Valerio, Luis G., Jr. Sadrieh, Nakissa TI In silico modeling to predict drug-induced phospholipidosis SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Phospholipidosis; Drug safety; In silico toxicology ID AMPHIPHILIC DRUGS; CLASSIFICATION; CONSTRUCTION; HEPATOCYTES; INDUCTION; AGREEMENT; RAT AB Drug-induced phospholipidosis (DIPL) is a preclinical finding during pharmaceutical drug development that has implications on the course of drug development and regulatory safety review. A principal characteristic of drugs inducing DIPL is known to be a cationic amphiphilic structure. This provides evidence for a structure-based explanation and opportunity to analyze properties and structures of drugs with the histopathologic findings for DIPL. In previous work from the FDA, in silico quantitative structure-activity relationship (QSAR) modeling using machine learning approaches has shown promise with a large dataset of drugs but included unconfirmed data as well. In this study, we report the construction and validation of a battery of complementary in silico QSAR models using the FDA's updated database on phospholipidosis, new algorithms and predictive technologies, and in particular, we address high performance with a high-confidence dataset The results of our modeling for DIPL include rigorous external validation tests showing 80-81% concordance. Furthermore, the predictive performance characteristics include models with high sensitivity and specificity, in most cases above >= 80% leading to desired high negative and positive predictivity. These models are intended to be utilized for regulatory toxicology applied science needs in screening new drugs for DIPL. Published by Elsevier Inc. C1 [Choi, Sydney S.; Kim, Jae S.; Valerio, Luis G., Jr.; Sadrieh, Nakissa] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak 51 Room 4128,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM luis.valerio@fda.hhs.gov FU ORISE Research Participation Program at the Center for Drug Evaluation and Research (CDER) FX The authors thank Dr. James Willard for his review and useful suggestions on the manuscript and also thank Esther Kim, Amabel Orogo and Dena Rad for their contribution to the DIPL database. This project was supported in part by an appointment to the ORISE Research Participation Program at the Center for Drug Evaluation and Research (CDER) administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER. NR 33 TC 13 Z9 13 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 1 PY 2013 VL 269 IS 2 BP 195 EP 204 DI 10.1016/j.taap.2013.03.010 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 139LF UT WOS:000318583500013 PM 23541745 ER PT J AU Loring, Z Canos, DA Selzman, K Herz, ND Silverman, H MaCurdy, TE Worrall, CM Kelman, J Ritchey, ME Pina, IL Strauss, DG AF Loring, Zak Canos, Daniel A. Selzman, Kimberly Herz, Naomi D. Silverman, Henry MaCurdy, Thomas E. Worrall, Christopher M. Kelman, Jeffrey Ritchey, Mary E. Pina, Ileana L. Strauss, David G. TI Left Bundle Branch Block Predicts Better Survival in Women Than Men Receiving Cardiac Resynchronization Therapy Long-Term Follow-Up of similar to 145,000 Patients SO JACC-HEART FAILURE LA English DT Article DE cardiac resynchronization therapy; left bundle branch block; sex AB Objectives The goal of this study was to test the hypothesis that in recipients of cardiac resynchronization therapy defibrillators (CRT-D), conventional left bundle branch block (LBBB) diagnosis predicts better survival in women than in men. Background New York Heart Association class I and II patients without LBBB do not benefit from CRT-D, and women have better survival after CRT-D than men. Separate analysis suggests that QRS duration thresholds for LBBB diagnosis differ according to sex, and conventional LBBB electrocardiographic criteria are falsely positive in men more frequently than in women. Methods We analyzed Medicare records from 144,642 CRT-D recipients between 2002 and 2008 that were followed up for up to 90 months. Medicare billing data were used to determine age, sex, race, and comorbidities. Hazard ratios (HRs) were calculated to assess if conventional LBBB diagnosis had different prognostic significance according to sex. Results In univariate analysis, LBBB was associated with a 31% reduction in death in women (HR: 0.69 [95% confidence interval (CI): 0.67 to 0.71]) but only a 16% reduction in death in men (HR: 0.84 [95% CI: 0.82 to 0.85]). In multivariable analyses controlling for comorbidities, LBBB was associated with a 26% reduction in death in women (HR: 0.74 [95% CI: 0.71 to 0.77]) and a 15% reduction in death in men (HR: 0.85 [95% CI: 0.83 to 0.87]). A significant interaction (p < 0.0001) between sex and LBBB was seen. Conclusions LBBB diagnosis is associated with greater survival in women than in men receiving CRT-D, and this discrepancy is not explained by differences in measured comorbidities. Possible explanations for this difference include that LBBB may have different prognostic significance according to sex or that LBBB diagnosis is more often false-positive in men compared with women. (c) 2013 by the American College of Cardiology Foundation C1 [Loring, Zak; Canos, Daniel A.; Selzman, Kimberly; Herz, Naomi D.; Ritchey, Mary E.; Pina, Ileana L.; Strauss, David G.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Loring, Zak] Duke Univ, Sch Med, Durham, NC USA. [Selzman, Kimberly] Univ Utah, Dept Internal Med, Sch Med, Div Cardiol, Salt Lake City, UT 84112 USA. [Silverman, Henry; MaCurdy, Thomas E.] Acumen LLC, SafeRx, Burlingame, CA USA. [Worrall, Christopher M.; Kelman, Jeffrey] Ctr Med Serv, Baltimore, MD USA. [Worrall, Christopher M.; Kelman, Jeffrey] Ctr Medicaid Serv, Baltimore, MD USA. [Pina, Ileana L.] Albert Einstein Coll Med, Div Cardiol, Bronx, NY 10467 USA. RP Strauss, DG (reprint author), Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO 62-1126, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov NR 29 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 2213-1779 EI 2213-1787 J9 JACC-HEART FAIL JI JACC-Heart Fail. PD JUN PY 2013 VL 1 IS 3 BP 237 EP 244 DI 10.1016/j.jchf.2013.03.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA V41GU UT WOS:000209535500009 PM 24621876 ER PT J AU Giger, M Toledano, A Myers, K Jiang, Y AF Giger, M. Toledano, A. Myers, K. Jiang, Y. TI Past, Present and Future Roles of ROC Analysis in Medical Imaging and Quantitative Image Analysis SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 [Giger, M.; Jiang, Y.] Univ Chicago, Chicago, IL 60637 USA. [Toledano, A.] Biostat Consulting, Kensington, MD USA. [Myers, K.] US FDA, Off Sci & Engn Labs, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 JUN PY 2013 VL 40 IS 6 DI 10.1118/1.4815603 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI4QM UT WOS:000336849900013 ER PT J AU Sharma, D Badano, A AF Sharma, D. Badano, A. TI DQE of CsI Microcolumnar X-Ray Detectors Using Hybridmantis and Lubberts & apos; Formulation SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 [Sharma, D.; Badano, A.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 JUN PY 2013 VL 40 IS 6 DI 10.1118/1.4815662 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA AI4QM UT WOS:000336849900078 ER PT J AU Mollan, TL Alayash, AI AF Mollan, Todd L. Alayash, Abdu I. TI Redox Reactions of Hemoglobin: Mechanisms of Toxicity and Control SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID MYOGLOBIN; HEME AB In the last several years, significant work has been done studying hemoglobin (Hb) oxidative reactions and clearance mechanisms using both in vitro and in vivo model systems. One active research area involves the study of molecular chaperones and other proteins that are thought to mitigate the toxicity of acellular Hb. For example, the plasma protein haptoglobin (Hp) and the pre-erythroid protein alpha-hemoglobin-stabilizing protein (AHSP) bind to acellular Hb and alpha-subunits of Hb, respectively, to reduce these adverse effects. Moreover, there has been significant work studying hemopexin and alpha-1 microglobulin, both of which are thought to be involved with hemin degradation. These studies have coincided with the timely publication of the first crystal structure of the Hb-Hp complex. In constructing this Forum, we have invited a number of researchers in the area of Hb and myoglobin (Mb) redox biochemistry, as well as those who have contributed fundamentally to our knowledge of Hp function. Our goal has been to update this critically important research area, because we believe that it will ultimately impact the practice of transfusion medicine in a number of important ways. Antioxid. Redox Signal. 18, 2251-2253. C1 [Mollan, Todd L.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, NIH Bldg 29,Rm 112 8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU NHLBI NIH HHS [HL110900, P01 HL110900] NR 14 TC 7 Z9 7 U1 0 U2 19 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2013 VL 18 IS 17 BP 2251 EP 2253 DI 10.1089/ars.2013.5195 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 133QF UT WOS:000318153400002 PM 23330885 ER PT J AU Cooper, CE Schaer, DJ Buehler, PW Wilson, MT Reeder, BJ Silkstone, G Svistunenko, DA Bulow, L Alayash, AI AF Cooper, Chris E. Schaer, Dominik J. Buehler, Paul W. Wilson, Michael T. Reeder, Brandon J. Silkstone, Gary Svistunenko, Dimitri A. Bulow, Leif Alayash, Abdu I. TI Haptoglobin Binding Stabilizes Hemoglobin Ferryl Iron and the Globin Radical on Tyrosine beta 145 SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID HYDROGEN-PEROXIDE; MASS-SPECTROMETRY; ELECTRON-TRANSFER; HEME; COMPLEX; OXIDATION; PROTEINS; OXYGEN; SITE; IDENTIFICATION AB Aim: Hemoglobin (Hb) becomes toxic when released from the erythrocyte. The acute phase protein haptoglobin (Hp) binds avidly to Hb and decreases oxidative damage to Hb itself and to the surrounding proteins and lipids. However, the molecular mechanism underpinning Hp protection is to date unclear. The aim of this study was to use electron paramagnetic resonance (EPR) spectroscopy, stopped flow optical spectrophotometry, and site-directed mutagenesis to explore the mechanism and specifically the role of specific tyrosine residues in this protection. Results: Following peroxide challenge Hb produces reactive oxidative intermediates in the form of ferryl heme and globin free radicals. Hp binding increases the steady state level of ferryl formation during Hb-catalyzed lipid peroxidation, while at the same time dramatically inhibiting the overall reaction rate. This enhanced ferryl stability is also seen in the absence of lipids and in the presence of external reductants. Hp binding is not accompanied by a decrease in the pK of ferryl protonation; the protonated ferryl species still forms, but is intrinsically less reactive. Ferryl stabilization is accompanied by a significant increase in the concentration of the peroxide-induced tyrosine free radical. EPR spectral parameters and mutagenesis studies suggest that this radical is located on tyrosine 145, the penultimate C-terminal amino acid on the beta Hb subunit. Innovation: Hp binding decreases both the ferryl iron and free radical reactivity of Hb. Conclusion: Hp protects against Hb-induced damage in the vasculature, not by preventing the primary reactivity of heme oxidants, but by rendering the resultant protein products less damaging. Antioxid. Redox Signal. 18, 2264-2273. C1 [Cooper, Chris E.; Wilson, Michael T.; Reeder, Brandon J.; Silkstone, Gary; Svistunenko, Dimitri A.] Univ Essex, Sch Biol Sci, Colchester CO4 3SQ, Essex, England. [Schaer, Dominik J.] Univ Zurich Hosp, Dept Internal Med, Zurich, Switzerland. [Buehler, Paul W.; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Bulow, Leif] Lund Univ, Dept Pure & Appl Biochem, Lund, Sweden. RP Cooper, CE (reprint author), Univ Essex, Sch Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM ccooper@essex.ac.uk OI Cooper, Chris/0000-0003-0381-3990 FU UK Biotechnology and Biological Sciences Research Council [BBSRC BB/F007663/1, BB/FOF/209]; Swiss National Science Foundation [31-120658] FX The authors thank Kristian Kallberg and Khuanpiroon Ratanasopa (Lund University) for assistance with the mutagenesis and purification of proteins. The authors would like to thank the UK Biotechnology and Biological Sciences Research Council (BBSRC BB/F007663/1 and BB/FOF/209) and the Swiss National Science Foundation (Grant 31-120658) for financial support. P.W.B. and A.I.A. acknowledge CBER's Critical Path Funding. NR 45 TC 17 Z9 17 U1 2 U2 19 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2013 VL 18 IS 17 BP 2264 EP 2273 DI 10.1089/ars.2012.4547 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 133QF UT WOS:000318153400004 PM 22702311 ER PT J AU Bonaventura, C Henkens, R Alayash, AI Banerjee, S Crumbliss, AL AF Bonaventura, Celia Henkens, Robert Alayash, Abdu I. Banerjee, Sambuddha Crumbliss, Alvin L. TI Molecular Controls of the Oxygenation and Redox Reactions of Hemoglobin SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID SICKLE-CELL-DISEASE; NITRITE REDUCTASE-ACTIVITY; ROOT EFFECT HEMOGLOBINS; FREE-RADICAL REACTIONS; HEME-PROTEINS; S-NITROSOHEMOGLOBIN; BLOOD SUBSTITUTES; OXIDATIVE STRESS; SPECTROELECTROCHEMICAL METHOD; NITROSATIVE STRESS AB Significance: The broad classes of O-2-binding proteins known as hemoglobins (Hbs) carry out oxygenation and redox functions that allow organisms with significantly different physiological demands to exist in a wide range of environments. This is aided by allosteric controls that modulate the protein's redox reactions as well as its O-2-binding functions. Recent Advances: The controls of Hb's redox reactions can differ appreciably from the molecular controls for Hb oxygenation and come into play in elegant mechanisms for dealing with nitrosative stress, in the malarial resistance conferred by sickle cell Hb, and in the as-yet unsuccessful designs for safe and effective blood substitutes. Critical Issues: An important basic principle in consideration of Hb's redox reactions is the distinction between kinetic and thermodynamic reaction control. Clarification of these modes of control is critical to gaining an increased understanding of Hb-mediated oxidative processes and oxidative toxicity in vivo. Future Directions: This review addresses emerging concepts and some unresolved questions regarding the interplay between the oxygenation and oxidation reactions of structurally diverse Hbs, both within red blood cells and under acellular conditions. Developing methods that control Hb-mediated oxidative toxicity will be critical to the future development of Hb-based blood substitutes. Antioxid. Redox Signal. 18, 2298-2313. C1 [Bonaventura, Celia; Henkens, Robert] Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. [Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Banerjee, Sambuddha; Crumbliss, Alvin L.] Duke Univ, Dept Chem, Durham, NC 27706 USA. RP Bonaventura, C (reprint author), Duke Univ, Marine Lab, Nicholas Sch Environm, Beaufort, NC 28516 USA. EM bona@duke.edu FU National Science Foundation [CHE 0809466]; Duke University FX A.L.C. thanks the National Science Foundation (CHE 0809466) and Duke University for financial support and the hospitality of the Santa Fe Institute during the period when this review was written. NR 127 TC 10 Z9 11 U1 2 U2 36 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2013 VL 18 IS 17 BP 2298 EP 2313 DI 10.1089/ars.2012.4947 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 133QF UT WOS:000318153400007 PM 23198874 ER PT J AU Varnado, CL Mollan, TL Birukou, I Smith, BJZ Henderson, DP Olson, JS AF Varnado, Cornelius L. Mollan, Todd L. Birukou, Ivan Smith, Bryan J. Z. Henderson, Douglas P. Olson, John S. TI Development of Recombinant Hemoglobin-Based Oxygen Carriers SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID FUNCTIONAL HUMAN-HEMOGLOBIN; SEQUENCE-SPECIFIC PROTEOLYSIS; ESCHERICHIA-COLI BL21(DE3); INTESTINAL BLOOD-FLOW; HUMAN NORMAL ADULT; TRANSGENIC SWINE; ALPHA-HEMOGLOBIN; SACCHAROMYCES-CEREVISIAE; HEMORRHAGIC-SHOCK; NITRIC-OXIDE AB Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli. The physiological suitability of this material can be enhanced using protein-engineering strategies to address specific efficacy and toxicity issues. Mutagenesis of Hb can (i) adjust dioxygen affinity over a 100-fold range, (ii) reduce nitric oxide (NO) scavenging over 30-fold without compromising dioxygen binding, (iii) slow the rate of autooxidation, (iv) slow the rate of hemin loss, (v) impede subunit dissociation, and (vi) diminish irreversible subunit denaturation. Recombinant Hb production is potentially unlimited and readily subjected to current good manufacturing practices, but may be restricted by cost. Acellular Hb-based O-2 carriers have superior shelf-life compared to red blood cells, are universally compatible, and provide an alternative for patients for whom no other alternative blood products are available or acceptable. Critical Issues: Remaining objectives include increasing Hb stability, mitigating iron-catalyzed and iron-centered oxidative reactivity, lowering the rate of hemin loss, and lowering the costs of expression and purification. Although many mutations and chemical modifications have been proposed to address these issues, the precise ensemble of mutations has not yet been identified. Future Directions: Future studies are aimed at selecting various combinations of mutations that can reduce NO scavenging, autooxidation, oxidative degradation, and denaturation without compromising O-2 delivery, and then investigating their suitability and safety in vivo. Antioxid. Redox Signal. 18, 2314-2328. C1 [Varnado, Cornelius L.; Olson, John S.] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA. [Mollan, Todd L.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Birukou, Ivan] Duke Univ, Dept Biochem, Durham, NC USA. [Smith, Bryan J. Z.; Henderson, Douglas P.] Univ Texas Permian Basin, Dept Biol, Odessa, TX 79762 USA. RP Olson, JS (reprint author), Rice Univ, Dept Biochem & Cell Biol, POB 1892,MS 140, Houston, TX 77005 USA. EM olson@rice.edu OI Olson, John/0000-0002-0760-5403 FU National Institutes of Health (NIH) [HL47020, GM35649, HL110900, HL079992]; University of Texas Louis Stokes Alliance for Minority Participation Funds (Equipment Funds, UT Permian Basin); Robert A. Welch Foundation Grant [C-0612]; Institute of Biosciences and Bioengineering NIH Biotechnology Pre-doctoral Training Grant [GM008362]; Baylor College of Medicine Hematology Training Program [T32 DK60445] FX The authors would like to thank Betsy Poindexter for helpful discussions regarding the costs associated with blood utilization in the United States. This work was supported by the National Institutes of Health (NIH) under grants HL47020 (J.S.O.), GM35649 (J.S.O.), HL110900(JSO), HL079992 (D.P.H.), University of Texas Louis Stokes Alliance for Minority Participation Funds (Equipment Funds, UT Permian Basin) (D.P.H.), and Robert A. Welch Foundation Grant C-0612 (I.B., J.S.O., T.L.M.). T.L.M. received support from the Institute of Biosciences and Bioengineering NIH Biotechnology Pre-doctoral Training Grant (GM008362) and C.L.V. received funding from the Baylor College of Medicine Hematology Training Program (T32 DK60445). NR 164 TC 22 Z9 24 U1 1 U2 66 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2013 VL 18 IS 17 BP 2314 EP 2328 DI 10.1089/ars.2012.4917 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 133QF UT WOS:000318153400008 PM 23025383 ER PT J AU Hansen, DK George, NI White, GE Abdel-Rahman, A Pellicore, LS Fabricant, D AF Hansen, Deborah K. George, Nysia I. White, Gene E. Abdel-Rahman, Ali Pellicore, Linda S. Fabricant, Daniel TI Questionable Conclusions in the Article "Cardiovascular Toxicity of Citrus aurantium in Exercised Rats'' Response SO CARDIOVASCULAR TOXICOLOGY LA English DT Letter C1 [Hansen, Deborah K.] US FDA, Div Syst Biol Branch, NCTR, Jefferson, AR 72079 USA. [George, Nysia I.] US FDA, Div Bioinformat & Biostat, NCTR, Jefferson, AR 72079 USA. [White, Gene E.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Abdel-Rahman, Ali; Fabricant, Daniel] US FDA, Off Nutr Labeling & Dietary Supplements, CFSAN, College Pk, MD 20740 USA. [Pellicore, Linda S.] US FDA, Off New Drugs, CDER, Silver Spring, MD 20903 USA. RP Hansen, DK (reprint author), US FDA, Div Syst Biol Branch, NCTR, Jefferson, AR 72079 USA. EM deborah.hansen@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1530-7905 J9 CARDIOVASC TOXICOL JI Cardiovasc. Toxicol. PD JUN PY 2013 VL 13 IS 2 BP 182 EP 183 DI 10.1007/s12012-013-9209-z PG 2 WC Cardiac & Cardiovascular Systems; Toxicology SC Cardiovascular System & Cardiology; Toxicology GA 130NL UT WOS:000317924900010 PM 23589039 ER PT J AU Kanungo, J Cuevas, E Ali, SF Paule, MG AF Kanungo, Jyotshna Cuevas, Elvis Ali, Syed F. Paule, Merle G. TI Ketamine induces motor neuron toxicity and alters neurogenic and proneural gene expression in zebrafish SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE neurotoxicity; ketamine; motor neuron; transgenic zebrafish; gene expression ID DEVELOPING RAT-BRAIN; LATERAL INHIBITION; SPINAL-CORD; CELL-DEATH; IN-VIVO; APOPTOTIC NEURODEGENERATION; XENOPUS-EMBRYOS; NMDA RECEPTORS; MODEL SYSTEM; NOTCH AB Ketamine, a noncompetitive antagonist of N-methyl-d-aspartate-type glutamate receptors, is a pediatric anesthetic that has been shown to be neurotoxic in rodents and nonhuman primates when administered during the brain growth spurt. Recently, the zebrafish has become an attractive model for toxicity assays, in part because the predictive capability of the zebrafish model, with respect to chemical effects, compares well with that from mammalian models. In the transgenic (hb9:GFP) embryos used in this study, green fluorescent protein (GFP) is expressed in the motor neurons, facilitating the visualization and analysis of motor neuron development in vivo. In order to determine whether ketamine induces motor neuron toxicity in zebrafish, embryos of these transgenic fish were treated with different concentrations of ketamine (0.5 and 2.0mm). For ketamine exposures lasting up to 20h, larvae showed no gross morphological abnormalities. Analysis of GFP-expressing motor neurons in the live embryos, however, revealed that 2.0mm ketamine adversely affected motor neuron axon length and decreased cranial and motor neuron populations. Quantitative reverse transcriptase-polymerase chain reaction analysis demonstrated that ketamine down-regulated the motor neuron-inducing zinc finger transcription factor Gli2b and the proneural gene NeuroD even at 0.5mm concentration, while up-regulating the expression of the proneural gene Neurogenin1 (Ngn1). Expression of the neurogenic gene, Notch1a, was suppressed, indicating that neuronal precursor generation from uncommitted cells was favored. These results suggest that ketamine is neurotoxic to motor neurons in zebrafish and possibly affects the differentiating/differentiatedneurons rather than neuronal progenitors. Published 2011. This article is a US Government work and is in the public domain in the USA. C1 [Kanungo, Jyotshna; Cuevas, Elvis; Ali, Syed F.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research/US Food and Drug Administration FX This work was supported by the National Center for Toxicological Research/US Food and Drug Administration. We thank Melanie Dumas for her help in zebrafish breeding. NR 86 TC 20 Z9 20 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JUN PY 2013 VL 33 IS 6 BP 410 EP 417 DI 10.1002/jat.1751 PG 8 WC Toxicology SC Toxicology GA 133BN UT WOS:000318112500002 PM 22045596 ER PT J AU Van Doren, JM Kleinmeier, D Hammack, TS Westerman, A AF Van Doren, Jane M. Kleinmeier, Dania Hammack, Thomas S. Westerman, Ann TI Prevalence, serotype diversity, and antimicrobial resistance of Salmonella in imported shipments of spice offered for entry to the United States, FY2007-FY2009 SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella contamination; Microbiological quality; Spice; Salmonella serotype diversity; Salmonella antimicrobial resistance; Food safety ID MICROBIOLOGICAL QUALITY; ESSENTIAL OILS; INFECTIOUS DIARRHEA; FOODS; HERBS; SUSCEPTIBILITY; SEROVARS; CONTAMINATION; TYPHIMURIUM; PRODUCTS AB In response to increased concerns about spice safety, the U.S. FDA initiated research to characterize the prevalence of Salmonella in imported spices. Shipments of imported spices offered for entry to the United Sates were sampled during the fiscal years 2007-2009. The mean shipment prevalence for Salmonella was 0.066 (95% Cl 0.057-0.076). A wide diversity of Salmonella serotypes was isolated from spices; no single serotype constituted more than 7% of the isolates. A small percentage of spice shipments were contaminated with antimicrobial-resistant Salmonella strains (8.3%). Trends in shipment prevalence for Salmonella associated with spice properties, extent of processing, and export country, were examined. A larger proportion of shipments of spices derived from fruit/seeds or leaves of plants were contaminated than those derived from the bark/flower of spice plants. Salmonella prevalence was larger for shipments of ground/cracked capsicum and coriander than for shipments of their whole spice counterparts. No difference in prevalence was observed between shipments of spice blends and non-blended spices. Some shipments reported to have been subjected to a pathogen reduction treatment prior to being offered for U.S. entry were found contaminated. Statistical differences in Salmonella shipment prevalence were also identified on the basis of export country. Published by Elsevier Ltd. C1 [Van Doren, Jane M.; Kleinmeier, Dania; Hammack, Thomas S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Westerman, Ann] US FDA, Off Regulatory Affairs, Silver Spring, MD 20993 USA. RP Van Doren, JM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jane.vandoren@fda.hhs.gov FU U.S. FDA FX The authors thank and acknowledge the hundreds of Office of Regulatory Affairs (ORA) field staff within FDA's District offices who participated in the sampling associated with this study, including Consumer Safety Officers (CSO) and Inspectors (CSI) who collected spice shipment information and samples, and laboratory scientists who analyzed the spice samples for presence of Salmonella, serotyping and antimicrobial resistance. We also thank Claudine Kabera (FDA/CVM) and Linda Fabbri and Mercedes Loftis (FDA/ORA) who provided additional information about the entries sampled, test results, and methods used. The authors wish to recognize and thank Regis Pouillot (FDA/CFSAN) for his comments and suggestions on the statistical analyses used in this study as well as Patrick McDermott and Maureen Davidson (FDA/CVM) for their comments and suggestions on the antimicrobial susceptibility results discussed. This work was funded by the U.S. FDA. The results of this study will be incorporated into the risk profile on pathogens and filth in spices being development by FDA and, we thank the following risk profile team members who reviewed and commented on this manuscript: Vikas Gill, Obianugu Nsofor, Mickey Parish, and George C. Ziobro (FDA/CFSAN; Martin Muckenfuss (FDA/ORA); and Karen Neil and Laura Gieraltowski (CDC/OID). Additional scientists from CDC and FDA also provided helpful comments during the preparation of this manuscript. NR 75 TC 13 Z9 13 U1 0 U2 20 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2013 VL 34 IS 2 BP 239 EP 251 DI 10.1016/j.fm.2012.10.002 PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 126PO UT WOS:000317633600001 PM 23541190 ER PT J AU Gopinath, G Hari, K Jain, R Mammel, MK Kothary, MH Franco, AA Grim, CJ Jarvis, KG Sathyamoorthy, V Hu, L Datta, AR Patel, IR Jackson, SA Gangiredla, J Kotewicz, ML LeClerc, JE Wekell, M McCardell, BA Solomotis, MD Tall, BD AF Gopinath, G. Hari, K. Jain, R. Mammel, M. K. Kothary, M. H. Franco, A. A. Grim, C. J. Jarvis, K. G. Sathyamoorthy, V. Hu, L. Datta, A. R. Patel, I. R. Jackson, S. A. Gangiredla, J. Kotewicz, M. L. LeClerc, J. E. Wekell, M. McCardell, B. A. Solomotis, M. D. Tall, B. D. TI The Pathogen-annotated Tracking Resource Network (PATRN) system: A web-based resource to aid food safety, regulatory science, and investigations of foodborne pathogens and disease SO FOOD MICROBIOLOGY LA English DT Article DE Pathogen data analysis platform; Web-based pathogen tracking database system ID ESCHERICHIA-COLI O157H7; ENTEROBACTER-SAKAZAKII; UNITED-STATES; BIOINFORMATICS RESOURCE; CLINICAL SPECIMENS; CRONOBACTER; IDENTIFICATION; INSTITUTE; DATABASE; PULSENET AB Investigation of foodborne diseases requires the capture and analysis of time-sensitive information on microbial pathogens that is derived from multiple analytical methods and sources. The web-based Pathogen-annotated Tracking Resource Network (PATRN) system (www.patrn.net) was developed to address the data aggregation, analysis, and communication needs important to the global food safety community for the investigation of foodborne disease. PATRN incorporates a standard vocabulary for describing isolate metadata and provides a representational schema for a prototypic data exchange standard using a novel data loading wizard for aggregation of assay and attribution information. PATRN currently houses expert-curated, high-quality "foundational datasets" consisting of published experimental results from conventional assays and next generation analysis platforms for isolates of Escherichia coli, Listeria monocytogenes, and Salmonella, Shigella, Vibrio and Cronobacter species. A suite of computational tools for data mining, clustering, and graphical representation is available. Within PATRN, the public curated data repository is complemented by a secure private workspace for user-driven analyses, and for sharing data among collaborators. To demonstrate the data curation, loading wizard features, and analytical capabilities of PATRN, three use-case scenarios are presented. Use-case scenario one is a comparison of the distribution and prevalence of plasmid-encoded virulence factor genes among 249 Cronobacter strains with similar attributes to that of nine Cronobacter isolates from recent cases obtained between March and October, 2010-2011. To highlight PATRN's data management and trend finding tools, analysis of datasets, stored in PATRN as part of an ongoing surveillance project to identify the predominant molecular serogroups among Cronobacter sakazakii isolates observed in the USA is shown. Use-case scenario two demonstrates the secure workspace available for private users to upload and analyze sensitive data, and for collating cross-platform datasets to identify and validate congruent datapoints. SNP datasets from WGS assemblies and pan-genome microarrays are analyzed in a combinatorial fashion to determine relatedness of 33 Salmonella enterica strains to six strains collected as part of an outbreak investigation. Use-case scenario three utilizes published surveillance results that describe the incidence and sources of O157:H7 E. coli isolates associated with a produce pre-harvest surveillance study that occurred during 2002-2006. In summary, PATRN is a web-based integrated platform containing tools for the management, analysis and visualization of data about foodborne pathogens. Published by Elsevier Ltd. C1 [Gopinath, G.; Mammel, M. K.; Kothary, M. H.; Franco, A. A.; Grim, C. J.; Jarvis, K. G.; Sathyamoorthy, V.; Hu, L.; Datta, A. R.; Patel, I. R.; Jackson, S. A.; Gangiredla, J.; Kotewicz, M. L.; LeClerc, J. E.; Wekell, M.; McCardell, B. A.; Solomotis, M. D.; Tall, B. D.] US FDA, CFSAN, Laurel, MD 20708 USA. [LeClerc, J. E.] US FDA, CFSAN, College Pk, MD 20740 USA. [Grim, C. J.; Jarvis, K. G.; Hu, L.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Hari, K.; Jain, R.] cBio Inc, Fremont, CA USA. RP Tall, BD (reprint author), US FDA, MOD Facil 1, Virulence Mech Branch, Div Virulence Assessment,OARSA,Ctr Food Safety &, Room 3607,HFS 025,8301 MuirKirk Rd, Laurel, MD 20708 USA. EM ben.tall@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 61 TC 2 Z9 2 U1 3 U2 71 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2013 VL 34 IS 2 BP 303 EP 318 DI 10.1016/j.fm.2013.01.001 PG 16 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 126PO UT WOS:000317633600008 PM 23541197 ER PT J AU Kang, L Tian, LL AF Kang, Le Tian, Lili TI Estimation of the volume under the ROC surface with three ordinal diagnostic categories SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Box-Cox type transformation; Diagnostic accuracy; Kernel smoothing; Three ordinal diagnostic categories; Volume under the ROC surface ID BANDWIDTH SELECTION; CURVES; MASS; MARKERS; TESTS AB With three ordinal diagnostic categories, the most commonly used measure for the overall diagnostic accuracy is the volume under the ROC surface (VUS), which is the extension of the area under the ROC curve (AUC) for binary diagnostic outcomes. This article proposes two kernel smoothing based approaches for estimation of the VUS. In an extensive simulation study, the proposed estimators are compared with the existing parametric and nonparametric estimators in terms of bias and root mean square error. A real data example of 203 participants from a cohort study for the detection of Glycan biomarkers for liver cancer is discussed. (C) 2013 Elsevier B.V. All rights reserved. C1 [Kang, Le] US FDA, Silver Spring, MD 20993 USA. [Tian, Lili] SUNY Buffalo, Dept Biostat, Buffalo, NY 14214 USA. RP Tian, LL (reprint author), SUNY Buffalo, Dept Biostat, 706 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. EM ltian@buffalo.edu NR 29 TC 7 Z9 7 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JUN PY 2013 VL 62 BP 39 EP 51 DI 10.1016/j.csda.2013.01.004 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 111QY UT WOS:000316537000004 ER PT J AU Imam, SZ Trickler, W Kimura, S Binienda, ZK Paule, MG Slikker, W Li, SL Clark, RA Ali, SF AF Imam, Syed Z. Trickler, William Kimura, Shinya Binienda, Zbigniew K. Paule, Merle G. Slikker, William, Jr. Li, Senlin Clark, Robert A. Ali, Syed F. TI Neuroprotective Efficacy of a New Brain-Penetrating C-Abl Inhibitor in a Murine Parkinson's Disease Model SO PLOS ONE LA English DT Article ID TYROSINE KINASE INHIBITOR; DOPAMINERGIC NEUROTOXICITY; IMATINIB; ACTIVATION; RESISTANCE; MUTATIONS; LEUKEMIA; GENE AB Experimental evidence suggests that oxidative and nitrative mechanisms account for much of the dopaminergic neuronal injury in Parkinson's disease (PD). The ubiquitously expressed non-receptor tyrosine kinase c-Abl is activated by oxidative stress and thus, may play a role in redox-mediated neurodegeneration. Recently, we reported that c-Abl is activated in PD and that a c-Abl inhibitor mitigated neuronal damage in a PD animal model, suggesting a novel neuroprotective therapeutic approach. In the studies presented here, we evaluated the efficacy of a potent and clinically relevant second-generation irreversible Abl kinase inhibitor, INNO-406, as a therapeutic agent for PD. Our studies reveal that INNO-406 is capable of preventing the progression of dopaminergic neuronal damage in a toxin-induced C57 mouse model of PD. Using bovine brain microvessel endothelium as an in vitro blood-brain barrier (BBB) model, we detected rapid and significant transfer of INNO-406. Additionally, pharmacokinetic analyses demonstrated significant nanomolar concentrations of INNO-406 in brain in the presence or absence of MPTP administration, however, INNO-406 did not alter the brain levels of MPP+ in MPTP-treated mice. Finally, we showed that 10 mg/kg of INNO-406 given to C57 mice for one week before MPTP treatment (4620 mg/kg i.p., every 2 h) and then for one week after MPTP treatment decreased the loss of dopamine in the striatum by 45% and the loss of TH+ neurons in substantia nigra pars compacts by 40%. This treatment regimen also abrogated activation of c-Abl, tyrosine phosphorylation of the Abl substrate and E3-ubiquitin ligase parkin, and accumulation of the toxic parkin substrate AIMP2. We propose that compounds of the INNO-406 class of Abl inhibitors will be useful new neuroprotective drugs for the treatment of PD-like pathology in preclinical systems that should be easily translated to the clinic. C1 [Imam, Syed Z.; Trickler, William; Binienda, Zbigniew K.; Paule, Merle G.; Slikker, William, Jr.; Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Imam, Syed Z.; Li, Senlin; Clark, Robert A.] UT Hlth Sci Ctr, Dept Med, San Antonio, TX USA. [Imam, Syed Z.] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. [Kimura, Shinya] Saga Univ, Fac Med, Dept Internal Med, Div Hematol Resp Med & Oncol, Saga 840, Japan. RP Imam, SZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM syed.imam@fda.hhs.gov FU Michael J. Fox Foundation; Parkinson's Disease Foundation; San Antonio Area Foundation; American Parkinson Disease Association; Executive Research Council of UTHSCSA FX This work was supported by grants from Michael J. Fox Foundation, Parkinson's Disease Foundation, San Antonio Area Foundation, American Parkinson Disease Association and Executive Research Council of UTHSCSA. The funders had no role in study design, data collection and analysis, decision to publish or presentation of the manuscript. NR 26 TC 20 Z9 21 U1 2 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 31 PY 2013 VL 8 IS 5 AR e65129 DI 10.1371/journal.pone.0065129 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156DC UT WOS:000319799900183 PM 23741470 ER PT J AU Grim, CJ Kotewicz, ML Power, KA Gopinath, G Franco, AA Jarvis, KG Yan, QQ Jackson, SA Sathyamoorthy, V Hu, L Pagotto, F Iversen, C Lehner, A Stephan, R Fanning, S Tall, BD AF Grim, Christopher J. Kotewicz, Michael L. Power, Karen A. Gopinath, Gopal Franco, Augusto A. Jarvis, Karen G. Yan, Qiong Q. Jackson, Scott A. Sathyamoorthy, Venugopal Hu, Lan Pagotto, Franco Iversen, Carol Lehner, Angelika Stephan, Roger Fanning, Seamus Tall, Ben D. TI Pan-genome analysis of the emerging foodborne pathogen Cronobacter spp. suggests a species-level bidirectional divergence driven by niche adaptation SO BMC GENOMICS LA English DT Article ID INFANT MILK FORMULA; ENTEROBACTER-SAKAZAKII; THERMAL-RESISTANCE; VIBRIO-CHOLERAE; V. CHOLERAE; RPOB GENE; SEQUENCE; FOOD; IDENTIFICATION; PERSISTENCE AB Background: Members of the genus Cronobacter are causes of rare but severe illness in neonates and preterm infants following the ingestion of contaminated infant formula. Seven species have been described and two of the species genomes were subsequently published. In this study, we performed comparative genomics on eight strains of Cronobacter, including six that we sequenced (representing six of the seven species) and two previously published, closed genomes. Results: We identified and characterized the features associated with the core and pan genome of the genus Cronobacter in an attempt to understand the evolution of these bacteria and the genetic content of each species. We identified 84 genomic regions that are present in two or more Cronobacter genomes, along with 45 unique genomic regions. Many potentially horizontally transferred genes, such as lysogenic prophages, were also identified. Most notable among these were several type six secretion system gene clusters, transposons that carried tellurium, copper and/or silver resistance genes, and a novel integrative conjugative element. Conclusions: Cronobacter have diverged into two clusters, one consisting of C. dublinensis and C. muytjensii (Cdub-Cmuy) and the other comprised of C. sakazakii, C. malonaticus, C. universalis, and C. turicensis, (Csak-Cmal-Cuni-Ctur) from the most recent common ancestral species. While several genetic determinants for plant-association and human virulence could be found in the core genome of Cronobacter, the four Cdub-Cmuy clade genomes contained several accessory genomic regions important for survival in a plant-associated environmental niche, while the Csak-Cmal-Cuni-Ctur clade genomes harbored numerous virulence-related genetic traits. C1 [Grim, Christopher J.; Kotewicz, Michael L.; Gopinath, Gopal; Franco, Augusto A.; Jarvis, Karen G.; Jackson, Scott A.; Sathyamoorthy, Venugopal; Hu, Lan; Tall, Ben D.] FDA, CFSAN, Laurel, MD USA. [Grim, Christopher J.; Hu, Lan] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Power, Karen A.; Yan, Qiong Q.; Fanning, Seamus] Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, UCD Ctr Food Safety, Dublin 2, Ireland. [Power, Karen A.; Yan, Qiong Q.; Fanning, Seamus] WHO Collaborating Ctr Cronobacter, Dublin, Ireland. [Pagotto, Franco] Hlth Canada, Bur Dangers Microbiens, Bur Microbial Hazards, Food Directorate,Direct Aliments, Ottawa, ON K1A 0L2, Canada. [Pagotto, Franco] Ctr Recherches Sir FG Banting, Sir FG Banting Res Ctr, Ottawa, ON, Canada. [Iversen, Carol] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. [Lehner, Angelika; Stephan, Roger] Univ Zurich, Inst Food Safety & Hyg, Zurich, Switzerland. RP Tall, BD (reprint author), FDA, CFSAN, Laurel, MD USA. EM ben.tall@fda.hhs.gov OI Fanning, Seamus/0000-0002-1922-8836; Tall, Ben/0000-0003-0399-3629 FU U.S. FDA FX We thank Lisa Sadzewicz and Luke Tallon and other support members of the Institute for Genome Sciences at the University of Maryland for their contributions to this work. We thank Christopher Elkins, Barbara McCardell, and Kevin Gaido for their help in reviewing this manuscript. The funds supporting this work were obtained internally through U.S. FDA appropriations. NR 54 TC 20 Z9 21 U1 1 U2 30 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAY 31 PY 2013 VL 14 AR 366 DI 10.1186/1471-2164-14-366 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 161DY UT WOS:000320173100001 PM 23724777 ER PT J AU Reddy, MK Nixon, C Wyatt, SA Croley, TR AF Reddy, Muntha K. Nixon, Christopher Wyatt, Shane A. Croley, Timothy R. TI A robust high-throughput sample preparation and liquid chromatography/tandem mass spectrometry method for the quantitation of beta-lyase metabolites of sulfur mustard as 1,1 '-sulfonylbis-[2-(methylthio)ethane] in human urine SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID BIOLOGICAL FATE; ALLEGED ATTACK; GAS; THIODIGLYCOL; 1,1'-THIOBIS(2-CHLOROETHANE); VICTIMS AB RATIONALE Sulfur mustard (HD) is a major chemical warfare agent threat to humans. Since World War I, several incidents of human exposure to sulfur mustard have been reported. In order to assist health professionals during an exposure event and support biological monitoring, a rapid analytical method is required to measure the exposure of humans to HD. METHOD The -lyase metabolites of HD, 1-methylsulfinyl-2-[2-(methylthio)ethylsulfonyl]ethane (MSMTESE) and 1,1-sulfonylbis[2-(methylsulfinyl)ethane] (SBMSE) were reduced to the single biomarker, 1,1-sulfonylbis-[2-(methylthio)ethane] (SBMTE), using titanium(III) chloride. High-throughput sample preparation was performed on a Tecan Freedom EVO liquid handler and analysis was performed by electrospray ionization liquid chromatography and tandem mass spectrometry (LC/MS/MS) in the multiple-reaction monitoring mode. RESULTS Each analytical run consisted of a matrix blank, calibration standards (0.1100ng/mL), low quality controls (QCs), 2.5ng/mL, and high QCs, 25.0ng/mL, of SBMTE in human urine. The method was validated with 20 analytical runs performed by four analysts. The mean calculated concentrations of the low and high QCs were 2.52 and 25.5ng/mL with relative standard deviations of 3.6% and 2.3%, respectively. CONCLUSION This semi-automated method has few manual transfer steps, thus minimizing common manual errors and saving time. Therefore, this method would be very helpful to responding laboratories in a large-scale exposure event related to HD. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Reddy, Muntha K.; Nixon, Christopher; Wyatt, Shane A.] Commonwealth Virginia, Div Consolidated Lab Serv, Richmond, VA 23219 USA. [Croley, Timothy R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Reddy, MK (reprint author), Commonwealth Virginia, Div Consolidated Lab Serv, 600 N 5th St, Richmond, VA 23219 USA. EM kesava.muntha@dgs.virginia.gov FU Department of Health and Human Services Centers for Disease Control and Prevention [U90/CCU317014] FX We acknowledge funding of this research by the Department of Health and Human Services Centers for Disease Control and Prevention grant # U90/CCU317014. NR 13 TC 3 Z9 3 U1 4 U2 52 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD MAY 30 PY 2013 VL 27 IS 10 BP 1128 EP 1134 DI 10.1002/rcm.6541 PG 7 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 131IZ UT WOS:000317987900005 PM 23592117 ER PT J AU Zhang, YB Ferguson, SA Watanabe, F Jones, Y Xu, Y Biris, AS Hussain, S Ali, SF AF Zhang, Yongbin Ferguson, Sherry A. Watanabe, Fumiya Jones, Yvonne Xu, Yang Biris, Alexandru S. Hussain, Saber Ali, Syed F. TI Silver Nanoparticles Decrease Body Weight and Locomotor Activity in Adult Male Rats SO SMALL LA English DT Article DE silver nanoparticles; behavioral activity; neurotoxicity; rats ID TISSUE DISTRIBUTION; ORAL TOXICITY; IN-VITRO; CELLS; CYTOTOXICITY; PERMEABILITY; GENOTOXICITY; NANOSILVER C1 [Zhang, Yongbin; Jones, Yvonne] US FDA, Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ferguson, Sherry A.; Ali, Syed F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Watanabe, Fumiya; Xu, Yang; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Hussain, Saber] USAF, Appl Biotechnol Branch, Human Effectiveness Directorate, Res Lab, Wright Patterson AFB, OH 45433 USA. RP Zhang, YB (reprint author), US FDA, Nanotechnol Core Facil, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM yongbin.zhang@fda.hhs.gov; sherry.ferguson@fda.hhs.gov FU US Air Force Research Laboratory at the National Center for Toxicological Research/FDA (Jefferson, AR) FX This document has been reviewed in accordance with United States Food and Drug Administration (FDA) policy and approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the FDA. This research was supported in part by an appointment to the Postgraduate Research Participation Program with the US Air Force Research Laboratory at the National Center for Toxicological Research/FDA (Jefferson, AR) administered by the Oak Ridge Institute of Science and Education (Oak Ridge, TN) through an interagency agreement between the US Department of Energy, US Air Force Research Laboratory/Applied Biotechnology Branch, and the US Food and Drug Administration. NR 26 TC 15 Z9 15 U1 3 U2 17 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1613-6810 J9 SMALL JI Small PD MAY 27 PY 2013 VL 9 IS 9-10 SI SI BP 1715 EP 1720 DI 10.1002/smll.201201548 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 146FT UT WOS:000319076000026 PM 23335405 ER PT J AU Ottesen, AR Pena, AG White, JR Pettengill, JB Li, C Allard, S Rideout, S Allard, M Hill, T Evans, P Strain, E Musser, S Knight, R Brown, E AF Ottesen, Andrea R. Pena, Antonio Gonzalez White, James R. Pettengill, James B. Li, Cong Allard, Sarah Rideout, Steven Allard, Marc Hill, Thomas Evans, Peter Strain, Errol Musser, Steven Knight, Rob Brown, Eric TI Baseline survey of the anatomical microbial ecology of an important food plant: Solanum lycopersicum (tomato) SO BMC MICROBIOLOGY LA English DT Article DE Tomato microflora; 16S; 18S; Metagenomics; Phyllosphere; Solanum lycopersicum; Tomato organs; Microbial ecology; Baseline microflora; Tomatome ID MULTILOCUS GENOTYPE DATA; RIBOSOMAL-RNA; DIVERSITY; TRICHOMES; WILD; EVOLUTION; INFERENCE; RESOURCE AB Background: Research to understand and control microbiological risks associated with the consumption of fresh fruits and vegetables has examined many environments in the farm to fork continuum. An important data gap however, that remains poorly studied is the baseline description of microflora that may be associated with plant anatomy either endemically or in response to environmental pressures. Specific anatomical niches of plants may contribute to persistence of human pathogens in agricultural environments in ways we have yet to describe. Tomatoes have been implicated in outbreaks of Salmonella at least 17 times during the years spanning 1990 to 2010. Our research seeks to provide a baseline description of the tomato microbiome and possibly identify whether or not there is something distinctive about tomatoes or their growing ecology that contributes to persistence of Salmonella in this important food crop. Results: DNA was recovered from washes of epiphytic surfaces of tomato anatomical organs; leaves, stems, roots, flowers and fruits of Solanum lycopersicum (BHN602), grown at a site in close proximity to commercial farms previously implicated in tomato-Salmonella outbreaks. DNA was amplified for targeted 16S and 18S rRNA genes and sheared for shotgun metagenomic sequencing. Amplicons and metagenomes were used to describe "native" bacterial microflora for diverse anatomical parts of Virginia-grown tomatoes. Conclusions: Distinct groupings of microbial communities were associated with different tomato plant organs and a gradient of compositional similarity could be correlated to the distance of a given plant part from the soil. Unique bacterial phylotypes (at 95% identity) were associated with fruits and flowers of tomato plants. These include Microvirga, Pseudomonas, Sphingomonas, Brachybacterium, Rhizobiales, Paracocccus, Chryseomonas and Microbacterium. The most frequently observed bacterial taxa across aerial plant regions were Pseudomonas and Xanthomonas. Dominant fungal taxa that could be identified to genus with 18S amplicons included Hypocrea, Aureobasidium and Cryptococcus. No definitive presence of Salmonella could be confirmed in any of the plant samples, although 16S sequences suggested that closely related genera were present on leaves, fruits and roots. C1 [Ottesen, Andrea R.; Pettengill, James B.; Li, Cong; Allard, Sarah; Allard, Marc; Hill, Thomas; Evans, Peter; Strain, Errol; Musser, Steven; Brown, Eric] US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Mol Methods & Subtyping, College Pk, MD 20740 USA. [White, James R.] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA. [Pena, Antonio Gonzalez; Knight, Rob] Univ Maryland, Sch Med, IGS Inst Genome Sci, Baltimore, MD 21201 USA. [Rideout, Steven] Virginia Polytech Inst & State Univ, Eastern Shore AREC, Painter, VA 23420 USA. RP Ottesen, AR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Mol Methods & Subtyping, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM andrea.ottesen@fda.hhs.gov RI Knight, Rob/D-1299-2010 NR 34 TC 39 Z9 40 U1 11 U2 96 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD MAY 24 PY 2013 VL 13 AR 114 DI 10.1186/1471-2180-13-114 PG 11 WC Microbiology SC Microbiology GA 160YI UT WOS:000320156000001 PM 23705801 ER PT J AU Yu, WL Jiang, YL Pikis, A Cheng, W Bai, XH Ren, YM Thompson, J Zhou, CZ Chen, YX AF Yu, Wei-Li Jiang, Yong-Liang Pikis, Andreas Cheng, Wang Bai, Xiao-Hui Ren, Yan-Min Thompson, John Zhou, Cong-Zhao Chen, Yuxing TI Structural Insights into the Substrate Specificity of a 6-Phospho-beta-glucosidase BglA-2 from Streptococcus pneumoniae TIGR4 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; BINDING CASSETTE TRANSPORTERS; GLYCOSYL HYDROLASES; BETA-GLUCOSIDASE; PHOSPHOTRANSFERASE SYSTEM; LACTOCOCCUS-LACTIS; CRYSTAL-STRUCTURE; MECHANISM; PROTEINS; BACTERIA AB The 6-phospho-beta-glucosidase BglA-2 (EC 3.2.1.86) from glycoside hydrolase family 1 (GH-1) catalyzes the hydrolysis of beta-1,4-linked cellobiose 6-phosphate (cellobiose-6'P) to yield glucose and glucose 6-phosphate. Both reaction products are further metabolized by the energy-generating glycolytic pathway. Here, we present the first crystal structures of the apo and complex forms of BglA-2 with thiocellobiose-6'P (a non-metabolizable analog of cellobiose-6'P) at 2.0 and 2.4 angstrom resolution, respectively. Similar to other GH-1 enzymes, the overall structure of BglA-2 from Streptococcus pneumoniae adopts a typical (beta/alpha)(8) TIM-barrel, with the active site located at the center of the convex surface of the beta-barrel. Structural analyses, in combination with enzymatic data obtained from site-directed mutant proteins, suggest that three aromatic residues, Tyr(126), Tyr(303), and Trp(338), at subsite +1 of BglA-2 determine substrate specificity with respect to 1,4-linked 6-phospho-beta-glucosides. Moreover, three additional residues, Ser(424), Lys(430), and Tyr(432) of BglA-2, were found to play important roles in the hydrolytic selectivity toward phosphorylated rather than non-phosphorylated compounds. Comparative structural analysis suggests that a tryptophan versus a methionine/alanine residue at subsite -1 may contribute to the catalytic and substrate selectivity with respect to structurally similar 6-phospho-beta-galactosidases and 6-phospho-beta-glucosidases assigned to the GH-1 family. C1 [Yu, Wei-Li; Jiang, Yong-Liang; Cheng, Wang; Bai, Xiao-Hui; Ren, Yan-Min; Zhou, Cong-Zhao; Chen, Yuxing] Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China. [Yu, Wei-Li; Jiang, Yong-Liang; Cheng, Wang; Bai, Xiao-Hui; Ren, Yan-Min; Zhou, Cong-Zhao; Chen, Yuxing] Univ Sci & Technol China, Sch Life Sci, Hefei 230027, Anhui, Peoples R China. [Pikis, Andreas; Thompson, John] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zhou, CZ (reprint author), Univ Sci & Technol China, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China. EM zcz@ustc.edu.cn; cyxing@ustc.edu.cn RI Zhou, Cong-Zhao/E-9174-2011; Chen, Yuxing/P-4156-2014 OI Zhou, Cong-Zhao/0000-0002-6881-7151; Chen, Yuxing/0000-0002-7560-1922 FU National Institutes of Health, NIDCR, Intramural Research Program; Ministry of Science and Technology of China [2009CB918800]; National Natural Science Foundation of China [31270781]; Research Fund for the Doctoral Program of Higher Education of China [20123402110004] FX This work was supported, in whole or in part, by the National Institutes of Health, NIDCR, Intramural Research Program. This work was also supported by Ministry of Science and Technology of China Grant 2009CB918800, National Natural Science Foundation of China Grant 31270781, and Research Fund for the Doctoral Program of Higher Education of China Grant 20123402110004. NR 43 TC 5 Z9 5 U1 1 U2 10 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 24 PY 2013 VL 288 IS 21 BP 14949 EP 14958 DI 10.1074/jbc.M113.454751 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 151HU UT WOS:000319452100025 PM 23580646 ER PT J AU MacMahon, S Mazzola, E Begley, TH Diachenko, GW AF MacMahon, Shaun Mazzola, Eugene Begley, Timothy H. Diachenko, Gregory W. TI Analysis of Processing Contaminants in Edible Oils. Part 1. Liquid Chromatography-Tandem Mass Spectrometry Method for the Direct Detection of 3-Monochloropropanediol Monoesters and Glycidyl Esters SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 3-monochloropropanediol; 3-MCPD; glycidol; glycidyl esters; LC-MS/MS; processing contaminants; edible oils ID FATTY-ACID ESTERS; ELAEIS-GUINEENSIS OIL; 3-CHLORO-1,2-PROPANEDIOL 3-MCPD; 3-CHLOROPROPANE-1,2-DIOL; MONOCHLOROPROPANEDIOL AB A new analytical method has been developed and validated for the detection of glycidyl esters (GEs) and 3-monochloropropanediol (3-MCPD) monoesters in edible oils. The target compounds represent two classes of potentially carcinogenic chemical contaminants formed during the processing of edible oils. Target analytes are separated from edible oil matrices using a two-step solid-phase extraction (SPE) procedure. The extracts are then analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). Chromatographic conditions that separate sn-1 and sn-2 monoesters of 3-MCPD have been developed for the first time. The method has been validated for GEs, sn-1 3-MCPD monoesters of lauric, myristic, linolenic, linoleic, oleic, and stearic acids, and sn-2 3-MCPD monoesters of oleic and palmitic acids in coconut, olive, and palm oils using an external calibration curve. The range of average recoveries and relative standard deviations (RSDs) across the three oil matrices at three spiking concentrations are 84-115% (3-16% RSD) for the GEs, 95-113% (1-10% RSD) for the sn-1 3-MCPD monoesters, and 76.8-103% (5.1-11.2% RSD) for the sn-2 3-MCPD monoesters, with limits of quantitation at or below 30 ng/g for the GEs, 60 ng/g for sn-1 3-MCPD monoesters, and 180 ng/g for sn-2 3-MCPD monoesters. C1 [MacMahon, Shaun; Mazzola, Eugene; Begley, Timothy H.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP MacMahon, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM shaun.macmahon@fda.hhs.gov NR 30 TC 17 Z9 17 U1 2 U2 75 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 22 PY 2013 VL 61 IS 20 BP 4737 EP 4747 DI 10.1021/jf4005803 PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 152SL UT WOS:000319551300009 PM 23590632 ER PT J AU MacMahon, S Begley, TH Diachenko, GW AF MacMahon, Shaun Begley, Timothy H. Diachenko, Gregory W. TI Analysis of Processing Contaminants in Edible Oils. Part 2. Liquid Chromatography-Tandem Mass Spectrometry Method for the Direct Detection of 3-Monochloropropanediol and 2-Monochloropropanediol Diesters SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE 3-monochloropropanediol; 3-MCPD; 2-MCPD; LC-MS/MS; processing contaminants; edible oils ID FATTY-ACID ESTERS; ELAEIS-GUINEENSIS OIL; 3-CHLORO-1,2-PROPANEDIOL 3-MCPD; MONOCHLOROPROPANEDIOL; CELLS AB A method was developed and validated for the detection of fatty acid diesters of 2-monochloropropanediol (2-MCPD) and 3-monochloropropanediol (3-MCPD) in edible oils. These analytes are potentially carcinogenic chemical contaminants formed during edible oil processing. After separation from oil matrices using a two-step solid-phase extraction (SPE) procedure, the target compounds are quantitated using liquid chromatography tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). The first chromatographic conditions have been developed that separate intact diesters of 2-MCPD and 3-MCPD, allowing for their individual quantitation. The method has been validated for 28 3-MCPD diesters of lauric, myristic, palmitic, linolenic, linoleic, oleic, and stearic acids in coconut, olive, and palm oils, as well as 3 2-MCPD diesters, using an external calibration curve. The range of average recoveries and relative standard deviations (RSDs) across the three oil matrices at three spiking concentrations are 88-118% (2-16% RSD) with maximum limits of quantitation of 30 ng/g (ppb). C1 [MacMahon, Shaun; Begley, Timothy H.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP MacMahon, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, S100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM shaun.macmahon@fda.hhs.gov NR 26 TC 13 Z9 14 U1 1 U2 55 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 22 PY 2013 VL 61 IS 20 BP 4748 EP 4757 DI 10.1021/jf400581g PG 10 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 152SL UT WOS:000319551300010 PM 23590587 ER PT J AU Liao, CD Wong, JW Zhang, K Hayward, DG Lee, NS Trucksess, MW AF Liao, Chia-Ding Wong, Jon W. Zhang, Kai Hayward, Douglas G. Lee, Nathaniel S. Trucksess, Mary W. TI Multi-mycotoxin Analysis of Finished Grain and Nut Products Using High-Performance Liquid Chromatography-Triple-Quadrupole Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE mycotoxins; LC-MS/MS; multi-mycotoxin analysis; finished cereal and nut products ID SOLID-PHASE EXTRACTION; LC-MS/MS; TRICHOTHECENE MYCOTOXINS; AGRICULTURAL COMMODITIES; SAMPLE CLEANUP; PISTACHIO NUTS; FOOD MATRICES; HT-2 TOXINS; AFLATOXINS; ZEARALENONE AB Mycotoxins in foods have long been recognized as potential health hazards due to their toxic and carcinogenic properties. A simple and rapid method was developed to detect 26 mycotoxins (aflatoxins, ochratoxins, fumonisins, trichothecenes, and ergot alkaloids) in corn, rice, wheat, almond, peanut, and pistachio products using high-performance liquid chromatography-triple-quadrupole mass spectrometry. Test portions of homogenized grain or nut products were extracted with acetonitrile/water (85:15, v/v), followed by high-speed centrifugation and dilution with water. Mean recoveries (+/- standard deviations) were 84 +/- 6, 89 +/- 6, 97 +/- 9, 87 +/- 12, 104 +/- 16, and 92 +/- 18% from corn, rice, wheat, almond, peanut, and pistachio products, respectively, and the matrix-dependent instrument quantitation limits ranged from 0.2 to 12.8 mu g/kg, depending on the mycotoxin. Matrix effects, as measured by the slope ratios of matrix-matched and solvent-only calibration curves, revealed primarily suppression and were more pronounced in nuts than in grains. The measured mycotoxin concentrations in 11 corn and wheat reference materials were not different from the certified concentrations. Nineteen mycotoxins were identified and measured in 35 of 70 commercial grain and nut products, ranging from 0.3 +/- 0.1 mu g/kg (aflatoxin B-1 in peanuts) to 1143 +/- 87 mu g/kg (fumonisin B-1 in corn flour). This rapid and efficient method was shown to be rugged and effective for the multiresidue analysis of mycotoxins in finished grain and nut products. C1 [Liao, Chia-Ding; Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.; Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Liao, Chia-Ding] Taiwan Food & Drug Adm, Dept Hlth, Taipei 115, Taiwan. [Lee, Nathaniel S.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Liao, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM cdliao@fda.gov.tw; jon.wong@fda.hhs.gov NR 43 TC 19 Z9 19 U1 4 U2 76 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 22 PY 2013 VL 61 IS 20 BP 4771 EP 4782 DI 10.1021/jf4000677 PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 152SL UT WOS:000319551300013 PM 23614683 ER PT J AU Vaclavik, L Vaclavikova, M Begley, TH Krynitsky, AJ Rader, JI AF Vaclavik, Lukas Vaclavikova, Marta Begley, Timothy H. Krynitsky, Alexander J. Rader, Jeanne I. TI Determination of Multiple Mycotoxins in Dietary Supplements Containing Green Coffee Bean Extracts Using Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-MS/MS) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE mycotoxins; green coffee bean extracts; dietary supplements; liquid chromatography-mass spectrometry ID OCHRATOXIN-A; PESTICIDE-RESIDUES; PLANT TOXINS; LONG-TERM; FOOD; ANTIOBESITY; AFLATOXINS; CAFFEINE; CEREALS; FUNGI AB An ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the determination of 34 mycotoxins in dietary supplements containing green coffee bean (GCB) extracts was developed, evaluated, and used in the analysis of 50 commercial products. A QuEChERS-like procedure was used for isolation of target analytes from the examined matrices. Average recoveries of the analytes were in the range of 75-110%. The precision of the method expressed as relative Standard deviation was below 12%. Limits of detection (LODs) and limits of quantitation (LOQs) ranged from 1.0 to 50.0 mu g/kg and from 2.5 to 100 mu/kg, respectively. Due to matrix effects, the method of standard additions was used to ensure accurate quantitation. Ochratoxin A, ochratoxin B, fumonisin B1 and mycophenolic acid were found in 36%, 32%, 10%, and 16% of tested products, respectively. Mycotoxins occurred in the following concentration ranges: ochratoxin A, <1.0-136.9 mu g/kg; ochratoxin B, <1.0-20.2 mu g/kg; fumonisin B-1, <50.0-415.0 mu g/kg; mycophenolic acid, <5.0-395.0 mu g/kg. High-resolution mass spectrometry operated in full MS and MS/MS mode was used to confirm the identities of the reported compounds. C1 [Vaclavik, Lukas; Vaclavikova, Marta; Begley, Timothy H.; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Vaclavik, L (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM Lukas.Vaclavik@fda.hhs.gov FU Center for Food Safety and Applied Nutrition FX L.V. and M.V. acknowledge support by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 36 TC 24 Z9 24 U1 10 U2 70 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 22 PY 2013 VL 61 IS 20 BP 4822 EP 4830 DI 10.1021/jf401139u PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 152SL UT WOS:000319551300019 PM 23631685 ER PT J AU Ai, ZH Gao, ZT Zhang, LZ He, WW Yin, JJ AF Ai, Zhihui Gao, Zhiting Zhang, Lizhi He, Weiwei Yin, Jun Jie TI Core-Shell Structure Dependent Reactivity of Fe@Fe2O3 Nanowires on Aerobic Degradation of 4-Chlorophenol SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Article ID ZERO-VALENT IRON; AQUEOUS SUSPENSIONS; FENTON SYSTEM; NANOPARTICLES; REAGENT; OXYGEN; SPECTROSCOPY; OXIDATION; MAGNETITE; EFFICIENT AB In this study, core-shell Fe@Fe2O3 nanowires with different iron oxide shell thickness were synthesized through tuning water-aging time after the reduction of ferric ions with sodium borohydride without any stirring. We found that these Fe@Fe2O3 nanowires exhibited interesting core shell structure dependent reactivity on the aerobic degradation of 4-chlorophenol. Characterization results revealed that the core shell structure dependent aerobic oxidative reactivity of Fe@Fe2O3 nanowires was arisen from the combined effects of incrassated iron oxide shell and more surface bound ferrous ions on amorphous iron oxide shell formed during the water-aging process. The incrassated iron oxide shell would gradually block the outward electron transfer from iron core for the subsequent two electron molecular oxygen activation, but more surface bound ferrous ions on iron oxide shell with prolonging aging time could favor the single electron molecular oxygen activation, which was confirmed by electron spin resonance spectroscopy with spin trap technique. The mineralization of 4-chlorophenol was monitored by total organic carbon measurement and the oxidative degradation intermediates were analyzed by gas chromatography-mass spectrometry. This study provides new physical insight on the molecular oxygen activation mechanism of nanoscale zerovalent iron and its application on aerobic pollutant removal. C1 [Ai, Zhihui; Gao, Zhiting; Zhang, Lizhi] Cent China Normal Univ, Coll Chem, Inst Environm Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China. [He, Weiwei; Yin, Jun Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Zhang, LZ (reprint author), Cent China Normal Univ, Coll Chem, Inst Environm Chem, Key Lab Pesticide & Chem Biol,Minist Educ, Wuhan 430079, Peoples R China. EM zhanglz@mail.ccnu.edu.cn RI Yin, Jun Jie /E-5619-2014 FU National Science Foundation of China [21073069, 91023010, 21173093, 21177048]; Changjiang Scholars and Innovative Research Team in University [IRT0953]; regulatory science grant under the FDA Nanotechnology CORES Program; Office of Cosmetics and Colors, CFSAN/FDA FX This work was supported by National Science Foundation of China (Grants 21073069, 91023010, 21173093, and 21177048), and Changjiang Scholars and Innovative Research Team in University (Grant IRT0953), and a regulatory science grant under the FDA Nanotechnology CORES Program and by the Office of Cosmetics and Colors, CFSAN/FDA (W.H and J.Y). This article is not an official US Food and Drug Administration (FDA) guidance or policy statement. No official support or endorsement by the US FDA is intended or should be inferred. NR 40 TC 66 Z9 70 U1 31 U2 212 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD MAY 21 PY 2013 VL 47 IS 10 BP 5344 EP 5352 DI 10.1021/es4005202 PG 9 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 154WY UT WOS:000319708600047 PM 23618059 ER PT J AU Karzai, FH Madan, RA Apolo, AB Ning, YMM Parnes, HL Arlen, PM Beatson, MA Harold, N Couvillon, A Wright, JJ Chen, C Dawson, NA Gulley, JL Figg, WD Dahut, WL AF Karzai, Fatima H. Madan, Ravi Amrit Apolo, Andrea Borghese Ning, Yangmin M. Parnes, Howard L. Arlen, Philip M. Beatson, Melony A. Harold, Nancy Couvillon, Anna Wright, John Joseph Chen, Clara Dawson, Nancy Ann Gulley, James L. Figg, William Douglas Dahut, William L. TI Use of supportive measures to improve outcome and decrease toxicity in docetaxel-based antiangiogenesis combinations in metastatic castrate resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol & Biol, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. NCI, US FDA, Silver Spring, MD USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. Neogenix Oncol, Rockville, MD USA. NCI, Rockville, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Georgetown Lombardi Comprehens Canc Ctr, Washington, DC USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA e16017 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419604209 ER PT J AU Komiya, T Blumenthal, GM Ballas, MS Dechowdhury, R Manu, M Fioravanti, S Hornyak, TJ Wank, S Weinstein, D Morris, J Hewitt, SM Memmott, R Dennis, PA Morrow, B AF Komiya, Takefumi Blumenthal, Gideon Michael Ballas, Marc S. Dechowdhury, Roopa Manu, Michell Fioravanti, Suzanne Hornyak, Thomas J. Wank, Stephen Weinstein, Douglas Morris, Jennifer Hewitt, Stephen M. Memmott, Regan Dennis, Phillip A. Morrow, Betsy TI A pilot study of sirolimus (S) in subjects with Cowden syndrome (CS) with germ-line mutations in PTEN. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. US FDA, Silver Spring, MD USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Maryland Oncol Hematol, Silver Spring, MD USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIDDK, Bethesda, MD 20892 USA. NCI, Laboraory Pathol, Gaithersburg, MD USA. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2532 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601050 ER PT J AU Weiss, M Gertz, MA Little, RF Rajkumar, V Jacobus, SJ Abonour, R Anderson, KC Barlogie, B Callander, NS Gorak, EJ Matous, J Mills, GM Kane, RC Katz, MS Jensen, L Omel, J Orlowski, RZ Richardson, PGG Munshi, NC AF Weiss, Matthias Gertz, Morie A. Little, Richard F. Rajkumar, Vincent Jacobus, Susanna J. Abonour, Rafat Anderson, Kenneth Carl Barlogie, Bart Callander, Natalie Scott Gorak, Edward J. Matous, Jeffrey Mills, Glenn Morris Kane, Robert C. Katz, Michael S. Jensen, LeeAnn Omel, James Orlowski, Robert Z. Richardson, Paul Gerard Guy Munshi, Nikhil C. TI Strategies to overcome barriers to accrual (BtA) to NCI-sponsored clinical trials: A project of the NCI-Myeloma Steering Committee Accrual Working Group (NCI-MYSC AWG) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. Mayo Clin, Rochester, MN USA. NCI, Rockville, MD USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA. Myeloma Inst Res & Therapy, Little Rock, AR USA. Univ Wisconsin, Madison, WI USA. Geisinger Med Ctr, Danville, PA 17822 USA. Rocky Mt Canc Centers, Denver, CO USA. LSU Hlth Sci Ctr, Shreveport, LA USA. US FDA, Silver Spring, MD USA. Int Myeloma Fdn, North Hollywood, CA USA. Patient Advocate, Rockville, MD USA. Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. VA Boston Healthcare Syst, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 8592 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419602687 ER PT J AU Yang, J Mehrotra, N Zhao, H Giusti, RM Demko, S Keegan, P Booth, B Rahman, NA AF Yang, Jun Mehrotra, Nitin Zhao, Hong Giusti, Ruthann Marie Demko, Suzanne Keegan, Patricia Booth, Brian Rahman, Nam Atiqur TI Characterization of the exposure-response relationship leading to recommendations for dosing optimization in a new drug application review. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 04, 2013 CL Chicago, IL SP Amer Soc Clin Oncol C1 [Yang, Jun; Mehrotra, Nitin; Zhao, Hong; Giusti, Ruthann Marie; Demko, Suzanne; Keegan, Patricia; Booth, Brian; Rahman, Nam Atiqur] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2013 VL 31 IS 15 SU S MA 2510 PG 1 WC Oncology SC Oncology GA AG4VY UT WOS:000335419601028 ER PT J AU Taylor, KA Holquist, CA AF Taylor, Kellie A. Holquist, Carol A. TI More on Confusion of Drug Names SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Taylor, Kellie A.; Holquist, Carol A.] US FDA, Silver Spring, MD USA. RP Taylor, KA (reprint author), US FDA, Silver Spring, MD USA. EM kellie.taylor@fda.hhs.gov NR 5 TC 0 Z9 0 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 2013 VL 368 IS 20 BP 1946 EP 1947 DI 10.1056/NEJMc1302801 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 143VK UT WOS:000318896200022 PM 23675670 ER PT J AU Bhalli, JA Ding, W Shaddock, JG Pearce, MG Dobrovolsky, VN Heflich, RH AF Bhalli, Javed A. Ding, Wei Shaddock, Joseph G. Pearce, Mason G. Dobrovolsky, Vasily N. Heflich, Robert H. TI Evaluating the weak in vivo micronucleus response of a genotoxic carcinogen, Aristolochic acids SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Bone marrow; Red blood cells; Pig-a assay; Comet assay; Hprt lymphocyte assay ID ETHYL-N-NITROSOUREA; DNA ADDUCT FORMATION; PIG-A; COMET ASSAY; SALMONELLA-TYPHIMURIUM; HUMAN-LYMPHOCYTES; MUTATION ASSAY; BONE-MARROW; END-POINTS; MUTAGENICITY AB Aristolochic acids (AAs) are carcinogenic plant toxins that are relatively strong gene mutagens, both in vitro and in vivo, but weak inducers of micronuclei in vivo. In order to clarify the reasons for these disparate responses, we evaluated the genotoxicity of AAs in F344 rats using several assays that respond to DNA damage in bone marrow. Groups of 7- to 8-week-old male rats (n = 6) were gavaged with 0, 2.75, 5.5, and 11 mg/kg AAs for 28 days or with 0, 11, 22, and 30 mg/kg AAs for 3 days. Day 1 being the first day of treatment, Pig-a mutant frequencies (MFs) were assayed in peripheral blood erythrocytes up to Day 56 for the 28-day treatment or Day 42 for the 3-day treatment; micronuclei were assayed in peripheral blood reticulocytes on Day 4 (both treatment protocols) and on Day 29 of the 28-day treatment protocol; and at the final sampling times (Day 59 or Day 42), the animals were sacrificed and Hprt mutant lymphocytes were measured. In a separate study, the Comet assay was performed on liver, kidney, and bone marrow of animals gavaged with 0, 11, 22, and 30 mg/kg AAs for 4 days and sacrificed 3 h after the last treatment. While only weak increases in micronucleated reticulocyte frequency were observed in treated animals, Pig-a MFs increased in a dose- and time-dependent manner with both treatment schedules. Lymphocyte Hprt mutant frequencies also increased dose dependently in treated animals, and the Comet assay detected elevated levels of DNA damage in all the tissues evaluated. These findings indicate that the DNA damage produced by AAs in rat bone marrow is a weak inducer of micronuclei but a relatively strong inducer of gene mutation. Published by Elsevier B.V. C1 [Bhalli, Javed A.; Ding, Wei; Shaddock, Joseph G.; Pearce, Mason G.; Dobrovolsky, Vasily N.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Heflich, RH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov FU U.S. Food and Drug Administration/National Center for Toxicological Research; U.S. National Institute of Environmental Health Sciences [R44ES018017]; Oak Ridge Institute for Science and Education FX This work was supported by institutional funds from the U.S. Food and Drug Administration/National Center for Toxicological Research. Prototype kits supplied free of charge by Litron Laboratories were used to conduct the Pig-a assays. The contribution by Litron Laboratories was supported by a grant from the U.S. National Institute of Environmental Health Sciences, no. R44ES018017. JAB was supported by a postdoctoral appointment administered by the Oak Ridge Institute for Science and Education. NR 39 TC 7 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 15 PY 2013 VL 753 IS 2 BP 82 EP 92 DI 10.1016/j.mrgentox.2013.03.002 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 160BF UT WOS:000320090500004 PM 23500662 ER PT J AU Sridhara, R Mandrekar, SJ Dodd, LE AF Sridhara, Rajeshwari Mandrekar, Sumithra J. Dodd, Lori E. TI Missing Data and Measurement Variability in Assessing Progression-Free Survival Endpoint in Randomized Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR PROGRESSION; ONCOLOGY; CANCER; METAANALYSIS AB Progression-free survival (PFS) is frequently used as the primary efficacy endpoint in the evaluation of cancer treatment that is considered for marketing approval. Missing or incomplete data problems become more acute with a PFS endpoint (compared with overall survival). In a given clinical trial, it is common to observe incomplete data due to premature treatment discontinuation, missed or flawed assessments, change of treatment, lack of follow-up, and unevaluable data. When incomplete data issues are substantial, interpretation of the data becomes tenuous. Plans to prevent, minimize, or properly analyze incomplete data are critical for generalizability of results from the clinical trial. Variability in progressive disease measurement between radiologists further contributes to data problems with a PFS endpoint. The repercussions of this on phase III clinical trials are complex and depend on several factors, including the magnitude of the variability and whether there is a systematic reader evaluation bias favoring one treatment arm particularly in open-label trials. (C) 2013 AACR. C1 [Sridhara, Rajeshwari] US FDA, CDER OTS OB DBV, Silver Spring, MD 20993 USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Mandrekar, Sumithra J.] Mayo Clin, Div Biomed Stat & Informat, Rochester, MN USA. RP Sridhara, R (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rajeshwari.sridhara@fda.hhs.gov; doddl@mail.nih.gov NR 22 TC 10 Z9 10 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2013 VL 19 IS 10 BP 2613 EP 2620 DI 10.1158/1078-0432.CCR-12-2938 PG 8 WC Oncology SC Oncology GA 144AO UT WOS:000318911600005 PM 23669421 ER PT J AU Zhang, JJ Zhang, LJ Chen, HY Murgo, AJ Dodd, LE Pazdur, R Sridhara, R AF Zhang, Jenny J. Zhang, Lijun Chen, Huanyu Murgo, Anthony J. Dodd, Lori E. Pazdur, Richard Sridhara, Rajeshwari TI Assessment of Audit Methodologies for Bias Evaluation of Tumor Progression in Oncology Clinical Trials SO CLINICAL CANCER RESEARCH LA English DT Article ID METAANALYSIS AB As progression-free survival (PFS) has become increasingly used as the primary endpoint in oncology phase III trials, the U.S. Food and Drug Administration (FDA) has generally required a complete-case blinded independent central review (BICR) of PFS to assess and reduce potential bias in the investigator or local site evaluation. However, recent publications and FDA analyses have shown a high correlation between local site evaluation and BICR assessments of the PFS treatment effect, which questions whether complete-case BICR is necessary. One potential alternative is to use BICR as an audit tool to detect evaluation bias in the local site evaluation. In this article, the performance characteristics of two audit methods proposed in the literature are evaluated on 26 prospective, randomized phase III registration trials in nonhematologic malignancies. The results support that a BICR audit to assess potential bias in the local site evaluation is a feasible approach. However, implementation and logistical challenges need further consideration and discussion. (C) 2013 AACR. C1 [Zhang, Jenny J.; Zhang, Lijun; Chen, Huanyu; Sridhara, Rajeshwari] US FDA, Div Biometr 5, Off Biostat, Off Translat Sci, Silver Spring, MD 20993 USA. [Murgo, Anthony J.; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Off New Drugs, Ctr Drug Evaluat Res, Silver Spring, MD 20993 USA. [Dodd, Lori E.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. RP Sridhara, R (reprint author), US FDA, WO21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rajeshwari.sridhara@fda.hhs.gov NR 8 TC 8 Z9 8 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2013 VL 19 IS 10 BP 2637 EP 2645 DI 10.1158/1078-0432.CCR-12-3364 PG 9 WC Oncology SC Oncology GA 144AO UT WOS:000318911600008 PM 23532893 ER PT J AU Lontok, E Mani, N Harrington, PR Miller, V AF Lontok, Erik Mani, Nina Harrington, Patrick R. Miller, Veronica TI Closing in on the Target: Sustained Virologic Response in Hepatitis C Virus Genotype 1 Infection Response-Guided Therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Article DE direct-acting antiviral (DAA); hepatitis C virus (HCV); lower limit of quantitation (LLOQ) ID INTERFERON-ALPHA-2B PLUS RIBAVIRIN; ALPHA-2A (40 KD)/RIBAVIRIN; AMERICAN ASSOCIATION; ANTIVIRAL THERAPY; BOCEPREVIR; TELAPREVIR; MANAGEMENT; UPDATE; ASSAYS; RNA AB Retrospective analyses of the boceprevir and telaprevir phase 3 trial data demonstrate the clinical relevance of detected but not quantifiable hepatitis C virus (HCV) genotype 1 RNA during treatment. These analyses illustrate the importance of using precise and standard terminology in reporting low-level HCV RNA results for consistent data collection across clinical trials, and to ensure optimal virologic response-guided treatment decision making in clinical practice. In the context of currently available quantitative HCV RNA assays, we clarify that unquantifiable HCV RNA should be classified as target detected or target not detected, as both have been shown to reflect clinically different qualitative HCV RNA levels during treatment. Additionally, use of terms such as "undetectable" or "below limit of detection" should be avoided as such terms are imprecise, not consistently defined, and often misinterpreted. C1 [Lontok, Erik; Mani, Nina; Miller, Veronica] Univ Calif Berkeley, Forum Collaborat HIV Res, Washington, DC 20036 USA. [Harrington, Patrick R.] US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Div Antiviral Prod, Silver Spring, MD USA. RP Lontok, E (reprint author), Univ Calif Berkeley, Forum Collaborat HIV Res, 1608 Rhode Isl Ave NW,Ste 212, Washington, DC 20036 USA. EM elontok@hivforum.org FU Forum for Collaborative HIV Research for the HCV Drug Development Advisory Group Project FX Staff work involved in the writing of the manuscript (E. L., N. M., and V. M.) was supported by unrestricted grants received by the Forum for Collaborative HIV Research for the HCV Drug Development Advisory Group Project. NR 38 TC 4 Z9 4 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 MAY 15 PY 2013 VL 56 IS 10 BP 1466 EP 1470 DI 10.1093/cid/cit025 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 140EF UT WOS:000318636500020 PM 23362287 ER PT J AU Toh, S Baker, MA Brown, JS Kornegay, C Platt, R AF Toh, Sengwee Baker, Meghan A. Brown, Jeffrey S. Kornegay, Cynthia Platt, Richard CA Mini-Sentinel Investigators TI Rapid Assessment of Cardiovascular Risk Among Users of Smoking Cessation Drugs Within the US Food and Drug Administration's Mini-Sentinel Program SO JAMA INTERNAL MEDICINE LA English DT Letter ID VARENICLINE; METAANALYSIS C1 [Toh, Sengwee; Baker, Meghan A.; Brown, Jeffrey S.; Platt, Richard] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Toh, Sengwee; Baker, Meghan A.; Brown, Jeffrey S.; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Kornegay, Cynthia] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Toh, S (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM darrentoh@post.harvard.edu RI Toh, Sengwee/D-7567-2017; OI Toh, Sengwee/0000-0002-5160-0810; Kawatkar, Aniket/0000-0001-6810-6467 FU PHS HHS [HHSF223200910006] NR 9 TC 14 Z9 14 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAY 13 PY 2013 VL 173 IS 9 BP 817 EP 819 DI 10.1001/jamainternmed.2013.3004 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 159JN UT WOS:000320041800024 PM 23529063 ER PT J AU Ji, Y Wang, SJ AF Ji, Yuan Wang, Sue-Jane TI Modified Toxicity Probability Interval Design: A Safer and More Reliable Method Than the 3+3 Design for Practical Phase I Trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CONTINUAL REASSESSMENT METHOD; CLINICAL-TRIALS; SOLID TUMORS; CANCER AB The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes. (C) 2013 by American Society of Clinical Oncology C1 [Ji, Yuan] NorthShore Univ HealthSyst, Ctr Clin & Res Informat, Evanston, IL 60201 USA. [Wang, Sue-Jane] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Ji, Y (reprint author), NorthShore Univ HealthSyst, Ctr Clin & Res Informat, 1001 Univ Pl, Evanston, IL 60201 USA. EM yji@northshore.org NR 21 TC 24 Z9 25 U1 0 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 10 PY 2013 VL 31 IS 14 BP 1785 EP + DI 10.1200/JCO.2012.45.7903 PG 12 WC Oncology SC Oncology GA 141ZW UT WOS:000318766300018 PM 23569307 ER PT J AU Hayward, DG Wong, JW Shi, F Zhang, K Lee, NS DiBenedetto, AL Hengel, MJ AF Hayward, Douglas G. Wong, Jon W. Shi, Feng Zhang, Kai Lee, Nathaniel S. DiBenedetto, Alex L. Hengel, Mathew J. TI Multiresidue Pesticide Analysis of Botanical Dietary Supplements Using Salt-out Acetonitrile Extraction, Solid-Phase Extraction Cleanup Column, and Gas Chromatography-Triple Quadrupole Mass Spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID LIQUID-CHROMATOGRAPHY; GINSENG ROOT; ORGANOCHLORINE PESTICIDES; SAMPLE PREPARATION; RESIDUES; VEGETABLES; FRUITS; PRODUCE; CONTAMINANTS; METALS AB Dietary supplements form an increasing part of the American diet, yet broadly applicable multiresidue pesticide methods have not been evaluated for many of these supplements. A method for the analysis of 310 pesticides, isomers, and pesticide metabolites in dried botanical dietary supplements has been developed and validated. Sample preparation involved acetonitrile:water added to the botanical along with anhydrous magnesium sulfate and sodium chloride for extraction, followed by cleanup with solid-phase extraction using a tandem cartridge consisting of graphitized carbon black (GCB) and primary secondary amine sorbent (PSA). Pesticides were measured by gas chromatography-tandem mass spectrometry. Accuracy and precision were evaluated through fortifications of 24 botanicals at 10, 25, 100, and 500 mu g/kg. Mean pesticide recoveries and relative standard deviations (RSDs) for all botanicals were 97%, 91%, 90%, and 90% and 15%, 10%, 8%, and 6% at 10, 25, 100, and 500 mu g/kg, respectively. The method was applied to 21 incurred botanicals. Quinoxyfen was measured in hops (100-620 mu g/kg). Tetraconazole (48 mu g/kg), tetramethrin (15 mu g/kg), methamidophos (50 pg/kg), and chlorpyrifos (93 mu g/kg) were measured in licorice, mallow, tea, and tribulus, respectively. Quintozene, its metabolites and contaminants (pentachloroaniline, pentachlorobenzene, pentachloroanisole, and pentachlorothioanisole and hexachlorobenzene and tecnazene, respectively), with hexachlorocyclohexanes and DDT were identified in ginseng sources along with azoxystrobin, diazinon, and dimethomorph between 0.7 and 2800 mu g/kg. Validation with these botanicals demonstrated the extent of this method's applicability for screening 310 pesticides in a wide array of botanical dietary supplements. C1 [Hayward, Douglas G.; Wong, Jon W.; Zhang, Kai] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lee, Nathaniel S.; DiBenedetto, Alex L.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Hengel, Mathew J.] Univ Calif Davis, Dept Environm Toxicol, IR Lab 4, Davis, CA 95616 USA. RP Hayward, DG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 706, College Pk, MD 20740 USA. EM douglas.hayward@fda.hhs.gov; jon.wong@fda.hhs.gov FU Office of Dietary Supplements, National Institutes of Health FX We appreciate the Office of Dietary Supplements, National Institutes of Health for financial support of this research through an interagency agreement and the United States Environmental Protection Agency, National Pesticide Repository, Ft. Meade, MD for providing a majority of the pesticide standards used in these studies. NR 32 TC 20 Z9 22 U1 9 U2 91 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD MAY 7 PY 2013 VL 85 IS 9 BP 4686 EP 4693 DI 10.1021/ac400481w PG 8 WC Chemistry, Analytical SC Chemistry GA 141WB UT WOS:000318756100067 PM 23534560 ER PT J AU Husten, CG Deyton, LR AF Husten, Corinne G. Deyton, Lawrence R. TI Tobacco Control 1 Understanding the Tobacco Control Act: efforts by the US Food and Drug Administration to make tobacco-related morbidity and mortality part of the USA's past, not its future SO LANCET LA English DT Article ID SMOKING-CESSATION; CONTROL PROGRAM; IMPACT; CIGARETTES; BENEFITS; HEALTH AB The USA has a rich history of public health efforts to reduce morbidity and mortality from tobacco use. Comprehensive tobacco-prevention programmes, when robustly implemented, reduce the prevalence of youth and adult smoking, decrease cigarette consumption, accelerate declines in tobacco-related deaths, and diminish healthcare costs from tobacco-related diseases. Effective public health interventions include raising the price of tobacco products, smoke-free policies, counter-marketing campaigns, advertising restrictions, augmenting access to treatment for tobacco use through insurance coverage and telephone help lines, and comprehensive approaches to prevent children and adolescents from accessing tobacco products. The US Food and Drug Administration (FDA) has six major areas of regulatory authority: regulation of tobacco products; regulation of the advertising, marketing, and promotion of tobacco products; regulation of the distribution and sales of tobacco products; enforcement of the provisions of the Tobacco Control Act and tobacco regulations; regulatory science to support FDA authorities and activities; and public education about the harms of tobacco products and to support FDA regulatory actions. With passing of the Family Smoking Prevention and Tobacco Control Act (Tobacco Control Act) in June, 2009, important new regulatory approaches were added to the tobacco prevention and control arsenal. C1 [Husten, Corinne G.] US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. [Deyton, Lawrence R.] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. RP Husten, CG (reprint author), US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. EM corinne.husten@fda.hhs.gov NR 43 TC 26 Z9 26 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAY 4 PY 2013 VL 381 IS 9877 BP 1570 EP 1580 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 139UF UT WOS:000318609600032 PM 23642698 ER PT J AU Battistel, MD Pendrill, R Widmalm, G Freedberg, DI AF Battistel, Marcos D. Pendrill, Robert Widmalm, Goeran Freedberg, Daron I. TI Direct Evidence for Hydrogen Bonding in Glycans: A Combined NMR and Molecular Dynamics Study SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID HETERONUCLEAR COUPLING-CONSTANTS; NUCLEAR-MAGNETIC-RESONANCE; AQUEOUS-SOLUTION; NEUTRON-DIFFRACTION; 1,3-AND 1,4-DIOLS; HYDROXYL PROTONS; SUCROSE; SPECTROSCOPY; WATER; EQUILIBRIUM AB We introduce the abundant hydroxyl groups of glycans as NMR handle's and structural probes to expand the repertoire of tools for structure function studies on glycans in solution. To this end, we present the facile detection and assignment of hydroxyl groups in a Wide range of sample concentrations (0.5-1700 mM) and temperatures, ranging from -5 to 25 degrees C.,We then exploit this information to directly detect hydrogen bonds, well-known for their importance in molecular structural determination through NMR. Via HSQC-TOCSY, we were able to determine the directionality; of these hydrogen bonds in sucrose Furthermore, by means Of molecular dynamics simulations in conjunction with NMR, we establish that one Out of the three detected hydrogen bonds arises from intermolecular interactions. This finding may shed light on glycan glycan interactions and glycan recognition by proteins. C1 [Battistel, Marcos D.; Freedberg, Daron I.] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Pendrill, Robert; Widmalm, Goeran] Univ Stockholm, Arrhenius Lab, Dept Organ Chem, S-10691 Stockholm, Sweden. RP Freedberg, DI (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM daron.freedberg@fda.hhs.gov FU CBER/FDA; Swedish Research Council FX We gratefully acknowledge helpful discussions with Drs. Dennis A. Torchia, Hugo Azurmendi, and Bingwu Yu. This work was supported by intramural funds from CBER/FDA (M.D.B. and D.I.F.) and a grant from the Swedish Research Council (R.P. and G.W.). Computing resources were kindly provided by the Center for Parallel Computers (PDC), Stockholm, Sweden. NR 63 TC 15 Z9 15 U1 2 U2 45 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAY 2 PY 2013 VL 117 IS 17 BP 4860 EP 4869 DI 10.1021/jp400402b PG 10 WC Chemistry, Physical SC Chemistry GA 138UY UT WOS:000318536700015 PM 23531151 ER PT J AU Mosholder, AD Mathew, J Alexander, JJ Smith, H Nambiar, S AF Mosholder, Andrew D. Mathew, Justin Alexander, John J. Smith, Harry Nambiar, Sumathi TI Cardiovascular Risks with Azithromycin and Other Antibacterial Drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MORTALITY; PNEUMONIA; DEATH C1 [Mosholder, Andrew D.; Mathew, Justin] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol 2, Silver Spring, MD USA. [Alexander, John J.; Nambiar, Sumathi] US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Div Antiinfect Prod, Silver Spring, MD USA. [Smith, Harry] US FDA, Ctr Drug Evaluat & Res, Off Commun, Div Hlth Commun, Silver Spring, MD USA. RP Mosholder, AD (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol 2, Silver Spring, MD USA. NR 5 TC 36 Z9 39 U1 1 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 2 PY 2013 VL 368 IS 18 BP 1665 EP 1668 DI 10.1056/NEJMp1302726 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 134MN UT WOS:000318214400014 PM 23635046 ER PT J AU Wang, C Liu, F Fogle, CM Paule, MG Slikker, W AF Wang, C. Liu, F. Fogle, C. M. Paule, M. G. Slikker, W. TI L-CARNITINE AMELIORATES PROPOFOL-INDUCED TOXICITY IN RAT EMBRYONIC NEURAL STEM CELLS SO ANESTHESIA AND ANALGESIA LA English DT Meeting Abstract CT Annual Meeting of the International-Anesthesia-Research-Society CY MAY 04-07, 2013 CL San Diego, CA SP Int Anesthesia Res Soc C1 [Wang, C.; Liu, F.; Fogle, C. M.; Paule, M. G.; Slikker, W.] Natl Ctr Toxicol Res, Jefferson, AR 72079 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 0003-2999 EI 1526-7598 J9 ANESTH ANALG JI Anesth. Analg. PD MAY PY 2013 VL 116 SU 1 MA S327 BP 266 EP 266 PG 1 WC Anesthesiology SC Anesthesiology GA 300CJ UT WOS:000330441700231 ER PT J AU Bewernitz, M Garnett, C Gottlieb, K Krudys, K Mulberg, AE Johnson, AP Rajpal, A Wang, YM Zhou, L Bugin, K Mehrotra, N AF Bewernitz, Michael Garnett, Christine Gottlieb, Klaus Krudys, Kevin Mulberg, Andrew E. Johnson, Aisha P. Rajpal, Anil Wang, Yow-Ming Zhou, Lin Bugin, Kevin Mehrotra, Nitin TI Assessment of Adalimumab Dose Selection for Adult Ulcerative Colitis Using Exposure-Response Analyses SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Meeting Abstract C1 [Bewernitz, Michael] US FDA, Div Clin Pharmacol 1, OCP, Silver Spring, MD USA. [Gottlieb, Klaus; Mulberg, Andrew E.; Johnson, Aisha P.; Rajpal, Anil; Bugin, Kevin] US FDA, Div Gastroenterol & Inborn Errors Prod, Off New Drugs, Silver Spring, MD USA. [Garnett, Christine; Krudys, Kevin; Mehrotra, Nitin] US FDA, Div Pharmacometr, OCP, Silver Spring, MD USA. [Wang, Yow-Ming; Zhou, Lin] US FDA, Div Clin Pharmacol 3, OCP, Silver Spring, MD USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD MAY PY 2013 VL 40 SU 1 BP S44 EP S45 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295OS UT WOS:000330126000041 ER PT J AU Ma, LA Ji, P Wang, YN Zhao, L Xu, Y Doddapaneni, S Sahajwalla, CG AF Ma, Lian Ji, Ping Wang, Yaning Zhao, Liang Xu, Yun Doddapaneni, Suresh Sahajwalla, Chandrahas G. TI Exposure-Response Modeling and Simulation of the Efficacy Endpoints in Rheumatoid Arthritis SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Meeting Abstract C1 [Ma, Lian; Ji, Ping; Zhao, Liang; Xu, Yun; Doddapaneni, Suresh; Sahajwalla, Chandrahas G.] US FDA, Div Clin Pharmacol 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Wang, Yaning] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD MAY PY 2013 VL 40 SU 1 BP S73 EP S73 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295OS UT WOS:000330126000075 ER PT J AU Yu, JY Chung, S Zadezensky, I Mehrotra, N AF Yu, Jing-yu Chung, Sang Zadezensky, Immo Mehrotra, Nitin TI Exposure-Response Analysis to Assess the Proposed Starting Dose of Pasireotide for the Treatment of Cushing's Disease SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Meeting Abstract C1 [Yu, Jing-yu; Mehrotra, Nitin] US FDA, Div Pharmacometr, Off Clin Pharmacol, CDER, Silver Spring, MD USA. [Chung, Sang; Zadezensky, Immo] US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X EI 1573-8744 J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD MAY PY 2013 VL 40 SU 1 BP S120 EP S121 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 295OS UT WOS:000330126000130 ER PT J AU Liu, NT Lefcourt, AM Nou, XW Shelton, DR Zhang, GD Lo, YM AF Liu, Nancy T. Lefcourt, Alan M. Nou, Xiangwu Shelton, Daniel R. Zhang, Guodong Lo, Y. Martin TI Native Microflora in Fresh-Cut Produce Processing Plants and Their Potentials for Biofilm Formation SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI; BACTERIAL BIOFILMS; FOOD-INDUSTRY; DISINFECTION; O157H7; MICROORGANISMS; CONTAMINATION; ENVIRONMENT; VEGETABLES; RESISTANCE AB Representative food contact and nonfood contact surfaces in two mid-sized, fresh-cut processing facilities were sampled for microbiological analyses after routine daily sanitization. Mesophilic and psychrotrophic bacteria on the sampled surfaces were isolated by plating on nonselective bacterial media. Alternatively, bacteria were isolated after an incubation period that allowed the formation of heterogeneous biofilms on stainless steel beads. Of over 1,000 tested isolates, most were capable of forming biofilms, with approximately 30% being strong or moderate biofilm formers. Selected isolates (117) were subjected to species identification by using the Biolog Gen III microbial identification system. They distributed among 23 genera, which included soil bacteria, plant-related bacteria, coliforms, and opportunistic plant-or human-pathogenic bacteria. The most commonly identified bacteria species were Pseudomonas fluorescens, Rahnella aquatilis, and Ralstonia insidiosa. The high prevalence of R. insidiosa, a strong biofilm former, and P. fluorescens, a moderate biofilm former, suggests that they were established residents in the sampled plants. These results suggest that native microflora capable of forming biofilms are widely distributed in fresh-produce processing environments. C1 [Liu, Nancy T.; Lo, Y. Martin] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20740 USA. [Liu, Nancy T.; Lefcourt, Alan M.; Nou, Xiangwu; Shelton, Daniel R.] ARS, USDA, Environm Microbial & Food Safety Lab, Beltsville, MD 20705 USA. [Zhang, Guodong] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Microbiol, College Pk, MD 20740 USA. RP Nou, XW (reprint author), ARS, USDA, Environm Microbial & Food Safety Lab, Bldg 173 BARC East,Powder Mill Rd, Beltsville, MD 20705 USA. EM Xiangwu.nou@ars.usda.gov NR 24 TC 16 Z9 16 U1 2 U2 23 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2013 VL 76 IS 5 BP 827 EP 832 DI 10.4315/0362-028X.JFP-12-433 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FN UT WOS:000326080500011 PM 23643124 ER PT J AU Lin, A Kase, JA Moore, MM Son, I Tran, N Clotilde, LM Jarvis, K Jones, K Kasturi, K Nabe, K Nucci, M Wagley, GS Wang, F Ge, BL Hammack, TS AF Lin, Andrew Kase, Julie A. Moore, Michelle M. Son, Insook Tran, Nelly Clotilde, Laurie M. Jarvis, Karen Jones, Kelly Kasturi, Kuppuswamy Nabe, Khamphet Nucci, Melissa Wagley, Gail S. Wang, Fei Ge, Beilei Hammack, Thomas S. TI Multilaboratory Validation of a Luminex Microbead-Based Suspension Array for the Identification of the 11 Most Clinically Relevant Shiga Toxin-Producing Escherichia coli O Serogroups SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PATHOGENS AB Rapid and high-throughput identification and serotyping of Shiga toxin-producing Escherichia coli (STEC) O serogroups is important for detecting, investigating, and controlling STEC infection outbreaks and removing hazardous products from commerce. A Luminex microbead-based suspension array has been developed to identify the 11 most clinically relevant STEC serogroups: O26, O45, O91, O103, O104, O111, O113, O121, O128, O145, and O157. Here we present results of a blinded multilaboratory collaborative study involving 10 participants from nine laboratories using 55 unknown strains. From the total 495 analyses, two false-positive and three false- negative results were obtained, indicating the assay to be a rapid, high-throughput, and robust method for identifying clinically relevant STEC serogroups. C1 [Lin, Andrew; Clotilde, Laurie M.] US FDA, Alameda, CA 94502 USA. [Kase, Julie A.; Son, Insook; Hammack, Thomas S.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Moore, Michelle M.] US FDA, Pacific Reg Lab Northwest, Appl Technol Ctr, Bothell, WA 98021 USA. [Tran, Nelly] US FDA, Pacific Reg Lab Southwest, Irvine, CA 92612 USA. [Jarvis, Karen] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessments, Laurel, MD 20708 USA. [Jones, Kelly; Wang, Fei; Ge, Beilei] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Kasturi, Kuppuswamy] US FDA, Northeast Reg Lab, Jamaica, NY 11433 USA. [Nabe, Khamphet] US FDA, Pacific Reg Lab Northwest, Bothell, WA 98021 USA. [Nucci, Melissa] US FDA, Denver Dist Lab, Lakewood, CO 80225 USA. [Wagley, Gail S.] US FDA, Southeast Reg Lab, Atlanta, GA 30309 USA. RP Lin, A (reprint author), US FDA, Alameda, CA 94502 USA. EM andrew.lin@fda.hhs.gov FU California State University Program for Education and Research in Biotechnology FX The authors thank the STEC Center (National Food Safety and Toxicology Center, Michigan State University, East Lansing), J. Mark Carter (U.S. Department of Agriculture, Agricultural Research Services, Albany, CA), the Ohio Department of Agriculture (Reynoldsburg), Pennsylvania State University (University Park), FDA, Applied Technology Center (Bothell, WA), U.S. Department of Agriculture, Microbiological Data Program (Manassas, VA), and the Orange County Public Health Laboratory (Santa Ana, CA) for generously sharing their bacterial cultures. The authors also thank the FDA San Francisco District Laboratory, the FDA Office of Regulatory Science, and CFSAN Office of Regulatory Science for their support of this research. This work was supported by the California State University Program for Education and Research in Biotechnology. NR 11 TC 6 Z9 6 U1 0 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2013 VL 76 IS 5 BP 867 EP 870 DI 10.4315/0362-028X.JFP-12-468 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FN UT WOS:000326080500017 PM 23643130 ER PT J AU Ziobro, GC McElroy, KM AF Ziobro, George C. McElroy, Kevin M. TI Fluorometric Detection of Active Alkaline Phosphatase and Gamma-Glutamyl Transferase in Fluid Dairy Products from Multiple Species SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SHORT-TIME PASTEURIZER; HIGH-TEMPERATURE; MILK; INACTIVATION; TRANSPEPTIDASE; LACTOPEROXIDASE; ENZYMES AB Over the past 80 years, a variety of methods have been developed to detect underpasteurized or improperly pasteurized milks used in dairy products. Existing methods are hampered by duration of analysis, poor reproducibility, and in some cases the use of hazardous chemicals. To overcome these issues, two new methods have been developed using fluorogenic substrates for two marker enzymes, alkaline phosphatase and gamma-glutamyl transferase. In 30 min, up to 18 samples can be analyzed in triplicate by both methods on two separate 96-well plates. Sample preparation is not necessary for liquid milks when using these methods. The relative standard deviation for each assay is less than 9%, and the correlation coefficient for results of the two methods is greater than 0.98. Using the new methods, milks from four species and nine commercially available liquid milk products were tested. The new methods were also tested directly against an existing phosphatase method (Fluorophos) in spiked whole milk samples. C1 [Ziobro, George C.; McElroy, Kevin M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [McElroy, Kevin M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. [McElroy, Kevin M.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37830 USA. RP Ziobro, GC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM george.ziobro@fda.hhs.gov NR 31 TC 0 Z9 0 U1 1 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2013 VL 76 IS 5 BP 892 EP 898 DI 10.4315/0362-028X.JFP-12-302 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240FN UT WOS:000326080500023 PM 23643136 ER PT J AU Akkoyunlu, M Katsenelson, N Uslu, K Allman, W AF Akkoyunlu, Mustafa Katsenelson, Nora Uslu, Kadriye Allman, Windy TI Crucial role for TACI in TLR activation and macrophage phenotype determination SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Akkoyunlu, Mustafa; Katsenelson, Nora; Uslu, Kadriye; Allman, Windy] FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1206 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100205 ER PT J AU Alam, M Kuo, J Babu, U Ganies, D Pereira, M Williams, K AF Alam, Mohammad Kuo, Jennifer Babu, Uma Ganies, Dennis Pereira, Marion Williams, Kristina TI IL17A receptor (IL17RA) signaling is important for protection against oral infection with Listeria monocytogenes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Alam, Mohammad; Kuo, Jennifer; Babu, Uma; Ganies, Dennis; Pereira, Marion; Williams, Kristina] US FDA, Immunobiol DVA, Ctr Food Safety & Nutr, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4011 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104080 ER PT J AU Babu, U Balan, K Bigley, E Pereira, M Black, T Olejnik, N Keltner, Z Scott, M Sprnado, R AF Babu, Uma Balan, Kannan Bigley, Elmer Pereira, Marion Black, Thomas Olejnik, Nicholas Keltner, Zachary Scott, Michael Sprnado, Robert TI Effects of maternal silver acetate exposure on immune biomarkers in a rodent model SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Babu, Uma; Balan, Kannan; Bigley, Elmer; Pereira, Marion; Black, Thomas; Olejnik, Nicholas; Keltner, Zachary; Scott, Michael; Sprnado, Robert] US FDA, CFSAN, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1030 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100030 ER PT J AU Costales, M Alam, MS Williams, K AF Costales, Matthew Alam, Mohammad Samiul Williams, Kristina TI CD73 regulates nitric oxide production and inflammatory responses in Salmonella infected RAW 264.7 macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Costales, Matthew; Alam, Mohammad Samiul; Williams, Kristina] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4223 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105040 ER PT J AU Franco, A Damdinsuren, B Dement-Brown, J Li, HF Tolnay, M AF Franco, Andrea Damdinsuren, Bazarragchaa Dement-Brown, Jessica Li, Huifang Tolnay, Mate TI Human Fc receptor-like 5 interacts with key signaling proteins in B cells (P1116) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Franco, Andrea; Damdinsuren, Bazarragchaa; Dement-Brown, Jessica; Li, Huifang; Tolnay, Mate] US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987100117 ER PT J AU Huang, C D'Agnillo, F Golding, B AF Huang, Coty D'Agnillo, Felice Golding, Basil TI Poly (I:C) induces human endothelial barrier dysfunction by disrupting tight junction expression of claudin-5 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Huang, Coty; D'Agnillo, Felice; Golding, Basil] US FDA, DH, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4197 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105014 ER PT J AU Konduru, K Shurtleff, A Bavari, S Kaplan, G AF Konduru, Krishnamurthy Shurtleff, Amy Bavari, Sina Kaplan, Gerardo TI Evaluation of ebolavirus glycoprotein Fc fusion protein as a subunit vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Konduru, Krishnamurthy; Kaplan, Gerardo] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Shurtleff, Amy; Bavari, Sina] US Army Med Res Inst Infect Dis, Ft Detrick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4417 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105231 ER PT J AU Myers, M Deaver, C Peters, S Swaim, H Yancy, H AF Myers, Michael Deaver, Christine Peters, Sharla Swaim, Heidi Yancy, Haile TI Molecular characterization of an alternative model of inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Myers, Michael; Deaver, Christine; Peters, Sharla; Swaim, Heidi; Yancy, Haile] US FDA, Ctr Vet Med, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P1347 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987101096 ER PT J AU Ragheb, J Bushar, N AF Ragheb, Jack Bushar, Nicholas TI CD40L at the interface of the innate and adaptive immune responses. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Ragheb, Jack; Bushar, Nicholas] NIH, Immunol Lab, US FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P5206 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987107067 ER PT J AU Sakala, I Yankelevich, WJ Kjer-Nielsen, L Fairlie, D Rossjohn, J McCluskey, J Hoft, D Hansen, T AF Sakala, Isaac Yankelevich, Wei-Jen Kjer-Nielsen, Lars Fairlie, David Rossjohn, Jamie McCluskey, James Hoft, Daniel Hansen, Ted TI How MAIT cells control the growth of intracellular mycobacteria SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Sakala, Isaac; Hansen, Ted] Washington Univ, Dept Pathol & Immunol, Sch Med St Louis, St Louis, MO USA. [Yankelevich, Wei-Jen] US FDA, Bethesda, MD 20014 USA. [Kjer-Nielsen, Lars; McCluskey, James] Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. [Fairlie, David] Univ Queensland, Inst Mol Biosci, Div Chem & Struct Biol, Brisbane, Qld, Australia. [Hoft, Daniel] St Louis Univ, Sch Med, Divison Infect Dis Allergy & Immunol, St Louis, MO USA. [Rossjohn, Jamie] Monash Univ, Sch Biomed Sci, Dept Biochem & Mol Biol, Melbourne, Vic 3004, Australia. [Rossjohn, Jamie] Monash Univ, Australian Res Council Ctr Excellence Struct & Fu, Melbourne, Vic 3004, Australia. [Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales. [Hoft, Daniel] St Louis Univ, Sch Med, Dept Internal Med, St Louis, MO USA. [Hoft, Daniel] St Louis Univ, Sch Med, Dept Mol Microbiol, St Louis, MO USA. RI McCluskey, James/A-1291-2007 OI McCluskey, James/0000-0002-8597-815X NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4381 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105195 ER PT J AU Schaeffer, J Laddy, D Wachholder, R Anantha, R Imam, Z Morris, S Derrick, S Hokey, D AF Schaeffer, Jacqueline Laddy, Dominick Wachholder, Robert Anantha, Ravi Imam, Zakari Morris, Sheldon Derrick, Steven Hokey, David TI Efficacy of a prime/boost regimen including BCG and recombinant protein in an HN878 challenge of C57BL/6 mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Schaeffer, Jacqueline; Laddy, Dominick; Wachholder, Robert; Anantha, Ravi; Imam, Zakari; Hokey, David] Aeras, Rockville, MD USA. [Morris, Sheldon; Derrick, Steven] US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4296 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987105111 ER PT J AU Toomer, O Do, A Pereira, M Williams, K AF Toomer, Ondulla Do, Andrew Pereira, Marion Williams, Kristina TI The effect of simulated gastric and intestinal digestion on temporal stability and immunoreactivity of peanut, almond and pine nut protein allergens SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Toomer, Ondulla; Do, Andrew; Pereira, Marion; Williams, Kristina] US FDA, CFSAN OARSA DVA Immunobiol, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA 622 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987108043 ER PT J AU Zaitseva, M Endo, Y Romantseva, T Godling, H AF Zaitseva, Marina Endo, Yukinori Romantseva, Tatiana Godling, Hana TI Multiple pathways are employed by TLR and NOD agonists to induce PGE2 production in primary human monocytes and macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Zaitseva, Marina; Endo, Yukinori; Romantseva, Tatiana; Godling, Hana] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2013 VL 190 MA P4163 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104231 ER PT J AU Zelikoff, J Willis, D Degheidy, H Zhang, Q Umbreit, T Goering, P AF Zelikoff, Judith Willis, Daniel Degheidy, Heba Zhang, Qin Umbreit, Thomas Goering, Peter TI Immune cell profiles in response to silver nanoparticles associated with medical devices SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT 100th Annual Meeting of the American-Association-of-Immunologists CY MAY 03-07, 2013 CL Honolulu, HI SP Amer Assoc Immunologists C1 [Zelikoff, Judith; Willis, Daniel] NYU, Sch Med, Tuxedo Pk, NY USA. [Degheidy, Heba; Zhang, Qin; Umbreit, Thomas; Goering, Peter] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 MAY 1 PY 2013 VL 190 MA P3357 PG 1 WC Immunology SC Immunology GA 199ID UT WOS:000322987104032 ER PT J AU Brugnara, C Adamson, J Auerbach, M Kane, R Macdougall, I Mast, A AF Brugnara, Carlo Adamson, John Auerbach, Michael Kane, Robert Macdougall, Iain Mast, Alan TI Iron Deficiency: What Are the Future Trends in Diagnostics and Therapeutics? SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Brugnara, Carlo] Harvard Univ, Sch Med, Dept Lab Med, Boston Childrens Hosp, Boston, MA USA. [Adamson, John] Univ Calif San Diego, Dept Med, Div Hematol Oncol, La Jolla, CA 92093 USA. [Auerbach, Michael] Georgetown Univ, Sch Med, Washington, DC USA. [Kane, Robert] Ctr Drug Evaluat & Res, Div Hematol Prod, Silver Spring, MD USA. [Macdougall, Iain] Kings Coll Hosp NHS Fdn Trust, Renal Unit, London, England. [Mast, Alan] BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI USA. RP Brugnara, C (reprint author), Boston Childrens Hosp, 300 Longwood Ave,Bader 760, Boston, MA 02115 USA. EM carlo.brugnara@childrens.harvard.edu NR 0 TC 6 Z9 7 U1 0 U2 7 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD MAY PY 2013 VL 59 IS 5 BP 740 EP 745 DI 10.1373/clinchem.2012.182071 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 179UU UT WOS:000321547700007 PM 23150055 ER PT J AU Fotaki, N Gray, V Kesisoglou, F Mayock, S Mirza, T Salt, A Selen, A AF Fotaki, Nikoletta Gray, Vivian Kesisoglou, Filippos Mayock, Steve Mirza, Tahseen Salt, Alger Selen, Arzu TI Survey Results for In Vitro-In Vivo Correlations (IVIVC): Critical Variables for Success SO DISSOLUTION TECHNOLOGIES LA English DT Article AB This report summarizes the results of the "In Vitro-In Vivo Correlations (IVIVC): Critical Variables for Success" survey organized by the In Vitro Release and Dissolution Testing (IVRDT) and the QbD and Product Performance AAPS Focus Groups. This was a web-based survey conducted over a 26-day period from Wednesday, June 29, 2011, to Sunday, July 24, 2011, and results were initially presented at the 2011 AAPS Annual Meeting and Exposition. The goal was to describe the current views from scientists across academia, industry, and regulatory agencies on the adoption, utility, and benefits of IVIVCs and to begin identifying potentially critical variables for their success. Questions in the survey cover their development, use, and success. C1 [Fotaki, Nikoletta] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. [Gray, Vivian] Dissolut Technol, Hockessin, DE 19707 USA. [Kesisoglou, Filippos] Merck Sharp & Dohme Corp, Biopharmaceut Product Value Enhancement Pharmaceu, West Point, PA USA. [Mayock, Steve] Collegium Pharmaceut Inc, Canton, MA USA. [Mirza, Tahseen] US FDA, Off Mfg & Product Qual, Off Compliance, CDER, Silver Spring, MD USA. [Salt, Alger] GlaxoSmithKline, Product Dev Lab Automat & Platforms, Res Triangle Pk, NC USA. [Selen, Arzu] US FDA, Off New Drug Qual Assessment, CDER, Silver Spring, MD USA. RP Fotaki, N (reprint author), Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England. EM n.fotaki@bath.ac.uk NR 0 TC 1 Z9 1 U1 1 U2 5 PU DISSOLUTION TECHNOLOGIES, INC PI HOCKESSIN PA 9 YORKRIDGE TRAIL, HOCKESSIN, DE 19707-9633 USA SN 1521-298X J9 DISSOLUT TECHNOL JI Dissolut. Technol. PD MAY PY 2013 VL 20 IS 2 BP 48 EP 50 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 179SK UT WOS:000321541400007 ER PT J AU Read, EK Bradley, SA Smitka, TA Agarabi, CD Lute, SC Brorson, KA AF Read, Erik K. Bradley, Scott A. Smitka, Tim A. Agarabi, Cyrus D. Lute, Scott C. Brorson, Kurt A. TI Fermentanomics informed amino acid supplementation of an antibody producing mammalian cell culture SO BIOTECHNOLOGY PROGRESS LA English DT Article DE antibody; bioreactor; fermentanomics; glycans; hybridoma; monoclonal ID CHO-CELLS; MONOCLONAL-ANTIBODIES; EFFECTOR FUNCTIONS; GLYCOSYLATION; BIOREACTORS; METABOLISM; PRODUCTIVITY; SPECTROSCOPY; QUALITY; PH AB Fermentanomics, or a global understanding of a culture state on the molecular level empowered by advanced techniques like NMR, was employed to show that a model hybridoma culture supplied with glutamine and glucose depletes aspartate, cysteine, methionine, tryptophan, and tyrosine during antibody production. Supplementation with these amino acids prevents depletion and improves culture performance. Furthermore, no significant changes were observed in the distribution of glycans attached to the IgG3 in cultures supplemented with specific amino acids, arguing that this strategy can be implemented without fear of impact on important product quality attributes. In summary, a targeted strategy of quantifying media components and designing a supplementation strategy can improve bioprocess cell cultures when enpowered by fermentanomics tools. Published 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:745-753, 2013 C1 [Read, Erik K.; Lute, Scott C.; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. [Bradley, Scott A.; Smitka, Tim A.] Eli Lilly & Co, Small Mol Design & Dev, Indianapolis, IN 46285 USA. [Agarabi, Cyrus D.] US FDA, Div Prod Qual Res, CDER, Silver Spring, MD USA. RP Brorson, KA (reprint author), US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. EM kurt.brorson@fda.hhs.gov FU FDA Division of Monoclonal Antibodies; Oak Ridge Institute for Science and Education; Critical Path Program [1500]; Eli Lilly division of Analytical Sciences Research Development FX This work was funded by the FDA Division of Monoclonal Antibodies, the Oak Ridge Institute for Science and Education, and Critical Path Program project #1500. Additional support was provided by Eli Lilly division of Analytical Sciences Research & Development. The authors thank Theresa Gutierrez Lugo (CDER/FDA) for incisive comments on the manuscript. SAB and TAS thank Andreas Kaerner for his valuable insight and review of the work. Views expressed in this article are those of the authors and do not necessarily represent official policy of the US FDA or US Government. The authors have no conflicts of interest. NR 41 TC 20 Z9 20 U1 0 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 2013 VL 29 IS 3 BP 745 EP 753 DI 10.1002/btpr.1728 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 164CV UT WOS:000320387300018 PM 23606649 ER PT J AU Nochetto, CB Stine, CB Reimschuessel, R AF Nochetto, Cristina B. Stine, Cynthia B. Reimschuessel, Renate TI Development and Validation of a Method for the Simultaneous Determination and Confirmation of Melamine and Cyanuric Acid in Fish Kidney by LC/MS/MS SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MASS-SPECTROMETRIC DETECTION; LIQUID-CHROMATOGRAPHY; CATS; DOGS; CYROMAZINE; TOXICITY; RESIDUES AB A method was validated to simultaneously determine and confirm melamine and cyanuric acid in fish kidneys by LC/MS/MS. This method is capable of detecting both compounds in a single procedure, whether present as free compounds or bound together as the melamine cyanurate complex in both channel catfish (Ictalurus punctatus) and rainbow trout (Oncorhynchus mykiss) kidneys. Residues are extracted with no additional cleanup and analyzed by LC/MS/MS using external standard calibration. The method is capable of quantifying residues over a range of 0.4 to 50 mu g/g. For both compounds and species of fish tested, the LOD is estimated to be 0.1 mu g/g and the LOQ 0.4 mu g/g. Recoveries and RSDs are 83 to 101% and 2 to 8%, respectively. In catfish, matrix effects are higher for melamine than cyanuric acid. In rainbow trout, similar matrix effects are found for both compounds. C1 [Nochetto, Cristina B.; Stine, Cynthia B.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Nochetto, CB (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM cristina.nochetto@fda.hhs.gov NR 32 TC 2 Z9 2 U1 1 U2 15 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2013 VL 96 IS 3 BP 663 EP 669 DI 10.5740/jaoacint.12-303 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 164RU UT WOS:000320428000028 ER PT J AU Xu, Y Noonan, GO Begley, TH AF Xu, Y. Noonan, G. O. Begley, T. H. TI Migration of perfluoroalkyl acids from food packaging to food simulants SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE fluorochemical; packaging; migration ID HUMAN EXPOSURE; PERFLUOROOCTANESULFONATE; PERFLUOROCHEMICALS AB A broad range of fluorochemicals is used to impart oil and water barrier properties to paper and paperboard food packaging. Many of the fluorochemicals are applied to paper and paperboard as complex mixtures containing reaction products and by-products and unreacted starting materials. This work primarily focussed on the determination of seven perfluorocarboxylic acids (PFCAs) in two commercially available food contact papers: a di-perfluoro-alkyloxy-amino-acid and a perfluoroalkyl phosphate surfactant. In addition, the migration of the PFCAs into five food simulants from two commercial packages was evaluated. All seven PFCAs were detected in the range of 700-2220 mu gkg(-1) of paper, while three perfluoroalkyl sulphonates were under the LOD. Results from migration tests showed that migration depends on paper characteristics, time and food simulant. The percentage of migration after 10 days at 40 degrees C ranged from 4.8% to 100% for the two papers and different food simulants. C1 [Xu, Y.; Noonan, G. O.; Begley, T. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Xu, Y.] US FDA, Ctr Biol Evaluat Dept, Kensington, MD USA. RP Noonan, GO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM Gregory.Noonan@fda.hhs.gov NR 15 TC 5 Z9 5 U1 3 U2 32 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1944-0049 EI 1944-0057 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD MAY 1 PY 2013 VL 30 IS 5 BP 899 EP 908 DI 10.1080/19440049.2013.789556 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 166QA UT WOS:000320571000015 PM 23701306 ER PT J AU Tu, EY Shoff, ME Gao, WH Joslin, CE AF Tu, Elmer Y. Shoff, Megan E. Gao, Weihua Joslin, Charlotte E. TI Effect of Low Concentrations of Benzalkonium Chloride on Acanthamoebal Survival and Its Potential Impact on Empirical Therapy of Infectious Keratitis SO JAMA OPHTHALMOLOGY LA English DT Article ID CONTACT-LENS SOLUTION; MULTISTATE OUTBREAK; CORNEAL ULCERS; RABBIT EYES; FUSARIUM; DISINFECTION; ANTIBIOTICS; PENETRATION; PILOCARPINE; STATES AB Importance: The significant antiacanthamoebal effect of benzalkonium chloride, at or below concentrations used for preservation of common ophthalmic preparations, should be understood both when choosing empiric antibiotic therapy for infectious keratitis and when assessing the persistent rise in Acanthamoeba cases in the United States since 2003. Objective: To characterize the antiacanthamoebal efficacy of low concentrations of benzalkonium chloride (BAK) for drug preservation and therapeutic effect against Acanthamoeba. Design: Experimental study with a review of the literature. Setting: Laboratory. Exposures: A concentration of 104 trophozoites of 3 well-characterized clinical strains of Acanthamoeba were exposed at 0.5, 2.0, 3.5, 5.0, and 6.5 hours to BAK (0.001%, 0.002%, and 0.003%), moxifloxacin hydrochloride (0.5%), and moxifloxacin (0.5%) + BAK(0.001% and 0.003%) with hydrogen peroxide (3%) and amoeba saline controls. Main Outcomes and Measures: Amoeba survival was calculated using the most probable number method recorded as log kill values. The relationship of BAK concentration and exposure time as well as the relative effect of BAK and moxifloxacin on acanthamoebal survival were analyzed. Results: Amoebicidal activity of BAK is both time dependent and concentration dependent in pooled and strain-stratified analyses (P<.001). Moxifloxacin demonstrated no significant independent inhibitory effect or additive effect to BAK efficacy on acanthamoebal survival. The profound antiacanthamoebal effect of BAK, 0.003%, was similar to that of hydrogen peroxide for certain strains. Conclusions and Relevance: Low concentrations of BAK, previously demonstrated to concentrate and persist in ocular surface epithelium, exhibit significant antiacanthamoebal activity in vitro at or below concentrations found in commercially available ophthalmic anti-infectives. The unexplained persistence of the Acanthamoeba keratitis outbreak in the United States, clusters abroad, and clinical studies reporting resolution or modification of Acanthamoeba keratitis without specific antiacanthamoebal therapy suggests that other contributing factors should be considered, including changes in the formulations used for empirical therapy of presumed infectious keratitis occurring in the same period. C1 [Tu, Elmer Y.; Joslin, Charlotte E.] Univ Illinois, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. [Gao, Weihua] Univ Illinois, Ctr Clin & Translat Sci, Chicago, IL 60612 USA. [Joslin, Charlotte E.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL 60612 USA. [Shoff, Megan E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Tu, EY (reprint author), Univ Illinois, Dept Ophthalmol & Visual Sci, 1855 W Taylor St,M-C 648,Room 3-164, Chicago, IL 60612 USA. EM etu@uic.edu NR 42 TC 3 Z9 3 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6165 J9 JAMA OPHTHALMOL JI JAMA Ophthalmol. PD MAY PY 2013 VL 131 IS 5 BP 595 EP 600 DI 10.1001/jamaophthalmol.2013.1644 PG 6 WC Ophthalmology SC Ophthalmology GA 163JY UT WOS:000320333300005 PM 23519403 ER PT J AU Ferguson, S Law, CD AF Ferguson, Sherry Law, C. Delbert TI Developmental methylphenidate (MPH) treatment has sex- and age-specific effects on locomotor activity of Sprague-Dawley rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Ferguson, Sherry; Law, C. Delbert] FDA, NCTR, Div Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 80 EP 81 DI 10.1016/j.ntt.2013.03.027 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900033 ER PT J AU Paule, MG AF Paule, Merle G. TI Minimally-invasive procedures for monitoring onset, time-course, and intensity of general anesthetic-induced developmental neurotoxicity: Imaging and behavior SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 83 EP 83 DI 10.1016/j.ntt.2013.03.034 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900040 ER PT J AU Maier, KL Law, CD Ferguson, SA AF Maier, Kaitlyn L. Law, C. Delbert Ferguson, Sherry A. TI Developmental methylphenidate treatment does not alter novel object recognition in male female rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Maier, Kaitlyn L.; Law, C. Delbert; Ferguson, Sherry A.] US FDA, Div Neurotoxicol, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 86 EP 86 DI 10.1016/j.ntt.2013.03.045 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900051 ER PT J AU Panos, J Law, CD Ferguson, S AF Panos, John Law, C. Delbert Ferguson, Sherry TI Developmental methylphenidate (MPH) treatment in rats: Few effects on spatial memory (SM) in the Morris water (MWM) and Barnes mazes (BM) SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 37th Annual Meeting of the Neurobehavioral-Teratology-Society Held in Conjunction with the 53rd Annual Meeting of the Teratology-Society / 26th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 22-26, 2013 CL Tucson, AZ SP Neurobehavioral Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Panos, John; Law, C. Delbert; Ferguson, Sherry] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2013 VL 37 BP 88 EP 88 DI 10.1016/j.ntt.2013.03.052 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 164SD UT WOS:000320428900058 ER PT J AU Anez, G Grinev, A Chancey, C Ball, C Akolkar, N Land, KJ Winkelman, V Stramer, SL Kramer, LD Rios, M AF Anez, German Grinev, Andriyan Chancey, Caren Ball, Christopher Akolkar, Namita Land, Kevin J. Winkelman, Valerie Stramer, Susan L. Kramer, Laura D. Rios, Maria TI Evolutionary Dynamics of West Nile Virus in the United States, 1999-2011: Phylogeny, Selection Pressure and Evolutionary Time-Scale Analysis SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID US BLOOD-DONORS; MOLECULAR EVOLUTION; PURIFYING SELECTION; MAXIMUM-LIKELIHOOD; BAYESIAN-INFERENCE; GENETIC-VARIATION; SUBURBAN CHICAGO; COMPLETE GENOME; NORTH-AMERICA; EPIDEMIOLOGY AB West Nile virus (WNV), an arbovirus maintained in a bird-mosquito enzootic cycle, can infect other vertebrates including humans. WNV was first reported in the US in 1999 where, to date, three genotypes belonging to WNV lineage I have been described (NY99, WN02, SW/WN03). We report here the WNV sequences obtained from two birds, one mosquito, and 29 selected human samples acquired during the US epidemics from 2006-2011 and our examination of the evolutionary dynamics in the open-reading frame of WNV isolates reported from 1999-2011. Maximum-likelihood and Bayesian methods were used to perform the phylogenetic analyses and selection pressure analyses were conducted with the HyPhy package. Phylogenetic analysis identified human WNV isolates within the main WNV genotypes that have circulated in the US. Within genotype SW/WN03, we have identified a cluster with strains derived from blood donors and birds from Idaho and North Dakota collected during 2006-2007, termed here MW/WN06. Using different codon-based and branch-site selection models, we detected a number of codons subjected to positive pressure in WNV genes. The mean nucleotide substitution rate for WNV isolates obtained from humans was calculated to be 5.06x10(-4) substitutions/site/year (s/s/y). The Bayesian skyline plot shows that after a period of high genetic variability following the introduction of WNV into the US, the WNV population appears to have reached genetic stability. The establishment of WNV in the US represents a unique opportunity to understand how an arbovirus adapts and evolves in a naive environment. We describe a novel, well-supported cluster of WNV formed by strains collected from humans and birds from Idaho and North Dakota. Adequate genetic surveillance is essential to public health since new mutants could potentially affect viral pathogenesis, decrease performance of diagnostic assays, and negatively impact the efficacy of vaccines and the development of specific therapies. C1 [Anez, German; Grinev, Andriyan; Chancey, Caren; Akolkar, Namita; Rios, Maria] US FDA, Lab Emerging Pathogens, DETTD OBRR CBER, Bethesda, MD 20014 USA. [Ball, Christopher] Idaho Bur Labs, Boise, ID USA. [Land, Kevin J.] Bonfils Blood Ctr, Denver, CO USA. [Winkelman, Valerie] Creat Testing Solut, Tempe, AZ USA. [Stramer, Susan L.] Amer Red Cross, Gaithersburg, MD USA. [Kramer, Laura D.] New York State Dept Hlth, Albany, NY USA. [Kramer, Laura D.] SUNY Albany, Sch Publ Hlth, Albany, NY USA. RP Anez, G (reprint author), US FDA, Lab Emerging Pathogens, DETTD OBRR CBER, Bethesda, MD 20014 USA. EM german.anez@fda.hhs.gov; andriyan.grinev@fda.hhs.gov; maria.rios@fda.hhs.gov OI Anez, German/0000-0001-5361-3001 FU U.S. Food and Drug Administration Intramural Program FX This study was supported by the 2006-2012 U.S. Food and Drug Administration Intramural Program. This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 54 TC 19 Z9 20 U1 0 U2 26 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1935-2735 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD MAY PY 2013 VL 7 IS 5 AR e2245 DI 10.1371/journal.pntd.0002245 PG 12 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 158SW UT WOS:000319994400045 PM 23738027 ER PT J AU Howard, T AF Howard, T. TI Navigating Pregnancy and Lactation Labeling without Letters: A Review of the Proposed Changes to Product Labeling SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Howard, T.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 279 EP 279 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100016 ER PT J AU Reid, LL AF Reid, L. L. TI The Animal Data: Making it Clear and Relevant SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Reid, L. L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 279 EP 279 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100017 ER PT J AU Sahin, L AF Sahin, L. TI Data Collection Methods for Use of Medications in Pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Sahin, L.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 280 EP 280 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100020 ER PT J AU Tabacova, S Szarfman, A AF Tabacova, S. Szarfman, A. TI Adverse Developmental Events Reported to US FDA in Association with Maternal Use of Topiramate in Pregnancy SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Tabacova, S.; Szarfman, A.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 300 EP 300 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100058 ER PT J AU Slikker, W Zhang, X Paule, MG Newport, GD Liu, F Callicott, R Liu, S Berridge, M Apana, SM Wang, C AF Slikker, W., Jr. Zhang, X. Paule, M. G. Newport, G. D. Liu, F. Callicott, R. Liu, S. Berridge, M. Apana, S. M. Wang, C. TI MicroPET/CT Imaging of [18F]-FEPPA in the Nonhuman Primate: A Potential Biomarker of Pathogenic Processes Associated with Anesthetic-Induced Neurotoxicity SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Slikker, W., Jr.; Zhang, X.; Paule, M. G.; Newport, G. D.; Liu, F.; Callicott, R.; Liu, S.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Berridge, M.; Apana, S. M.] 3D Imaging LLC, Little Rock, AR USA. [Berridge, M.; Apana, S. M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RI Liu, Shuliang/J-4696-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 312 EP 312 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100080 ER PT J AU Inselman, AL Nakamura, N Mcintyre, B Foster, PMD Harrouk, W Hansen, DK AF Inselman, A. L. Nakamura, N. Mcintyre, B. Foster, P. M. D. Harrouk, W. Hansen, D. K. TI Preliminary Results from Prenatal Toxicity Study of Oxybenzone in Rats SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Inselman, A. L.; Nakamura, N.; Hansen, D. K.] US FDA, NCTR, Jefferson, AR USA. [Mcintyre, B.; Foster, P. M. D.] NIEHS, NTP, Res Triangle Pk, NC 27709 USA. [Harrouk, W.] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 313 EP 313 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100081 ER PT J AU Fisher, JE Reid, LL AF Fisher, J. E. Reid, L. L. TI Male-Mediated Developmental Toxicity: Recommendations on Male Contraceptive Use in Clinical Trials and Approved Drug Labeling SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Fisher, J. E.; Reid, L. L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 327 EP 327 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100107 ER PT J AU Chen, X Nolen, G Hansen, DK Fisher, E Harrouk, W Tassinari, MS Inselman, AL AF Chen, X. Nolen, G. Hansen, D. K. Fisher, E. Harrouk, W. Tassinari, M. S. Inselman, A. L. TI Developing Osteoblasts As an Endpoint for the Mouse Embryonic Stem Cell Test in Prediction Toxicology SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 [Chen, X.; Nolen, G.; Hansen, D. K.] US FDA, NCTR, Jefferson, AR USA. [Fisher, E.; Harrouk, W.; Tassinari, M. S.; Inselman, A. L.] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2013 VL 97 IS 5 SI SI BP 341 EP 341 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 171MB UT WOS:000320932100133 ER PT J AU Beveridge, R Fox, J Higgins, SA Kohn, M Mahoney, JJ Newcomer, LN von Eschenbach, A AF Beveridge, Roy Fox, John Higgins, Susan A. Kohn, Martin Mahoney, John J. Newcomer, Lee N. von Eschenbach, Andrew TI The Changing Oncology Landscape: Evolution or Revolution? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Article AB Complex challenges face all players in the oncology landscape, from health care policy leaders and third-party payers, to practicing physicians and nurses, to patients and their families. In these unsteady economic times, possible answers proposed by some may represent part of the problem to others. A distinguished panel assembled at the NCCN 18th Annual Conference: Advancing the Standard of Cancer Care to explore the changing oncology landscape. This article is the synopsis of that discussion, with panelists shedding light on such issues as the astronomic cost of medical care, the need for clinicians to think outside the formulary, and the therapeutic decision-making process in the new world of "big data." C1 [Beveridge, Roy] US Oncol, The Woodlands, TX USA. [Beveridge, Roy] US Oncol Network, The Woodlands, TX USA. [Beveridge, Roy] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. [Higgins, Susan A.] Yale Univ, Sch Med, Div Obstet & Gynecol, New Haven, CT 06520 USA. [Higgins, Susan A.] Smilow Canc Hosp, Multidisciplinary Gynecol Dis Team Unit, New Haven, CT USA. [Higgins, Susan A.] Therapeut Radiol Residency Training Program, New Haven, CT USA. IBM Res Corp, Care Delivery Syst, San Jose, CA USA. [Kohn, Martin] Pitney Bowes Inc, Stamford, CT USA. [Mahoney, John J.] UnitedHlth Grp, Minneapolis, MN USA. [Newcomer, Lee N.] Pk Nicollet Hlth Serv, St Louis Pk, MN USA. [Newcomer, Lee N.] Samaritan Hlth Initiat Inc, Montgomery, TX USA. [von Eschenbach, Andrew] US FDA, Rockville, MD 20857 USA. [von Eschenbach, Andrew] NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 3 U2 11 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAY PY 2013 VL 11 IS 5.5 SI SI BP 636 EP 638 PG 3 WC Oncology SC Oncology GA 159TX UT WOS:000320071300003 PM 23704232 ER PT J AU Pandey, GS Yanover, C Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Yanover, Chen Howard, Tom E. Sauna, Zuben E. TI Polymorphisms in the F8 Gene and MHC-II Variants as Risk Factors for the Development of Inhibitory AntiFactor VIII Antibodies during the Treatment of Hemophilia A: A Computational Assessment SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID T-CELL RESPONSES; MILD HEMOPHILIA; KINETIC STABILITY; COMPLEXES; BINDING; FVIII; PREVENTION; MOLECULES; MUTATION; EPITOPE AB The development of neutralizing anti-drug-antibodies to the Factor VIII protein-therapeutic is currently the most significant impediment to the effective management of hemophilia A. Common non-synonymous single nucleotide polymorphisms (ns-SNPs) in the F8 gene occur as six haplotypes in the human population (denoted H1 to H6) of which H3 and H4 have been associated with an increased risk of developing anti-drug antibodies. There is evidence that CD4+ T-cell response is essential for the development of anti-drug antibodies and such a response requires the presentation of the peptides by the MHC-class-II (MHC-II) molecules of the patient. We measured the binding and half-life of peptide-MHC-II complexes using synthetic peptides from regions of the Factor VIII protein where ns-SNPs occur and showed that these wild type peptides form stable complexes with six common MHC-II alleles, representing 46.5% of the North American population. Next, we compared the affinities computed by NetMHCIIpan, a neural network-based algorithm for MHC-II peptide binding prediction, to the experimentally measured values and concluded that these are in good agreement (area under the ROC-curve of 0.778 to 0.972 for the six MHC-II variants). Using a computational binding predictor, we were able to expand our analysis to (a) include all wild type peptides spanning each polymorphic position; and (b) consider more MHC-II variants, thus allowing for a better estimation of the risk for clinical manifestation of anti-drug antibodies in the entire population (or a specific sub-population). Analysis of these computational data confirmed that peptides which have the wild type sequence at positions where the polymorphisms associated with haplotypes H3, H4 and H5 occur bind MHC-II proteins significantly more than a negative control. Taken together, the experimental and computational results suggest that wild type peptides from polymorphic regions of FVIII constitute potential T-cell epitopes and thus could explain the increased incidence of anti-drug antibodies in hemophilia A patients with haplotypes H3 and H4. C1 [Pandey, Gouri Shankar; Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. RP Pandey, GS (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM zuben.sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 FU Food and Drug Administration's Modernization of Science program; National Heart, Lung and Blood Institute, NIH [1RC2-HL101851, HL-71130, HL-72533]; Bayer Healthcare Corporation, Bayer Haemophilia Awards Program; Baxter Healthcare Corporation; Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine FX This work was supported by the Food and Drug Administration's Modernization of Science program to ZES. Research conducted in the laboratory of TEH is funded by grants from the National Heart, Lung and Blood Institute, NIH (1RC2-HL101851, HL-71130 and HL-72533) as well as from Bayer Healthcare Corporation, Bayer Haemophilia Awards Program, Baxter Healthcare Corporation, and the Clinical Translational Science Institute at the University of Southern California's Keck School of Medicine. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 30 TC 9 Z9 9 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAY PY 2013 VL 9 IS 5 AR e1003066 DI 10.1371/journal.pcbi.1003066 PG 11 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 159FX UT WOS:000320032100027 PM 23696725 ER PT J AU Gorovits, B Alley, SC Bilic, S Booth, B Kaur, S Oldfield, P Purushothama, S Rao, C Shord, S Siguenza, P AF Gorovits, Boris Alley, Stephen C. Bilic, Sanela Booth, Brian Kaur, Surinder Oldfield, Phillip Purushothama, Shobha Rao, Chetana Shord, Stacy Siguenza, Patricia TI Bioanalysis of antibody-drug conjugates: American Association of Pharmaceutical Scientists Antibody-Drug Conjugate Working Group position paper SO BIOANALYSIS LA English DT Article ID ACUTE MYELOID-LEUKEMIA; LIGAND-BINDING ASSAYS; BIOTECHNOLOGY PRODUCTS; IN-VIVO; THERAPEUTIC ANTIBODIES; GEMTUZUMAB OZOGAMICIN; MASS-SPECTROMETRY; LINKER STABILITY; HOST ANTIBODIES; CYTOTOXIC DRUG AB Antibody drug conjugates (ADCs) typically consist of a cytotoxic drug covalently bound to an antibody by a linker. These conjugates have the potential to substantially improve efficacy and reduce toxicity compared with cytotoxic small-molecule drugs. Since ADCs are generally complex heterogeneous mixtures of multiple species, these novel therapeutic products present unique bioanalytical challenges. The growing number of ADCs being developed across the industry suggests the need for alignment of the bioanalytical methods or approaches used to assess the multiple species and facilitate consistent interpretation of the bioanalytical data. With limited clinical data, the current strategies that can be used to provide insight into the relationship between the multiple species and the observed clinical safety and efficacy are still evolving. Considerations of the bioanalytical strategies for ADCs based on the current industry practices that take into account the complexity and heterogeneity of ADCs are discussed. C1 [Gorovits, Boris] Pfizer, Andover, MA 01810 USA. [Alley, Stephen C.] Seattle Genet Inc, Bothell, WA USA. [Bilic, Sanela] Novartis, E Hanover, NJ USA. [Booth, Brian; Shord, Stacy] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Kaur, Surinder; Siguenza, Patricia] Genentech Inc, Redwood City, CA USA. [Purushothama, Shobha] Biogen Idec Inc, Cambridge, MA USA. RP Gorovits, B (reprint author), Pfizer, 1 Burtt Rd, Andover, MA 01810 USA. EM boris.gorovits@pfizer.com NR 37 TC 50 Z9 53 U1 0 U2 19 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD MAY PY 2013 VL 5 IS 9 BP 997 EP 1006 DI 10.4155/BIO.13.38 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 158FR UT WOS:000319955400009 PM 23641692 ER PT J AU Cutts, FT Izurieta, HS Rhoda, DA AF Cutts, Felicity T. Izurieta, Hector S. Rhoda, Dale A. TI Measuring Coverage in MNCH: Design, Implementation, and Interpretation Challenges Associated with Tracking Vaccination Coverage Using Household Surveys SO PLOS MEDICINE LA English DT Review ID IMMUNIZATION COVERAGE; ORAL-FLUID; DEVELOPING-COUNTRIES; COMPUTER-SIMULATION; CHILD VACCINATION; INCOME COUNTRIES; FIELD-EVALUATION; MOTHERS REPORTS; HEALTH SURVEYS; MEASLES AB Vaccination coverage is an important public health indicator that is measured using administrative reports and/or surveys. The measurement of vaccination coverage in low-and middle-income countries using surveys is susceptible to numerous challenges. These challenges include selection bias and information bias, which cannot be solved by increasing the sample size, and the precision of the coverage estimate, which is determined by the survey sample size and sampling method. Selection bias can result from an inaccurate sampling frame or inappropriate field procedures and, since populations likely to be missed in a vaccination coverage survey are also likely to be missed by vaccination teams, most often inflates coverage estimates. Importantly, the large multi-purpose household surveys that are often used to measure vaccination coverage have invested substantial effort to reduce selection bias. Information bias occurs when a child's vaccination status is misclassified due to mistakes on his or her vaccination record, in data transcription, in the way survey questions are presented, or in the guardian's recall of vaccination for children without a written record. There has been substantial reliance on the guardian's recall in recent surveys, and, worryingly, information bias may become more likely in the future as immunization schedules become more complex and variable. Finally, some surveys assess immunity directly using serological assays. Sero-surveys are important for assessing public health risk, but currently are unable to validate coverage estimates directly. To improve vaccination coverage estimates based on surveys, we recommend that recording tools and practices should be improved and that surveys should incorporate best practices for design, implementation, and analysis. C1 [Izurieta, Hector S.] Food & Drug Adm, Rockville, MD USA. [Rhoda, Dale A.] Battelle Mem Inst, Columbus, OH 43201 USA. EM felicity.cutts@lshtm.ac.uk NR 66 TC 30 Z9 30 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1549-1676 J9 PLOS MED JI PLos Med. PD MAY PY 2013 VL 10 IS 5 AR e1001404 DI 10.1371/journal.pmed.1001404 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 154JK UT WOS:000319670900006 PM 23667334 ER PT J AU Hassan, M Tan, X Welle, E Ilev, I AF Hassan, Moinuddin Tan, Xin Welle, Elissa Ilev, Ilko TI Fiber-optic Fourier transform infrared spectroscopy for remote label-free sensing of medical device surface contamination SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID PROBE AB As a potential major source of biochemical contamination, medical device surfaces are of critical safety concerns in the clinical practice and public health. The development of innovative sensing methods for accurate and real-time detection of medical device surface contamination is essential to protect patients from high risk infection. In this paper, we demonstrate an alternative fiber-optic Fourier Transform Infrared (FTIR) spectroscopy based sensing approach for remote, non-contact, and label-free detection of biochemical contaminants in the mid-infrared (mid-IR) region. The sensing probe is designed using mid-IR hollow fibers and FTIR measurements are carried out in reflection mode. Bovine Serum Albumin (BSA) and bacterial endotoxin of different concentrations under thoroughly dry condition are used to evaluate the detection sensitivity. The devised system can identify <= 0.0025% (<= 4 x 10(11) molecules) BSA and 0.5% (0.5 EU/ml) endotoxin concentration. The developed sensing approach may be applied to detect various pathogens that pose public health threats. C1 [Hassan, Moinuddin; Tan, Xin; Welle, Elissa; Ilev, Ilko] US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Welle, Elissa] Cornell Univ, Coll Engn, Ithaca, NY 14853 USA. RP Hassan, M (reprint author), US FDA, Opt Therapeut & Med Nanophoton Lab, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM moinuddin.hassan@fda.hhs.gov OI Welle, Elissa/0000-0001-5141-7656 FU Medical Counter Measure initiative (MCMi) of Center for Devices and Radiological Health (CDRH), U.S. Food and Drug Administration (FDA) FX This study is supported by the intramural research program of Medical Counter Measure initiative (MCMi) of Center for Devices and Radiological Health (CDRH), U.S. Food and Drug Administration (FDA). NR 16 TC 5 Z9 5 U1 3 U2 15 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAY PY 2013 VL 84 IS 5 AR 053101 DI 10.1063/1.4803182 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 158UO UT WOS:000319999300002 PM 23742526 ER PT J AU Debing, Y Kaplan, GG Neyts, J Jochmans, D AF Debing, Yannick Kaplan, Gerardo G. Neyts, Johan Jochmans, Dirk TI Rapid and convenient assays to assess potential inhibitory activity on in vitro hepatitis A replication SO ANTIVIRAL RESEARCH LA English DT Article DE Hepatitis A virus; Antiviral assay; Interferon; Amantadine; Enterovirus inhibitor ID VIRUS-REPLICATION; ANTIVIRAL ACTIVITY; CELLS; SUPERINFECTION; INTERFERON; AMANTADINE; INFECTION; VARIANTS; PROTEASE; INVITRO AB Three different antiviral assays were developed for the in vitro screening of inhibitors of the hepatitis A virus (HAV) of which (i) a cytopathic effect reduction assay suitable for medium-to-high-throughput screening and (ii) two virus yield reduction assays (based on quantification of viral RNA) for genotypes IB and IIIA. The assays were validated for antiviral studies with interferon-alpha (IFN alpha) and amantadine HCl, two known inhibitors of HAV replication. IFN alpha effectively inhibited HAV replication, whereas the activity of amantadine HCl appeared to be strain-dependent. Employing these assays, we assessed the effect of the known enterovirus inhibitors pleconaril, rupintrivir and enviroxime on HAV replication. Pleconaril exhibited some very moderate activity, the effect of rupintrivir proved to be strain-dependent. Enviroxime did not inhibit HAV replication, suggesting that phosphatidylinositol-4-kinase III beta is not crucial in the HAV life cycle. (C) 2013 Elsevier B.V. All rights reserved. C1 [Debing, Yannick; Neyts, Johan; Jochmans, Dirk] Rega Inst, Dept Microbiol & Immunol, B-3000 Louvain, Belgium. [Kaplan, Gerardo G.] US FDA, Lab Hepatitis & Related Emerging Agents, DETTD OBRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Neyts, J (reprint author), Rega Inst, Dept Microbiol & Immunol, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM johan.neyts@rega.kuleuven.be OI JOCHMANS, DIRK/0000-0002-9265-6028; Debing, Yannick/0000-0001-6566-9408 FU KU Leuven, geconcerteerde onderzoeksactie [GOA/10/014]; EU [260644] FX We would like to thank Stijn Delmotte for excellent technical assistance. We are also grateful to Jolien Nelissen for critical editing of the manuscript and to Kai Dallmeier, Suzanne Kaptein and Hendrik Thibaut for input on experiments and figures. Yannick Debing is a fellow of the Research Foundation - Flanders (FWO). This work is supported by KU Leuven, geconcerteerde onderzoeksactie (GOA/10/014) and EU FP7 project SILVER (260644). NR 37 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAY PY 2013 VL 98 IS 2 BP 325 EP 331 DI 10.1016/j.antiviral.2013.03.016 PG 7 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 154YF UT WOS:000319711900023 PM 23528258 ER PT J AU Hu, ZL Patel, IR Mukherjee, A AF Hu, Zonglin Patel, Isha R. Mukherjee, Amit TI Genetic analysis of the roles of agaA, agaI, and agaS genes in the N-acetyl-D-galactosamine and D-galactosamine catabolic pathways in Escherichia coli strains O157:H7 and C SO BMC MICROBIOLOGY LA English DT Article ID AMINO SUGAR METABOLISM; GLUCOSAMINE-6-PHOSPHATE DEAMINASE; NAG REGULON; OPERON; K-12; PURIFICATION; MECHANISM; HISTIDINE; ISOMERASE; BACTERIA AB Background: The catabolic pathways of N-acetyl-D-galactosamine (Aga) and D-galactosamine (Gam) in E. coli were proposed from bioinformatic analysis of the aga/gam regulon in E. coli K-12 and later from studies using E. coli C. Of the thirteen genes in this cluster, the roles of agaA, agaI, and agaS predicted to code for Aga-6-P-deacetylase, Gam-6-P deaminase/isomerase, and ketose-aldolase isomerase, respectively, have not been experimentally tested. Here we study their roles in Aga and Gam utilization in E. coli O157:H7 and in E. coli C. Results: Knockout mutants in agaA, agaI, and agaS were constructed to test their roles in Aga and Gam utilization. Knockout mutants in the N-acetylglucosamine (GlcNAc) pathway genes nagA and nagB coding for GlcNAc-6-P deacetylase and glucosamine-6-P deaminase/isomerase, respectively, and double knockout mutants Delta agaA Delta nagA and Delta agaI Delta nagB were also constructed to investigate if there is any interplay of these enzymes between the Aga/Gam and the GlcNAc pathways. It is shown that Aga utilization was unaffected in Delta agaA mutants but Delta agaA Delta nagA mutants were blocked in Aga and GlcNAc utilization. E. coli C Delta nagA could not grow on GlcNAc but could grow when the aga/gam regulon was constitutively expressed. Complementation of Delta agaA Delta nagA mutants with either agaA or nagA resulted in growth on both Aga and GlcNAc. It was also found that Delta agaI, Delta nagB, and Delta agaI Delta nagB mutants were unaffected in utilization of Aga and Gam. Importantly, Delta agaS mutants were blocked in Aga and Gam utilization. Expression analysis of relevant genes in these strains with different genetic backgrounds by real time RT-PCR supported these observations. Conclusions: Aga utilization was not affected in Delta agaA mutants because nagA was expressed and substituted for agaA. Complementation of Delta agaA Delta nagA mutants with either agaA or nagA also showed that both agaA and nagA can substitute for each other. The Delta agaI, Delta nagB, and Delta agaI Delta nagB mutants were not affected in Aga and Gam utilization indicating that neither agaI nor nagB is involved in the deamination and isomerization of Gam-6-P. We propose that agaS codes for Gam-6-P deaminase/isomerase in the Aga/Gam pathway. C1 [Hu, Zonglin; Patel, Isha R.; Mukherjee, Amit] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Mukherjee, A (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM amit.mukherjee@fda.hhs.gov NR 27 TC 2 Z9 2 U1 2 U2 10 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD MAY 1 PY 2013 VL 13 AR 94 DI 10.1186/1471-2180-13-94 PG 16 WC Microbiology SC Microbiology GA 154HN UT WOS:000319665100001 PM 23634833 ER PT J AU Antunes, AMM Wolf, B Oliveira, MC Beland, FA Marques, MM AF Antunes, Alexandra M. M. Wolf, Benjamin Conceicao Oliveira, M. Beland, Frederick A. Matilde Marques, M. TI 2 '-Deoxythymidine Adducts from the Anti-HIV Drug Nevirapine SO MOLECULES LA English DT Article DE nevirapine; non-nucleoside reverse transcriptase inhibitor; carcinogenicity; DNA adducts; palladium catalysis ID TO-CHILD TRANSMISSION; REVERSE-TRANSCRIPTASE INHIBITOR; INDUCED SKIN RASH; DNA-ADDUCTS; BIOACTIVATION; SINGLE; TOXICITY; DERIVATIVES; NUCLEOSIDE; ZIDOVUDINE AB Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used against HIV-1. Currently, NVP is the most widely used anti-HIV drug in developing countries, both in combination therapy and to prevent mother-to-child transmission of HIV. Despite its efficacy against HIV, NVP produces a variety of toxic responses, including hepatotoxicity and skin rash. It is also associated with increased incidences of hepatoneoplasias in rodents. In addition, epidemiological data suggest that NNRTI use is a risk factor for non-AIDS-defining cancers in HIV-positive patients. Current evidence supports the involvement of metabolic activation to reactive electrophiles in NVP toxicity. NVP metabolism includes oxidation to 12-hydroxy-NVP; subsequent Phase II sulfonation produces an electrophilic metabolite, 12-sulfoxy-NVP, capable of reacting with DNA to yield covalent adducts. Since 2'-deoxythymidine (dT) adducts from several alkylating agents are regarded as having significant mutagenic/carcinogenic potential, we investigated the formation of NVP-dT adducts under biomimetic conditions. Toward this goal, we initially prepared and characterized synthetic NVP-dT adduct standards using a palladium-mediated Buchwald-Hartwig coupling strategy. The synthetic standards enabled the identification, by LC-ESI-MS, of 12-(2'-deoxythymidin-N3-yl)-nevirapine (N3-NVP-dT) in the enzymatic hydrolysate of salmon testis DNA reacted with 12-mesyloxy-NVP, a synthetic surrogate for 12-sulfoxy-NVP. N3-NVP-dT, a potentially cytotoxic and mutagenic DNA lesion, was also the only dT-specific adduct detected upon reaction of dT with 12-mesyloxy-NVP. Our data suggest that N3-NVP-dT may be formed in vivo and play a role in the hepatotoxicity and/or putative hepatocarcinogenicity of NVP. C1 [Antunes, Alexandra M. M.; Wolf, Benjamin; Conceicao Oliveira, M.; Matilde Marques, M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Antunes, AMM (reprint author), Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM alexandra.antunes@ist.utl.pt; matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Oliveira, Maria Conceicao/0000-0002-3068-4920 FU Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PTDC/QUI-QUI/113910/2009, PEst-OE/QUI/UI0100/2011]; National Center for Toxicological Research/U.S. Food and Drug Administration [Y1ES1027]; National Institute of Environmental Health Sciences/National Toxicology Program FX We thank the Portuguese NMR and MS Networks (IST-UTL Center) for providing access to the facilities. This work was supported in part by Fundacao para a Ciencia e a Tecnologia (FCT), Portugal, through grants PTDC/QUI-QUI/113910/2009 and PEst-OE/QUI/UI0100/2011, and by Interagency Agreement Y1ES1027 between the National Center for Toxicological Research/U.S. Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. NR 45 TC 4 Z9 4 U1 0 U2 20 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1420-3049 J9 MOLECULES JI Molecules PD MAY PY 2013 VL 18 IS 5 BP 4955 EP 4971 DI 10.3390/molecules18054955 PG 17 WC Chemistry, Organic SC Chemistry GA 151FU UT WOS:000319446900010 PM 23624649 ER PT J AU Harrison, LM Balan, KV Babu, US AF Harrison, Lisa M. Balan, Kannan V. Babu, Uma S. TI Dietary Fatty Acids and Immune Response to Food-Borne Bacterial Infections SO NUTRIENTS LA English DT Review DE fatty acids; immune response; food-borne; infection ID LISTERIA-MONOCYTOGENES INFECTION; ENTEROHEMORRHAGIC ESCHERICHIA-COLI; CAMPYLOBACTER-JEJUNI COLONIZATION; RESISTANT STAPHYLOCOCCUS-AUREUS; SALMONELLA-ENTERITIDIS INFECTION; AGED BROILER-CHICKENS; CELLS IN-VITRO; CAPRYLIC-ACID; METHICILLIN-RESISTANT; ANTIBACTERIAL ACTIVITY AB Functional innate and acquired immune responses are required to protect the host from pathogenic bacterial infections. Modulation of host immune functions may have beneficial or deleterious effects on disease outcome. Different types of dietary fatty acids have been shown to have variable effects on bacterial clearance and disease outcome through suppression or activation of immune responses. Therefore, we have chosen to review research across experimental models and food sources on the effects of commonly consumed fatty acids on the most common food-borne pathogens, including Salmonella sp., Campylobacter sp., Shiga toxin-producing Escherichia coli, Shigella sp., Listeria monocytogenes, and Staphylococcus aureus. Altogether, the compilation of literature suggests that no single fatty acid is an answer for protection from all food-borne pathogens, and further research is necessary to determine the best approach to improve disease outcomes. C1 [Harrison, Lisa M.; Balan, Kannan V.; Babu, Uma S.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Harrison, LM (reprint author), US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM lisa.plemons@fda.hhs.gov; kannan.balan@fda.hhs.gov; uma.babu@fda.hhs.gov NR 130 TC 10 Z9 10 U1 4 U2 32 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6643 J9 NUTRIENTS JI Nutrients PD MAY PY 2013 VL 5 IS 5 BP 1801 EP 1822 DI 10.3390/nu5051801 PG 22 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 151CW UT WOS:000319439200020 PM 23698167 ER PT J AU Brock, WJ Somps, CJ Torti, V Render, JA Jamison, J Rivera, MI AF Brock, William J. Somps, Christopher J. Torti, Vince Render, James A. Jamison, Jeffrey Rivera, Maria I. TI Ocular Toxicity Assessment From Systemically Administered Xenobiotics: Considerations in Drug Development SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Review DE ocular; drug development; pathology; in vivo methods; regulatory ID SPRAGUE-DAWLEY RATS; CORNEAL OPACITIES; LIGHT DAMAGE; LABORATORY-ANIMALS; HARDERIAN-GLAND; TAPETAL CHANGES; SPATIAL VISION; ISCEV STANDARD; BEAGLE DOGS; EYE LESIONS AB The eye is a unique sensory structure, which must be evaluated for toxicity to determine the safety of drugs, industrial chemicals, and consumer products. Changes in the structure and/or function of ocular tissues following systemic administration of a potential new drug in preclinical animal models can result in significant delays in the development of a new therapeutic and in some cases lead to termination of the development. The ability to detect and characterize ocular toxicity in preclinical models and to predict risk in patients is critically dependent on the preclinical testing strategy, the availability and use of state-of-the-art ocular safety assessment tools, and the knowledge of drug mechanism of action and the current regulatory environment. This review describes the design and execution of toxicity studies with the incorporation of current methods for in vivo assessment of ocular toxicity, including methods for detecting early changes in the eye. In addition, anatomical differences among laboratory animals, preparation of globes for examination, and iatrogenic and spontaneous ocular findings are described that can affect interpretation of toxicological findings. Finally, the correlation between nonclinical outcomes and clinical evaluations is discussed in terms of expected therapeutic uses, indications, and regulatory consequences of ocular effects. C1 [Brock, William J.] Brock Sci Consulting, Montgomery Village, MD 20886 USA. [Somps, Christopher J.] Pfizer Inc, Groton, CT 06340 USA. [Torti, Vince] Pfizer, La Jolla, CA USA. [Render, James A.] NAMSA, Northwood, OH USA. [Jamison, Jeffrey] Ophthy DS Inc, Mattawan, MI USA. [Jamison, Jeffrey] MPI Res, Mattawan, MI USA. [Rivera, Maria I.] FDA, White Oak, MD USA. RP Brock, WJ (reprint author), Brock Sci Consulting, 19909 Hamil Circle, Montgomery Village, MD 20886 USA. EM billbrock@comcast.net NR 112 TC 2 Z9 2 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2013 VL 32 IS 3 BP 171 EP 188 DI 10.1177/1091581813484500 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 148FD UT WOS:000319227700001 PM 23616147 ER PT J AU Azad, BB Banerjee, S Pullambhatla, M Lacerda, S Foss, C Ivkov, R Pomper, M AF Azad, Behnam Babak Banerjee, Sangeeta Pullambhatla, Mrudula Lacerda, Silvia Foss, Catherine Ivkov, Robert Pomper, Martin TI Development and biological evaluation of a PSMA-targeted BNF nanoparticle SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Azad, Behnam Babak; Banerjee, Sangeeta; Pullambhatla, Mrudula; Foss, Catherine; Pomper, Martin] Johns Hopkins Univ, Dept Radiol, Baltimore, MD USA. [Lacerda, Silvia] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Ivkov, Robert; Pomper, Martin] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2013 VL 56 SU 1 MA P170 BP S257 EP S257 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 140ZD UT WOS:000318694100258 ER PT J AU Jarow, JP Fang, X Hammad, TA AF Jarow, Jonathan P. Fang, Xin Hammad, Tarek A. TI Variability of Semen Parameters with Time in Placebo Treated Men SO JOURNAL OF UROLOGY LA English DT Article DE testis; semen; reference values; infertility, male; placebo effect ID WITHIN-SUBJECT; REGIONAL DIFFERENCES; SPERM COUNT; QUALITY; ABSTINENCE; SPERMATOGENESIS; FINASTERIDE; EJACULATE; HORMONES; SAMPLES AB Purpose: We describe the variability of semen parameters with time in normal men receiving placebo. We also report the impact of season and geographic region, among other variables, on these parameters. Materials and Methods: Data from the placebo arms of 5 randomized, controlled trials were pooled. All trials set minimum standards for semen parameters as an eligibility criterion for entry. Semen parameters examined include volume, density, motility, total count, total motile count and morphology. Mixed model repeated measure analysis was used for statistical analysis. Coefficients of variation for each semen parameter and the percent change from baseline were calculated. Results: The mean within-subject coefficient of variation for each semen parameter ranged from a low of 10% to a high of almost 50%. The contribution of season and region to variability was negligible. The reduction in variability with an increasing number of samples per time point had decreasing returns beyond 2 samples. Conclusions: There was considerable variation in semen parameters with time in subjects who received placebo. Variation could not be attributed to season or region. We observed a general negative trend in semen parameters in this population selected for normal baseline semen parameters, which was likely due to the placebo response or to regression toward the mean. C1 [Jarow, Jonathan P.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. [Fang, Xin] US FDA, Ctr Drug Evaluat & Res, Off Biometr, Silver Spring, MD USA. [Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Jarow, JP (reprint author), WO22 Room 5387,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jonathan.jarow@fda.hhs.gov NR 30 TC 3 Z9 3 U1 0 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 MAY PY 2013 VL 189 IS 5 BP 1825 EP 1829 DI 10.1016/j.juro.2012.11.077 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 148QZ UT WOS:000319262900069 PM 23159587 ER PT J AU Gatti, J Brinker, A Avigan, M AF Gatti, Jasmine Brinker, Allen Avigan, Mark TI Spontaneous Reports of Seizure in Association With Leuprolide (Lupron Depot), Goserelin (Zoladex Implant), and Naferelin (Synarel Nasal Spray) SO OBSTETRICS AND GYNECOLOGY LA English DT Letter C1 [Gatti, Jasmine; Brinker, Allen; Avigan, Mark] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Gatti, J (reprint author), US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 1 TC 1 Z9 1 U1 1 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 MAY PY 2013 VL 121 IS 5 BP 1107 EP 1107 DI 10.1097/AOG.0b013e31828c9cb3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 139SU UT WOS:000318605400027 PM 23635751 ER PT J AU Gustafson, C Roizen, MF AF Gustafson, Craig Roizen, Michael F. TI Michael Roizen, MD: Motivating Patients to Live Younger and the Fatal Flaw of Wellness Programs SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 [Roizen, Michael F.] NIH, Bethesda, MD USA. [Roizen, Michael F.] US FDA, Advisory Comm, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD MAY-JUN PY 2013 VL 19 IS 3 BP 48 EP 54 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 142TZ UT WOS:000318821800007 ER PT J AU Axelson, M Liu, K Jiang, XP He, K Wang, J Zhao, H Kufrin, D Palmby, T Dong, ZD Russell, AM Miksinski, S Keegan, P Pazdur, R AF Axelson, Michael Liu, Ke Jiang, Xiaoping He, Kun Wang, Jian Zhao, Hong Kufrin, Dubravka Palmby, Todd Dong, Zedong Russell, Anne Marie Miksinski, Sarah Keegan, Patricia Pazdur, Richard TI U.S. Food and Drug Administration Approval: Vismodegib for Recurrent, Locally Advanced, or Metastatic Basal Cell Carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PATHWAY INHIBITOR VISMODEGIB; SKIN-CANCER; HEDGEHOG; THERAPY; SINGLE AB The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies. (c) 2013 AACR. C1 [Axelson, Michael; Liu, Ke; Kufrin, Dubravka; Palmby, Todd; Keegan, Patricia; Pazdur, Richard] US FDA, Off New Drugs, Off Hematol & Oncol Prod, Silver Spring, MD USA. [Jiang, Xiaoping; He, Kun] US FDA, Off Biostat, Silver Spring, MD USA. [Wang, Jian; Zhao, Hong] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah] US FDA, Ctr Drug Evaluat & Res, Off New Drug Qual Assessment, Silver Spring, MD USA. RP Keegan, P (reprint author), US FDA, Div Oncol Prod 2, 10903 New Hampshire Ave,Bldg 22,Room 2183, Silver Spring, MD 20993 USA. EM patricia.keegan@fda.hhs.gov NR 20 TC 41 Z9 41 U1 1 U2 10 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 MAY 1 PY 2013 VL 19 IS 9 BP 2289 EP 2293 DI 10.1158/1078-0432.CCR-12-1956 PG 5 WC Oncology SC Oncology GA 136KX UT WOS:000318361900004 PM 23515405 ER PT J AU Loring, Z Strauss, DG Gerstenblith, G Tomaselli, GF Weiss, RG Wu, KC AF Loring, Zak Strauss, David G. Gerstenblith, Gary Tomaselli, Gordon F. Weiss, Robert G. Wu, Katherine C. TI Cardiac MRI scar patterns differ by sex in an implantable cardioverter-defibrillator and cardiac resynchronization therapy cohort SO HEART RHYTHM LA English DT Article DE Cardiac magnetic resonance imaging; Implantable cardioverter-defibrillators; Cardiac resynchronization therapy; Gender ID LEFT-VENTRICULAR DYSFUNCTION; INFARCT TISSUE HETEROGENEITY; RANDOMIZED-CONTROLLED-TRIALS; MAGNETIC-RESONANCE; HEART-FAILURE; MYOCARDIAL SCAR; ISCHEMIC CARDIOMYOPATHY; PRIMARY PREVENTION; GENDER-DIFFERENCES; WOMEN AB BACKGROUND Recent meta-analyses suggest that the effectiveness of cardiac devices may differ between genders. Compared to men, women may not benefit as much from implantable cardioverter-defibrillators (ICDs), yet benefit more from cardiac resynchronization therapy (CRT). Myocardial scar burden is associated with increased incidence of appropriate ICD shocks but decreased response to CRT and may explain gender differences in device benefit. OBJECTIVE To test the hypothesis that the extent of myocardial scar is Less in women than men. METHODS In 235 patients referred for primary prevention ICDs who underwent cardiac magnetic resonance imaging, we compared scar size by gender. Analyses were performed for all patients (ICD cohort) and those receiving biventricular pacemakers (CRT subgroup). RESULTS In the ICD cohort, women (vs men) had a higher prevalence of nonischemic cardiomyopathy (NICM; 64% vs 39%; P < .001), which accounted for a smaller overall scar burden (0.5% vs 13%, P < .01). Likewise, in the CRT subgroup, the higher prevalence of NICM in women (83% vs 46%; P = .01) also contributed to a smaller scar size (0% vs 13%; P < .01). Women also had significantly Less scarring of the inferolateral Left ventricular wall. CONCLUSIONS In a cohort of patients undergoing clinically indicated ICD and CRT, women had Less myocardial scar than did men. This difference was primarily driven by a higher prevalence of NICM in women. These findings may have important implications for the future study of gender disparities in ICD and CRT outcomes. C1 [Loring, Zak; Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Loring, Zak] Duke Univ, Sch Med, Durham, NC USA. [Gerstenblith, Gary; Tomaselli, Gordon F.; Weiss, Robert G.; Wu, Katherine C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. RP Wu, KC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, 600 N Wolfe St Carnegie 568, Baltimore, MD 21287 USA. EM kwu@jhmi.edu FU Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University; National Heart, Lung, and Blood Institute's National Institutes of Health [HL103812, HL91062, HL61912]; Office of Women's Health at the US Food and Drug Administration FX The results of this project were presented at the HRS 2012: Heart Rhythm Society 33rd Annual Scientific Sessions on May 11 in Boston, MA. This project was supported by the Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University and by the National Heart, Lung, and Blood Institute's National Institutes of Health grants (HL103812 to Dr Wu, HL91062 to Dr Tomaselli, and HL61912 to Dr Weiss) as well as in part by the Office of Women's Health at the US Food and Drug Administration administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. The custom research software tool Cine Tool was obtained through a research agreement between Dr Wu and GE Healthcare. Dr Wu receives modest royalties for the licensing rights to use the gray zone methodology described in this article. NR 35 TC 6 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD MAY PY 2013 VL 10 IS 5 BP 659 EP 665 DI 10.1016/j.hrthm.2013.01.003 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 140QY UT WOS:000318671200014 PM 23313802 ER PT J AU Morrison, TM Meyer, CA Fillinger, MF Fairman, RM Glickman, MH Cambria, RP Farber, MA Naslund, TC Fail, PS Elmore, JR White, RA Dall'Olmo, CA Williams, DM AF Morrison, Tina M. Meyer, Clark A. Fillinger, Mark F. Fairman, Ron M. Glickman, Marc H. Cambria, Richard P. Farber, Mark A. Naslund, Thomas C. Fail, Peter S. Elmore, James R. White, Rodney A. Dall'Olmo, Carlo A. Williams, David M. TI Eligiblity for Endovascular Repair of Short Neck Abdominal Aortic Aneurysms SO JOURNAL OF VASCULAR SURGERY LA English DT Meeting Abstract CT Vascular Annual Meeting of the Society-for-Vascular-Surgery (SVS) CY MAY 30-JUN 01, 2013 CL San Francisco, CA SP Soc Vasc Surg (SVS) C1 [Morrison, Tina M.; Meyer, Clark A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Fillinger, Mark F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Fairman, Ron M.] Univ Penn, Med Ctr, Philadelphia, PA 19104 USA. [Glickman, Marc H.] Sentara Norfolk Gen Hosp, Norfolk, VA USA. [Cambria, Richard P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Farber, Mark A.] Univ N Carolina, Med Ctr, Chapel Hill, NC USA. [Naslund, Thomas C.] Vanderbilt Univ Sch Med, Nashville, TN USA. [Fail, Peter S.] Cardiovasc Inst South, Houma, LA USA. [Elmore, James R.] Geisinger Med Ctr, Danville, PA 17822 USA. [White, Rodney A.] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Dall'Olmo, Carlo A.] Michigan Vasc Ctr, Flint, MI USA. [Williams, David M.] Univ Michigan, Med Ctr, Ann Arbor, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2013 VL 57 IS 5 SU S BP 24S EP 24S PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 140VV UT WOS:000318685300042 ER PT J AU Torres-Aponte, JM Luce, RR Hunsperger, E Munoz-Jordan, JL Beltran, M Vergne, E Arguello, DF Garcia, EJ Sun, W Tomashek, KM AF Torres-Aponte, Jomil M. Luce, Richard R. Hunsperger, Elizabeth Munoz-Jordan, Jorge L. Beltran, Manuela Vergne, Edgardo Argueello, D. Fermin Garcia, Enid J. Sun, Wellington Tomashek, Kay M. TI Enhanced West Nile Virus Surveillance in a Dengue-Endemic Area-Puerto Rico, 2007 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID IMMUNOGLOBULIN-G ANTIBODIES; BLOOD-DONORS; NEW-YORK; ENCEPHALITIS; MANIFESTATIONS; HEMISPHERE; INFECTION; MOSQUITOS; EPIDEMIC; OUTBREAK AB In June of 2007, West Nile virus (WNV) was detected in sentinel chickens and blood donors in Puerto Rico, where dengue virus (DENV) is hyperendemic. Enhanced human surveillance for acute febrile illness (AFI) began in eastern Puerto Rico on July 1, 2007. Healthcare providers submitted specimens from AFI cases for WNV and DENV virology and serology testing. Over 6 months, 385 specimens were received from 282 cases; 115 (41%) specimens were DENV laboratory-positive, 86 (31%) specimens were laboratory-indeterminate, and 32 (11%) specimens were laboratory-negative for WNV and DENV. One WNV infection was detected by anti-WNV immunoglobulin M (IgM) antibody and confirmed by a plaque reduction neutralization test. DENV and WNV infections could not be differentiated in 27 cases (10%). During a period of active WNV transmission, enhanced human surveillance identified one case of symptomatic WNV infection. Improved diagnostic methods are needed to allow differentiation of WNV and DENV in dengue-endemic regions. C1 [Torres-Aponte, Jomil M.] Puerto Rico Dept Hlth, Epidemiol & Res Off, San Juan, PR 00920 USA. [Hunsperger, Elizabeth; Munoz-Jordan, Jorge L.; Beltran, Manuela; Vergne, Edgardo; Argueello, D. Fermin; Tomashek, Kay M.] Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Dis, San Juan, PR USA. [Luce, Richard R.] Ctr Dis Control & Prevent, Ctr Global Hlth, Libreville, Gabon. [Garcia, Enid J.] Univ Puerto Rico, Sch Med, San Juan, PR 00936 USA. [Sun, Wellington] US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Rockville, MD 20857 USA. RP Torres-Aponte, JM (reprint author), Puerto Rico Dept Hlth, Epidemiol & Res Off, 1324 Calle Canada, San Juan, PR 00920 USA. EM dzq9@cdc.gov; dwe5@cdc.gov; enh4@cdc.gov; ckq2@cdc.gov; mvb6@cdc.gov; edv1@cdc.gov; dla7@cdc.gov; enid.garcia3@upr.edu; wellington.sun@fda.hhs.gov; kct9@cdc.gov NR 30 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAY PY 2013 VL 88 IS 5 BP 997 EP 1002 DI 10.4269/ajtmh.12.0575 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 136WR UT WOS:000318394600030 PM 23478583 ER PT J AU Chen, HF Chen, XM Hu, Y Yan, HJ AF Chen, Haifeng Chen, Xuemei Hu, Yuan Yan, Huijun TI Reproducibility, fidelity, and discriminant validity of linear RNA amplification for microarray-based identification of major human enteric viruses SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Humanenteric viruses; DNA microarray; Linear RNA amplification; Single-stranded cDNA ID REVERSE TRANSCRIPTION-PCR; DNA MICROARRAY; INFECTIONS; HYBRIDIZATION; NOROVIRUSES; TARGETS; SYSTEMS AB Human enteric viruses are inherently a group of viruses that confer similar or overlapping clinical symptoms and pose a challenge for correct etiological diagnosis. DNA microarray technology has emerged to be of major interest to detect broad range of viral pathogens including enteric viruses. However, this approach requires a relative large amount of target nucleic acid for hybridization analysis. This feature limits its further applicability. To address this challenge, we evaluated a novel single primer linear isothermal amplification (Ribo-SPIA) procedure for preparation of single-stranded cDNA (sscDNA) from minute amount of starting RNA for microarray-based simultaneous detection and identification of three major human enteric viruses including hepatitis A virus, norovirus, and coxsachievirus B2. We performed a series of tests using different amounts of input RNA ranging from 30 ng to 55 pg to assess amplification yield, reproducibility, analytical sensitivity, and fidelity. We demonstrated that as little as 55 pg of viral RNA could produce adequate material by Ribo-SPIA to enable successful identification by microarray analysis without compromising detection specificity. Pairwise comparison of technical replicates hybridized to the microarrays by regression analysis showed excellent reproducibility in the appropriate sensitivity range. We also showed that the use of sscDNA as labeled targets offered increased microarray detection accuracy over complementary RNA generated by traditional T7 in vitro transcription amplification method. C1 [Chen, Haifeng] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Chen, Xuemei] Southern Med Univ, Sch Publ Hlth & Trop Med, Guangzhou, Guangdong, Peoples R China. [Hu, Yuan] US FDA, Microbiol Branch, ORA, Jamaica, NY USA. [Yan, Huijun] Sun Yat Sen Univ, Dept Microbiol, Zhongshan Sch Med, Guangzhou 510275, Guangdong, Peoples R China. RP Chen, HF (reprint author), US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM haifeng.chen@fda.hhs.gov NR 27 TC 3 Z9 4 U1 1 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD MAY PY 2013 VL 97 IS 9 BP 4129 EP 4139 DI 10.1007/s00253-013-4769-1 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 127FF UT WOS:000317681800034 PM 23455564 ER PT J AU Wieslander, B Wu, KC Loring, Z Andersson, LG Frank, TF Gerstenblith, G Tomaselli, GF Weiss, RG Wagner, GS Ugander, M Strauss, DG AF Wieslander, Bjorn Wu, Katherine C. Loring, Zak Andersson, Linus G. Frank, Terry F. Gerstenblith, Gary Tomaselli, Gordon F. Weiss, Robert G. Wagner, Galen S. Ugander, Martin Strauss, David G. TI Localization of myocardial scar in patients with cardiomyopathy and left bundle branch block using electrocardiographic Selvester QRS scoring SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article DE Selvester QRS score; Myocardial scar localization; Left bundle branch block; Cardiac resynchronization therapy; Cardiomyopathy ID CARDIAC-RESYNCHRONIZATION THERAPY; QUANTITATIVE ANATOMIC FINDINGS; CARDIOVASCULAR MAGNETIC-RESONANCE; LATE GADOLINIUM-ENHANCEMENT; INFARCT SIZE; HEART-FAILURE; VENTRICULAR HYPERTROPHY; SYSTEM; SPECIFICITY; QUANTIFICATION AB Introduction: Outcome of cardiac resynchronization therapy is severely worsened by myocardial scar at the left ventricular (LV) pacing site. We aimed to describe the diagnostic performance of electrocardiographic (ECG) criteria based on the Selvester QRS scoring system, first in localizing myocardial scar and second in screening for any non-septal scar in patients with strictly defined LBBB. Methods and Results: In 39 cardiomyopathy patients with LBBB, 17 with scar, 22 without scar, late gadolinium-enhancement cardiac magnetic resonance images (CMR-LGE) and 12-lead ECGs were analyzed for scar presence in 5 LV wall segments. The ECG criteria with the best diagnostic performance in detecting scar in each segment and in the four non-septal segments together were identified. Criteria for detecting non-septal scar had 75% (95% CI: 51%-90%) sensitivity, 95% (78%-99%) specificity, 92% (67%-99%) positive predictive value and 84% (65%-94%) negative predictive value. For each individual wall segment, 40%--60% sensitivities and 77%-100% specificities were found. Conclusions: The 12-lead ECG can convey information about scar presence and location in this population of cardiomyopathy patients with LBBB. ECG screening criteria for scar in potential CRT LV pacing sites were identified. Further exploration is required to determine the clinical utility of the 12-lead ECG in combination with other imaging modalities to screen for scar in potential LV pacing sites in CRT candidates. Published by Elsevier Inc. C1 [Wieslander, Bjorn; Andersson, Linus G.; Ugander, Martin] Karolinska Inst, Dept Clin Physiol, Cardiac MR Grp, S-10401 Stockholm, Sweden. [Wieslander, Bjorn; Andersson, Linus G.; Ugander, Martin] Karolinska Univ Hosp, Stockholm, Sweden. [Wieslander, Bjorn; Andersson, Linus G.; Wagner, Galen S.] Duke Clin Res Inst, Durham, NC USA. [Wu, Katherine C.; Frank, Terry F.; Gerstenblith, Gary; Tomaselli, Gordon F.; Weiss, Robert G.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Loring, Zak] Duke Univ, Sch Med, Durham, NC USA. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Strauss, DG (reprint author), 10903 New Hampshire Ave 62-1126, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov OI Ugander, Martin/0000-0003-3665-2038 FU National Heart, Lung, and Blood Institute; National Institutes of Health [HL103812, HL91062, HL61912]; DW Reynolds Foundation; FDA Critical Path Initiative FX The study was supported by the National Heart, Lung, and Blood Institute, National Institutes of Health (HL103812 to K.C.W., HL91062 to G.F.T., and HL61912 to R.G.W.), the DW Reynolds Foundation and the FDA Critical Path Initiative. NR 37 TC 9 Z9 9 U1 0 U2 5 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAY-JUN PY 2013 VL 46 IS 3 BP 249 EP 255 DI 10.1016/j.jelectrocard.2013.02.006 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 137SL UT WOS:000318457600010 PM 23540937 ER PT J AU Melillo, AA Foreman, O Elkins, KL AF Melillo, Amanda A. Foreman, Oded Elkins, Karen L. TI IL-12R beta 2 is critical for survival of primary Francisella tularensis LVS infection SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokines; bacterial infections; adaptive immunity; vaccines; host-pathogen interactions ID LIVE VACCINE STRAIN; INTRACELLULAR BACTERIUM; T-CELLS; INTERLEUKIN-12 IL-12; PROTECTIVE IMMUNITY; GAMMA-INTERFERON; STAT4 ACTIVATION; BRUCELLA-ABORTUS; IN-VIVO; B-CELLS AB Using a panel of vaccines that provided different degrees of protection, we previously identified the IL-12 receptor subunit beta 2 as a mediator, whose relative expression correlated with strength of protection against secondary lethal challenge of vaccinated mice with an intracellular bacterium, the LVS of Francisella tularensis. The present study therefore tested the hypothesis that IL-12R beta 2 is an important mediator in resistance to LVS by directly examining its role during infections. IL-12R beta 2 KO mice were highly susceptible to LVS primary infection, administered i. d. or i. n. The LD50 of LVS infection of KO mice were 2 logs lower than those of WT mice, regardless of route. Five days after infection with LVS, bacterial organ burdens were significantly higher in IL-12R beta 2 KO mice. IL12R beta 2 KO mice infected with lethal doses of LVS had more severe liver pathology, including significant increases in the liver enzymes ALT and AST. Despite decreased levels of IFN-gamma, LVS-vaccinated IL-12R beta 2 KO mice survived large lethal LVS secondary challenge. Consistent with in vivo protection, in vitro intramacrophage LVS growth was well-controlled in cocultures containing WT or IL-12R beta 2 KO LVS-immune splenocytes. Thus, survival of secondary LVS challenge was not strictly dependent on IL-12R beta 2. However, IL-12R beta 2 is important in parenteral and mucosal host resistance to primary LVS infection and in the ability of WT mice to clear LVS infection and serves to restrict liver damage. C1 [Melillo, Amanda A.; Elkins, Karen L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Foreman, Oded] Jackson Lab, Sacramento, CA USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod, CBER, 1401 Rockville Pike,HFM-431, Rockville, MD 20852 USA. EM karen.elkins@fda.hhs.gov FU U.S. National Institute of Allergy and Infectious Diseases [Y1-AI-6153-01/224-06-1322]; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported, in part, by an interagency agreement with the U.S. National Institute of Allergy and Infectious Diseases (Y1-AI-6153-01/224-06-1322). This project was supported, in part, by an appointment to the Research Participation Program at the CBER, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We are grateful to our CBER colleagues, Dr. Roberto De Pascalis, Sherry Kurtz, Dr. Jonathan Swoboda, Dr. Siobhan Cowley, Dr. Kris Kolibab, as well as Dr. Wendy Watford of the University of Georgia, for thoughtful and comprehensive reviews of the manuscript. NR 40 TC 10 Z9 10 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAY PY 2013 VL 93 IS 5 BP 657 EP 667 DI 10.1189/jlb.1012485 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 136ZX UT WOS:000318404700004 PM 23440500 ER PT J AU Allec, N Abbaszadeh, S Scott, CC Karim, KS Lewin, JM AF Allec, Nicholas Abbaszadeh, Shiva Scott, Chris C. Karim, Karim S. Lewin, John M. TI Evaluating noise reduction techniques while considering anatomical noise in dual-energy contrast-enhanced mammography SO MEDICAL PHYSICS LA English DT Article DE noise reduction; anatomical noise; dual-energy imaging; mammography ID ALGORITHM AB Purpose: The authors describe modifications to previously developed cascaded systems analysis to include the anatomical noise in evaluation of dual-energy noise reduction techniques. Previous models have ignored the anatomical noise in theoretical analysis of noise reduction techniques. The inclusion of anatomical noise leads to more accurate estimation of potential noise reduction improvements and optimization. Methods: The model is applied to dual-energy contrast-enhanced mammography. The effect of linear noise reduction filters on the anatomical noise is taken into account using cascaded systems analysis. The noise model is included in the ideal observer detectability for performance evaluation of the noise reduction techniques. Results: Dual-energy image noise with and without including the effect of anatomical noise in noise reduction technique analysis is reported. The theoretical model is compared with clinical images from a previous dual-energy contrast enhanced mammography clinical study and good agreement is observed. The results suggest that the inclusion of anatomical noise in the evaluation and comparison of noise reduction techniques is highly warranted for more accurate analysis. Conclusions: This work establishes a useful extension to dual-energy cascaded systems analysis for maximizing image quality using noise reduction techniques. The extension includes the effect of linear image filtering, such as that used for noise reduction, on anatomical noise. The results suggest that the inclusion of anatomical noise in the evaluation of noise reduction techniques can lead to more accurate optimization, noise, and performance estimations. (C) 2013 American Association of Physicists in Medicine. C1 [Allec, Nicholas; Abbaszadeh, Shiva; Scott, Chris C.; Karim, Karim S.] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. [Lewin, John M.] Diversified Radiol Colorado Res Inst, Denver, CO 80204 USA. RP Allec, N (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. EM nallec@uwaterloo.ca FU Natural Sciences and Engineering Research Council of Canada (NSERC); Ontario Research Fund Research Excellence (ORF-RE) FX This research was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Ontario Research Fund Research Excellence (ORF-RE). NR 11 TC 1 Z9 1 U1 0 U2 13 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 MAY PY 2013 VL 40 IS 5 AR 051904 DI 10.1118/1.4799841 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139AO UT WOS:000318553900029 PM 23635274 ER PT J AU Sisniega, A Zbijewski, W Badal, A Kyprianou, IS Stayman, JW Vaquero, JJ Siewerdsen, JH AF Sisniega, A. Zbijewski, W. Badal, A. Kyprianou, I. S. Stayman, J. W. Vaquero, J. J. Siewerdsen, J. H. TI Monte Carlo study of the effects of system geometry and antiscatter grids on cone-beam CT scatter distributions SO MEDICAL PHYSICS LA English DT Article DE cone-beam CT; x-ray scatter; antiscatter grid; image quality; Monte Carlo; GPU ID X-RAY SCATTER; IMAGE QUALITY EVALUATION; FLAT-PANEL DETECTORS; COMPUTED-TOMOGRAPHY; BREAST CT; MICRO-CT; DIGITAL RADIOGRAPHY; COHERENT SCATTERING; RADIATION-THERAPY; PHOTON TRANSPORT AB Purpose: The proliferation of cone-beam CT (CBCT) has created interest in performance optimization, with x-ray scatter identified among the main limitations to image quality. CBCT often contends with elevated scatter, but the wide variety of imaging geometry in different CBCT configurations suggests that not all configurations are affected to the same extent. Graphics processing unit (GPU) accelerated Monte Carlo (MC) simulations are employed over a range of imaging geometries to elucidate the factors governing scatter characteristics, efficacy of antiscatter grids, guide system design, and augment development of scatter correction. Methods: A MC x-ray simulator implemented on GPU was accelerated by inclusion of variance reduction techniques (interaction splitting, forced scattering, and forced detection) and extended to include x-ray spectra and analytical models of antiscatter grids and flat-panel detectors. The simulator was applied to small animal (SA), musculoskeletal (MSK) extremity, otolaryngology (Head), breast, interventional C-arm, and on-board (kilovoltage) linear accelerator (Linac) imaging, with an axis-to-detector distance (ADD) of 5, 12, 22, 32, 60, and 50 cm, respectively. Each configuration was modeled with and without an antiscatter grid and with (i) an elliptical cylinder varying 70-280 mm in major axis; and (ii) digital murine and anthropomorphic models. The effects of scatter were evaluated in terms of the angular distribution of scatter incident upon the detector, scatter-to-primary ratio (SPR), artifact magnitude, contrast, contrast-to-noise ratio (CNR), and visual assessment. Results: Variance reduction yielded improvements in MC simulation efficiency ranging from similar to 17-fold (for SA CBCT) to similar to 35-fold (for Head and C-arm), with the most significant acceleration due to interaction splitting (similar to 6 to similar to 10-fold increase in efficiency). The benefit of a more extended geometry was evident by virtue of a larger air gap-e.g., for a 16 cm diameter object, the SPR reduced from 1.5 for ADD = 12 cm (MSK geometry) to 1.1 for ADD = 22 cm (Head) and to 0.5 for ADD = 60 cm (C-arm). Grid efficiency was higher for configurations with shorter air gap due to a broader angular distribution of scattered photons-e.g., scatter rejection factor similar to 0.8 for MSK geometry versus similar to 0.65 for C-arm. Grids reduced cupping for all configurations but had limited improvement on scatter-induced streaks and resulted in a loss of CNR for the SA, Breast, and C-arm. Relative contribution of forward-directed scatter increased with a grid (e.g., Rayleigh scatter fraction increasing from similar to 0.15 without a grid to similar to 0.25 with a grid for the MSK configuration), resulting in scatter distributions with greater spatial variation (the form of which depended on grid orientation). Conclusions: A fast MC simulator combining GPU acceleration with variance reduction provided a systematic examination of a range of CBCT configurations in relation to scatter, highlighting the magnitude and spatial uniformity of individual scatter components, illustrating tradeoffs in CNR and artifacts and identifying the system geometries for which grids are more beneficial (e.g., MSK) from those in which an extended geometry is the better defense (e.g., C-arm head imaging). Compact geometries with an antiscatter grid challenge assumptions of slowly varying scatter distributions due to increased contribution of Rayleigh scatter. (c) 2013 American Association of Physicists in Medicine. C1 [Sisniega, A.; Zbijewski, W.; Stayman, J. W.; Siewerdsen, J. H.] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. [Sisniega, A.; Vaquero, J. J.] Univ Carlos III Madrid, Dept Bioingn & Ingn Aeroespacial, ES-28911 Madrid, Spain. [Badal, A.; Kyprianou, I. S.] US FDA, CDRH, OSEL, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. [Siewerdsen, J. H.] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21287 USA. [Siewerdsen, J. H.] Johns Hopkins Univ, Russell H Morgan Dept Radiol, Baltimore, MD 21205 USA. RP Zbijewski, W (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21205 USA. EM wzbijewski@jhu.edu RI Vaquero, Juan Jose/D-3033-2009 OI Vaquero, Juan Jose/0000-0001-9200-361X FU Carestream Health Inc. (Rochester, NY); National Institutes of Health (NIH) Grant [2R01-CA-112163]; FPU grant (Spanish Ministry of Education); AMIT project; RECAVA-RETIC Network [TEC2010-21619-C04-01, TEC2011-28972-C02-01, PI11/00616]; ARTEMIS program (Comunidad de Madrid); PreDiCT-TB partnership FX The authors thank Yoshito Otake, Ph. D. (Johns Hopkins University) for assistance with GPU cone-beam reconstruction, and John Boone, Ph. D. (University of California Davis) for providing the digital breast phantom. The research was supported by academic-industry partnership with Carestream Health Inc. (Rochester, NY) and National Institutes of Health (NIH) Grant No. 2R01-CA-112163. A. Sisniega is supported by FPU grant (Spanish Ministry of Education), AMIT project, RECAVA-RETIC Network, Project Nos. TEC2010-21619-C04-01, TEC2011-28972-C02-01, and PI11/00616 (Spanish Ministry of Science and Education), ARTEMIS program (Comunidad de Madrid), and PreDiCT-TB partnership. NR 75 TC 27 Z9 27 U1 1 U2 25 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 MAY PY 2013 VL 40 IS 5 AR 051915 DI 10.1118/1.4801895 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139AO UT WOS:000318553900040 PM 23635285 ER PT J AU Young, S Bakic, PR Myers, KJ Jennings, RJ Park, S AF Young, Stefano Bakic, Predrag R. Myers, Kyle J. Jennings, Robert J. Park, Subok TI A virtual trial framework for quantifying the detectability of masses in breast tomosynthesis projection data SO MEDICAL PHYSICS LA English DT Article DE virtual trials; breast tomosynthesis; task-specific; image quality; projections; model observers ID FLAT-PANEL IMAGER; CONE-BEAM CT; DIGITAL MAMMOGRAPHY; ACQUISITION PARAMETERS; COMPUTER-SIMULATION; HOTELLING OBSERVERS; SOFTWARE PHANTOM; 3D SIMULATION; MODEL; PERFORMANCE AB Purpose: Digital breast tomosynthesis (DBT) is a promising breast cancer screening tool that has already begun making inroads into clinical practice. However, there is ongoing debate over how to quantitatively evaluate and optimize these systems, because different definitions of image quality can lead to different optimal design strategies. Powerful and accurate tools are desired to extend our understanding of DBT system optimization and validate published design principles. Methods: The authors developed a virtual trial framework for task-specific DBT assessment that uses digital phantoms, open-source x-ray transport codes, and a projection-space, spatial-domain observer model for quantitative system evaluation. The authors considered evaluation of reconstruction algorithms as a separate problem and focused on the information content in the raw, unfiltered projection images. Specifically, the authors investigated the effects of scan angle and number of angular projections on detectability of a small (3 mm diameter) signal embedded in randomly-varying anatomical backgrounds. Detectability was measured by the area under the receiver-operating characteristic curve (AUC). Experiments were repeated for three test cases where the detectability-limiting factor was anatomical variability, quantum noise, or electronic noise. The authors also juxtaposed the virtual trial framework with other published studies to illustrate its advantages and disadvantages. Results: The large number of variables in a virtual DBT study make it difficult to directly compare different authors' results, so each result must be interpreted within the context of the specific virtual trial framework. The following results apply to 25% density phantoms with 5.15 cm compressed thickness and 500 mu m(3) voxels (larger 500 mu m(2) detector pixels were used to avoid voxel-edge artifacts): 1. For raw, unfiltered projection images in the anatomical-variability-limited regime, AUC appeared to remain constant or increase slightly with scan angle. 2. In the same regime, when the authors fixed the scan angle, AUC increased asymptotically with the number of projections. The threshold number of projections for asymptotic AUC performance depended on the scan angle. In the quantum- and electronic-noise dominant regimes, AUC behaviors as a function of scan angle and number of projections sometimes differed from the anatomy-limited regime. For example, with a fixed scan angle, AUC generally decreased with the number of projections in the electronic-noise dominant regime. These results are intended to demonstrate the capabilities of the virtual trial framework, not to be used as optimization rules for DBT. Conclusions: The authors have demonstrated a novel simulation framework and tools for evaluating DBT systems in an objective, task-specific manner. This framework facilitates further investigation of image quality tradeoffs in DBT. (c) 2013 American Association of Physicists in Medicine. C1 [Young, Stefano] Univ Arizona, Coll Opt Sci, Tucson, AZ 85721 USA. [Bakic, Predrag R.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Myers, Kyle J.; Jennings, Robert J.; Park, Subok] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering (NIBIB); Oak Ridge Institute for Science Education (ORISE) Research Participation Program at the Center for Devices and Radiological Health (CDRH) of the FDA; FDA Office of Women's Health FX The author would like to acknowledge Dr. Matthew Kupinski for helpful discussions and reading early drafts, Drs. Jonathan Boswell and Andreu Badal for their computing expertise and help in the use of the FDA in-house compute cluster and Monte Carlo codes, Dr. Harrison Barrett for his thoughts on noise, and Mr. Kyle Anderson for his early work on PenVT. The authors would also like to acknowledge funding support from the National Institute of Biomedical Imaging and Bioengineering (NIBIB), the Oak Ridge Institute for Science Education (ORISE) Research Participation Program at the Center for Devices and Radiological Health (CDRH) of the FDA, and the FDA Office of Women's Health. NR 62 TC 20 Z9 20 U1 0 U2 17 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 MAY PY 2013 VL 40 IS 5 AR 051914 DI 10.1118/1.4800501 PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 139AO UT WOS:000318553900039 PM 23635284 ER PT J AU Ulrich, LC Joseph, FD Lewis, DY Koenig, RL AF Ulrich, Linda C. Joseph, Francesca D. Lewis, Debra Y. Koenig, Robert L. TI FDA's Pediatric Device Consortia: National Program Fosters Pediatric Medical Device Development SO PEDIATRICS LA English DT Article DE medical devices; Pediatric Device Consortia Grant Program; Pediatric Medical Device Safety and Improvement Act; pediatrics ID UNITED-STATES AB OBJECTIVES: This article reports on the progress made in addressing pediatric medical device needs through the establishment of the Pediatric Device Consortia Grant Program. Pediatric practitioners should be aware of both the imperative for well-studied devices for children and the existence of recently created resources to help foster the development of such products. METHODS: This article discusses some of the challenges associated with pediatric device development and describes the implementation of section 305 of the Pediatric Medical Device Safety and Improvement Act of 2007. This statute called for the creation of nonprofit consortia to facilitate the development, production, and distribution of pediatric medical devices. RESULTS: A summary of the accomplishments of the pediatric device consortia is presented. Eleven million dollars have been awarded to 5 consortia since 2009. As of July 2012, they have collectively assisted in the development of 219 pediatric device ideas. The consortia provide innovators with both mentorship and services to help advance proposed pediatric device projects, including assistance with prototyping, identification of potential funding sources, preclinical and clinical trial design, and introductions to potential manufacturers. CONCLUSIONS: Currently, 5 federally funded pediatric device consortia exist to help advance the development of potential pediatric devices. These consortia serve as a national resource for those with ideas for medical devices that may advance the health and well-being of children. C1 [Ulrich, Linda C.; Joseph, Francesca D.; Lewis, Debra Y.; Koenig, Robert L.] US FDA, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. RP Ulrich, LC (reprint author), US FDA, Off Orphan Prod Dev, WO 32-5271,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM linda.ulrich@fda.hhs.gov NR 6 TC 11 Z9 11 U1 0 U2 1 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 MAY PY 2013 VL 131 IS 5 BP 981 EP 985 DI 10.1542/peds.2012-1534 PG 5 WC Pediatrics SC Pediatrics GA 135EO UT WOS:000318270700061 PM 23569100 ER PT J AU West, SL Squiers, LB McCormack, L Southwell, BG Brouwer, ES Ashok, M Lux, L Boudewyns, V O'Donoghue, A Sullivan, HW AF West, Suzanne L. Squiers, Linda B. McCormack, Lauren Southwell, Brian G. Brouwer, Emily S. Ashok, Mahima Lux, Linda Boudewyns, Vanessa O'Donoghue, Amie Sullivan, Helen W. TI Communicating quantitative risks and benefits in promotional prescription drug labeling or print advertising SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE risk; benefit; communication; drug advertising; literature review; pharmacoepidemiology ID RANDOMIZED CONTROLLED-TRIAL; BREAST-CANCER; PRESENTATION FORMATS; TREATMENT DECISIONS; TREATMENT CHOICES; PROSTATE-CANCER; INFORMATION; PROBABILITIES; NUMERACY; GRAPHICS AB Purpose Under the Food, Drug, and Cosmetic Act, all promotional materials for prescription drugs must strike a fair balance in presentation of risks and benefits. How to best present this information is not clear. We sought to determine if the presentation of quantitative risk and benefit information in drug advertising and labeling influences consumers', patients', and clinicians' information processing, knowledge, and behavior by assessing available empirical evidence. Methods We used PubMed for a literature search, limiting to articles published in English from 1990 forward. Two reviewers independently reviewed the titles and abstracts for inclusion, after which we reviewed the full texts to determine if they communicated risk/benefit information either: (i) numerically (e.g., percent) versus non-numerically (e.g., using text such as increased risk) or (ii) numerically using different formats (e.g., 25% of patients, one in four patients, or use of pictographs). We abstracted information from included articles into standardized evidence tables. The research team identified a total of 674 relevant publications, of which 52 met our inclusion criteria. Of these, 37 focused on drugs. Results and conclusions Presenting numeric information appears to improve understanding of risks and benefits relative to non-numeric presentation; presenting both numeric and non-numeric information when possible may be best practice. No single specific format or graphical approach emerged as consistently superior. Numeracy and health literacy also deserve more empirical attention as moderators. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [West, Suzanne L.; Squiers, Linda B.; McCormack, Lauren; Southwell, Brian G.; Brouwer, Emily S.; Ashok, Mahima; Lux, Linda; Boudewyns, Vanessa] RTI Int, Res Triangle Pk, NC USA. [West, Suzanne L.; Brouwer, Emily S.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA. [Southwell, Brian G.] Univ N Carolina, Sch Journalism & Mass Commun, Chapel Hill, NC 27515 USA. [Brouwer, Emily S.] Univ Kentucky, Coll Pharm, Inst Pharmaceut Outcomes & Policy, Lexington, KY USA. [O'Donoghue, Amie; Sullivan, Helen W.] US FDA, Silver Spring, MD USA. RP West, SL (reprint author), RTI Int Social Policy Hlth & Econ Res, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM swest@rti.org RI Boudewyns, Vanessa/G-5713-2013; OI Boudewyns, Vanessa/0000-0002-1777-290X; Southwell, Brian/0000-0001-5091-8782 FU U.S. Food and Drug Administration FX This work was funded by the U.S. Food and Drug Administration. Parts of this discussion have been presented at the 2012 International Conference on Pharmacoepidemiology and Risk Management, Barcelona, Spain, and presented to the Food and Drug Administration Risk Communication Advisory Committee, which posted an earlier full report on its website in coordination with the November 17, 2011 committee meeting. NR 56 TC 9 Z9 9 U1 5 U2 19 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2013 VL 22 IS 5 BP 447 EP 458 DI 10.1002/pds.3416 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 137MH UT WOS:000318439500001 PM 23440924 ER PT J AU Kulldorff, M Dashevsky, I Avery, TR Chan, AK Davis, RL Graham, D Platt, R Andrade, SE Boudreau, D Gunter, MJ Herrinton, LJ Pawloski, PA Raebel, MA Roblin, D Brown, JS AF Kulldorff, Martin Dashevsky, Inna Avery, Taliser R. Chan, Arnold K. Davis, Robert L. Graham, David Platt, Richard Andrade, Susan E. Boudreau, Denise Gunter, Margaret J. Herrinton, Lisa J. Pawloski, Pamala A. Raebel, Marsha A. Roblin, Douglas Brown, Jeffrey S. TI Drug safety data mining with a tree-based scan statistic SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pharmacovigilance; drug safety surveillance; adverse events; data mining; scan statistics; clusters; pharmacoepidemiology ID VACCINE SAFETY; ADVERSE EVENTS; ACTIVE SURVEILLANCE; SIGNAL GENERATION; REPORTING SYSTEM; TERBINAFINE; NETWORK; TRANSPLANTATION; ITRACONAZOLE; MULTICENTER AB Purpose In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drugevent pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. Methods We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Results Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. Conclusion The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drugevent pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R.; Platt, Richard; Brown, Jeffrey S.] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R.; Platt, Richard; Brown, Jeffrey S.] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Chan, Arnold K.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Chan, Arnold K.] i3 Drug Safety, Waltham, MA USA. [Davis, Robert L.; Roblin, Douglas] Kaiser Permanente Georgia, Atlanta, GA USA. [Graham, David] US FDA, Off Drug Safety, Rockville, MD 20857 USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, Worcester, MA USA. [Andrade, Susan E.] Fallon Community Hlth Plan, Worcester, MA USA. [Boudreau, Denise] Grp Hlth Res Inst, Seattle, WA USA. [Gunter, Margaret J.] Lovelace Clin Fdn, Albuquerque, NM USA. [Herrinton, Lisa J.] Kaiser Permanente Northern Calif, Oakland, CA USA. [Pawloski, Pamala A.] HealthPartners Inst Res & Educ, Minneapolis, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Denver, CO USA. RP Kulldorff, M (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM martin_kulldorff@hms.harvard.edu OI Chan, Kinwei/0000-0001-8161-1986; Kulldorff, Martin/0000-0002-5284-2993 FU Agency for Healthcare Research and Quality (AHRQ) [U18 HS 010391] FX This work was funded by the Agency for Healthcare Research and Quality (AHRQ), through a grant to the HMO Research Network Center for Education and Research on Therapeutics (CERT), grant number U18 HS 010391. We thank Anita Wagner for help with the drug classification, David Smith for contributing data from Kaiser Permanente Northwest, and both of them together with Sascha Dublin for valuable comments NR 41 TC 8 Z9 8 U1 1 U2 28 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2013 VL 22 IS 5 BP 517 EP 523 DI 10.1002/pds.3423 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 137MH UT WOS:000318439500009 PM 23512870 ER PT J AU Li, Q Andrade, SE Cooper, WO Davis, RL Dublin, S Hammad, TA Pawloski, PA Pinheiro, SP Raebel, MA Scott, PE Smith, DH Dashevsky, I Haffenreffer, K Johnson, KE Toh, S AF Li, Qian Andrade, Susan E. Cooper, William O. Davis, Robert L. Dublin, Sascha Hammad, Tarek A. Pawloski, Pamala A. Pinheiro, Simone P. Raebel, Marsha A. Scott, Pamela E. Smith, David H. Dashevsky, Inna Haffenreffer, Katherine Johnson, Karin E. Toh, Sengwee TI Validation of an algorithm to estimate gestational age in electronic health plan databases SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE algorithm; database; gestational age; maternal exposure; pharmacoepidemiology; pregnancy; validation studies ID MAJOR CONGENITAL-MALFORMATIONS; BIRTH-DEFECTS; ADMINISTRATIVE DATA; CLINICAL ESTIMATE; EARLY-PREGNANCY; MEDICATION USE; UNITED-STATES; EXPOSURE; RISK; DEPRESSION AB Purpose To validate an algorithm that uses delivery date and diagnosis codes to define gestational age at birth in electronic health plan databases. Methods Using data from 225384 live born deliveries to women aged 1545years in 20012007 within eight of the 11 health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program, we compared (1) the algorithm-derived gestational age versus the gold-standard gestational age obtained from the infant birth certificate file and (2) the prenatal exposure status of two antidepressants (fluoxetine and sertraline) and two antibiotics (amoxicillin and azithromycin) as determined by the algorithm-derived versus the gold-standard gestational age. Results The mean algorithm-derived gestational age at birth was lower than the mean obtained from the birth certificate file among singleton deliveries (267.9 vs 273.5days) but not among multiple-gestation deliveries (253.9 vs 252.6days). The algorithm-derived prenatal exposure to the antidepressants had a sensitivity and a positive predictive value of 95%, and a specificity and a negative predictive value of almost 100%. Sensitivity and positive predictive value were both 90%, and specificity and negative predictive value were both >99% for the antibiotics. Conclusions A gestational age algorithm based upon electronic health plan data correctly classified medication exposure status in most live born deliveries, but trimester-specific misclassification may be higher for drugs typically used for short durations. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Li, Qian] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine; Toh, Sengwee] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Li, Qian; Dashevsky, Inna; Haffenreffer, Katherine; Toh, Sengwee] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Davis, Robert L.] Southeast Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Dublin, Sascha; Johnson, Karin E.] Grp Hlth Res Inst, Seattle, WA USA. [Hammad, Tarek A.; Pinheiro, Simone P.; Scott, Pamela E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pawloski, Pamala A.] HealthPartners Inst Educ & Res, Bloomington, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Smith, David H.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. RP Toh, S (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave 6th Floor, Boston, MA 02215 USA. EM darrentoh@post.harvard.edu RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Silver Spring, MD, USA) [HHSF223200510012C, HHSF223200510009C, HHSF223200510008C]; National Institute on Aging [K23AG028954]; Group Health Research Institute internal funds FX This study was supported through funding from contracts HHSF223200510012C, HHSF223200510009C, and HHSF223200510008C from the U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Silver Spring, MD, USA). Dr. Dublin was funded by a Paul Beeson Career Development Award from the National Institute on Aging, grant K23AG028954, and by Group Health Research Institute internal funds. The content is solely the responsibility of the authors and does not necessarily represent the official views or endorsement of the Food and Drug Administration, the National Institute on Aging, or the National Institutes of Health. NR 27 TC 9 Z9 9 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2013 VL 22 IS 5 BP 524 EP 532 DI 10.1002/pds.3407 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 137MH UT WOS:000318439500010 PM 23335117 ER PT J AU Mintz, PD AF Mintz, Paul D. TI Informed Consent for Blood Transfusion and The Joint Commission SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 US FDA, Div Hematol, Off Blood Res & Review, Rockville, MD 20857 USA. RP Mintz, PD (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2013 VL 139 IS 5 BP 693 EP 693 DI 10.1309/AJCPPEX1LOSNQGXM PG 1 WC Pathology SC Pathology GA 131MA UT WOS:000317996600015 PM 23596121 ER PT J AU Nekhai, S Kumari, N Foster, A Diaz, S Kovalskyy, D Gordeuk, VR Dhawan, S AF Nekhai, Sergei Kumari, Namita Foster, Altreisha Diaz, Sharmin Kovalskyy, Dmytro Gordeuk, Victor R. Dhawan, Subhash TI HIV-1 INFECTION AND IRON: ROLE OF HEME-OXYGENASE-1 AND FERROPORTIN SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Meeting Abstract C1 [Nekhai, Sergei; Kumari, Namita; Foster, Altreisha; Diaz, Sharmin] Howard Univ, Washington, DC USA. [Kovalskyy, Dmytro] Natl Taras Shvchenko Univ, Kiev, Ukraine. [Gordeuk, Victor R.] Univ Illinois, Chicago, IL USA. [Dhawan, Subhash] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD MAY PY 2013 VL 88 IS 5 BP E123 EP E123 PG 1 WC Hematology SC Hematology GA 132BT UT WOS:000318043500201 ER PT J AU Cavaille-Coll, M Bala, S Velidedeoglu, E Hernandez, A Archdeacon, P Gonzalez, G Neuland, C Meyer, J Albrecht, R AF Cavaille-Coll, M. Bala, S. Velidedeoglu, E. Hernandez, A. Archdeacon, P. Gonzalez, G. Neuland, C. Meyer, J. Albrecht, R. TI Summary of FDA Workshop on Ischemia Reperfusion Injury in Kidney Transplantation SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE Clinical trials; delayed graft function; efficacy; endpoints; ischemia reperfusion injury; safety ID DELAYED GRAFT FUNCTION; HISTIDINE-TRYPTOPHAN-KETOGLUTARATE; DONOR RENAL-TRANSPLANTATION; RANDOMIZED CONTROLLED-TRIAL; MACHINE PERFUSION; COLD-STORAGE; MOLECULAR PHENOTYPE; PROTOCOL BIOPSIES; ACUTE REJECTION; CARDIAC DEATH AB The Food and Drug Administration (FDA) held an open public workshop in September 2011 to discuss the current state of science related to the effects of ischemia reperfusion injury (IRI) on outcomes in kidney transplantation. Topics included the development of IRI and delayed graft function (DGF), histology and biomarkers, donor factors, recipient factors, organ quality and organ preservation by means of cold storage solutions or machine perfusion. Various mechanisms of injury and maladaptive response to IRI were discussed as potential targets of intervention. Animal models evaluating specific pathophysiological pathways were presented, as were the limitations of extrapolating animal results to humans. Clinical trials of various drug products administered in the peri-transplant period were summarized; a few demonstrated early improvements in DGF, but none demonstrated an improvement in late graft function. Clinical trial design for IRI and DGF were also discussed. C1 [Cavaille-Coll, M.; Bala, S.; Velidedeoglu, E.; Meyer, J.; Albrecht, R.] US FDA, Div Transplant & Ophthalmol Prod, Off Antimicrobial Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hernandez, A.; Gonzalez, G.; Neuland, C.] US FDA, Div Reprod Gastrorenal & Urol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Archdeacon, P.] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Meyer, J (reprint author), US FDA, Div Transplant & Ophthalmol Prod, Off Antimicrobial Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM joette.meyer@fda.hhs.gov NR 62 TC 41 Z9 41 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2013 VL 13 IS 5 BP 1134 EP 1148 DI 10.1111/ajt.12210 PG 15 WC Surgery; Transplantation SC Surgery; Transplantation GA 135GR UT WOS:000318277100006 PM 23566221 ER PT J AU Pawar, RS Tamta, H Ma, J Krynitsky, AJ Grundel, E Wamer, WG Rader, JI AF Pawar, Rahul S. Tamta, Hemlata Ma, Jun Krynitsky, Alexander J. Grundel, Erich Wamer, Wayne G. Rader, Jeanne I. TI Updates on chemical and biological research on botanical ingredients in dietary supplements SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE Botanicals; Dietary supplements; Geranium; 1,3-Dimethylamylamine; Bitter melon; Momordicosides; Hepatotoxicity ID MOMORDICA-CHARANTIA L; CUCURBITANE-TYPE TRITERPENOIDS; DRUG-INDUCED HEPATOTOXICITY; ISOLATED MAJOR COMPOUNDS; HEPATOMA HEPARG CELLS; IN-VITRO; MASS-SPECTROMETRY; FUNCTIONAL FOODS; ESSENTIAL OIL; HEPG2 CELLS AB Increased use of dietary supplements is a phenomenon observed worldwide. In the USA, more than 40 % of the population recently reported using complementary and alternative medicines, including botanical dietary supplements. Perceptions that such dietary supplements are natural and safe, may prevent disease, may replace prescription medicines, or may make up for a poor diet, play important roles in their increased use. Toxicity of botanical dietary supplements may result from the presence of naturally occurring toxic constituents or from contamination or adulteration with pharmaceutical agents, heavy metals, mycotoxins, pesticides, or bacteria, misidentification of a plant species in a product, formation of electrophilic metabolites, organ-specific reactions, or botanical-drug interactions. The topics discussed in this review illustrate several issues in recent research on botanical ingredients in dietary supplements. These include (1) whether 1,3-dimethylamylamine is a natural constituent of rose geranium (Pelargonium graveolens), (2) how analysis of the components of dietary supplements containing bitter melon (Momordica charantia) is essential to understanding their potential biological effects, and (3) how evolving methods for in vitro studies on botanical ingredients can contribute to safety evaluations. The virtual explosion in the use of botanical ingredients in hundreds of products presents a considerable challenge to the analytical community, and the need for appropriate methods cannot be overstated. We review recent developments and use of newer and increasingly sensitive methods that can contribute to increasing the safety and quality of botanical ingredients in dietary supplements. C1 [Pawar, Rahul S.; Tamta, Hemlata; Ma, Jun; Krynitsky, Alexander J.; Grundel, Erich; Wamer, Wayne G.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Pawar, RS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Rahul.Pawar@fda.hhs.gov FU US FDA FX The authors thank Aruna Weerasooriya (University of Mississippi, Oxford, MS, USA) for providing the photographs of P. graveolens and M. charantia. Some of the work reported here was supported by the appointment of H.T. to the Research Fellowship Program of the US FDA administered by the Oak Ridge Institute of Science and Education. NR 84 TC 12 Z9 13 U1 3 U2 83 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2013 VL 405 IS 13 BP 4373 EP 4384 DI 10.1007/s00216-012-6691-2 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131DK UT WOS:000317972200008 PM 23322353 ER PT J AU Pawar, RS Krynitsky, AJ Rader, JI AF Pawar, Rahul S. Krynitsky, Alexander J. Rader, Jeanne I. TI Sweeteners from plants-with emphasis on Stevia rebaudiana (Bertoni) and Siraitia grosvenorii (Swingle) SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE Natural sweeteners; Stevia rebaudiana; Steviol glycosides; Siraitia grosvenorii; Mogrosides; Dietary supplements; Generally recognized as safe status ID CHROMATOGRAPHY-MASS SPECTROMETRY; LUO-HAN-GUO; LIQUID-CHROMATOGRAPHY; MIRACLE FRUIT; NATURAL SWEETENER; GLYCOSIDES; ORIGIN; MOGROSIDES; PROTEINS; LEAVES AB In addition to their widely recognized use as dietary supplement ingredients, plant-derived compounds are increasingly used as natural sweeteners. The search for nonnutritive sweeteners has been stimulated over the last 20-30 years by concern over demonstrated or suspected relationships between consumption of sucrose and high-fructose corn syrups and a variety of health-related conditions. In the USA, there is increased use of plant extracts known to contain highly sweet terpenoids. Purified extracts of Stevia rebaudiana (Bertoni) containing the diterpene glycosides stevioside and rebaudioside A are popular as sweeteners and are also used as dietary supplements, and soft drinks and nutritional and energy shakes incorporating extracts of Siraitia grosvenorii (Swingle) fruits containing sweet triterpene glycosides such as mogroside V are also on the market. Here, we review recent studies on these two important sources of noncaloric natural sweeteners, including analytical methods used to identify and quantify specific constituents and structural features relating to their sweetness. We also review the generally recognized as safe status of specific components and their status with respect to review by the Joint FAO/WHO Expert Committee on Food Additives. C1 [Pawar, Rahul S.; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Pawar, RS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM rahul.pawar@fda.hhs.gov NR 74 TC 20 Z9 20 U1 18 U2 167 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2013 VL 405 IS 13 BP 4397 EP 4407 DI 10.1007/s00216-012-6693-0 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131DK UT WOS:000317972200010 PM 23341001 ER PT J AU Rader, JI Pawar, RS AF Rader, Jeanne I. Pawar, Rahul S. TI Primary constituents of blue cohosh: quantification in dietary supplements and potential for toxicity SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE Blue cohosh; Caulophyllum thalictroides; Alkaloids; Saponins; Dietary supplements ID CROOKED CALF DISEASE; CAULOPHYLLUM-THALICTROIDES; LIQUID-CHROMATOGRAPHY; LUPIN ALKALOIDS; QUINOLIZIDINE ALKALOIDS; TRITERPENE GLYCOSIDES; NONTERATOGENIC LUPINS; MOMORDICA-CHARANTIA; GAS-CHROMATOGRAPHY; SAPONINS AB Dietary supplements containing dried roots or extracts of the roots and/or rhizomes of blue cohosh (Caulophyllum thalictroides) are widely available. This botanical has a long history of use by Native Americans and its use continues to the present day. The primary constituents of blue cohosh are its alkaloids and saponins. The structures of the alkaloids magnoflorine, baptifoline, anagyrine, and N-methylcytisine have been known for many years. The last 10 years have seen a great increase in isolation and identification of the large number of saponins present in blue cohosh. Important developments in nuclear magnetic resonance techniques have contributed substantially to the increase in elucidation of the structures of the complex saponins. Several authors have described quantitative methods for both the alkaloids and saponins in blue cohosh. Such methods have made it possible to quantify these constituents in dietary supplements containing this botanical ingredient. Concentrations of both alkaloids and saponins vary substantially in dietary supplements of blue cohosh. The nicotinic alkaloid, N-methylcytisine, a potent toxicant, has been found in all dietary supplements of blue cohosh analyzed. The teratogenic alkaloid anagyrine has been found in some but not all dietary supplements. C1 [Rader, Jeanne I.; Pawar, Rahul S.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Jeanne.Rader@fda.hhs.gov NR 63 TC 4 Z9 4 U1 0 U2 11 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2013 VL 405 IS 13 BP 4409 EP 4417 DI 10.1007/s00216-013-6783-7 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131DK UT WOS:000317972200011 PM 23420136 ER PT J AU Schantz, MM Sander, LC Sharpless, KE Wise, SA Yen, JH NguyenPho, A Betz, JM AF Schantz, Michele M. Sander, Lane C. Sharpless, Katherine E. Wise, Stephen A. Yen, James H. NguyenPho, Agnes Betz, Joseph M. TI Development of botanical and fish oil standard reference materials for fatty acids SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Fatty acid; Omega-3; Omega-6; Plant oil; Fish oil; Reference material ID EXTRACT AB As part of a collaboration with the National Institutes of Health's Office of Dietary Supplements and the Food and Drug Administration's Center for Drug Evaluation and Research, the National Institute of Standards and Technology has developed Standard Reference Material (SRM) 3274 Botanical Oils Containing Omega-3 and Omega-6 Fatty Acids and SRM 3275 Omega-3 and Omega-6 Fatty Acids in Fish Oil. SRM 3274 consists of one ampoule of each of four seed oils (3274-1 Borage (Borago officinalis), 3274-2 Evening Primrose (Oenothera biennis), 3274-3 Flax (Linium usitatissimum), and 3274-4 Perilla (Perilla frutescens)), and SRM 3275 consists of two ampoules of each of three fish oils (3275-1 a concentrate high in docosahexaenoic acid, 3275-2 an anchovy oil high in docosahexaenoic acid and eicosapentaenoic acid, and 3275-3 a concentrate containing 60 % long-chain omega-3 fatty acids). Each oil has certified and reference mass fraction values for up to 20 fatty acids. The fatty acid mass fraction values are based on results from analyses using gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC/MS). These SRMs will complement other reference materials currently available with mass fractions for similar analytes and are part of a series of SRMs being developed for dietary supplements. C1 [Schantz, Michele M.; Sander, Lane C.; Sharpless, Katherine E.; Wise, Stephen A.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Yen, James H.] NIST, Stat Engn Div, Gaithersburg, MD 20899 USA. [NguyenPho, Agnes] US FDA, CDER, Silver Spring, MD 20993 USA. [Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Schantz, MM (reprint author), NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. EM michele.schantz@nist.gov OI Sharpless, Katherine/0000-0001-6569-198X NR 21 TC 5 Z9 5 U1 1 U2 31 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD MAY PY 2013 VL 405 IS 13 BP 4531 EP 4538 DI 10.1007/s00216-013-6747-y PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 131DK UT WOS:000317972200023 PM 23371533 ER PT J AU Wang, SJ Hsu, JC Posch, M AF Wang, Sue-Jane Hsu, Jason C. Posch, Martin TI MCP2011The 7th international conference on multiple comparison procedures SO BIOMETRICAL JOURNAL LA English DT Editorial Material ID SPECIAL-ISSUE C1 [Wang, Sue-Jane] Johns Hopkins Univ, US FDA, Baltimore, MD 20993 USA. [Hsu, Jason C.] Ohio State Univ, Columbus, OH 43210 USA. [Posch, Martin] Med Univ Vienna, Ctr Med Stat Informat & Intelligent Syst, Vienna, Austria. RP Wang, SJ (reprint author), Johns Hopkins Univ, US FDA, Baltimore, MD 20993 USA. EM suejane.wang@fda.hhs.gov RI Posch, Martin/C-7907-2009 OI Posch, Martin/0000-0001-8499-8573 NR 6 TC 1 Z9 1 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD MAY PY 2013 VL 55 IS 3 BP 271 EP 274 DI 10.1002/bimj.201300025 PG 4 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 134TI UT WOS:000318237100001 PM 23620457 ER PT J AU Wang, SJ Bretz, F Dmitrienko, A Hsu, J Hung, HMJ Huque, M Koch, G AF Wang, Sue-Jane Bretz, Frank Dmitrienko, Alex Hsu, Jason Hung, H. M. James Huque, Mohammad Koch, Gary TI Panel forum on multiple comparison procedures: A commentary from a complex trial design and analysis plan SO BIOMETRICAL JOURNAL LA English DT Article DE Alpha propagation; Correlation; decision path partition test; Dose-endpoint pair; Fisher's protected least significance difference; Multiplicity-at-combined-trial level (or programwise type I error); Parallel gatekeeping; Single hierarchical chain; truncated and regular Hommel-based gatekeeping ID CLINICAL-TRIALS AB Motivated by a complex study design aiming at a definitive evidential setting, a panel forum among academia, industry, and US regulatory statistical scientists was held at the 7th International Conference on Multiple Comparison Procedures (MCP) to comment on the multiplicity problem. It is well accepted that studywise or familywise, type I error rate control is the norm for confirmatory trials. But, it is an uncharted territory regarding the criteria beyond a single confirmatory trial. The case example describes a Phase III program consisting of two placebo-controlled multiregional clinical trials identical in design intended to support registration for treatment of a chronic condition in the lung. The case presents a sophisticated multiplicity problem in several levels: four primary endpoints, two doses, two studies, two regions with different regulatory requirements, one major protocol amendment on the original statistical analysis plan, which the panelists had a chance to study before the forum took place. There were differences in professional perspectives among the panelists laid out by sections. Nonetheless, irrespective of the amendment, it may be arguable whether the two studies are poolable for the analysis of two primary endpoints prespecified. How should the study finding be reported in a scientific journal if one health authority approves while the other does not? It is tempting to address the Phase III program level multiplicity motivated by the increasing complexity of the partial hypotheses framework posed that are across studies. A novel thinking of the MCP procedures beyond individual-study level (studywise or familywise as predefined) and across multiple-study level (experimentwise and sometimes programwise) will become an important research problem expected to face with scientific and regulatory challenges. C1 [Wang, Sue-Jane; Hung, H. M. James; Huque, Mohammad] US FDA, Silver Spring, MD 20993 USA. [Wang, Sue-Jane; Hung, H. M. James] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Bretz, Frank] Novartis, CH-4002 Basel, Switzerland. [Bretz, Frank] Hannover Med Sch, D-30625 Hannover, Germany. [Dmitrienko, Alex] Quintiles, Durham, NC 27703 USA. [Hsu, Jason] Ohio State Univ, Columbus, OH 43210 USA. [Huque, Mohammad] Georgia So Univ, Jiann Ping Hsu Coll Publ Hlth, Statesboro, GA 30458 USA. [Koch, Gary] Univ N Carolina, Chapel Hill, NC 27599 USA. RP Wang, SJ (reprint author), US FDA, HFD 700,WO 21,MailStop Room 3562,10903 New Hampsh, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov RI Bretz, Frank/F-6927-2014 NR 21 TC 2 Z9 2 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD MAY PY 2013 VL 55 IS 3 BP 275 EP 293 DI 10.1002/bimj.201200047 PG 19 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 134TI UT WOS:000318237100002 PM 23553537 ER PT J AU Hung, HMJ Wang, SJ AF Hung, H. M. James Wang, Sue-Jane TI Multiple comparisons in complex clinical trial designs SO BIOMETRICAL JOURNAL LA English DT Article DE Experiment-wise; Evidence-setting; Group sequential; Interim analysis; Replication; Strength of evidence; Strong control; Study-wise ID END-POINTS; TESTS; BONFERRONI AB Multiple comparisons have drawn a great deal of attention in evaluation of statistical evidence in clinical trials for regulatory applications. As the clinical trial methodology is increasingly more complex to properly take into consideration many practical factors, the multiple testing paradigm widely employed for regulatory applications may not suffice to interpret the results of an individual trial and of multiple trials. In a large outcome trial, an increasing need of studying more than one dose complicates a proper application of multiple comparison procedures. Additional challenges surface when a special endpoint, such as mortality, may need to be tested with multiple clinical trials combined, especially under group sequential designs. Another interesting question is how to study mortality or morbidity endpoints together with symptomatic endpoints in an efficient way, where the former type of endpoints are often studied in only one single trial but the latter type of endpoints are usually studied in at least two independent trials. This article is devoted to discussion of insufficiency of such a widely used paradigm applying only per-trial based multiple comparison procedures and to expand the utility of the procedures to such complex trial designs. A number of viable expanded strategies are stipulated. C1 [Hung, H. M. James] US FDA, Div Biometr 1, OB OTS CDER, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] US FDA, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB OTS CDER, 10903 New Hampshire Ave,HFD 710, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 27 TC 3 Z9 3 U1 3 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD MAY PY 2013 VL 55 IS 3 BP 420 EP 429 DI 10.1002/bimj.201200048 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 134TI UT WOS:000318237100011 PM 23620458 ER PT J AU Alosh, M Huque, MF AF Alosh, Mohamed Huque, Mohammad F. TI Multiplicity considerations for subgroup analysis subject to consistency constraint SO BIOMETRICAL JOURNAL LA English DT Article DE Consistency ensured multiplicity methods; Subgroup analysis; Targeted subgroup; Treatment-by-subgroup interaction ID RANDOMIZED CLINICAL-TRIALS; END-POINTS; BONFERRONI; ISSUES; TESTS AB A significant heterogeneity in response across subgroups of a clinical trial implies that the average response from the overall population might not characterize the treatment effect; and as noted by different regulatory guidances, can cause concerns in interpreting study findings and might lead to restricting treatment labeling. However, along with the challenges raised by the heterogeneity, recently there has been growing interest in taking advantage of the expected variability in response across subgroups to increase the chance of success of a trial by designing the trial with objectives of establishing efficacy claims for the total population and a targeted subgroup. For such trials, there have been several approaches to address the multiplicity issue with the two paths of success. This manuscript advocates the utility of setting a threshold on the treatment effect for the subgroups at the design stage to guide determination of the population labeling when significant findings for the total population have been established. Specifically, it proposes that licensing treatment for the total population requires, in addition to significant findings for this population, that the treatment effect in the least benefited (complementary) subgroup meets the treatment effect threshold at a minimum; otherwise, the treatment would be restricted to the targeted subgroup only. Setting such a threshold can be based on clinical considerations, including toxicity and adverse events, in addition to treatment effect in the subgroup. This manuscript expands some of the multiplicity approaches to account for the threshold requirement and investigates the impact of the threshold requirement on study power. C1 [Alosh, Mohamed] CDER FDA, Div Biometr 3, OTS, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] CDER FDA, Off Biostat, OTS, Silver Spring, MD 20993 USA. RP Alosh, M (reprint author), CDER FDA, Div Biometr 3, OTS, Silver Spring, MD 20993 USA. EM Mohamed.Alosh@fda.hhs.gov NR 20 TC 10 Z9 10 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD MAY PY 2013 VL 55 IS 3 BP 444 EP 462 DI 10.1002/bimj.201200065 PG 19 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 134TI UT WOS:000318237100013 PM 23585158 ER PT J AU Burkhart, KK Abernethy, D AF Burkhart, Keith K. Abernethy, Darrell TI Drugs highly associated with infusion reactions enhance nitric oxide signaling SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 [Burkhart, Keith K.; Abernethy, Darrell] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD MAY PY 2013 VL 51 IS 4 MA 163 BP 325 EP 326 PG 2 WC Toxicology SC Toxicology GA 130SD UT WOS:000317938600174 ER PT J AU Martinez, MN Antonovic, L Court, M Dacasto, M Fink-Gremmels, J Kukanich, B Locuson, C Mealey, K Myers, MJ Trepanier, L AF Martinez, Marilyn N. Antonovic, Leposava Court, Michael Dacasto, Mauro Fink-Gremmels, Johanna Kukanich, Butch Locuson, Chuck Mealey, Katrina Myers, Michael J. Trepanier, Lauren TI Challenges in exploring the cytochrome P450 system as a source of variation in canine drug pharmacokinetics SO DRUG METABOLISM REVIEWS LA English DT Review DE Canine; drug metabolism; enzyme inhibitors; enzyme substrates; interspecies differences; orthologs; pharmacogenomics ID DOG LIVER-MICROSOMES; AMINO-ACID-SEQUENCES; PREGNANE-X-RECEPTOR; HUMAN CYP2B6 GENE; IN-VITRO; BEAGLE DOGS; SUBSTRATE-SPECIFICITY; CLINICAL-SIGNIFICANCE; MESSENGER-RNA; STEREOSELECTIVE METABOLISM AB The cytochrome P450 (CYP) superfamily constitutes a collection of enzymes responsible for the metabolism of a wide array of endo-and xenobiotic compounds. Much of the knowledge on substrate specificity and genetic identification of the various CYP isoforms is derived from research in rodents and humans and only limited information has been captured in the dog. Currently, there exist many gaps in our knowledge of canine CYP diversity as a result of the paucity of studies focusing on canine CYPs, canine CYP polymorphisms, and the therapeutic consequences of these genetic variants. Challenges engendered by this lack of information is further amplified by inter-and intraspecies differences in the specificity and affinity of substrates and inhibitors, prohibiting a simple extrapolation of probe substances used in human CYP research. This creates a need to develop and validate canine-specific CYP probes. Failure to understand this potential metabolic and pharmacogenomic diversity can also influence the interpretation of data generated in dogs to support human drug development. It is with these objectives in mind that we provide an overview of what is currently known about canine CYPs with the hope that it will encourage further exploration into this important area of research. C1 [Martinez, Marilyn N.; Myers, Michael J.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Antonovic, Leposava] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Court, Michael; Mealey, Katrina] Washington State Univ, Dept Vet Clin Sci, Pullman, WA 99164 USA. [Dacasto, Mauro] Univ Padua, Dipartimento Biomed Comparata & Alimentaz, Padua, Italy. [Fink-Gremmels, Johanna] Univ Utrecht, Dept Vet Pharmacol Pharmacotherapy & Toxicol, Utrecht, Netherlands. [Kukanich, Butch] Kansas State Univ, Dept Anat & Physiol, Manhatten, NY USA. [Locuson, Chuck] Pharmaprogressio Consulting, Rochester, MN USA. [Trepanier, Lauren] Washington State Univ, Coll Vet Med, Dept Vet Clin Sci, Pullman, WA 99164 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7520 Standish Pl,HFV 100, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 135 TC 12 Z9 12 U1 0 U2 18 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 EI 1097-9883 J9 DRUG METAB REV JI Drug Metab. Rev. PD MAY PY 2013 VL 45 IS 2 BP 218 EP 230 DI 10.3109/03602532.2013.765445 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 130NI UT WOS:000317924500004 PM 23432217 ER PT J AU Toro, M Najjar, MB Ju, WT Brown, E Zhao, SH Meng, JH AF Toro, Magaly Najjar, Mohamed Badaoui Ju, Wenting Brown, Eric Zhao, Shaohua Meng, Jianghong TI Molecular Serogrouping of Shiga Toxin-Producing Escherichia coli Using Suspension Array SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID MULTIPLEX PCR; IDENTIFICATION; GENES AB A suspension array assay was developed for molecular serotyping of the seven most prevalent Shiga toxin-producing Escherichia coli (STEC) serogroups (O26, O45, O103, O111, O121, O145, and O157). Fluorescence values of 59 STEC were 30 to >270 times greater than the signals of negative controls, demonstrating the method's effectiveness for the molecular serotyping of STEC. C1 [Toro, Magaly; Najjar, Mohamed Badaoui; Ju, Wenting; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Brown, Eric] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Brown, Eric] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu RI Toro, Magaly/F-6525-2011 OI Toro, Magaly/0000-0002-6280-2215 FU Joint Institute for Food Safety & Applied Nutrition (JIFSAN) at the University of Maryland FX We thank Drs. Pina Fratamico and Peter Feng for providing some STEC strains for this study, and to Dr. Lydia Rump for her thoughtful comments. We are grateful to Dr. Frank Siewerdt for advising in the statistical analysis. The study was supported in part by funding from the Joint Institute for Food Safety & Applied Nutrition (JIFSAN) at the University of Maryland. NR 11 TC 3 Z9 3 U1 0 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD MAY PY 2013 VL 10 IS 5 BP 478 EP 480 DI 10.1089/fpd.2012.1352 PG 3 WC Food Science & Technology SC Food Science & Technology GA 134OW UT WOS:000318223100013 PM 23531122 ER PT J AU Parunov, L Shibeko, A Li, W Ataullakhanov, F Lee, T Ovanesov, M AF Parunov, L. Shibeko, A. Li, W. Ataullakhanov, F. Lee, T. Ovanesov, M. TI Low concentrations of activated factor XI promote spatial clot growth in the absence of factor XI activation SO HAEMOPHILIA LA English DT Meeting Abstract C1 [Parunov, L.; Shibeko, A.; Li, W.; Lee, T.; Ovanesov, M.] US FDA, Off Blood Res & Review, CBER, Bethesda, MD 20014 USA. [Ataullakhanov, F.] Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. NR 0 TC 0 Z9 0 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD MAY PY 2013 VL 19 IS 3 BP 469 EP 469 PG 1 WC Hematology SC Hematology GA 132OM UT WOS:000318078400077 ER PT J AU Eby, JC Gray, MC Warfel, JM Paddock, CD Jones, TF Day, SR Bowden, J Poulter, MD Donato, GM Merkel, TJ Hewlett, EL AF Eby, Joshua C. Gray, Mary C. Warfel, Jason M. Paddock, Christopher D. Jones, Tara F. Day, Shandra R. Bowden, James Poulter, Melinda D. Donato, Gina M. Merkel, Tod J. Hewlett, Erik L. TI Quantification of the Adenylate Cyclase Toxin of Bordetella pertussis In Vitro and during Respiratory Infection SO INFECTION AND IMMUNITY LA English DT Article ID POLYMERASE-CHAIN-REACTION; VIRULENCE FACTORS; EPITHELIAL-CELLS; LETHAL FACTOR; HEMOLYTIC ACTIVITIES; BACILLUS-ANTHRACIS; INSERTION-SEQUENCE; HUMAN NEUTROPHILS; ESCHERICHIA-COLI; CR3 CD11B/CD18 AB Whooping cough results from infection of the respiratory tract with Bordetella pertussis, and the secreted adenylate cyclase toxin (ACT) is essential for the bacterium to establish infection. Despite extensive study of the mechanism of ACT cytotoxicity and its effects over a range of concentrations in vitro, ACT has not been observed or quantified in vivo, and thus the concentration of ACT at the site of infection is unknown. The recently developed baboon model of infection mimics the prolonged cough and transmissibility of pertussis, and we hypothesized that measurement of ACT in nasopharyngeal washes (NPW) from baboons, combined with human and in vitro data, would provide an estimate of the ACT concentration in the airway during infection. NPW contained up to similar to 10(8) CFU/ml B. pertussis and 1 to 5 ng/ml ACT at the peak of infection. Nasal aspirate specimens from two human infants with pertussis contained bacterial concentrations similar to those in the baboons, with 12 to 20 ng/ml ACT. When similar to 10(8) CFU/ml of a laboratory strain of B. pertussis was cultured in vitro, ACT production was detected in 60 min and reached a plateau of similar to 60 ng/ml in 6 h. Furthermore, when bacteria were brought into close proximity to target cells by centrifugation, intoxication was increased 4-fold. Collectively, these data suggest that at the bacterium-target cell interface during infection of the respiratory tract, the concentration of ACT can exceed 100 ng/ml, providing a reference point for future studies of ACT and pertussis pathogenesis. C1 [Eby, Joshua C.; Gray, Mary C.; Day, Shandra R.; Donato, Gina M.; Hewlett, Erik L.] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. [Warfel, Jason M.; Merkel, Tod J.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Paddock, Christopher D.; Jones, Tara F.] Ctr Dis Control & Prevent, Infect Dis Pathol Branch, Atlanta, GA USA. [Poulter, Melinda D.] Univ Virginia, Dept Pathol, Med Ctr, Charlottesville, VA 22903 USA. RP Hewlett, EL (reprint author), Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA. EM eh2v@virginia.edu FU NIH, NIAID [5 RO1 AI1018000, 1K08AI081900-01, 2T32AI007046-36]; Food and Drug Administration; NIH/NIAID [Y1-AI-1727-01]; NIH National Center for Research Resources [P40RR012317, 5R24RR016556-10] FX This work was supported by funding from the NIH, NIAID (grants 5 RO1 AI1018000 [E.L.H.] and 1K08AI081900-01 [J.C.E.]), Food and Drug Administration and NIH/NIAID interagency agreement Y1-AI-1727-01 (T.J.M.), the NIH National Center for Research Resources (grants P40RR012317 and 5R24RR016556-10 [T.J.M.]), and an Infectious Diseases Training Grant from the NIH, NIAID (grant 2T32AI007046-36 [S.R.D.]). NR 72 TC 22 Z9 22 U1 0 U2 14 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2013 VL 81 IS 5 BP 1390 EP 1398 DI 10.1128/IAI.00110-13 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126AE UT WOS:000317582700002 PM 23429530 ER PT J AU Schmeisser, F Friedman, R Besho, J Lugovtsev, V Soto, J Wang, W Weiss, C Williams, O Xie, H Ye, ZP Weir, JP AF Schmeisser, Falko Friedman, Rachel Besho, Joseph Lugovtsev, Vladimir Soto, Jackeline Wang, Wei Weiss, Carol Williams, Ollie Xie, Hang Ye, Zhiping Weir, Jerry P. TI Neutralizing and protective epitopes of the 2009 pandemic influenza H1N1 hemagglutinin SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE Hemagglutinin; monoclonal antibody; protective epitopes ID MONOCLONAL-ANTIBODIES; ANTIGENIC STRUCTURE; UNITED-STATES; VIRUS; COMPLEMENT; HUMANS; NEURAMINIDASE; ENHANCEMENT; PSEUDOTYPES; RESPONSES AB Aims and Methods To facilitate antigenic characterization of the influenza A 2009 pandemic H1N1 [A(H1N1)pdm09] hemagglutinin (HA), we generated a panel of murine monoclonal antibodies (mAbs) using as the immunogen mammalian-derived virus-like particles containing the HA of the A/California/04/2009 virus. The antibodies were specific for the A/California/04/2009 HA, and individual mAbs suitable for use in several practical applications including ELISA, immunofluorescence, and Western blot analysis were identified. Results and Conclusions As the panel of mAbs included antibodies with hemagglutination inhibition (HI) and virus neutralizing activities, this allowed identification and characterization of potentially important antigenic and neutralizing epitopes of the A/California/04/2009 HA and comparison of those epitopes with the HAs of other influenza viruses including seasonal H1N1 viruses as well as the A/South Carolina/1918 and A/New Jersey/1976 H1N1 viruses. Three mAbs with the highest HI and neutralizing titers were able to provide passive protection against virus challenge. Two other mAbs without HI or neutralizing activities were able to provide partial protection against challenge. HA epitopes recognized by the strongest neutralizing mAbs in the panel were identified by isolation and selection of virus escape mutants in the presence of individual mAbs. Cloned viruses resistant to HI and antibody neutralization were sequenced to identify mutations, and two unique mutations (D127E and G155E) were identified, both near the antigenic site Sa. Using human post-vaccination sera, however, there were no differences in HI titer between A/California/04/2009 and either escape mutant, suggesting that these single mutations were not sufficient to abrogate a protective antibody response to the vaccine. C1 [Schmeisser, Falko; Friedman, Rachel; Besho, Joseph; Lugovtsev, Vladimir; Soto, Jackeline; Wang, Wei; Weiss, Carol; Williams, Ollie; Xie, Hang; Ye, Zhiping; Weir, Jerry P.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Weir, JP (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM jerry.weir@fda.hhs.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU Biomedical Advanced Research and Development Authority, Department of Health and Human Services FX MDCK cells were a gift from Dr. Jacqueline Katz (CDC, Atlanta, GA, USA). We thank Dr. Maryna Eichelberger and Dr. Keith Peden for critical review of the manuscript. This work was supported in part by the Biomedical Advanced Research and Development Authority, Department of Health and Human Services. Rachel Friedman and Joseph Besho were participants of the Oak Ridge Institute for Science and Education program at CBER. NR 40 TC 7 Z9 8 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1750-2640 J9 INFLUENZA OTHER RESP JI Influenza Other Respir. Viruses PD MAY PY 2013 VL 7 IS 3 BP 480 EP 490 DI 10.1111/irv.12029 PG 11 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 131XX UT WOS:000318033100036 PM 23122228 ER PT J AU Pogribny, IP Tryndyak, VP Pogribna, M Shpyleva, S Surratt, G Da Costa, GG Beland, FA AF Pogribny, Igor P. Tryndyak, Volodymyr P. Pogribna, Marta Shpyleva, Svitlana Surratt, Gordon Da Costa, Goncalo Gamboa Beland, Frederick A. TI Modulation of intracellular iron metabolism by iron chelation affects chromatin remodeling proteins and corresponding epigenetic modifications in breast cancer cells and increases their sensitivity to chemotherapeutic agents SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE breast cancer; iron metabolism; histone modifications; DNA methylation ID REGULATED GENE-1 NDRG1; HISTONE DEMETHYLATION; DNA-DAMAGE; METHYLATION; APOPTOSIS; TRANSCRIPTION; MECHANISMS; FAMILY; LSD1; RECRUITMENT AB Iron plays a vital role in the normal functioning of cells via the regulation of essential cellular metabolic reactions, including several DNA and histone-modifying proteins. The metabolic status of iron and the regulation of epigenetic mechanisms are well-balanced and tightly controlled in normal cells; however, in cancer cells these processes are profoundly disturbed. Cancer-related abnormalities in iron metabolism have been corrected through the use of iron-chelating agents, which cause an inhibition of DNA synthesis, G(1)-S phase arrest, an inhibition of epithelial-to-mesenchymal transition, and the activation of apoptosis. In the present study, we show that, in addition to these well-studied molecular mechanisms, the treatment of wild-type TP53 MCF-7 and mutant TP53 MDA-MB-231 human breast cancer cells with desferrioxamine (DFO), a model iron chelator, causes significant epigenetic alterations at the global and gene-specific levels. Specifically, DFO treatment decreased the protein levels of the histone H3 lysine 9 demethylase, Jumonji domain-containing protein 2A (JMJD2A), in the MCF-7 and MDA-MB-231 cells and down-regulated the levels of the histone H3 lysine 4 demethylase, lysine-specific demethylase 1 (LSD1), in the MDA-MB-231 cells. These changes were accompanied by alterations in corresponding metabolically sensitive histone marks. Additionally, we demonstrate that DFO treatment activates apoptotic programs in MCF-7 and MDA-MB-231 cancer cells and enhances their sensitivity to the chemotherapeutic agents, doxorubicin and cisplatin; however, the mechanisms underlying this activation differ. The induction of apoptosis in wild-type TP53 MCF-7 cells was p53-dependent, triggered mainly by the down-regulation of the JMJD2A histone demethylase, while in mutant TP53 MDA-MB-231 cells, the activation of the p53-independent apoptotic program was driven predominantly by the epigenetic up-regulation of p21. C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Pogribna, Marta; Shpyleva, Svitlana; Surratt, Gordon; Da Costa, Goncalo Gamboa; Beland, Frederick A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 46 TC 9 Z9 9 U1 0 U2 12 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 EI 1791-2423 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 2013 VL 42 IS 5 BP 1822 EP 1832 DI 10.3892/ijo.2013.1855 PG 11 WC Oncology SC Oncology GA 132FN UT WOS:000318053400037 PM 23483119 ER PT J AU Shaheen, BW Nayak, R Foley, SL Boothe, DM AF Shaheen, Bashar W. Nayak, Rajesh Foley, Steven L. Boothe, Dawn M. TI Chromosomal and plasmid-mediated fluoroquinolone resistance mechanisms among broad-spectrum-cephalosporin-resistant Escherichia coli isolates recovered from companion animals in the USA SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE qnr; qepA; aac(6)-Ib-cr; topoisomerase IV; ESBLs ID QUINOLONE RESISTANCE; MULTIDRUG-RESISTANCE; UNITED-STATES; PARC MUTATIONS; EFFLUX PUMPS; QEPA; QNR; AAC(6')-IB-CR; PREVALENCE; ENZYME AB To determine the prevalence of plasmid-mediated quinolone resistance (PMQR) determinants and investigate mutations in gyrase and topoisomerase genes that may contribute to increased fluoroquinolone resistance in canine and feline Escherichia coli isolates in the USA that displayed reduced susceptibility to extended-spectrum cephalosporins. This study was undertaken because previous epidemiological studies identified a potential correlation between extended-spectrum cephalosporins and fluoroquinolone resistance. Isolates (n54) with reduced susceptibility to ceftazidime or cefotaxime were screened by PCR for the presence of PMQR determinants and gyrase and topoisomerase genes were sequenced. Isolates were further characterized by conjugation and phylogenetic analyses. PMQR determinants aac(6)-Ib-cr, qnrS and qepA were identified in 30, 23 and 5 isolates, respectively. Multiple mutations were identified in the quinolone resistance-determining region, including the novel substitutions of Glu-84Ala and Leu-88Gln in ParC and Arg-432Ser and Glu-460Val in ParE. The isolate that exhibited the highest level of enrofloxacin resistance (MIC 256 mg/L) had a double mutation in gyrA (Ser-83Leu and Asp-87Asn) and a triple mutation in parC (Ser-80Ile, Glu-84Gly and a novel mutation, Leu-88Gln). The presence of PMQR genes increased the ciprofloxacin MIC values 4-fold to 8-fold in transconjugants relative to the recipient strain. Approximately 39 of the isolates belonged to phylogenetic group D and 30 to group B2, which typically contain an increased number of virulence determinants compared with other groups. Novel mutations in topoisomerase genes and PMQR determinants aac(6)-Ib-cr, qnrS and qepA genes were detected among extended-spectrum -lactamase-producing E. coli in the USA. C1 [Shaheen, Bashar W.; Nayak, Rajesh; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Boothe, Dawn M.] Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. RP Nayak, R (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM rajesh.nayak@fda.hhs.gov FU US FDA; Oak Ridge Institute for Science and Education FX This work was supported by US FDA funds. B. W. S. is supported by the Oak Ridge Institute for Science and Education. NR 20 TC 16 Z9 17 U1 1 U2 25 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2013 VL 68 IS 5 BP 1019 EP 1024 DI 10.1093/jac/dks514 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 132YR UT WOS:000318105100007 PM 23302578 ER PT J AU Lee, K Ahn, H Moon, H Kodell, RL Chen, JJ AF Lee, Kyewon Ahn, Hongshik Moon, Hojin Kodell, Ralph L. Chen, James J. TI Multinomial Logistic Regression Ensembles SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Class prediction; Ensemble; Logistic regression; Majority voting; Multinomial logit; Random partition ID HIGH-DIMENSIONAL DATA; GASTROINTESTINAL HEMORRHAGE; CLASSIFICATION; FORESTS AB This article proposes a method for multiclass classification problems using ensembles of multinomial logistic regression models. A multinomial logit model is used as a base classifier in ensembles from random partitions of predictors. The multinomial logit model can be applied to each mutually exclusive subset of the feature space without variable selection. By combining multiple models the proposed method can handle a huge database without a constraint needed for analyzing high-dimensional data, and the random partition can improve the prediction accuracy by reducing the correlation among base classifiers. The proposed method is implemented using R, and the performance including overall prediction accuracy, sensitivity, and specificity for each category is evaluated on two real data sets and simulation data sets. To investigate the quality of prediction in terms of sensitivity and specificity, the area under the receiver operating characteristic (ROC) curve (AUC) is also examined. The performance of the proposed model is compared to a single multinomial logit model and it shows a substantial improvement in overall prediction accuracy. The proposed method is also compared with other classification methods such as the random forest, support vector machines, and random multinomial logit model. C1 [Lee, Kyewon; Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Kodell, Ralph L.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Chen, James J.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Biometry Branch, Jefferson, AR 72079 USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM hahn@ams.sunysb.edu NR 15 TC 3 Z9 3 U1 4 U2 13 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD MAY 1 PY 2013 VL 23 IS 3 BP 681 EP 694 DI 10.1080/10543406.2012.756500 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 130XD UT WOS:000317952500013 PM 23611203 ER PT J AU Przepiorka, D Deisseroth, A Kane, R Kaminskas, E Farrell, AT Pazdur, R AF Przepiorka, Donna Deisseroth, Albert Kane, Robert Kaminskas, Edvardas Farrell, Ann T. Pazdur, Richard TI Gemtuzumab Ozogamicin SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ACUTE MYELOID-LEUKEMIA C1 [Przepiorka, Donna; Deisseroth, Albert; Kane, Robert; Kaminskas, Edvardas; Farrell, Ann T.; Pazdur, Richard] US FDA, Silver Spring, MD USA. RP Przepiorka, D (reprint author), US FDA, Silver Spring, MD USA. NR 6 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2013 VL 31 IS 13 BP 1699 EP 1700 DI 10.1200/JCO.2012.48.1887 PG 2 WC Oncology SC Oncology GA 133PU UT WOS:000318152200019 PM 23530094 ER PT J AU Zaitseva, M Shotwell, E Scott, J Cruz, S King, LR Manischewitz, J Diaz, CG Jordan, RA Grosenbach, DW Golding, H AF Zaitseva, Marina Shotwell, Elisabeth Scott, John Cruz, Stephanie King, Lisa R. Manischewitz, Jody Diaz, Claudia G. Jordan, Robert A. Grosenbach, Douglas W. Golding, Hana TI Effects of Postchallenge Administration of ST-246 on Dissemination of IHD-J-Luc Vaccinia Virus in Normal Mice and in Immune-Deficient Mice Reconstituted with T Cells SO JOURNAL OF VIROLOGY LA English DT Article ID ORTHOPOXVIRUS INFECTIONS; SMALLPOX VACCINATION; POXVIRUS INFECTIONS; MONKEYPOX VIRUS; PROTECTION; EXPRESSION; CHALLENGE; EFFICACY; GENE AB Whole-body bioimaging was used to study dissemination of vaccinia virus (VACV) in normal and in immune deficient (nu(-)/nu(-)) mice protected from lethality by postchallenge administration of ST-246. Total fluxes were recorded in the liver, spleen, lungs, and nasal cavities of live mice after intranasal infection with a recombinant IHD-J-Luc VACV expressing luciferase. Areas under the flux curve were calculated for individual mice to assess viral loads. Treatment for 2 to 5 days of normal BALB/c mice with ST-246 at 100 mg/kg starting 24 h postchallenge conferred 100% protection and reduced viral loads in four organs compared to control mice. Mice also survived after 5 days of treatment with ST-246 at 30 mg/kg, and yet the viral loads and poxes were higher in these mice compared to 100-mg/kg treatment group. Nude mice were not protected by ST-246 alone or by 10 million adoptively transferred T cells. In contrast, nude mice that received T cells and 7-day treatment with ST-246 survived infection and exhibited reduced viral loads compared to nonreconstituted and ST-246-treated mice after ST-246 was stopped. Similar protection of nude mice was achieved using adoptively transferred 1.0 and 0.1 million, but not 0.01 million, purified T cells or CD4(+) or CD8(+) T cells in conjunction with ST-246 treatment. These data suggest that ST-246 protects immunocompetent mice from lethality and reduces viral dissemination in internal organs and poxvirus lesions. Furthermore, immune-deficient animals with partial T cell reconstitution can control virus replication after a course of ST-246 and survive lethal vaccinia virus challenge. C1 [Zaitseva, Marina; Shotwell, Elisabeth; Cruz, Stephanie; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Scott, John] US FDA, Div Biostat, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Diaz, Claudia G.] US FDA, Div Biostat, Vet Serv, Bethesda, MD 20014 USA. [Jordan, Robert A.] Gilead Sci Inc, Foster City, CA 94404 USA. [Grosenbach, Douglas W.] Siga Technol Inc, Corvallis, OR USA. RP Zaitseva, M (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM marina.zaitseva@fda.hhs.gov OI Scott, John/0000-0002-9116-948X FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [IAA 224-06-1322]; FDA's Medical Countermeasure Initiative (MCMi) fund FX This project has been funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under IAA 224-06-1322, and by the FDA's Medical Countermeasure Initiative (MCMi) fund. NR 29 TC 2 Z9 2 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2013 VL 87 IS 10 BP 5564 EP 5576 DI 10.1128/JVI.03426-12 PG 13 WC Virology SC Virology GA 133QT UT WOS:000318155000022 PM 23468500 ER PT J AU Tang, S Guo, NN Patel, A Krause, PR AF Tang, Shuang Guo, Nini Patel, Amita Krause, Philip R. TI Herpes Simplex Virus 2 Expresses a Novel Form of ICP34.5, a Major Viral Neurovirulence Factor, through Regulated Alternative Splicing SO JOURNAL OF VIROLOGY LA English DT Article ID LATENCY-ASSOCIATED TRANSCRIPTS; CELL NUCLEAR ANTIGEN; READING FRAME P; GAMMA(1)34.5 PROTEIN; TYPE-1 ICP27; IN-VITRO; MALIGNANT GLIOMA; MESSENGER-RNA; GENE; INFECTION AB Herpes simplex virus 1 (HSV-1) and HSV-2, two closely related neurotropic human herpesviruses, achieve neurotropism through ICP34.5, a major viral neurovirulence factor. In this report, in addition to the full-length 38-kDa protein (ICP34.5 alpha), we identified a 28-kDa novel form of ICP34.5 (ICP34.5 beta) in HSV-2-infected cells. ICP34.5 beta is translated from unspliced ICP34.5 mRNA, with the retained intron introducing a premature stop codon. Thus, ICP34.5 beta lacks the C-terminal conserved GADD34 domain but includes 19 additional amino acids encoded by the intron. Although a fraction of both HSV-2 ICP34.5 proteins are detected in the nucleolus, ICP34.5 alpha is predominantly located in cytoplasm, and ICP34.5 beta is mainly detected more diffusely in the nucleus. ICP34.5 beta is unable to counteract PKR-mediated eIF2 phosphorylation but does not interfere with ICP34.5 alpha's function in this process. Efficient expression of ICP34.5 beta in cell culture assays is dependent on viral infection or expression of ICP27, a multifunctional immediate-early gene. The effect of ICP27 on the ICP34.5 beta protein level is attributed to its selective inhibition of ICP34.5 splicing, which results in increased expression of ICP34.5 beta but a reduced level of ICP34.5 alpha. The C-terminal KH3 domain but not the RNA binding domain of ICP27 is required for its specific inhibition of ICP34.5 splicing and promotion of ICP34.5 beta expression. Our results suggest that the expression of ICP34.5 alpha and ICP34.5 beta is tightly regulated in HSV-2 and likely contributes to viral pathogenesis. C1 [Tang, Shuang; Guo, Nini; Patel, Amita; Krause, Philip R.] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Krause, PR (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM philip.krause@fda.hhs.gov RI Tang, Shuang/F-9115-2014; OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536 FU Center for Biologics Evaluation and Research FX This study was supported by the intramural research programs of the Center for Biologics Evaluation and Research. NR 53 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2013 VL 87 IS 10 BP 5820 EP 5830 DI 10.1128/JVI.03500-12 PG 11 WC Virology SC Virology GA 133QT UT WOS:000318155000043 PM 23487469 ER PT J AU Hower, S Phillips, MC Brodsky, M Dameron, A Tamargo, MA Salazar, NC Jackson, CR Barrett, JB Davidson, M Davis, J Mukherjee, S Ewing, RY Gidley, ML Sinigalliano, CD Johns, L Johnson, FE Adebanjo, O Plano, LRW AF Hower, Suzanne Phillips, Matthew C. Brodsky, Micah Dameron, Adrienne Tamargo, Manuel A. Salazar, Norma C. Jackson, Charlene R. Barrett, John B. Davidson, Maureen Davis, Johnnie Mukherjee, Sampa Ewing, Ruth Y. Gidley, Maribeth L. Sinigalliano, Christopher D. Johns, Lisa Johnson, Frank E., III Adebanjo, Olufunmilola Plano, Lisa R. W. TI Clonally Related Methicillin-Resistant Staphylococcus aureus Isolated from Short-Finned Pilot Whales (Globicephala macrorhynchus), Human Volunteers, and a Bayfront Cetacean Rehabilitation Facility SO MICROBIAL ECOLOGY LA English DT Article ID PANTON-VALENTINE LEUKOCIDIN; CASSETTE CHROMOSOME MEC; MULTIPLEX PCR STRATEGY; UNITED-STATES; SKIN INFECTIONS; STRAIN USA300; NOSOCOMIAL TRANSMISSION; PSEUDOMONAS-AERUGINOSA; MRSA; EMERGENCE AB In May of 2011, a live mass stranding of 26 short-finned pilot whales (Globicephala macrorhynchus) occurred in the lower Florida Keys. Five surviving whales were transferred from the original stranding site to a nearby marine mammal rehabilitation facility where they were constantly attended to by a team of volunteers. Bacteria cultured during the routine clinical care of the whales and necropsy of a deceased whale included methicillin-sensitive and methicillin-resistant Staphylococcus aureus (MSSA and MRSA). In order to investigate potential sources or reservoirs of MSSA and MRSA, samples were obtained from human volunteers, whales, seawater, and sand from multiple sites at the facility, nearby recreational beaches, and a canal. Samples were collected on 3 days. The second collection day was 2 weeks after the first, and the third collection day was 2 months after the last animal was removed from the facility. MRSA and MSSA were isolated on each day from the facility when animals and volunteers were present. MSSA was found at an adjacent beach on all three collection days. Isolates were characterized by utilizing a combination of quantitative real-time PCR to determine the presence of mecA and genes associated with virulence, staphylococcal protein A typing, staphylococcal cassette chromosome mec typing, multilocus sequence typing, and pulsed field gel electrophoresis (PFGE). Using these methods, clonally related MRSA were isolated from multiple environmental locations as well as from humans and animals. Non-identical but genetically similar MSSA and MRSA were also identified from distinct sources within this sample pool. PFGE indicated that the majority of MRSA isolates were clonally related to the prototype human strain USA300. These studies support the notion that S. aureus may be shed into an environment by humans or pilot whales and subsequently colonize or infect exposed new hosts. C1 [Hower, Suzanne; Plano, Lisa R. W.] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Hower, Suzanne; Phillips, Matthew C.; Dameron, Adrienne; Tamargo, Manuel A.; Salazar, Norma C.; Plano, Lisa R. W.] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Brodsky, Micah] VMD Consulting, Miami, FL 33138 USA. [Jackson, Charlene R.; Barrett, John B.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Richard B Russell Res Ctr, USDA, Athens, GA 30605 USA. [Davidson, Maureen; Davis, Johnnie; Mukherjee, Sampa] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Ewing, Ruth Y.] Natl Ocean & Atmospher Adm, Natl Marine Fisheries Serv, Miami, FL 33149 USA. [Gidley, Maribeth L.; Sinigalliano, Christopher D.; Johns, Lisa; Johnson, Frank E., III; Adebanjo, Olufunmilola] NOAA, Atlantic Oceanog & Meteorol Lab, Miami, FL 33149 USA. [Phillips, Matthew C.; Gidley, Maribeth L.; Sinigalliano, Christopher D.; Plano, Lisa R. W.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA. [Gidley, Maribeth L.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Cooperat Inst Marine & Atmospher Studies, Miami, FL 33149 USA. RP Plano, LRW (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. EM lplano@miami.edu RI Sinigalliano, Christopher/A-8760-2014; gidley, maribeth/B-8335-2014 OI Sinigalliano, Christopher/0000-0002-9942-238X; gidley, maribeth/0000-0001-9583-8073 FU Hollings Scholarship Program of the NOAA Office of Education FX We would like to thank the Marine Mammal Conservancy for their assistance and cooperation during this study. We thank Alexander Costidis for performing the whale necropsy as well as the staff at the FWC Fish and Wildlife Research Institute, Marine Mammal Pathobiology Laboratory. We are grateful to Ari Bennett, Julie Hollenbeck, Heather Coit, Sharon Plano, Rebecca Weeks, Havek Kavoblock, Ryan Phillips, Danielle DeHowitt, and the Florida Department of Health for their assistance during the sample collections. We thank Dr. Helena Solo-Gabriele and Faiza Benahmed, for assistance in processing and storing samples. Thanks to Carlton Woods at Micrim Laboratory, Inc. for isolating MRSA from the whale samples and facilitating the transfer to University of Miami Miller School of Medicine. We also thank the Palm Beach Infectious Disease Institute for providing S. aureus clinical isolates for comparison. Additionally, we thank the Hollings Scholarship Program of the NOAA Office of Education for their support of the Hollings Scholar students involved in this project. Marine Mammal samples were collected as either diagnostic clinical samples or as salvage samples under NMFS Permit No. 932-1905/MA-009526. This publication represents the personal opinions of the authors and is not the official position of the contributing federal government agencies. No official endorsement of any product or commercial laboratory is made or implied by its use in this study. NR 128 TC 5 Z9 6 U1 5 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0095-3628 J9 MICROB ECOL JI Microb. Ecol. PD MAY PY 2013 VL 65 IS 4 BP 1024 EP 1038 DI 10.1007/s00248-013-0178-3 PG 15 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 134BD UT WOS:000318183800025 PM 23508733 ER PT J AU Plano, LRW Shibata, T Garza, AC Kish, J Fleisher, JM Sinigalliano, CD Gidley, ML Withum, K Elmir, SM Hower, S Jackson, CR Barrett, JB Cleary, T Davidson, M Davis, J Mukherjee, S Fleming, LE Solo-Gabriele, HM AF Plano, Lisa R. W. Shibata, Tomoyuki Garza, Anna C. Kish, Jonathan Fleisher, Jay M. Sinigalliano, Christopher D. Gidley, Maribeth L. Withum, Kelly Elmir, Samir M. Hower, Suzanne Jackson, Charlene R. Barrett, John B. Cleary, Timothy Davidson, Maureen Davis, Johnnie Mukherjee, Sampa Fleming, Lora E. Solo-Gabriele, Helena M. TI Human-Associated Methicillin-Resistant Staphylococcus aureus from a Subtropical Recreational Marine Beach SO MICROBIAL ECOLOGY LA English DT Article ID FECAL INDICATOR BACTERIA; SKIN INFECTIONS; NASAL CARRIAGE; MULTIPLEX PCR; UNITED-STATES; MANAGEMENT; MICROBES; SURVIVAL; SEAWATER; WATERS AB Reports of Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) detected in marine environments have occurred since the early 1990s. This investigation sought to isolate and characterize S. aureus from marine waters and sand at a subtropical recreational beach, with and without bathers present, in order to investigate possible sources and to identify the risks to bathers of exposure to these organisms. During 40 days over 17 months, 1,001 water and 36 intertidal sand samples were collected by either bathers or investigators at a subtropical recreational beach. Methicillin-sensitive S. aureus (MSSA) and MRSA were isolated and identified using selective growth media and an organism-specific molecular marker. Antimicrobial susceptibility, staphylococcal cassette chromosome mec (SCCmec) type, pulsed-field gel electrophoresis (PFGE) pattern, multi-locus sequence type (MLST), and staphylococcal protein A (spa) type were characterized for all MRSA. S. aureus was isolated from 248 (37 %) bather nearby water samples at a concentration range of < 2-780 colony forming units per ml, 102 (31 %) ambient water samples at a concentration range of < 2-260 colony forming units per ml, and 9 (25 %) sand samples. Within the sand environment, S. aureus was isolated more often from above the intertidal zone than from intermittently wet or inundated sand. A total of 1334 MSSA were isolated from 37 sampling days and 22 MRSA were isolated from ten sampling days. Seventeen of the 22 MRSA were identified by PFGE as the community-associated MRSA USA300. MRSA isolates were all SCCmec type IVa, encompassed five spa types (t008, t064, t622, t688, and t723), two MLST types (ST8 and ST5), and 21 of 22 isolates carried the genes for Panton-Valentine leukocidin. There was a correlation (r = 0.45; p = 0.05) between the daily average number of bathers and S. aureus in the water; however, no association between exposure to S. aureus in these waters and reported illness was found. This report supports the concept that humans are a potential direct source for S. aureus in marine waters. C1 [Plano, Lisa R. W.; Garza, Anna C.; Hower, Suzanne] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. [Plano, Lisa R. W.; Garza, Anna C.; Hower, Suzanne; Cleary, Timothy] Univ Miami, Miller Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. [Plano, Lisa R. W.; Shibata, Tomoyuki; Kish, Jonathan; Sinigalliano, Christopher D.; Gidley, Maribeth L.; Withum, Kelly; Elmir, Samir M.; Fleming, Lora E.; Solo-Gabriele, Helena M.] Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NSF NIEHS Oceans & Human Hlth Ctr, Miami, FL 33149 USA. [Shibata, Tomoyuki; Sinigalliano, Christopher D.; Gidley, Maribeth L.] NOAA, Atlantic Oceanog & Meteorol Lab, Miami, FL 33149 USA. [Shibata, Tomoyuki] No Illinois Univ, Publ Hlth Program, De Kalb, IL 60115 USA. [Shibata, Tomoyuki] No Illinois Univ, Hlth Educ Program, De Kalb, IL 60115 USA. [Kish, Jonathan; Fleming, Lora E.] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. [Fleisher, Jay M.] Nova SE Univ, Coll Osteopath Med, Publ Hlth Program, Ft Lauderdale, FL 33328 USA. [Elmir, Samir M.] Miami Dade Cty Hlth Dept, Miami, FL 33056 USA. [Jackson, Charlene R.; Barrett, John B.] ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Richard B Russell Res Ctr, USDA, Athens, GA 30605 USA. [Cleary, Timothy] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33136 USA. [Davidson, Maureen; Davis, Johnnie; Mukherjee, Sampa] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Fleming, Lora E.] Peninsula Coll Med & Dent, European Ctr Environm & Human Hlth, Truro TR1 3HD, Cornwall, England. [Solo-Gabriele, Helena M.] Univ Miami, Dept Civil Architectural & Environm Engn, Coral Gables, FL 33124 USA. RP Plano, LRW (reprint author), Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. EM lplano@miami.edu RI Sinigalliano, Christopher/A-8760-2014; gidley, maribeth/B-8335-2014; OI Sinigalliano, Christopher/0000-0002-9942-238X; gidley, maribeth/0000-0001-9583-8073; Fleisher, Jay/0000-0002-2553-2201 FU University of Miami through the Interdisciplinary Research Development Initiative; National Science Foundation (NSF); National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School [NSF 0CE0432368/0911373, NIEHS P50 ES12736]; NSF REU in Oceans and Human Health; NSF SGER in Oceans and Human Health [NSF SGER 0743987]; US EPA; US Centers for Disease Control and Prevention; Florida Departments of Health and of Environmental Protection; European Union Convergence Programme FX The University of Miami provided financial support through the Interdisciplinary Research Development Initiative. This study was also supported in part by National Science Foundation (NSF) and the National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School (NSF 0CE0432368/0911373 and NIEHS P50 ES12736] and NSF REU in Oceans and Human Health, the NSF SGER [NSF SGER 0743987] in Oceans and Human Health, the US EPA, the US Centers for Disease Control and Prevention, the Florida Departments of Health and of Environmental Protection, and the European Union Convergence Programme (to ECEHH at PCMD, University of Exeter). NR 65 TC 11 Z9 11 U1 2 U2 23 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0095-3628 J9 MICROB ECOL JI Microb. Ecol. PD MAY PY 2013 VL 65 IS 4 BP 1039 EP 1051 DI 10.1007/s00248-013-0216-1 PG 13 WC Ecology; Marine & Freshwater Biology; Microbiology SC Environmental Sciences & Ecology; Marine & Freshwater Biology; Microbiology GA 134BD UT WOS:000318183800026 PM 23553001 ER PT J AU Breger, J Baeva, L Agrawal, A Shindell, E Godar, DE AF Breger, Joyce Baeva, Larissa Agrawal, Anant Shindell, Eli Godar, Dianne E. TI UVB-Induced Inflammatory Cytokine Release, DNA Damage and Apoptosis of Human Oral Compared with Skin Tissue Equivalents SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS; ALLERGIC RHINITIS; LIGHTING SOURCES; CANCER; RISK; PHOTOTHERAPY; MUCOSA; REPAIR; CELLS; LASER AB People can get oral cancers from UV (290400nm) exposures. Besides high outdoor UV exposures, high indoor UV exposures to oral tissues can occur when consumers use UV-emitting tanning devices to either tan or whiten their teeth. We compared the carcinogenic risks of skin to oral tissue cells after UVB (290320nm) exposures using commercially available 3D-engineered models for human skin (EpiDerm), gingival (EpiGing) and oral (EpiOral) tissues. To compare the relative carcinogenic risks, we investigated the release of cytokines, initial DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), repair of CPDs and apoptotic cell numbers. We measured cytokine release using cytometric beads with flow cytometry and previously developed a fluorescent immunohistochemical assay to quantify simultaneously CPD repair rates and apoptotic cell numbers. We found that interleukin-8 (IL-8) release and the initial CPDs are significantly higher, whereas the CPD repair rates and apoptotic cell numbers are significantly lower for oral compared with skin tissue cells. Thus, the increased release of the inflammatory cytokine IL-8 along with inefficient CPD repair and decreased death rates for oral compared with skin tissue cells suggests that mutations are accumulating in the surviving population of oral cells increasing people's risks for getting oral cancers. C1 [Breger, Joyce] Johns Hopkins Univ, Baltimore, MD USA. [Baeva, Larissa; Agrawal, Anant; Godar, Dianne E.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Shindell, Eli] Univ Maryland, College Pk, MD 20742 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM dianne.godar@fda.hhs.gov OI GODAR, DIANNE/0000-0002-7690-5223 FU FDA's Critical Path Initiative FX The authors would like to thank the FDA's Critical Path Initiative for funding this research, Robert James for dosimetry of the UVB source, Fred Jordan for technical assistance and Sharon A. Miller for dose calculations. NR 35 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2013 VL 89 IS 3 BP 665 EP 670 DI 10.1111/php.12030 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 134RU UT WOS:000318232800017 PM 23253030 ER PT J AU Cao, JY Rebuli, ME Rogers, J Todd, KL Leyrer, SM Ferguson, SA Patisaul, HB AF Cao, Jinyan Rebuli, Meghan E. Rogers, James Todd, Karina L. Leyrer, Stephanie M. Ferguson, Sherry A. Patisaul, Heather B. TI Prenatal Bisphenol A Exposure Alters Sex-Specific Estrogen Receptor Expression in the Neonatal Rat Hypothalamus and Amygdala SO TOXICOLOGICAL SCIENCES LA English DT Article DE brain; endocrine disruptor; endocrine disruption; hypothalamus; development; sexually dimorphic; ethinyl estradiol ID ORGANIZATIONAL-ACTIVATIONAL HYPOTHESIS; POSTERODORSAL MEDIAL AMYGDALA; DEVELOPMENTAL TREATMENT; CIRCULATING ANDROGENS; POSTNATAL-DEVELOPMENT; ENDOCRINE DISRUPTION; NONHUMAN-PRIMATES; STRIA TERMINALIS; MESSENGER-RNA; HUMAN HEALTH AB Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals, early-life BPA exposure has been shown to alter sex-specific neural organization, neuroendocrine physiology, and behavior. The specific mechanisms underlying these brain-related outcomes, however, remain largely unknown, constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models. In the perinatal rat brain, estrogen is masculinizing, suggesting that BPA-induced perturbation of estrogen receptor (ESR) expression may underpin later in-life neuroendocrine effects. We hypothesized that prenatal BPA exposure alters sex-specific ESR1 (ER alpha) and ESR2 (ER beta) expression in postnatal limbic nuclei. Sprague Dawley rats were mated and gavaged on gestational days (GDs) 6-21 with vehicle, 2.5 or 25 mu g/kg bw/day BPA, or 5 or 10 mu g/kg bw/day ethinyl estradiol. An additional group was restrained but not gavaged (naive control). Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization. Relative to the vehicle group, significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes. Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the naive control group compared with the vehicle group, highlighting the potential for gavage to influence gene expression in the developing brain. These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low-dose prenatal BPA exposure. C1 [Cao, Jinyan; Rebuli, Meghan E.; Rogers, James; Todd, Karina L.; Leyrer, Stephanie M.; Patisaul, Heather B.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. [Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Patisaul, Heather B.] N Carolina State Univ, Keck Ctr Behav Biol, Raleigh, NC 27695 USA. RP Patisaul, HB (reprint author), N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. EM Heather_Patisaul@ncsu.edu FU National Institutes of Health [R01-16001-04S1] FX National Institutes of Health (R01-16001-04S1 to H.B.P.). NR 104 TC 49 Z9 51 U1 2 U2 31 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2013 VL 133 IS 1 BP 157 EP 173 DI 10.1093/toxsci/kft035 PG 17 WC Toxicology SC Toxicology GA 133LX UT WOS:000318141000015 PM 23457122 ER PT J AU Reesink, HW Davis, K Wong, J Schwartz, DWM Mayr, WR Devine, DV Georgsen, J Chiaroni, J Ferrera, V Roubinet, F Lin, CK O'Donovan, B Fitzgerald, JM Raspollini, E Villa, S Rebulla, P Makino, S Gounder, D Safwenberg, J Murphy, MF Staves, J Milkins, C Mercado, TC Illoh, OC Panzer, S AF Reesink, H. W. Davis, K. Wong, J. Schwartz, D. W. M. Mayr, W. R. Devine, D. V. Georgsen, J. Chiaroni, J. Ferrera, V. Roubinet, F. Lin, C. K. O'Donovan, B. Fitzgerald, J. M. Raspollini, E. Villa, S. Rebulla, P. Makino, S. Gounder, D. Safwenberg, J. Murphy, M. F. Staves, J. Milkins, C. Mercado, T. C. Illoh, O. C. Panzer, S. TI The use of the electronic (computer) cross-match SO VOX SANGUINIS LA English DT Letter C1 [Reesink, H. W.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Panzer, S.] Med Univ Vienna, Dept Blood Grp Serol & Transfus Med, Vienna, Austria. [Davis, K.] Royal Adelaide Hosp, Transfus Med SA Pathol, Adelaide, SA 5000, Australia. [Wong, J.] Australian Red Cross Blood Serv, Alexandria, NSW 2015, Australia. [Schwartz, D. W. M.; Mayr, W. R.] Med Univ Wien, Univ Clin Blutgruppenserol & Transfusionsmed, A-1090 Vienna, Austria. [Devine, D. V.] Canadian Blood Serv, UBC Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada. [Georgsen, J.] Odense Univ Hosp, South Danish Transfus Serv & Tissue Ctr, Dept Clin Immunol, DK-5000 Odense C, Denmark. [Chiaroni, J.; Ferrera, V.] Etab Francais Sang Alpes Mediterranee, F-13005 Marseille 05, France. [Roubinet, F.] Etab Francais Sang Pyrenees Mediterranee, F-31027 Toulouse 3, France. [Lin, C. K.] Hong Kong Red Cross Blood Transfus Serv, Kowloon, Hong Kong, Peoples R China. [O'Donovan, B.] St Vincents Univ Hosp, Blood Transfus Lab, Dublin 4, Ireland. [Fitzgerald, J. M.] St Vincents Univ Hosp, Dublin 4, Ireland. [Fitzgerald, J. M.] Irish Blood Transfus Serv, Natl Blood Ctr, Dublin 8, Ireland. [Raspollini, E.; Villa, S.] Fdn Ca Granda Osped Maggiore Policlin, Ctr Trasfus & Immunoematol, I-20122 Milan, Italy. [Rebulla, P.] Fdn Ca Granda Osped Maggiore Policlin, Ctr Transfus Med Cellular Therapy & Cryobiol, I-20122 Milan, Italy. [Makino, S.] Toranomon Gen Hosp, Dept Transfus Med, Minato Ku, Tokyo 1058470, Japan. [Gounder, D.] New Zealand Blood Serv, Auckland, New Zealand. [Safwenberg, J.] Univ Hosp, Clin Immunol & Transfus Med Blood Ctr, SE-75185 Uppsala, Sweden. [Murphy, M. F.] Oxford Univ Hosp, NHS Blood & Transplant, Oxford OX3 9BQ, England. [Murphy, M. F.] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9BQ, England. [Staves, J.] John Radcliffe Hosp, Blood Transfus Lab, Oxford OX3 9DU, England. [Milkins, C.] UK NEQAS BTLP, Watford WD18 0WP, England. [Mercado, T. C.; Illoh, O. C.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Reesink, HW (reprint author), Univ Amsterdam, Acad Med Ctr, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM internationalforum@kpnplanet.nl; kg.davis45@yahoo.com.au; jwong@redcrossblood.org.au; dieter.schwartz@meduniwien.ac.at; dana.devine@blood.ca; jacques.chiaroni@efs.sante.fr; virginie.ferrera-tourenc@efs.sante.fr; francis.roubinet@efs.sante.fr; cklin@ha.org.hk; b.odonovan@svuh.ie; joan.fitzgerald@ibts.ie; e.raspollini@policlinico.mi.it; prebulla@policlinico.mi.it; s-makino@toranomon.gr.jp; dhana.gounder@nzblood.co.nz; jan.safwenberg@akademiska.se; mike.murphy@nhsbt.nhs.uk; julie.staves@ouh.nhs.uk; clare.milkins@whht.nhs.uk; teresita.mercado@fda.hhs.gov; orieji.illoh@fda.hhs.gov; simon.panzer@meduniwien.ac.at RI Rebulla, Paolo/I-7684-2015 OI Rebulla, Paolo/0000-0002-3875-5754 NR 0 TC 3 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PD MAY PY 2013 VL 104 IS 4 BP 350 EP 364 DI 10.1111/vox.12003 PG 15 WC Hematology SC Hematology GA 133DV UT WOS:000318118500010 PM 23409706 ER PT J AU Chen, WQ Karnaukhova, E Lubec, G AF Chen, Wei-Qiang Karnaukhova, Elena Lubec, Gert TI The use of native gels for the concomitant determination of protein sequences and modifications by mass spectrometry with subsequent conformational and functional analysis of native proteins following electro-elution SO AMINO ACIDS LA English DT Article DE Conformation; CD; Protein structure; Native gel ID RESPIRATORY-CHAIN SUPERCOMPLEXES; CIRCULAR-DICHROISM; SPINACH THYLAKOIDS; C1BAR INHIBITOR; ATP SYNTHASE; COMPLEXES; CRYSTALLIZATION; ELECTROPHORESIS; RECONSTITUTION; MITOCHONDRIA AB The protocol consists of running a native gel with in-gel digestion by proteases, subsequent mass spectrometrical determination of protein sequence and modifications, followed by electro-elution and conformational analysis using melting point and circular dichroism. Finally, the eluted protein is tested for preserved function. Herein, C1 esterase inhibitor is applied on a native gel; in-gel digestion by proteases is carried out and peptides are identified by nano-LC-ESI-CID/ETD-MS/MS using an ion trap for generation of peptide sequences and protein modifications. Protein from replicate bands from the same gel is electro-eluted and used for determination of the melting point and used for circular dichroism analysis. Additional bands from the native gel are either in-gel digested with asparaginase to generate deamidation or PNGase F for deglycosylation, followed by mass spectrometry, conformational and functional studies. Preserved conformation and function of the C1 esterase inhibitor was shown. This protocol can be completed in 1 week. C1 [Chen, Wei-Qiang; Lubec, Gert] Med Univ Vienna, Dept Pediat, A-1090 Vienna, Austria. [Karnaukhova, Elena] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Lubec, G (reprint author), Med Univ Vienna, Dept Pediat, Wahringer Gurtel 18, A-1090 Vienna, Austria. EM chenweiqiang@gmail.com; elena.karnaukhova@fda.hhs.gov; gert.lubec@meduniwien.ac.at OI Lubec, Gert/0000-0002-6333-9461 NR 31 TC 1 Z9 2 U1 0 U2 19 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 MAY PY 2013 VL 44 IS 5 BP 1381 EP 1389 DI 10.1007/s00726-013-1477-1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127FI UT WOS:000317682100013 PM 23512611 ER PT J AU Mader, P Jones, PL Zhang, Y Cleland-Huang, J AF Maeder, Patrick Jones, Paul L. Zhang, Yi Cleland-Huang, Jane TI Strategic Traceability for Safety-Critical Projects SO IEEE SOFTWARE LA English DT Article C1 [Maeder, Patrick] Tech Univ Ilmenau, D-98684 Ilmenau, Germany. [Jones, Paul L.; Zhang, Yi] US FDA, Off Sci & Engn Labs, Rockville, MD 20857 USA. [Cleland-Huang, Jane] Depaul Univ, Sch Comp, Chicago, IL 60604 USA. RP Mader, P (reprint author), Tech Univ Ilmenau, D-98684 Ilmenau, Germany. EM patrick.maeder@tu-ilmenau.de; paul.jones@fda.hhs.gov; yi.zhang2@fda.hhs.gov; jhuang@cs.depaul.edu FU US National Science Foundation [CCF-0810924]; Austrian Science Fund (FWF) [M1268-N23]; German Research Foundation (DFG) [Ph49/8-1] FX The work in this article was partially funded by the US National Science Foundation grant #CCF-0810924, the Austrian Science Fund (FWF): M1268-N23, and the German Research Foundation (DFG): Ph49/8-1. NR 15 TC 13 Z9 13 U1 1 U2 6 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 0740-7459 J9 IEEE SOFTWARE JI IEEE Softw. PD MAY-JUN PY 2013 VL 30 IS 3 BP 58 EP 66 PG 9 WC Computer Science, Software Engineering SC Computer Science GA 125QR UT WOS:000317556900012 ER PT J AU Olumee-Shabon, Z Swain, T Smith, EA Tall, E Boehmer, JL AF Olumee-Shabon, Z. Swain, T. Smith, E. A. Tall, E. Boehmer, J. L. TI Proteomic analysis of differentially expressed proteins in caprine milk during experimentally induced endotoxin mastitis SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE proteomic analysis; endotoxin mastitis; milk protein; caprine ID CLINICAL MASTITIS; DAIRY-COWS; BOVINE-MILK; GOAT MILK; INFLAMMATION; SERUM; MODEL; ALLERGENICITY; CATHELICIDINS; NEUTROPHIL AB The goal of the current study was to identify proteins in goat milk before and at 18 h following intramammary challenge with lipopolysaccharide (LPS). Initial evaluation of protein profiles generated using 2-dimensional gel electrophoresis on skim milk samples from a group of 6 goats collected before challenge and at 18, 24, and 48 h after LPS challenge revealed little change in the abundance of casein proteins, and minimal changes in the presence or abundance of the plasma protein serum albumin, which is known to leak into milk during coliform mastitis in dairy cattle. Proteins in baseline milk samples and in milk from the same goats 18 h post-LPS challenge were excised from the gels, and peptides were sequenced using nano-flow liquid chromatography coupled with tandem mass spectrometry. Despite the overwhelming presence of casein proteins and beta-lactoglobulin, the lower abundance proteins beta-2-microglobulin, fatty acid-binding protein, serum albumin, and retinol-binding protein were detected in skim milk samples from healthy goats. Skim milk samples 18 h postchallenge were characterized by the sustained presence and abundance of the casein proteins, and by the presence of haptoglobin, serum amyloid A, lactoferrin, cathelicidin-1, and cathelicidin-3. No marked differences in the intensity of the spot corresponding to serum albumin were observed in gels of skim milk samples 18 h postchallenge, which could indicate that the breakdown of the blood milk barrier during endotoxin mastitis may not be as profound in goats as has been observed in dairy cattle. Nonetheless, the occurrence of an inflammatory response was supported by elevated somatic cell counts in the goat milk following inoculation with endotoxin, as well as by the presence of both antimicrobial and acute phase proteins. The results provide information about the composition of proteins in goat milk as well as added knowledge of the host response during endotoxin mastitis in goats. C1 [Olumee-Shabon, Z.; Swain, T.; Smith, E. A.; Tall, E.; Boehmer, J. L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Boehmer, JL (reprint author), Dept Vet Affairs Off Res Oversight, 810 Vermont Ave NW,10R, Washington, DC 20420 USA. EM jamie.boehmer@va.gov NR 31 TC 9 Z9 9 U1 2 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD MAY PY 2013 VL 96 IS 5 BP 2903 EP 2912 DI 10.3168/jds.2012-5956 PG 10 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 127ML UT WOS:000317703000020 PM 23498005 ER PT J AU King, KE Ha, L Ponnamperuma, RM Jay, S Weinberg, WC AF King, K. E. Ha, L. Ponnamperuma, R. M. Jay, S. Weinberg, W. C. TI Delta Np63 alpha in squamous cancer pathogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT International Investigative Dermatology Meeting CY MAY 08-11, 2013 CL Edinburgh, SCOTLAND SP European Soc Dermatol Res, Japanese Soc Investigat Dermatol, Soc Investigat Dermatol C1 [King, K. E.; Ha, L.; Ponnamperuma, R. M.; Weinberg, W. C.] US FDA, Mol Oncol Lab, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Jay, S.] SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD MAY PY 2013 VL 133 SU 1 MA 446 BP S76 EP S76 PG 1 WC Dermatology SC Dermatology GA 127KW UT WOS:000317698900443 ER PT J AU Xu, XM Gupta, A Sayeed, VA Khan, MA AF Xu, Xiaoming Gupta, Abhay Sayeed, Vilayat A. Khan, Mansoor A. TI Process analytical technology to understand the disintegration behavior of alendronate sodium tablets SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE alendronate; disintegration; process analytical technology; FBRM; disintegration onset; tablet; transit time; particle size; physicochemical ID ESOPHAGEAL TRANSIT; CRYSTALLIZATION PROCESSES; FORMULATIONS; ABSORPTION; CAPSULE; RATS AB Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:15131523, 2013 C1 [Xu, Xiaoming; Gupta, Abhay; Khan, Mansoor A.] US FDA, Div Prod Qual Res, OTR OPS, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] OPS, Off Gener Drugs, Rockville, MD 20855 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, OTR OPS, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov OI Xu, Xiaoming/0000-0003-1672-0830 FU Medical Countermeasures Initiative (MCMi) FX This project was supported by Medical Countermeasures Initiative (MCMi) for critical infrastructure development, and in part by an appointment to the ORISE Research Participation Program at CDER administered by the Oak Ridge Institute for Science and Education through an agreement between the U.S. Department of Energy and CDER. NR 18 TC 3 Z9 3 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2013 VL 102 IS 5 BP 1513 EP 1523 DI 10.1002/jps.23488 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 126ME UT WOS:000317620200013 PM 23450666 ER PT J AU Rostron, B AF Rostron, Brian TI NNAL Exposure by Race and Menthol Cigarette Use among US Smokers SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SERUM COTININE LEVELS; RACIAL-DIFFERENCES; CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; WHITE SMOKERS; NICOTINE; TOBACCO; BLACK; BIOMARKERS; METABOLITES; CANCER AB Introduction: Researchers have recently suggested that nicotine and carcinogen exposure as measured by biomarkers such as cotinine and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol) does not vary with cigarettes smoked per day (CPD) among Black smokers. Researchers have also suggested that nicotine exposure does not differ between menthol and nonmenthol smokers. In this study, we examine NNAL exposure for U.S. smokers by race, CPD, and menthol cigarette use. Methods: We analyzed urinary NNAL concentrations for more than 1500 everyday smokers participating in the National Health and Nutrition Examination Survey from 2007-2010. For purposes of comparison, we also analyzed serum cotinine concentrations for these smokers. We used linear regression analysis to estimate mean biomarker concentrations by CPD and race/ethnicity group and to examine the association between biomarker concentrations and menthol cigarette use by race/ethnicity group, controlling for other demographic and smoking characteristics. Results: Biomarker concentrations increased with CPD for White, Black, and Hispanic smokers although NNAL concentrations leveled off for Black smokers at lower CPD levels compared with other smokers. Mean NNAL concentrations were lower among menthol smokers compared with nonmenthol smokers among smokers overall (beta = -0.165,p = .032) and White smokers (beta = -0.207, p = .048). Conclusions: We find evidence in national health survey data that nicotine and carcinogen exposure generally increases with CPD across race/ethnicity groups although the pattern of NNAL exposure differs by race/ethnicity group at high CPD levels. We also find evidence of differences in NNAL exposure for menthol smokers compared with nonmenthol smokers among smokers overall and White smokers. C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Rostron, B (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20850 USA. EM brian.rostron@fda.hhs.gov NR 25 TC 5 Z9 5 U1 0 U2 9 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 MAY PY 2013 VL 15 IS 5 BP 950 EP 956 DI 10.1093/ntr/nts223 PG 7 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 128UZ UT WOS:000317796500012 PM 23089487 ER PT J AU Chen, M Zhang, J Wang, Y Liu, Z Kelly, R Zhou, G Fang, H Borlak, J Tong, W AF Chen, M. Zhang, J. Wang, Y. Liu, Z. Kelly, R. Zhou, G. Fang, H. Borlak, J. Tong, W. TI The Liver Toxicity Knowledge Base: A Systems Approach to a Complex End Point SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INJURY AB Drug-induced liver injury (DILI) is a major concern in public health management, drug development, and regulatory implementation. The Liver Toxicity Knowledge Base (LTKB) was developed with the specific aim of enhancing our understanding of DILI. It seeks to achieve improvement in DILI prediction through integrated analysis of diverse sources of drug-elicited data. The project has also produced a centralized resource of data as well as predictive models that will be useful for research and drug regulation. C1 [Chen, M.; Zhang, J.; Wang, Y.; Liu, Z.; Kelly, R.; Zhou, G.; Tong, W.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Fang, H.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Borlak, J.] Hannover Med Sch, Ctr Pharmacol & Toxicol, Hannover, Germany. RP Tong, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov FU German Federal Ministry for Education and Research as part of the Virtual Liver Network initiative [031 6154]; US Food and Drug Administration (FDA) FX J.B. receives funding from the German Federal Ministry for Education and Research as part of the Virtual Liver Network initiative (grant 031 6154). In addition, he gratefully acknowledges an ORISE stipend from the US Food and Drug Administration (FDA). NR 5 TC 16 Z9 17 U1 0 U2 2 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 MAY PY 2013 VL 93 IS 5 BP 409 EP 412 DI 10.1038/clpt.2013.16 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129JH UT WOS:000317834800022 PM 23486446 ER PT J AU Pfuhler, S Elespuru, R Aardema, MJ Doak, SH Donner, EM Honma, M Kirsch-Volders, M Landsiedel, R Manjanatha, M Singer, T Kim, JH AF Pfuhler, Stefan Elespuru, Rosalie Aardema, Marilyn J. Doak, Shareen H. Donner, E. Maria Honma, Masamitsu Kirsch-Volders, Micheline Landsiedel, Robert Manjanatha, Mugimane Singer, Tim Kim, James H. TI Genotoxicity of nanomaterials: Refining strategies and tests for hazard identification SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE nanomaterials; workshop; genotoxicity ID ALUMINUM-OXIDE NANOMATERIALS; IN-VITRO; EPITHELIAL-CELLS; CARBON NANOTUBES; DNA-DAMAGE; NANOPARTICLES; INDUCTION; ASSAY; MUTAGENICITY; ANEUPLOIDY AB A workshop addressing strategies for the genotoxicity assessment of nanomaterials (NMs) was held on October 23, 2010 in Fort Worth Texas, USA. The workshop was organized by the Environmental Mutagen Society and the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute. The workshop was attended by more than 80 participants from academia, regulatory agencies, and industry from North America, Europe and Japan. A plenary session featured summaries of the current status and issues related to the testing of NMs for genotoxic properties, as well as an update on international activities and regulatory approaches. This was followed by breakout sessions and a plenary session devoted to independent discussions of in vitro assays, in vivo assays, and the need for new assays or new approaches to develop a testing strategy for NMs. Each of the standard assays was critiqued as a resource for evaluation of NMs, and it became apparent that none was appropriate without special considerations or modifications. The need for nanospecific positive controls was questioned, as was the utility of bacterial assays. The latter was thought to increase the importance of including mammalian cell gene mutation assays into the test battery. For in-vivo testing, to inform the selection of appropriate tests or protocols, it was suggested to run repeated dose studies first to learn about disposition, potential accumulation, and possible tissue damage. It was acknowledged that mechanisms may be at play that a standard genotoxicity battery may not be able to capture. Environ. Mol. Mutagen. 54:229239, 2013. (c) 2013 Wiley Periodicals, Inc. C1 [Pfuhler, Stefan] Procter & Gamble Co, Miami Valley Innovat Ctr, Cincinnati, OH USA. [Elespuru, Rosalie] US FDA, Silver Spring, MD USA. [Aardema, Marilyn J.] Marilyn Aardema Consulting LLC, Fairfield, OH USA. [Doak, Shareen H.] Swansea Univ, Coll Med, Swansea, W Glam, Wales. [Donner, E. Maria] DuPont Haskell Global Ctr Hlth & Environm Sci, Newark, DE USA. [Honma, Masamitsu] Natl Inst Hlth Sci, Setagaya Ku, Tokyo, Japan. [Kirsch-Volders, Micheline] Vrije Univ Brussel, Brussels, Belgium. [Landsiedel, Robert] BASF SE, Ludwigshafen, Germany. [Manjanatha, Mugimane] US FDA, Jefferson, AZ USA. [Singer, Tim] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. RP Kim, JH (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. EM hesi@hesiglobal.org OI Doak, Shareen/0000-0002-6753-1987 FU Health Canada; Procter and Gamble Company FX Grant sponsor: Health Canada, The Procter and Gamble Company. Summary of a workshop of the Environmental Mutagen Society (EMS). NR 26 TC 13 Z9 14 U1 2 U2 31 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 MAY PY 2013 VL 54 IS 4 BP 229 EP 239 DI 10.1002/em.21770 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 122EA UT WOS:000317298300001 PM 23519787 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Adverse Events After Recombinant Human BMP2 in Nonspinal Orthopaedic Procedures SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID SURVEILLANCE AB The FDA has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) for treating acute, open tibial shaft fractures. However, the nature and frequency of complications after the use of rhBMP-2 in nonspinal orthopaedic surgery have not been well characterized. To determine what types of adverse events have been reported after the use of rhBMP-2, whether they were severe enough to require additional surgery, and after what types of operations these adverse events occurred. Adverse events reported to the FDA's Manufacturer and User Facility Device Experience database were reviewed and summarized. Through December 31, 2011, the FDA has received 62 reports of adverse events involving rhBMP-2 in nonspinal orthopaedic procedures. Surgical site infections and other wound complications, heterotopic bone, pseudarthrosis, and local inflammation were among the most commonly reported adverse events. Almost half of the reports (30 reports; 48%) stated that the patients required secondary interventions to address the reported adverse events. The majority (49 reports; 79%) described adverse events occurring after unapproved uses, such as management of tibial plateau fractures, treatment of congenital pseudarthrosis of the tibia, and humeral reconstruction. Serious adverse events can occur after the use of rhBMP-2 in nonspinal orthopaedic procedures and may necessitate additional surgery. Most events in this analysis occurred after off-label uses. Postmarketing review of adverse event reports remains an important approach for identifying potential safety concerns. C1 US FDA, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, HFM 222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 9 TC 26 Z9 27 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD MAY PY 2013 VL 471 IS 5 BP 1707 EP 1711 DI 10.1007/s11999-012-2684-x PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 117NB UT WOS:000316959100044 PM 23132207 ER PT J AU Ali, SF Tobon-Velasco, JC Pedraza-Chaverri, J Cuadrado, A Maldonado, PD Santamaria, A AF Ali, S. F. Tobon-Velasco, J. C. Pedraza-Chaverri, J. Cuadrado, A. Maldonado, P. D. Santamaria, A. TI Nrf2 in toxic models of degenerative disorders: an approache to Parkinson's and huntington's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Ali, S. F.; Santamaria, A.] NCTR, Div Neurotox, Neurochem Lab, Jefferson, AR USA. [Tobon-Velasco, J. C.; Maldonado, P. D.; Santamaria, A.] MVS SSA, Inst Nacl Neurol & Neurocirugia, Lab Aminoacids Excitadores, Mexico City, DF, Mexico. [Tobon-Velasco, J. C.; Pedraza-Chaverri, J.] Univ Nacl Autonoma Mexico, Dept Biol, Fac Quim, Mexico City, DF, Mexico. [Cuadrado, A.] Inst Invest Biomedades, Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 86 EP 86 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700168 ER PT J AU Simonyi, A Jiang, JH Zong, Y Lei, W Smith, RE Eaker, J Tran, K Smith, C Levine, RA Monroe, DM Menezes, EMD Sabaa-Srur, AU Luo, R Wycoff, W Fales, WH Fritsche, KL Sun, AY Sun, GY AF Simonyi, A. Jiang, J. H. Zong, Y. Lei, W. Smith, R. E. Eaker, J. Tran, K. Smith, C. Levine, R. A. Monroe, D. M. da Silva Menezes, E. M. Sabaa-Srur, A. U. Luo, R. Wycoff, W. Fales, W. H. Fritsche, K. L. Sun, A. Y. Sun, G. Y. TI Inhibitory effects of an acai (Euterpe oleracea Mart.) extract on inflammatory responses SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Simonyi, A.; Jiang, J. H.; Zong, Y.; Lei, W.; Luo, R.; Wycoff, W.; Fales, W. H.; Fritsche, K. L.; Sun, A. Y.; Sun, G. Y.] Univ Missouri, Columbia, MO USA. [da Silva Menezes, E. M.; Sabaa-Srur, A. U.] Univ Fed Rio de Janeiro, Rio De Janeiro, Brazil. [Smith, R. E.; Eaker, J.; Tran, K.; Smith, C.; Levine, R. A.; Monroe, D. M.] US FDA, Lenexa, KS USA. RI sebastianovitsch, stepan/G-8507-2013 NR 0 TC 0 Z9 0 U1 0 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 139 EP 139 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700296 ER PT J AU Tobon-Velasco, JC Pedraza-Chaverri, J Syed, FA Cuadrado, A Santamaria, A AF Tobon-Velasco, J. C. Pedraza-Chaverri, J. Syed, F. A. Cuadrado, A. Santamaria, A. TI Activation of Nrf2 and attenuation of NF-kB pathways by S-Allylcysteine, protects against 6-OHDA by modulating signaling kinase SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 24th Biennial Meeting of the International-Society-for-Neurochemistry and the American-Society-for-Neurochemistry CY APR 20-24, 2013 CL Cancun, MEXICO SP Int Soc Neurochemistry, Amer Soc Neurochemistry C1 [Tobon-Velasco, J. C.; Santamaria, A.] Natl Inst Neurol & Neurosurg, Mexico City, DF, Mexico. [Tobon-Velasco, J. C.; Pedraza-Chaverri, J.] Univ Nacl Autonoma Mexico, Fac Chem, Mexico City, DF, Mexico. [Syed, F. A.; Santamaria, A.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR USA. [Tobon-Velasco, J. C.; Cuadrado, A.] Autonomous Univ Madrid, Inst Biomed Res, E-28049 Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2013 VL 125 SU 1 SI SI BP 216 EP 217 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 117OB UT WOS:000316961700494 ER PT J AU Lusk, TS Strain, E Kase, JA AF Lusk, Tina S. Strain, Errol Kase, Julie A. TI Comparison of six commercial DNA extraction kits for detection of Brucella neotomae in Mexican and Central American-style cheese and other milk products SO FOOD MICROBIOLOGY LA English DT Article DE Brucella; Cheese; Milk; DNA extraction; Polymerase chain reaction ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; LISTERIA-MONOCYTOGENES; SOFT CHEESE; SPP.; IDENTIFICATION; SALMONELLA; BACTERIAL; ABORTUS AB Raw or inadequately pasteurized milk from infected animals and cheese made with such milk are a frequent vehicle for human brucellosis infection. Also, biological terrorism is a concern with certain Brucella spp. Due to matrix-associated real-time polymerase chain reaction (qPCR) inhibitors, robust sample preparations are crucial. We compared six commercial nucleic acid extraction kits using nine Mexican and Central American-style soft cheeses or creams and three liquid milk products inoculated with Brucella neotomae, a surrogate for pathogenic Brucella spp. Kits were evaluated by purity and quantity of DNA as determined by qPCR Ct values, reproducibility across cheese and milk types, and cost. At 10(7) CFU/g in four different cheeses, Qiagen statistically outperformed all other kits. When two cheese styles were inoculated at dual levels, Qiagen and High Pure kit extracted samples at 1.5 x 10(5) CFU/g produced average Ct values of 34-39, while PrepSEQ and MagMAX kit extracted samples exhibited higher or no Ct values. High Pure and Qiagen kits excelled also with liquid milk products. Considering matrices, inoculation levels, and kits evaluated, High Pure and Qiagen products produced Brucella DNA of high quality and quantity indicated by the lowest Ct values and were the least expensive. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Lusk, Tina S.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37830 USA. [Strain, Errol] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, College Pk, MD 20740 USA. [Kase, Julie A.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lusk, TS (reprint author), US FDA, Microbial Methods Dev Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Rm 3E-009,HFS-711, College Pk, MD 20740 USA. EM tina.lusk@fda.hhs.gov FU Center for Food Safety and Applied Nutrition FX This project was supported in part by an appointment (TSL) to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 21 TC 7 Z9 8 U1 3 U2 66 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2013 VL 34 IS 1 BP 100 EP 105 DI 10.1016/j.fm.2012.11.007 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 111NO UT WOS:000316528200014 PM 23498184 ER PT J AU Keller, SE VanDoren, JM Grasso, EM Halik, LA AF Keller, Susanne E. VanDoren, Jane M. Grasso, Elizabeth M. Halik, Lindsay A. TI Growth and survival of Salmonella in ground black pepper (Piper nigrum) SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella; Black pepper; Low water activity; Desiccation; Survival; Growth ID ESCHERICHIA-COLI; PEANUT BUTTER; MICROBIOLOGICAL QUALITY; LISTERIA-MONOCYTOGENES; ANTIMICROBIAL ACTIVITY; INOCULATED ALMONDS; WATER-ACTIVITY; SPICES; CONTAMINATION; RESISTANCE AB A four serovar cocktail of Salmonella was inoculated into ground black pepper (Piper nigrum) at different water activity (a(w)) levels at a starting level of 4-5 log cfu/g and incubated at 25 and at 35 degrees C. At 35 degrees C and a(w) of +/- 0.9886 0.0006, the generation time in ground black pepper was 31 3 mm with a lag time of 4 +/- 1 h. Growth at 25 degrees C had a longer lag, but generation time was not statistically different from growth at 35 degrees C. The a(w) threshold for growth was determined to be 0.9793 +/- 0.0027 at 35 degrees C. To determine survival during storage conditions, ground black pepper was inoculated at approximately 8 log cfu/g and stored at 25 and 35 degrees C at high (97% RH) and ambient (<= 40% RH) humidity. At high relative humidity, a(w) increased to approximately 0.8-0.9 after approximately 20 days at both temperatures and no Salmonella was detected after 100 and 45 days at 25 and 35 degrees C, respectively. Under ambient humidity, populations showed an initial decrease of 3-4 log cfu/g, then remained stable for over 8 months at 25 and 35 degrees C. Results of this study indicate Salmonella can readily grow at permissive a(w) in ground black pepper and may persist for an extended period of time under typical storage conditions. Published by Elsevier Ltd. C1 [Keller, Susanne E.; Halik, Lindsay A.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [VanDoren, Jane M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Grasso, Elizabeth M.] US FDA, Off Commissioner, Bedford Pk, IL 60501 USA. RP Keller, SE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM Susanne.Keller@fda.hhs.gov FU U.S. Food and Drug Administration; Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy FX This work was supported by the U.S. Food and Drug Administration and by appointments to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education (ORISE) through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 40 TC 18 Z9 18 U1 3 U2 58 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2013 VL 34 IS 1 BP 182 EP 188 DI 10.1016/j.fm.2012.12.002 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 111NO UT WOS:000316528200026 PM 23498196 ER PT J AU Deng, L Zhong, LL Struble, E Duan, HY Ma, L Harman, C Yan, HL Virata-Theimer, ML Zhao, Z Feinstone, S Alter, H Zhang, P AF Deng, Lu Zhong, Lilin Struble, Evi Duan, Hongying Ma, Li Harman, Christine Yan, Hailing Virata-Theimer, Maria Luisa Zhao, Zhong Feinstone, Stephen Alter, Harvey Zhang, Pei TI Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MONOCLONAL-ANTIBODIES; E2 PROTEIN; INFECTION; CHIMPANZEES; EPITOPES; VACCINE AB Hepatitis C virus (HCV) envelope glycoprotein E2 has been considered as a major target for vaccine design. Epitope II, mapped between residues 427-446 within the E2 protein, elicits antibodies that are either neutralizing or nonneutralizing. The fundamental mechanism of antibody-mediated neutralization at epitope II remains to be defined at the atomic level. Here we report the crystal structure of the epitope II peptide in complex with a monoclonal antibody (mAb#8) capable of neutralizing HCV. The complex structure revealed that this neutralizing antibody engages epitope II via interactions with both the C-terminal a-helix and the N-terminal loop using a bifurcated mode of action. Our structural insights into the key determinants for the antibody-mediated neutralization may contribute to the immune prophylaxis of HCV infection and the development of an effective HCV vaccine. C1 [Deng, Lu; Zhong, Lilin; Struble, Evi; Ma, Li; Harman, Christine; Yan, Hailing; Virata-Theimer, Maria Luisa; Zhao, Zhong; Zhang, Pei] US FDA, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. [Duan, Hongying; Feinstone, Stephen] US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Alter, Harvey] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Alter, H (reprint author), NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM halter@dtm.cc.nih.gov; pei.zhang@fda.hhs.gov FU Department of Energy Offices of Biological and Environmental Research and Basic Energy Sciences; National Center for Research Resources of the National Institutes of Health; Modernizing Science grant from the Center for Biologics Evaluation and Research, Food and Drug Administration FX We thank Drs. John Finlayson and Shan-Lu Liu for their comments on the manuscript and Drs. Tsan Xiao and Tengchuan Jin (National Institute of Allergy and Infectious Diseases) for providing the instrument for crystallization screening. We thank Howard Robinson (Brookhaven National Synchrotron Light Source) for X-ray data collection. Beamline X29 is supported by the Department of Energy Offices of Biological and Environmental Research and Basic Energy Sciences and by the National Center for Research Resources of the National Institutes of Health. This study was funded by a Modernizing Science grant from the Center for Biologics Evaluation and Research, Food and Drug Administration. NR 26 TC 19 Z9 19 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 30 PY 2013 VL 110 IS 18 BP 7418 EP 7422 DI 10.1073/pnas.1305306110 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 140UV UT WOS:000318682300066 PM 23589879 ER PT J AU Brady, RA Mocca, CP Prabhakara, R Plaut, RD Shirtliff, ME Merkel, TJ Burns, DL AF Brady, Rebecca A. Mocca, Christopher P. Prabhakara, Ranjani Plaut, Roger D. Shirtliff, Mark E. Merkel, Tod J. Burns, Drusilla L. TI Evaluation of Genetically Inactivated Alpha Toxin for Protection in Multiple Mouse Models of Staphylococcus aureus Infection SO PLOS ONE LA English DT Article ID CLUMPING FACTOR-A; SITE-DIRECTED MUTAGENESIS; NASAL CARRIAGE; INDUCED MASTITIS; GENE-EXPRESSION; IMMUNE-RESPONSE; BINDING PROTEIN; UNITED-STATES; MURINE MODEL; VACCINE AB Staphylococcus aureus is a major human pathogen and a leading cause of nosocomial and community-acquired infections. Development of a vaccine against this pathogen is an important goal. While S. aureus protective antigens have been identified in the literature, the majority have only been tested in a single animal model of disease. We wished to evaluate the ability of one S. aureus vaccine antigen to protect in multiple mouse models, thus assessing whether protection in one model translates to protection in other models encompassing the full breadth of infections the pathogen can cause. We chose to focus on genetically inactivated alpha toxin mutant HlaH35L. We evaluated the protection afforded by this antigen in three models of infection using the same vaccine dose, regimen, route of immunization, adjuvant, and challenge strain. When mice were immunized with HlaH35L and challenged via a skin and soft tissue infection model, HlaH35L immunization led to a less severe infection and decreased S. aureus levels at the challenge site when compared to controls. Challenge of HlaH35L-immunized mice using a systemic infection model resulted in a limited, but statistically significant decrease in bacterial colonization as compared to that observed with control mice. In contrast, in a prosthetic implant model of chronic biofilm infection, there was no significant difference in bacterial levels when compared to controls. These results demonstrate that vaccines may confer protection against one form of S. aureus disease without conferring protection against other disease presentations and thus underscore a significant challenge in S. aureus vaccine development. C1 [Brady, Rebecca A.; Mocca, Christopher P.; Prabhakara, Ranjani; Plaut, Roger D.; Merkel, Tod J.; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Shirtliff, Mark E.] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA. [Shirtliff, Mark E.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM drusilla.burns@fda.hhs.gov RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X FU Center for Biologics Evaluation and Research; Food and Drug Administration; National Institute of Allergy and Infectious Diseases, National Institutes of Health [R01AI69568, ARRA AI69568] FX This work was supported by the Intramural Research Program of the Center for Biologics Evaluation and Research, Food and Drug Administration, and by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (grants R01AI69568 and ARRA AI69568 to MES). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 46 TC 12 Z9 12 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2013 VL 8 IS 4 AR e63040 DI 10.1371/journal.pone.0063040 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 181JC UT WOS:000321662800074 PM 23658662 ER PT J AU Binienda, ZK Sarkar, S Mohammed-Saeed, L Gough, B Beaudoin, MA Ali, SF Paule, MG Imam, SZ AF Binienda, Zbigniew K. Sarkar, Sumit Mohammed-Saeed, Lamya Gough, Bobby Beaudoin, Michael A. Ali, Syed F. Paule, Merle G. Imam, Syed Z. TI Chronic exposure to rotenone, a dopaminergic toxin, results in peripheral neuropathy associated with dopaminergic damage SO NEUROSCIENCE LETTERS LA English DT Article DE Rotenone; Pesticides; Dopamine; Motor functions; Sciatic nerves ID PARKINSONS-DISEASE; PESTICIDE EXPOSURE; RATS; STRIATUM; FEATURES; MODELS AB Rotenone, a widely used pesticide, causes a syndrome in rats that replicates, both pathologically and behaviorally, the symptoms of Parkinson's disease (PD). In the present study, we sought to determine if a chronic exposure to rotenone, resulting in dopaminergic loss, could also lead to peripheral neuronal damage related to motor dysfunction. Adult male Sprague-Dawley rat's (n=14) were treated with rotenone (1 or 2 mg/kg, s.c., once daily) on days 1, 3, 6, 8, 10, 13, 15, 17, 21, 22, and 27 to minimize mortality. Control rats received vehicle (DMSO) injections. Animals were weighed on the days of injection and monitored daily. A mortality of 21% was observed in rotenone treated rats. The motor nerve conduction velocity (MCV) was assessed using action potentials detected from the tail muscle through surface receiver electrodes installed around the distal portion of the tail. Rats exposed to rotenone often developed hind limb paresis with a significant decrease in MCV as detected in tail nerves (p < 0.05). Animals were then sacrificed, either 24h after rotenone exposure on day 6 or 24h after the last dose of rotenone on day 27. The striatum and sciatic nerves were dissected on dry ice and flash-frozen and kept at 80 C until further analysis. Striatal dopamine (DA) was analyzed using HPLC-ECD and sciatic nerve pathology was analyzed for neurodegeneration. A time-dependent rotenone-induced striatal depletion of DA (60% after 7 days and 80% after 27 days) was observed. Furthermore, Neurofilament-neurofilament B, Flouro-Jade C and myelin basic protein analyses suggested a time-dependent rotenone-induced neurodegeneration in sciatic nerves. These data, for the first time, indicate an association between dopaminergic damage and peripheral motor nerve degeneration in an animal model of dopaminergic toxicity. Peripheral motor nerve dysfunction in rats following a chronic exposure to rotenone may serve not only as a relevant experimental model of motor neuropathy but also as a peripheral marker of dopaminergic neuronal damage to the central nervous system. Published by Elsevier Ireland Ltd. C1 [Binienda, Zbigniew K.; Sarkar, Sumit; Mohammed-Saeed, Lamya; Gough, Bobby; Ali, Syed F.; Paule, Merle G.; Imam, Syed Z.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Beaudoin, Michael A.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Dr, Jefferson, AR 72079 USA. EM Zbigniew.Binienda@fda.hhs.gov NR 13 TC 5 Z9 6 U1 1 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 29 PY 2013 VL 541 BP 233 EP 237 DI 10.1016/j.neulet.2013.02.047 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 138SX UT WOS:000318531400046 PM 23499956 ER PT J AU Salmon, DA Proschan, M Forshee, R Gargiullo, P Bleser, W Burwen, DR Cunningham, F Garman, P Greene, SK Lee, GM Vellozzi, C Yih, WK Gellin, B Lurie, N AF Salmon, Daniel A. Proschan, Michael Forshee, Richard Gargiullo, Paul Bleser, William Burwen, Dale R. Cunningham, Francesca Garman, Patrick Greene, Sharon K. Lee, Grace M. Vellozzi, Claudia Yih, W. Katherine Gellin, Bruce Lurie, Nicole CA H1N1 GBS Meta-Anal Working Grp TI Association between Guillain-Barre syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis SO LANCET LA English DT Article ID SAFETY DATALINK PROJECT; PRACTICE RESEARCH DATABASE; UNITED-STATES; IMMUNIZATION-SAFETY; VACCINATION; SURVEILLANCE; RECEIPT; PROGRAM; KINGDOM; COHORT AB Background The influenza A (H1N1) 2009 monovalent vaccination programme was the largest mass vaccination initiative in recent US history. Commensurate with the size and scope of the vaccination programme, a project to monitor vaccine adverse events was undertaken, the most comprehensive safety surveillance agenda in the USA to date. The adverse event monitoring project identified an increased risk of Guillain-Barre syndrome after vaccination; however, some individual variability in results was noted. Guillain-Barre syndrome is a rare but serious health disorder in which a person's own immune system damages their nerve cells, causing muscle weakness, sometimes paralysis, and infrequently death. We did a meta-analysis of data from the adverse event monitoring project to ascertain whether influenza A (H1N1) 2009 monovalent inactivated vaccines used in the USA increased the risk of Guillain-Barre syndrome. Methods Data were obtained from six adverse event monitoring systems. About 23 million vaccinated people were included in the analysis. The primary analysis entailed calculation of incidence rate ratios and attributable risks of excess cases of Guillain-Barre syndrome per million vaccinations. We used a self-controlled risk-interval design. Findings Influenza A (H1N1) 2009 monovalent inactivated vaccines were associated with a small increased risk of Guillain-Barre syndrome (incidence rate ratio 2.35, 95% CI 1.42-4.01, p=0.0003). This finding translated to about 1.6 excess cases of Guillain-Barre syndrome per million people vaccinated. Interpretation The modest risk of Guillain-Barre syndrome attributed to vaccination is consistent with previous estimates of the disorder after seasonal influenza vaccination. A risk of this small magnitude would be difficult to capture during routine seasonal influenza vaccine programmes, which have extensive, but comparatively less, safety monitoring. In view of the morbidity and mortality caused by 2009 H1N1 influenza and the effectiveness of the vaccine, clinicians, policy makers, and those eligible for vaccination should be assured that the benefits of inactivated pandemic vaccines greatly outweigh the risks. C1 [Salmon, Daniel A.; Bleser, William; Gellin, Bruce] Dept Hlth & Human Serv, Natl Vaccine Program Off, Off Assistant Secretary Hlth, Washington, DC USA. [Lurie, Nicole] Dept Hlth & Human Serv, Washington, DC USA. [Salmon, Daniel A.] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. [Proschan, Michael] NIH, Bethesda, MD 20892 USA. [Forshee, Richard; Burwen, Dale R.] US FDA, Rockville, MD 20857 USA. [Gargiullo, Paul; Vellozzi, Claudia] Ctr Dis Control & Prevent, Atlanta, GA USA. [Cunningham, Francesca] US Dept Vet Affairs, Hines, IL USA. [Garman, Patrick] US Dept Def, Washington, DC 20305 USA. [Greene, Sharon K.; Lee, Grace M.; Yih, W. Katherine] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Greene, Sharon K.; Lee, Grace M.; Yih, W. Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. RP Salmon, DA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD 21205 USA. EM dsalmon@jhsph.edu OI Jacobsen, Steven/0000-0002-8174-8533; Bleser, William/0000-0002-4640-8680 FU US Federal Government FX US Federal Government. NR 40 TC 55 Z9 55 U1 0 U2 74 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD APR 27 PY 2013 VL 381 IS 9876 BP 1461 EP 1468 DI 10.1016/S0140-6736(12)62189-8 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 139TK UT WOS:000318607300035 PM 23498095 ER PT J AU D'Agnillo, F Williams, MC Moayeri, M Warfel, JM AF D'Agnillo, Felice Williams, Matthew C. Moayeri, Mahtab Warfel, Jason M. TI Anthrax Lethal Toxin Downregulates Claudin-5 Expression in Human Endothelial Tight Junctions SO PLOS ONE LA English DT Article ID BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; INHALATIONAL ANTHRAX; BARRIER FUNCTION; GENE-EXPRESSION; VE-CADHERIN; EDEMA TOXIN; IN-VIVO; CELLS; PERMEABILITY AB Vascular leakage pathologies such as pleural effusion and hemorrhage are hallmarks of anthrax pathogenesis. We previously reported that anthrax lethal toxin (LT), the major virulence factor of anthrax, reduces barrier function in cultured primary human microvascular endothelial cells. Here, we show that LT-induced barrier dysfunction is accompanied by the reduced expression of the endothelial tight junction (TJ) protein claudin-5 but no change in the expression of other TJ components occludin, ZO-1, ZO-2, or the adherens junction (AJ) protein VE-cadherin. The downregulation of claudin-5 correlated temporally and dose-dependently with the reduction of transendothelial electrical resistance. LT-induced loss of claudin-5 was independent of cell death and preceded the appearance of actin stress fibers and altered AJ morphology. Pharmacological inhibition of MEK-1/2, two kinases that are proteolytically inactivated by LT, showed a similar reduction in claudin-5 expression. We found that LT reduced claudin-5 mRNA levels but did not accelerate the rate of claudin-5 degradation. Mice challenged with LT also showed significant reduction in claudin-5 expression. Together, these findings support a possible role for LT disruption of endothelial TJs in the vascular leakage pathologies of anthrax. C1 [D'Agnillo, Felice; Williams, Matthew C.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Warfel, Jason M.] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Moayeri, Mahtab] NIAID, Microbial Pathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM felice.dagnillo@fda.hhs.gov FU Food and Drug Administration FX This research was supported by grants from the intramural program of the Food and Drug Administration (FD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 56 TC 7 Z9 7 U1 0 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 23 PY 2013 VL 8 IS 4 AR e62576 DI 10.1371/journal.pone.0062576 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131QH UT WOS:000318008400200 PM 23626836 ER PT J AU Yang, L Price, ET Chang, CW Li, Y Huang, Y Guo, LW Guo, YL Kaput, J Shi, LM Ning, BT AF Yang, Lun Price, Elvin T. Chang, Ching-Wei Li, Yan Huang, Ying Guo, Li-Wu Guo, Yongli Kaput, Jim Shi, Leming Ning, Baitang TI Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters SO PLOS ONE LA English DT Article ID HUMAN LIVER; CYTOCHROME-P450 ENZYMES; HUMAN HEPATOCYTES; POLYMORPHISMS; BIOTRANSFORMATION; PHARMACOGENETICS; HEPATOTOXICITY; RECEPTORS; NETWORKS AB Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. C1 [Yang, Lun; Chang, Ching-Wei; Li, Yan; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Price, Elvin T.] Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. [Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA USA. RP Shi, LM (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. EM leming.shi@fda.hhs.gov; baitang.ning@fda.hhs.gov FU Postgraduate Research Program at the National Center for Toxicological Research FX LY, YL and LG were supported by appointments to the Postgraduate Research Program at the National Center for Toxicological Research administered by Oak Ridge Institute for Science Education through an interagency agreement between the United States Department of Energy and the Federal Drug Administration. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 43 TC 19 Z9 19 U1 1 U2 14 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 23 PY 2013 VL 8 IS 4 AR e60368 DI 10.1371/journal.pone.0060368 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 131QH UT WOS:000318008400004 PM 23637747 ER PT J AU Virnik, K Ni, YS Berkower, I AF Virnik, Konstantin Ni, Yisheng Berkower, Ira TI Enhanced expression of HIV and SIV vaccine antigens in the structural gene region of live attenuated rubella viral vectors and their incorporation into virions SO VACCINE LA English DT Article DE Live viral vectors; Rubella vaccine strain RA27/3; Stable expression; HIV MPER; SIV Gag; Antigen incorporation ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; RHESUS MACAQUES; NEUTRALIZING ANTIBODY; ENVELOPE GLYCOPROTEIN; NONSTRUCTURAL PROTEIN; CAPSID PROTEIN; CD4 BINDING; EPITOPE AB Despite the urgent need for an HIV vaccine, its development has been hindered by virus variability, weak immunogenicity of conserved epitopes, and limited durability of the immune response. For other viruses, difficulties with immunogenicity were overcome by developing live attenuated vaccine strains. However, there is no reliable method of attenuation for HIV, and an attenuated strain would risk reversion to wild type. We have developed rubella viral vectors, based on the live attenuated vaccine strain RA27/3, which are capable of expressing important HIV and SIV vaccine antigens. The rubella vaccine strain has demonstrated safety, immunogenicity, and long lasting protection in millions of children. Rubella vectors combine the growth and immunogenicity of live rubella vaccine with the antigenicity of HIV or SIV inserts. This is the first report showing that live attenuated rubella vectors can stably express HIV and SW vaccine antigens at an insertion site located within the structural gene region. Unlike the Not I site described previously, the new site accommodates a broader range of vaccine antigens without interfering with essential viral functions. In addition, antigens expressed at the structural site were controlled by the strong subgenomic promoter, resulting in higher levels and longer duration of antigen expression. The inserts were expressed as part of the structural polyprotein, processed to free antigen, and incorporated into rubella virions. The rubella vaccine strain readily infects rhesus macaques, and these animals will be the model of choice for testing vector growth in vivo and immunogenicity. Published by Elsevier Ltd. C1 [Virnik, Konstantin; Ni, Yisheng; Berkower, Ira] US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Immunoregulat Lab, Div Viral Prod, Off Vaccines,Ctr Biol, Bldg 29,Room 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov FU NIH Intramural AIDS Targeted Research Program FX We thank Dr. Suzanne Epstein and Dr. Konstantin Chumakov for reading the manuscript critically and Dr. Joel Beren and Dr. Carol Weiss for helpful discussions. This research was supported in part by the NIH Intramural AIDS Targeted Research Program. NR 42 TC 2 Z9 2 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 19 PY 2013 VL 31 IS 17 BP 2119 EP 2125 DI 10.1016/j.vaccine.2013.02.055 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 135ZO UT WOS:000318329400003 PM 23474312 ER PT J AU Elmgren, L Li, XG Wilson, C Ball, R Wang, JZ Cichutek, K Pfleiderer, M Kato, A Cavaleri, M Southern, J Jivapaisarnpong, T Minor, P Griffiths, E Sohn, Y Wood, D AF Elmgren, Lindsay Li, Xuguang Wilson, Carolyn Ball, Robert Wang, Junzhi Cichutek, Klaus Pfleiderer, Michael Kato, Atsushi Cavaleri, Marco Southern, James Jivapaisarnpong, Teeranart Minor, Philip Griffiths, Elwyn Sohn, Yeowon Wood, David TI A global regulatory science agenda for vaccines SO VACCINE LA English DT Review DE Vaccine regulation; Clinical trials; Post-marketing surveillance; Vaccine quality; Correlates of immunity; Vaccine standardization ID PNEUMOCOCCAL CONJUGATE VACCINE; ORAL POLIOVIRUS VACCINE; ADVERSE EVENTS; ENTEROVIRUS 71; NUCLEOTIDE-SEQUENCE; IMMUNE-RESPONSE; TRANSGENIC MICE; QUALITY-CONTROL; INFLUENZA-A; SAFETY AB The Decade of Vaccines Collaboration and development of the Global Vaccine Action Plan provides a catalyst and unique opportunity for regulators worldwide to develop and propose a global regulatory science agenda for vaccines. Regulatory oversight is critical to allow access to vaccines that are safe, effective, and of assured quality. Methods used by regulators need to constantly evolve so that scientific and technological advances are applied to address challenges such as new products and technologies, and also to provide an increased understanding of benefits and risks of existing products. Regulatory science builds on high-quality basic research, and encompasses at least two broad categories. First, there is laboratory-based regulatory science. Illustrative examples include development of correlates of immunity; or correlates of safety; or of improved product characterization and potency assays. Included in such science would be tools to standardize assays used for regulatory purposes. Second, there is science to develop regulatory processes. Illustrative examples include adaptive clinical trial designs; or tools to analyze the benefit-risk decision-making process of regulators; or novel pharmacovigilance methodologies. Included in such science would be initiatives to standardize regulatory processes (e.g., definitions of terms for adverse events [AEs] following immunization). The aim of a global regulatory science agenda is to transform current national efforts, mainly by well-resourced regulatory agencies, into a coordinated action plan to support global immunization goals. This article provides examples of how regulatory science has, in the past, contributed to improved access to vaccines, and identifies gaps that could be addressed through a global regulatory science agenda. The article also identifies challenges to implementing a regulatory science agenda and proposes strategies and actions to fill these gaps. A global regulatory science agenda will enable regulators, academics, and other stakeholders to converge around transformative actions for innovation in the regulatory process to support global immunization goals. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Elmgren, Lindsay; Li, Xuguang] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Wilson, Carolyn; Ball, Robert] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Wang, Junzhi] Natl Inst Food & Drug Control, Beijing, Peoples R China. [Cichutek, Klaus; Pfleiderer, Michael] Paul Ehrlich Inst, Langen, Germany. [Kato, Atsushi] Natl Inst Infect Dis, Tokyo, Japan. [Cavaleri, Marco] European Med Agcy, London, England. [Jivapaisarnpong, Teeranart] Minist Publ Hlth, Dept Med Sci, Inst Biol Prod, Bangkok, Thailand. [Minor, Philip] Natl Inst Biol Stand & Controls, Potters Bar, Herts, England. [Sohn, Yeowon] Korea Food & Drug Adm, Seoul, South Korea. [Wood, David] World Hlth Org, Geneva, Switzerland. [Wood, David] World Hlth Org, Qual Safety & Stand Team, Dept Immunizat Vaccines & Biol, CH-1211 Geneva 27, Switzerland. RP Wood, D (reprint author), World Hlth Org, Qual Safety & Stand Team, Dept Immunizat Vaccines & Biol, Ave Appia 20, CH-1211 Geneva 27, Switzerland. EM woodd@who.int NR 86 TC 14 Z9 15 U1 1 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 18 PY 2013 VL 31 SU 2 BP B163 EP B175 DI 10.1016/j.vaccine.2012.10.117 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 137TV UT WOS:000318462000019 PM 23598478 ER PT J AU Griffiths, P Plotkin, S Mocarski, E Pass, R Schleiss, M Krause, P Bialek, S AF Griffiths, Paul Plotkin, Stanley Mocarski, Edward Pass, Robert Schleiss, Mark Krause, Philip Bialek, Stephanie TI Desirability and feasibility of a vaccine against cytomegalovirus SO VACCINE LA English DT Review DE Vaccine; Prevention; Reinfection; Burden of disease; Hearing loss; Clinical trials ID PLACEBO-CONTROLLED TRIAL; GLYCOPROTEIN-B VACCINE; CD8(+) T-CELLS; VIRUS-INFECTION; IMMUNOCOMPROMISED HOSTS; ANTIRETROVIRAL THERAPY; TRANSPLANT RECIPIENTS; LIVER-TRANSPLANTATION; RENAL-TRANSPLANTATION; ELDERLY INDIVIDUALS AB Publication of a report from the Institute of Medicine in 2000 showing that a vaccine against cytomegalovirus (CMV) would likely be cost saving was very influential and encouraged the clinical evaluation of candidate vaccines. The major objective of a CMV vaccination program would be to reduce disease caused by congenital CMV infection, which is the leading viral cause of sensorineural hearing loss and neurodevelopmental delay. CMV has challenges as a vaccine target because it is a herpesvirus, it persists lifelong despite host immunity, infected individuals can be reinfected with new strains, overt disease occurs in those with immature or impaired immune systems and persons with this infection do not usually report symptoms. Nevertheless, natural immunity against CMV provides some protection against infection and disease, natural history studies have defined the serological and molecular biological techniques needed for endpoints in future clinical trials of vaccines and CMV is not highly communicable, suggesting that it may not be necessary to achieve very high levels of population immunity through vaccination in order to affect transmission. Three phase 2 CMV vaccine studies have been completed in the last 3 years and all report encouraging outcomes. A key international meeting was organized by the Food and Drug Administration in January 2012 at which interested parties from regulatory bodies, industry and academia discussed and prioritised designs for phase 2 and phase 3 clinical trials. Vaccines able to prevent primary infection with CMV and to boost the immune response of those already infected are desirable. The major target populations for a CMV vaccine include women of childbearing age and adolescents. Toddlers represent another potential population, since an effect of vaccine in this age group could potentially decrease transmission to adults. In addition, prospective recipients of transplants and patients with AIDS would be expected to benefit. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Griffiths, Paul] UCL, London, England. [Plotkin, Stanley] Univ Penn, Philadelphia, PA 19104 USA. [Mocarski, Edward] Emory Univ, Atlanta, GA 30322 USA. [Pass, Robert] Univ Alabama Birmingham, Birmingham, AL USA. [Schleiss, Mark] Univ Minnesota, Minneapolis, MN 55455 USA. [Krause, Philip] US FDA, Washington, DC 20204 USA. [Bialek, Stephanie] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Griffiths, P (reprint author), UCL Med Sch, Ctr Virol, Rowland Hill St, London NW3 2PF, England. EM p.griffiths@ucl.ac.uk OI Krause, Philip/0000-0002-1045-7536 FU Wellcome Trust [078332]; MedImmune, LLC FX Work in the authors' laboratories is supported by the following grants: Wellcome Trust 078332.; EM is a paid consultant in the area of CMV vaccines for MedImmune, LLC. All other authors declare that they have no personal conflicts of interest. NR 70 TC 46 Z9 49 U1 1 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 18 PY 2013 VL 31 SU 2 BP B197 EP B203 DI 10.1016/j.vaccine.2012.10.074 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 137TV UT WOS:000318462000023 PM 23598482 ER PT J AU Su, B Gao, L Meng, F Guo, LW Rothschild, J Gelman, IH AF Su, B. Gao, L. Meng, F. Guo, L-W Rothschild, J. Gelman, I. H. TI Adhesion-mediated cytoskeletal remodeling is controlled by the direct scaffolding of Src from FAK complexes to lipid rafts by SSeCKS/AKAP12 SO ONCOGENE LA English DT Article DE Src; SSeCKS/Gravin/AKAP12; FAK; caveolin-1; adhesion; actin-based cytoskeleton ID RECEPTOR TYROSINE KINASES; GROWTH-FACTOR RECEPTOR; HUMAN COLON-CANCER; C-SRC; ONCOGENIC TRANSFORMATION; SIGNAL-TRANSDUCTION; PROSTATE-CANCER; CELL-MIGRATION; BREAST-CANCER; IN-VIVO AB Metastatic cell migration and invasion are regulated by altered adhesion-mediated signaling to the actin-based cytoskeleton via activated Src-FAK complexes. Src-suppressed C-kinase substrate (SSeCKS, the rodent orthologue of human Gravin/AKAP12), whose expression is downregulated by oncogenic Src and in many human cancers, antagonizes oncogenic Src pathways including those driving neovascularization at metastatic sites, metastatic cell motility and invasiveness. This is likely manifested through its function as a scaffolder of F-actin and signaling proteins such as cyclins, calmodulin, protein kinase C and A. Here we show that in contrast to its ability to inhibit haptotaxis, SSeCKS increased prostate cancer cell adhesion to fibronectin and type I collagen in a FAK-dependent manner, correlating with a relative increase in FAK(poY397) levels. In contrast, SSeCKS suppressed adhesion-induced Src activation (Src(poY416)) and phosphorylation of FAK at Y925, a known Src substrate site. SSeCKS also induced increased cell spreading, cell flattening, integrin beta 1 clustering and formation of mature focal adhesion plaques. An in silico analysis identified a Src-binding domain on SSeCKS(aa 153-166) that is homologous to the Src-binding domain of caveolin-1, and this region is required for SSeCKS-Src interaction, for SSeCKS-enhanced Src activity and sequestration to lipid rafts and for SSeCKS-enhanced adhesion of MAT-LyLu and CWR22Rv1 prostate cancer cells. Our data suggest a model in which SSeCKS suppresses oncogenic motility by sequestering Src to caveolin-rich lipid rafts, thereby disengaging Src from FAK-associated adhesion and signaling complexes. Oncogene (2013) 32, 2016-2026; doi:10.1038/onc.2012.218; published online 18 June 2012 C1 [Su, B.; Gao, L.; Rothschild, J.; Gelman, I. H.] Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. [Meng, F.] SUNY Buffalo, Dept Physiol & Biophys, Buffalo, NY 14260 USA. [Guo, L-W] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gelman, IH (reprint author), Roswell Pk Canc Inst, Dept Canc Genet, Elm & Carlton St,CGP L2-309, Buffalo, NY 14263 USA. EM irwin.gelman@roswellpark.org FU NIH/NCI [CA94108, CA116430]; DoD [PC074228, PC101210]; NCI Comprehensive Cancer funds [P30-CA016056] FX We thank Toru Ouchi and Eugene Kandel for critical review of the manuscript, Kalle Saksela and Bruce Mayer for discussions on SH3 interactions and Bruce Mayer, Y Peter Wang and Tom Parsons for reagents. This work is supported by grants (IHG) CA94108, CA116430 (NIH/NCI), PC074228, PC101210 (DoD) and, in part, through NCI Comprehensive Cancer funds (P30-CA016056). NR 76 TC 17 Z9 17 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2013 VL 32 IS 16 BP 2016 EP 2026 DI 10.1038/onc.2012.218 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 130LY UT WOS:000317919900003 PM 22710722 ER PT J AU Harp, BP Miranda-Bermudez, E Barrows, JN AF Harp, Bhakti Petigara Miranda-Bermudez, Enio Barrows, Julie N. TI Determination of Seven Certified Color Additives in Food Products Using Liquid Chromatography SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE certified color additives; food; liquid chromatography-photodiode array detection; synthetic organic dyes ID YELLOW NO 6; SUBSIDIARY COLORS; SYNTHETIC DYES; SOFT DRINKS; SPECTRAL COMPILATION; EXPOSURE ASSESSMENT; ARRAY DETECTION; C-18 CARTRIDGE; FD; IDENTIFICATION AB This study describes a new method for determining FD&C Blue No. 1, FD&C Blue No. 2, FD&C Green No. 3, FD&C Red No. 3, FD&C Red No. 40, FD&C Yellow No. 5, and FD&C Yellow No. 6 in food products. These seven color additives are water-soluble dyes that are required to be batch certified by the U.S. Food and Drug Administration (FDA) before they may be used in food and other FDA-regulated products. In the new method, the color additives are extracted from a product using one of two procedures developed for various product types, isolated from the noncolored components, and analyzed by liquid chromatography with photodiode array detection. The method was validated by determining linearity, range, precision, recovery from various matrices, limit of detection, limit of quantitation, and relative standard deviation for each color additive. A survey of 44 food products, including beverages, frozen treats, powder mixes, gelatin products, candies, icings, jellies, spices, dressings, sauces, baked goods, and dairy products, found total color additives ranging from 1.9 to 1221 mg/kg. FDA intends to use the new method for conducting a rigorous, comprehensive dietary exposure assessment of certified color additives in products likely to be consumed by children. C1 [Harp, Bhakti Petigara; Miranda-Bermudez, Enio; Barrows, Julie N.] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Harp, BP (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Bhakti.Petigara@fda.hhs.gov NR 37 TC 15 Z9 15 U1 5 U2 54 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 17 PY 2013 VL 61 IS 15 BP 3726 EP 3736 DI 10.1021/jf400029y PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 129VS UT WOS:000317872700018 PM 23528012 ER PT J AU Hirsch, DS Shen, Y Dokmanovic, M Wu, WJ AF Hirsch, Dianne S. Shen, Yi Dokmanovic, Milos Wu, Wen Jin TI VPS34 lipid kinase activity is positively regulated by Src phosphorylation and is required for Src-mediated cellular transformation SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Hirsch, Dianne S.; Shen, Yi; Dokmanovic, Milos; Wu, Wen Jin] US FDA, CDER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA LB38 DI 10.1158/1538-7445.AM2013-LB-38 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220601288 ER PT J AU Lu, TP Chuang, EY Chen, JJ AF Lu, Tzu-Pin Chuang, Eric Y. Chen, James J. TI Identification of universal survival predictors in lung adenocarcinoma SO CANCER RESEARCH LA English DT Meeting Abstract CT 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR) CY APR 06-10, 2013 CL Washington, DC SP Amer Assoc Canc Res C1 [Lu, Tzu-Pin; Chen, James J.] Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Chuang, Eric Y.] Grad Inst Biomed Engn & Bioinformat, Tao Yuan, Taiwan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2013 VL 73 IS 8 SU 1 MA 4028 PG 1 WC Oncology SC Oncology GA AA6PP UT WOS:000331220603260 ER PT J AU Hampp, C Asal, N Lipowski, E Kauf, T Schneider, E Kubilis, P Winterstein, A AF Hampp, Christian Asal, Nabih Lipowski, Earlene Kauf, Teresa Schneider, Eileen Kubilis, Paul Winterstein, Almut TI Validity of Laboratory-based Surveillance for Detection of Respiratory Syncytial Virus Seasons SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE immunoprophylaxis; Medicaid; palivizumab; pediatrics; respiratory syncytial virus; seasonality; validity ID UNITED-STATES; HOSPITALIZATION; PALIVIZUMAB; INFECTIONS; PREVENTION; CHILDREN; INFANTS; BRONCHIOLITIS; FLORIDA AB In this study, we validated the Centers for Disease Control and Preventions use of a 10 threshold of median proportion of positive laboratory tests (median proportion positive (MPP)) to identify respiratory syncytial virus (RSV) seasons against a standard based on hospitalization claims. Medicaid fee-for-service recipients under 2 years of age from California, Florida, Illinois, and Texas (19992004), continuously eligible since birth, were categorized for each week as high-risk or low-risk with regard to RSV-related hospitalization based on medical and pharmacy claims data and birth certificates. Weeks were categorized as on-season if the RSV hospitalization incidence rate in high-risk children exceeded the seasonal peak of the incidence rate in low-risk children. Receiver operating characteristic (ROC) curves were used to measure the ability of MPP to discriminate between on-season and off-season weeks as determined from hospitalization data. Areas under the ROC curve ranged from 0.88 (95 confidence interval: 0.83, 0.92) in Illinois to 0.96 (95 confidence interval: 0.94, 0.98) in California. Requiring at least 5 positive tests in addition to the 10 MPP threshold optimized accuracy, as indicated by minimized root mean square errors. The 10 MPP with the added requirement of at least 5 positive tests is a valid method for identifying clinically significant RSV seasons across geographically diverse states. C1 [Hampp, Christian] US FDA, Div Epidemiol 1, Off Pharmacovigilance & Epidemiol, Off Surveillance & Epidemiol,Ctr Drug Evaluat & R, Silver Spring, MD 20993 USA. [Asal, Nabih; Winterstein, Almut] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol & Biostat, Gainesville, FL USA. [Asal, Nabih] Univ Florida, Coll Med, Dept Epidemiol, Gainesville, FL USA. [Lipowski, Earlene; Kauf, Teresa; Kubilis, Paul; Winterstein, Almut] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA. [Schneider, Eileen] Ctr Dis Control & Prevent, Div Viral Dis, Off Infect Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. RP Hampp, C (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM christian.hampp@fda.hhs.gov RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 FU Florida Agency for Healthcare Administration [MED054 under CFDA 93.778] FX This study was supported by a grant from the Florida Agency for Healthcare Administration (grant MED054 under CFDA 93.778). It was conducted in collaboration with the University of Florida Center for Medicaid and the Uninsured. NR 35 TC 3 Z9 3 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2013 VL 177 IS 8 BP 841 EP 851 DI 10.1093/aje/kws304 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 124AT UT WOS:000317435600014 PM 23479344 ER PT J AU Aslan, H Dey, R Meneses, C Castrovinci, P Jeronimo, SMB Oliva, G Fischer, L Duncan, RC Nakhasi, HL Valenzuela, JG Kamhawi, S AF Aslan, Hamide Dey, Ranadhir Meneses, Claudio Castrovinci, Philip Jeronimo, Selma Maria Bezerra Oliva, Gaetano Fischer, Laurent Duncan, Robert C. Nakhasi, Hira L. Valenzuela, Jesus G. Kamhawi, Shaden TI A New Model of Progressive Visceral Leishmaniasis in Hamsters by Natural Transmission via Bites of Vector Sand Flies SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article DE visceral leishmaniasis; Leishmania; Lutzomyia longipalpis; sand fly; vector; transmission; bite; intracardiac ID CUTANEOUS LEISHMANIASIS; LUTZOMYIA-LONGIPALPIS; PROTECTS HAMSTERS; SALIVARY PROTEIN; IN-VIVO; DONOVANI; IMMUNITY; INFANTUM; IMMUNOSUPPRESSION; INFECTION AB Background. Visceral leishmaniasis (VL) is transmitted by sand flies. Protection of needle-challenged vaccinated mice was abrogated in vector-initiated cutaneous leishmaniasis, highlighting the importance of developing natural transmission models for VL. Methods. We used Lutzomyia longipalpis to transmit Leishmania infantum or Leishmania donovani to hamsters. Vector-initiated infections were monitored and compared with intracardiac infections. Body weights were recorded weekly. Organ parasite loads and parasite pick-up by flies were assessed in sick hamsters. Results. Vector-transmitted L. infantum and L. donovani caused >= 5-fold increase in spleen weight compared with uninfected organs and had geometric mean parasite loads (GMPL) comparable to intracardiac inoculation of 10(7)-10(8) parasites, although vector-initiated disease progression was slower and weight loss was greater. Only vector-initiated L. infantum infections caused cutaneous lesions at transmission and distal sites. Importantly, 45.6%, 50.0%, and 33.3% of sand flies feeding on ear, mouth, and testicular lesions, respectively, were parasite-positive. Successful transmission was associated with a high mean percent of metacyclics (66%-82%) rather than total GMPL (2.0 x 10(4)-8.0 x 10(4)) per midgut. Conclusions. This model provides an improved platform to study initial immune events at the bite site, parasite tropism, and pathogenesis and to test drugs and vaccines against naturally acquired VL. C1 [Aslan, Hamide; Meneses, Claudio; Castrovinci, Philip; Valenzuela, Jesus G.; Kamhawi, Shaden] NIAID, VMBS, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Dey, Ranadhir; Duncan, Robert C.; Nakhasi, Hira L.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Jeronimo, Selma Maria Bezerra] Univ Fed Rio Grande do Norte, Ctr Biociencias, Dept Bioquim, BR-59072970 Natal, RN, Brazil. [Oliva, Gaetano] Univ Naples Federico II, Dept Vet Clin Sci, Naples, Italy. [Fischer, Laurent] MERIAL, Lyon, France. RP Kamhawi, S (reprint author), NIAID, VMBS, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Rm 2E-22, Rockville, MD 20852 USA. EM skamhawi@niaid.nih.gov RI Jeronimo, Selma/M-8672-2014; Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 FU Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Intramural Research Program of the Office of Blood Research and Review, Center for Biologics Research and Review, US Food and Drug Administration FX The study was funded by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health and by the Intramural Research Program of the Office of Blood Research and Review, Center for Biologics Research and Review, US Food and Drug Administration. Because R. D., R. C. D., H. L. N., J. G. V., and S. K. are government employees and this is government work, the work is in the public domain in the United States. Notwithstanding any other agreements, the NIH reserves the right to provide the work to PubMed Central for display and use by the public, and PubMed 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 36 TC 19 Z9 19 U1 0 U2 11 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2013 VL 207 IS 8 BP 1328 EP 1338 DI 10.1093/infdis/jis932 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 113WT UT WOS:000316700800018 PM 23288926 ER PT J AU Meyer, JM Archdeacon, P Albrecht, R AF Meyer, Joette M. Archdeacon, Patrick Albrecht, Renata TI FDA Perspective: Enrolment of Elderly Transplant Recipients in Clinical Trials SO TRANSPLANTATION LA English DT Article DE Elderly; FDA; Efficacy; Safety; Clinical trials ID PHASE-III; IMMUNOSUPPRESSION; CYCLOSPORINE; BELATACEPT; REGIMENS; BENEFIT AB Since 1989, the U. S. Food and Drug Administration (FDA) has encouraged the study of new drug and therapeutic products in elderly patients. However, despite the aging population in the United States, elderly patients continue to be underrepresented in clinical trials across a variety of therapeutic areas, including transplantation. The currently available tools for the FDA to encourage and require the evaluation and reporting of safety and efficacy information in elderly patients are summarized. Clinicians, sponsors, and investigators are encouraged to work with the FDA to expand the enrolment of elderly patients in clinical trials of transplantation. C1 [Meyer, Joette M.; Albrecht, Renata] US FDA, Div Transplant & Ophthalmol Prod, Off Antimicrobial Prod, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Archdeacon, Patrick] US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Albrecht, R (reprint author), US FDA, Div Transplant & Ophthalmol Prod, Off Antimicrobial Prod, Off New Drugs,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD USA. EM renata.albrecht@fda.hhs.gov NR 18 TC 5 Z9 5 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2013 VL 95 IS 7 BP 916 EP 918 DI 10.1097/TP.0b013e31828279d9 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 117YW UT WOS:000316990300013 PM 23380880 ER PT J AU Varga, Z Volokhov, DV Stipkovits, L Thuma, A Sellyei, B Magyar, T AF Varga, Zsuzsanna Volokhov, Dmitriy V. Stipkovits, Laszlo Thuma, Akos Sellyei, Boglarka Magyar, Tibor TI Characterization of Pasteurella multocida strains isolated from geese SO VETERINARY MICROBIOLOGY LA English DT Article DE Pasteurella multocida; Goose; Fowl cholera; Pasteurellosis ID 16S RIBOSOMAL-RNA; AVIAN CHOLERA; FOWL CHOLERA; PHENOTYPIC CHARACTERIZATION; GENOTYPIC CHARACTERIZATION; GENETIC DIVERSITY; SEQUENCE-ANALYSIS; VIRULENCE; VARIANTS; BOVINE AB Phenotypic and genotypic diversity of forty-two Pasteurella multocida isolates from geese were characterized by analysis of their capsular type, Heddleston serotype, biotype, fimbrial gene allele type, comparative outer membrane protein (OMP) electrophoresis patterns, and were analyzed using PCR for the presence of virulence-associated genes (toxA, tbpA, pfhA, hgbA, hgbB, nanH, nanB, fimA, hsf-1, and pmHAS). A sequence comparison of the thdF and rpoB housekeeping genes of twenty representative P. multocida strains from three different OMP groups demonstrated that seventeen strains were closely related phylogenetically to previously published strains of P. multocida subsp. multocida and P. multocida subsp. gallicida, and only three strains from geese were grouped with previously published strains of P. multocida subsp. septica. This study is the first report regarding the characterization of phenotypic and genotypic features of different P. multocida field strains isolated from geese with the different clinical representation of pasteurellosis and provide our overview on the usefulness of these in vitro tests for primary characterization of P. multocida strains for the epidemiological studies of fowl cholera. (C) 2013 Elsevier B.V. All rights reserved. C1 [Varga, Zsuzsanna; Sellyei, Boglarka; Magyar, Tibor] Hungarian Acad Sci, Agr Res Ctr, Vet Med Res Inst, H-1581 Budapest, Hungary. [Volokhov, Dmitriy V.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Stipkovits, Laszlo] RT Europe Res Ctr 9200, Mosonmagyarovar, Hungary. [Thuma, Akos] Vet Diagnost Directorate, Natl Food Chain Safety Off, H-1143 Budapest, Hungary. RP Varga, Z (reprint author), Hungarian Acad Sci, Vet Med Res Inst, Hungaria Krt 21, H-1143 Budapest, Hungary. EM vargazs@vmri.hu OI Sellyei, Boglarka/0000-0002-1926-8256 NR 34 TC 4 Z9 6 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD APR 12 PY 2013 VL 163 IS 1-2 BP 149 EP 156 DI 10.1016/j.vetmic.2012.12.023 PG 8 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 113DP UT WOS:000316647000018 PM 23391436 ER PT J AU Kohlstadt, I Wharton, G AF Kohlstadt, Ingrid Wharton, Gerold TI Clinician uptake of obesity-related drug information: a qualitative assessment using continuing medical education activities SO NUTRITION JOURNAL LA English DT Article DE Medication effects on appetite; Insulin resistance; Drug-related weight gain; Mental illness as a risk factor for obesity; Adverse metabolic drug effects; Drug safety research; Nutrition knowledge of primary care practitioners ID SAFETY; ADOLESCENTS; CHILDREN; TRIALS AB Background: Medications necessary for disease management can simultaneously contribute to weight gain, especially in children. Patients with preexisting obesity are more susceptible to medication-related weight gain. How equipped are primary care practitioners at identifying and potentially reducing medication-related weight gain? To inform this question germane to public health we sought to identify potential gaps in clinician knowledge related to metabolic adverse drug effects of weight gain. Methods: The study analyzed practitioner responses to the pre-activity questions of six continuing medical education (CME) activities from May 2009 through August 2010. Results: The 20,705 consecutive, self-selected respondents indicated varied levels of familiarity with adverse metabolic effects and psychiatric indications of atypical antipsychotics. Correct responses were lower than predicted for drug indications pertaining to autism (-17% predicted); drug effects on insulin resistance (-62% predicted); chronic disease risk in mental illness (-34% predicted); and drug safety research (-40% predicted). Pediatrician knowledge scores were similar to other primary care practitioners. Conclusions: Clinicians' knowledge of medication-related weight gain may lead them to overestimate the benefits of a drug in relation to its metabolic risks. The knowledge base of pediatricians appears comparable to their counterparts in adult medicine, even though metabolic drug effects in children have only become prevalent recently. C1 [Kohlstadt, Ingrid] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, Annapolis, MD 21401 USA. [Wharton, Gerold] US FDA, Off Pediat Therapeut, Silver Spring, MD USA. RP Kohlstadt, I (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Human Nutr, 198 Prince George St, Annapolis, MD 21401 USA. EM kohlstadt@outlook.com NR 19 TC 1 Z9 1 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2891 J9 NUTR J JI Nutr. J. PD APR 10 PY 2013 VL 12 AR 44 DI 10.1186/1475-2891-12-44 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 132ZN UT WOS:000318107300001 PM 23575242 ER PT J AU Genualdi, S DeJager, L Begley, T AF Genualdi, Susan DeJager, Lowri Begley, Timothy TI Assessments and Improvements in Methods for Monitoring Seafood Safety in Response to the Deepwater Horizon Oil Spill SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE SPME; oil spill; alkanes; PAHs ID SOLID-PHASE MICROEXTRACTION; POLYCHLORINATED-BIPHENYLS; PETROLEUM-HYDROCARBONS; N-PARAFFINS; FISH; IDENTIFICATION; BIODEGRADATION; SHELLFISH; SEAWATER; PRISTANE AB As a result of the April 2010 Deepwater Horizon oil spill, sensory testing protocols were established for reopening closed seafood harvest areas. In order to improve this method and quantitatively assess petrochemical taint, a new method using solid phase microextraction (SPME) and a 5975T transportable GC/MS was developed. This method can analyze 40 samples per instrument per day and could be an alternative to the human sensory panel. In seafood samples collected from supermarkets in the Washington D.C. area and the Gulf of Mexico, all compounds related to petrochemical taint were below the method detection limit (MDL) (0.14-2.6 ng/g). Additionally, to address consumer concerns regarding the presence of n-alkanes and iso-alkanes in seafood, these compounds were investigated in samples purchased in the Washington D.C. area and the Gulf of Mexico. Concentrations in Gulf of Mexico finfish ranged from 0.066 to 1.2 mg/kg, which is within the same background range of iso- and n-alkanes measured in seafood samples purchased in the Washington D.C. area (0.0072-1.6 mu g/g). These automated methods provide a transportable option to obtain rapid results for compounds indicative of petroleum taint and iso- and n-alkanes in case of a future disaster. C1 [Genualdi, Susan; DeJager, Lowri; Begley, Timothy] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Genualdi, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM susan.genualdi@fda.hhs.gov NR 24 TC 4 Z9 4 U1 0 U2 68 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR 10 PY 2013 VL 61 IS 14 BP 3542 EP 3547 DI 10.1021/jf305344z PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 125OG UT WOS:000317548500023 PM 23530736 ER PT J AU Szu, SC Hunt, S Xie, GL Robbins, JB Schneerson, R Gupta, RK Zhao, ZG Tan, XM AF Szu, Shousun C. Hunt, Steven Xie, Guilin Robbins, John B. Schneerson, Rachel Gupta, Rajesh K. Zhao, Zhigang Tan, Xiaomei TI A human IgG anti-Vi reference for Salmonella typhi with weight-based antibody units assigned SO VACCINE LA English DT Article DE Typhoid; Capsule; Vi; Antibody; Reference; Serum; Standard ID STANDARD REFERENCE SERUM; CAPSULAR POLYSACCHARIDE; CONJUGATE VACCINES; FEVER; CHILDREN; EFFICACY; IMMUNIZATION; CARRIERS; VIETNAM; ACID AB Recent data showing the high incidence of typhoid fever in young children, the demonstration of safety and efficacy of a Vi conjugate for this age group, the safety and similar immunogenicity in infants when administrated concurrently with EPI vaccines, together with the interests of manufacturers and investigators in studying such conjugate vaccines prompted us to prepare a human IgG anti-Vi standard to facilitate this work. Volunteers were injected with an investigational Vi-recombinant Pseudomonas aeruginosa exoprotein A (Vi-rEPA) conjugate vaccine. Plasmas with the highest levels of IgG anti-Vi were pooled. The IgG anti-Vi content of this preparation, assayed by precipitin analysis with purified Vi, was 33 mu g/ml. Accordingly, the estimated IgG anti-Vi protective level of 3.5 ELISA unit/ml, derived from our efficacy trial of Vi-rEPA in 2-5 years old children, is equivalent to 4.3 mu g/ml. This reagent is suitable for comparison of immune response of Vi conjugate vaccines or for other purposes requiring anti-Vi measurement. Published by Elsevier Ltd. C1 [Szu, Shousun C.; Hunt, Steven; Robbins, John B.; Schneerson, Rachel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Xie, Guilin; Zhao, Zhigang; Tan, Xiaomei] Lanzhou Inst Biol Prod, Lanzhou, Gansu, Peoples R China. [Gupta, Rajesh K.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Szu, SC (reprint author), NIH, Bldg 6,Room 1A06,9000 Rockville Pike, Bethesda, MD 20892 USA. EM szus@mail.nih.gov OI Hunt, Steven/0000-0003-3533-0627 FU National Institutes of Health, USA; Bill & Melinda Gates Foundation FX We thank Joni Trenbeath of Transfusion Transmitted Viruses Laboratory, Department of Transfusion Medicine, Clinical Center, NIH for molecular screening of the plasma, Dr. Xiao-mei Yang, Lanzhou Institute of Biologic Product, China for preparation of the plasma, Dr. James Kenney and Simleen Kaur of CBER, FDA, for formulation, filling and lyophilization of this preparation and Dr. Mark Miller of Fogarty International Center, NIH for help discussion. This work was supported by the National Institutes of Health, USA and a grant from the Bill & Melinda Gates Foundation. Contributions of Dr. Gupta to this study are an informal communication and represent his own best judgment. These comments do not bind or obligate FDA. NR 38 TC 8 Z9 10 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 8 PY 2013 VL 31 IS 15 BP 1970 EP 1974 DI 10.1016/j.vaccine.2013.02.006 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 125QY UT WOS:000317557600014 PM 23422143 ER PT J AU Afrooz, ARMN Khan, IA Hussain, SM Saleh, NB AF Afrooz, A. R. M. Nabiul Khan, Iftheker A. Hussain, Saber M. Saleh, Navid B. TI Mechanistic hetero-aggregation of gold nanoparticles in presence of nonionic polymer modified single-walled carbon nanotubes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Afrooz, A. R. M. Nabiul; Saleh, Navid B.] Univ S Carolina, Dept Civil & Environm Engn, Columbia, SC 29208 USA. [Khan, Iftheker A.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72709 USA. [Hussain, Saber M.] Air Force Res Lab, Human Effectiveness Directorate, Dayton, OH 45431 USA. EM afrooz@email.sc.edu NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 264-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303600107 ER PT J AU Brooks, S AF Brooks, Susanne TI Future directions and funding for food radiochemistry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Brooks, Susanne] US FDA, Food Emergency Response Network, Rockville, MD 20857 USA. EM susanne.brooks@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 221-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602613 ER PT J AU Brooks, SM AF Brooks, Susanne M. TI Standardizing of the FERN sampling protocols and forms SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Brooks, Susanne M.] US FDA, Food Emergency Response Network, Rockville, MD 20857 USA. EM Susanne.Brooks@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 220-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602612 ER PT J AU Brooks, SM AF Brooks, Susanne M. TI Description of FERN Radiological Cooperative Agreement Program activities SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Brooks, Susanne M.] US FDA, Food Emergency Response Network, Rockville, MD 20857 USA. EM susanne.brooks@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 219-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602611 ER PT J AU Cunningham, W AF Cunningham, William TI SOP for food sample preparation - application for radiological screening analyses SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Cunningham, William] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM william.cunningham@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 131-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602523 ER PT J AU Cunningham, W AF Cunningham, William TI Radionuclides in food - an update on FDA's on-going programs and emergency response activities SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Cunningham, William] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM william.cunningham@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 128-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602519 ER PT J AU Lin, ZC Healey, S Nevins, C Noonan, J AF Lin, Zhichao Healey, Stephanie Nevins, Crystal Noonan, John TI Method development and interlaboratory study for screening alpha and beta radioactivity in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Lin, Zhichao; Healey, Stephanie; Nevins, Crystal; Noonan, John] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. EM zhichao.lin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 200-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602595 ER PT J AU Lin, ZC Inn, KGW James, FJ AF Lin, Zhichao Inn, Kenneth G. W. James, Filliben J. TI Applying self-attenuation and coincidence-summing corrections for gamma-ray spectrometric analysis of foods using GESPECOR and LabSOCS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Lin, Zhichao] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. [Inn, Kenneth G. W.] NIST, Phys Lab, Gaithersburg, MD 20899 USA. [James, Filliben J.] NIST, Informat Technoloy Lab, Gaithersburg, MD 20899 USA. EM zhichao.lin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 173-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602565 ER PT J AU Lin, ZC Semkow, TM Abdul, B AF Lin, Zhichao Semkow, Thomas M. Abdul, Bari TI Rapid screening of Cm243+244 in foods by solid phase extraction: Liquid scintillation counting SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Lin, Zhichao] US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. [Semkow, Thomas M.; Abdul, Bari] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. EM zhichao.lin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 172-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602564 ER PT J AU McLaughlin, MA AF McLaughlin, Michael A. TI FERN 101 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [McLaughlin, Michael A.] US FDA, Food Emergency Response Network, Rockville, MD 20857 USA. EM Michael.McLaughlin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 217-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602609 ER PT J AU McLaughlin, MA Brooks, SM AF McLaughlin, Michael A. Brooks, Susanne M. TI FERN response to Fukushima SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Spring Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [McLaughlin, Michael A.; Brooks, Susanne M.] US FDA, Food Emergency Response Network, Rockville, MD 20857 USA. EM Michael.McLaughlin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 218-NUCL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 216SF UT WOS:000324303602610 ER PT J AU Alusta, P Buzatu, D Tarasenko, O Wilkes, J AF Alusta, Pierre Buzatu, Dan Tarasenko, Olga Wilkes, Jon TI Reliable and swift identification of Salmonella serovars by means of similarity assessment of pretreated mass spectra SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Alusta, Pierre; Buzatu, Dan; Tarasenko, Olga; Wilkes, Jon] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. EM pierre.alusta@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 268-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300241 ER PT J AU Barrows, JN AF Barrows, Julie N. TI US Food and Drug Administration regulation of color additives in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Barrows, Julie N.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. EM julie.barrows@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 41-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851305266 ER PT J AU Barrows, JN Belai, N Lipman, AL AF Barrows, Julie N. Belai, Nebebech Lipman, Arthur L. TI History of FDA regulation of color additives and colorants SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Barrows, Julie N.; Belai, Nebebech] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. [Lipman, Arthur L.] US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. EM julie.barrows@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 59-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300055 ER PT J AU Chang, C Li, XT Botros, L Moore, J Skinner, P Jablonski, J AF Chang, Claire Li, Xitong Botros, Lucy Moore, Jeffrey Skinner, Paden Jablonski, Joseph TI Chemometric analysis method evaluation for near infrared (NIR) spectroscopy: Detection of soybean and pea adulterants in skim milk powder (SMP) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Chang, Claire; Skinner, Paden; Jablonski, Joseph] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. [Li, Xitong] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Botros, Lucy; Moore, Jeffrey] US Pharmacopeial Convent Inc, Rockville, MD 20852 USA. EM claire.chang@fda.hhs.gov; joseph.jablonski@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 225-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300206 ER PT J AU Chiou, BS Bilbao-Sainz, C Valenzuela-Medina, D Klamczynski, A Milczarek, B Avena-Bustillos, R Du, WX Imam, S Glenn, G Orts, W AF Chiou, Bor-Sen Bilbao-Sainz, Cristina Valenzuela-Medina, Diana Klamczynski, Artur Milczarek, Becky Avena-Bustillos, Roberto Du, Wen-Xian Imam, Syed Glenn, Greg Orts, William TI Torrefaction of agricultural by-products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Chiou, Bor-Sen; Bilbao-Sainz, Cristina; Klamczynski, Artur; Imam, Syed; Glenn, Greg; Orts, William] US FDA, Albany, CA 94710 USA. [Valenzuela-Medina, Diana] Univ Pacific, Stockton, CA 95211 USA. [Milczarek, Becky; Avena-Bustillos, Roberto; Du, Wen-Xian] USDA, Albany, CA 94710 USA. EM bor-sen.chiou@ars.usda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 308-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300280 ER PT J AU Conklin, S Gray, P Heitkemper, D Kubachka, K Shockey, N AF Conklin, Sean Gray, Patrick Heitkemper, Doug Kubachka, Kevin Shockey, Nohora TI Extension of a method for speciation of arsenic in rice to other rice-based products, and propagation of the method to other laboratories SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Conklin, Sean; Gray, Patrick] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Heitkemper, Doug; Kubachka, Kevin; Shockey, Nohora] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM sean.conklin@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 304-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300276 ER PT J AU Genualdi, S Begley, T AF Genualdi, Susan Begley, Timothy TI Updated residual styrene in polystyrene food packaging and contained foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Genualdi, Susan; Begley, Timothy] US FDA, College Pk, MD 20740 USA. EM susan.genualdi@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 114-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300107 ER PT J AU Harp, BP Miranda-Bermudez, E Barrows, JN AF Harp, Bhakti Petigara Miranda-Bermudez, Enio Barrows, Julie N. TI Survey of certified color additives in food products marketed in the US using liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Harp, Bhakti Petigara; Miranda-Bermudez, Enio; Barrows, Julie N.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. EM julie.barrows@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 200-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300184 ER PT J AU Hoagland, MS Roth, WL Shackelford, ME Turowski, P Sheu, CW Komolprasert, V Zhang, K Begley, TH AF Hoagland, Martin S. Roth, William L. Shackelford, Mary E. Turowski, Petra Sheu, Chingju W. Komolprasert, Vanee Zhang, Kai Begley, Timothy H. TI Risk assessment of cyclic siloxanes octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Hoagland, Martin S.; Roth, William L.; Shackelford, Mary E.; Turowski, Petra; Sheu, Chingju W.; Komolprasert, Vanee] US FDA, Off Food Addit Safety, Div Food Contact Notificat, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhang, Kai; Begley, Timothy H.] US FDA, Off Regulatory Sci, Dept Analyt Chem, Method Dev Branch,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM martin.hoagland@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 141-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300130 ER PT J AU Khodakovskaya, MV Kim, BS Kim, JN Alimohammadi, M Dervishi, E Mustafa, T Lahiani, M Cernigla, C AF Khodakovskaya, Mariya V. Kim, Bong-Soo Kim, Jong Nam Alimohammadi, Mohammad Dervishi, Enkeleda Mustafa, Thikra Lahiani, Mohammed Cernigla, Carl TI Enhancement of plant productivity by nanotechnology with the assessment of potential environmental risks SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Khodakovskaya, Mariya V.; Alimohammadi, Mohammad; Lahiani, Mohammed] Univ Arkansas, Little Rock, AR 72204 USA. [Dervishi, Enkeleda; Mustafa, Thikra] Univ Arkansas, Ctr Integrat Nanotechnol Sci, Little Rock, AR 72204 USA. [Kim, Bong-Soo; Kim, Jong Nam] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM mvkhodakovsk@ualr.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 43-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300040 ER PT J AU Komolprasert, V AF Komolprasert, Vanee TI Evaluating packaging materials for use during the irradiation of prepackaged food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Komolprasert, Vanee] US FDA, Div Food Contact Notificat, Off Food Addit Safety, College Pk, MD 20740 USA. EM vanee.komolprasert@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 88-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300082 ER PT J AU Koontz, J Song, Y Juskelis, R Mehta, D AF Koontz, John Song, Yoon Juskelis, Rima Mehta, Devanshu TI Migration database of additives and contaminants in food packaging systems for use in predictive models SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Koontz, John; Song, Yoon] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Juskelis, Rima; Mehta, Devanshu] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. EM John.Koontz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 3 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 111-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300104 ER PT J AU Kozlowski, S AF Kozlowski, Steven TI Implementation of QbD SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Kozlowski, Steven] FDA Ctr Drug Evaluat & Res, Off Biotechnol Prod, Silver Spring, MD USA. EM abc@abc.org NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 84-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300918 ER PT J AU LaCasse, D Brorson, K AF LaCasse, Daniel Brorson, Kurt TI Mechanistic failure mode resolution and comparison of parvovirus retentive filters SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [LaCasse, Daniel] Pfizer, Biotherapeut R&D, Andover, MA 01810 USA. [Brorson, Kurt] US FDA, CDER, Silver Spring, MD 20905 USA. EM daniel.lacasse@pfizer.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 410-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851301235 ER PT J AU Lim, JH Howard, PC Linder, SW AF Lim, Jin-Hee Howard, Paul C. Linder, Sean W. TI Separation and characterization of nanostructures in feminine hygiene products SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Lim, Jin-Hee; Linder, Sean W.] US FDA Off Regulatory Affairs, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Howard, Paul C.] US FDA Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. EM jin.lim@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 73-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851305297 ER PT J AU McCarthy, A AF McCarthy, Annette TI FDA's regulation of nanomaterials used in food and food contact materials SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [McCarthy, Annette] US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. EM annette.mccarthy@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 93-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300087 ER PT J AU Mindak, WR Conklin, S AF Mindak, William R. Conklin, Sean TI Analysis for arsenic species in food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Mindak, William R.; Conklin, Sean] US FDA, Dept Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM william.mindak@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 300-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300272 ER PT J AU Mosley, SL AF Mosley, Sylvester L. TI Framework for FDA's review of food additives, color additives, GRAS substances, and food contact substances SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Mosley, Sylvester L.] US FDA, Dept Hlth & Human Serv, College Pk, MD 20740 USA. EM Sylvester.Mosley@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 57-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300053 ER PT J AU Nyman, PJ Begley, TH AF Nyman, Patricia J. Begley, Timothy H. TI Determination of volatile organic compounds in food by vacuum distillation sampling and gas chromatography/mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Nyman, Patricia J.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM patricia.nyman@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 175-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300161 ER PT J AU Nyman, PJ Begley, TH AF Nyman, Patricia J. Begley, Timothy H. TI Retrospective on the occurrence of select VOCs in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Nyman, Patricia J.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM patricia.nyman@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 102-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300096 ER PT J AU Pawar, RS Grundel, E Rader, JI Krynitsky, AJ Fardin-Kia, AR Knolhoff, AM Croley, TR Eason, M AF Pawar, Rahul S. Grundel, Erich Rader, Jeanne I. Krynitsky, Alexander J. Fardin-Kia, Ali Reza Knolhoff, Ann M. Croley, Timothy R. Eason, Michael TI Determination of biogenic amines in Acacia rigidula and its dietary supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Pawar, Rahul S.; Grundel, Erich; Rader, Jeanne I.; Krynitsky, Alexander J.; Fardin-Kia, Ali Reza; Knolhoff, Ann M.; Croley, Timothy R.] US FDA, Off Regulatory Sci, College Pk, MD 20740 USA. [Eason, Michael] Lady Bird Johnson Wildflower Ctr, Austin, TX 78739 USA. EM Rahul.Pawar@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 107-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300101 ER PT J AU Shah, R Dejager, LS Begley, T AF Shah, Romina Dejager, Lowri S. Begley, Timothy TI Simultaneous determination of 12 sweeteners in foods using UPLC-MS-MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Shah, Romina; Dejager, Lowri S.; Begley, Timothy] US FDA, College Pk, MD 20740 USA. EM romina.shah@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 77-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300071 ER PT J AU Song, YS Koontz, J Juskelis, R Zhao, K AF Song, Yoon S. Koontz, John Juskelis, Rima Zhao, Kun TI Effect of high pressure processing on migration characteristics in flexible packaging materials SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Song, Yoon S.; Koontz, John] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Juskelis, Rima; Zhao, Kun] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. EM yoon.song@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 115-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300108 ER PT J AU Spiller, PC Mindak, WR Zink, D Fitzpatrick, S AF Spiller, Philip C. Mindak, William R. Zink, Donald Fitzpatrick, Suzanne TI Arsenic in rice and rice products: FDA activities SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Spiller, Philip C.; Mindak, William R.; Zink, Donald; Fitzpatrick, Suzanne] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM philip.spiller@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 246-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300223 ER PT J AU Stanford, TB Liu, HL Hart, ME AF Stanford, Taylor B. Liu, Huanli Hart, Mark E. TI Effect of spent media isolated from Lactobacillus plantarum WCFS1 on biofilm formation by Staphylococcus aureus SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Stanford, Taylor B.] Ouachita Baptist Univ, Dept Chem, Arkadelphia, AR 71998 USA. [Liu, Huanli; Hart, Mark E.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM sta46946@obu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 364-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851302177 ER PT J AU Thurmond, S AF Thurmond, Scott TI US Food and Drug Administration's (FDA) safety assessment of food ingredients SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Thurmond, Scott] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Scott.Thurmond@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 142-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300131 ER PT J AU Tulio, AZ Jablonski, JE Jackson, LS AF Tulio, Artemio Z., Jr. Jablonski, Joseph E. Jackson, Lauren S. TI Rapid screening of flavonoids and organic acids in adulterated fruit juices using Exactive Orbitrap with SIEVE 2.0 SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Tulio, Artemio Z., Jr.; Jablonski, Joseph E.; Jackson, Lauren S.] US FDA, Ctr Food Safety & Appl Nutr, Bedford Pk, IL 60501 USA. EM artemio.tulio@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 81-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300075 ER PT J AU Tyburczy, C Rader, JI AF Tyburczy, Cynthia Rader, Jeanne I. TI Use of the 200 m SLB-IL111 gas chromatographic column for the quantitation of long chain polyunsaturated fatty acids in dietary supplements containing marine oils SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Tyburczy, Cynthia; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM cynthia.tyburczy@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 104-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300098 ER PT J AU Uplekar, SD Kuang, Z Brorson, KA LaCourse, WR Moreira, AR Rao, G AF Uplekar, Shaunak D. Kuang, Zheng Brorson, Kurt A. LaCourse, William R. Moreira, Antonio R. Rao, Govind TI pCO(2) profiles of cell culture for monoclonal antibody production in minibioreactors vs. bench scale bioreactors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Uplekar, Shaunak D.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem Biochem & Environm Engn, Baltimore, MD 21250 USA. [Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [LaCourse, William R.] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. [Kuang, Zheng] Johns Hopkins Univ, Dept Mol Biol & Genet, Sch Med, Baltimore, MD 21205 USA. EM shaunak1@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 196-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851301039 ER PT J AU Vaclavik, L Krynitsky, A Rader, JI AF Vaclavik, Lukas Krynitsky, Alexander Rader, Jeanne I. TI Application of ultra-high liquid chromatography-mass spectrometry (UHPLC-MS) for authenticity and safety control of dietary supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Vaclavik, Lukas; Krynitsky, Alexander; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Lukas.Vaclavik@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 79-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300073 ER PT J AU Vaclavikova, M Begley, T AF Vaclavikova, Marta Begley, Timothy TI LC-MS based analytical strategies for determination of mycotoxins in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Vaclavikova, Marta; Begley, Timothy] US FDA, Off Regulatory Sci, Div Analyt Chem, CFSAN, College Pk, MD 20740 USA. EM marta.vaclavikova@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 83-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851300077 ER PT J AU Xu, M Fu, TJ AF Xu, Meng Fu, Tong-Jen TI Approaches to quantify and compare the thermal stability of food allergens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 245th National Meeting of the American-Chemical-Society (ACS) CY APR 07-11, 2013 CL New Orleans, LA SP Amer Chem Soc C1 [Xu, Meng] IIT, Inst Food Safety & Hlth, Beddord Pk, IL 60501 USA. [Fu, Tong-Jen] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL 60501 USA. EM mxu9@hawk.iit.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2013 VL 245 MA 310-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 210RD UT WOS:000323851301141 ER PT J AU Southworth, MR Reichman, ME Unger, EF AF Southworth, Mary Ross Reichman, Marsha E. Unger, Ellis F. TI Dabigatran and Postmarketing Reports of Bleeding SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Southworth, Mary Ross; Reichman, Marsha E.; Unger, Ellis F.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Southworth, MR (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 4 TC 194 Z9 201 U1 0 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 4 PY 2013 VL 368 IS 14 BP 1272 EP 1274 DI 10.1056/NEJMp1302834 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 117YT UT WOS:000316989900002 PM 23484796 ER PT J AU Fiuza, JA Santiago, HD Selvapandiyan, A Gannavaram, S Ricci, ND Bueno, LL Bartholomeu, DC Correa-Oliveira, R Nakhasi, HL Fujiwara, RT AF Fiuza, Jacqueline Araujo Santiago, Helton da Costa Selvapandiyan, Angamuthu Gannavaram, Sreenivas Ricci, Natasha Delaqua Bueno, Lilian Lacerda Bartholomeu, Daniella Castanheira Correa-Oliveira, Rodrigo Nakhasi, Hira Lal Fujiwara, Ricardo Toshio TI Induction of immunogenicity by live attenuated Leishmania donovani centrin deleted parasites in dogs SO VACCINE LA English DT Article DE Canine visceral leishmaniasis; Vaccine; Attenuated parasite ID CANINE VISCERAL LEISHMANIASIS; CD4+ T-CELLS; PROTECTIVE IMMUNITY; SAPONIN ADJUVANT; GAMMA PRODUCTION; VACCINE; INFANTUM; CHAGASI; BRAZIL; PROMASTIGOTES AB Zoonotic visceral leishmaniasis, caused by the intracellular protozoan parasite Leishmania infantum, is a neglected tropical disease that is often fatal when untreated. Dogs are considered the main reservoir of L. infantum in zoonotic VL as the presence of infected dogs may increase the risk for human infection. Canine visceral leishmaniasis (CVL) is a major veterinary and public health problem in Southern Europe, Middle East and South America. Control of animal reservoirs relies on elimination of seropositive dogs in endemic areas. However, treatment of infected dogs is not considered a favorable approach as this can lead to emergence of drug resistance since the same drugs are used to treat human infections. Therefore, vaccination against CVL remains the best alternative in control of the animal reservoirs. In this study, we present data on the immunogenicity profile of a live attenuated parasite LdCen(-/-) in a canine infection model and compared it to that of Leishmune (R), a commercially available recombinant vaccine. The immunogenicity of the LdCen(-/-) parasites was evaluated by antibody secretion, production of intracytoplasmic and secreted cytokines, activation and proliferation of T cells. Vaccination with LdCen(-/-) resulted in high immunogenicity as revealed by the higher IgGTotal, IgG1, and IgG2 production and higher lympho-proliferative response. Further, LdCen(-/-) vaccinated dogs showed higher frequencies of activated CD4+ and CD8+ T cells, IFN-gamma production by CD8+ T cells, increased secretion of TNF-alpha and IL-12/IL-23p40 and decreased secretion of IL-4. These results contribute to the understanding of immunogenicity elicited by live attenuated L. donovani parasites and, consequently, to the development of effective vaccines against visceral leishmaniasis. (C) 2013 Elsevier Ltd. All rights reserved. C1 [Fiuza, Jacqueline Araujo; Correa-Oliveira, Rodrigo; Fujiwara, Ricardo Toshio] Fundacao Oswaldo Cruz, Lab Cellular & Mol Immunol, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil. [Fiuza, Jacqueline Araujo; Ricci, Natasha Delaqua; Bueno, Lilian Lacerda; Bartholomeu, Daniella Castanheira; Fujiwara, Ricardo Toshio] Univ Fed Minas Gerais, Dept Parasitol, Belo Horizonte, MG, Brazil. [Fiuza, Jacqueline Araujo; Gannavaram, Sreenivas; Nakhasi, Hira Lal] US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Santiago, Helton da Costa] Univ Fed Minas Gerais, Dept Biochem & Immunol, Belo Horizonte, MG, Brazil. [Selvapandiyan, Angamuthu] Inst Mol Med, New Delhi 110020, India. RP Fujiwara, RT (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Lab Imunol & Genom Parasitos, Dept Parasitol, Setor E4,Sala 167, Belo Horizonte, MG, Brazil. EM fujiwara@icb.ufmg.br RI Santiago, Helton/F-8704-2012; Bartholomeu, Daniella/J-4714-2015; Fujiwara, Ricardo/J-7579-2012 OI Santiago, Helton/0000-0002-5695-8256; Bartholomeu, Daniella/0000-0003-0974-7357; Fujiwara, Ricardo/0000-0002-4713-575X FU Fundacao de Amparo a Pesquisa do Estado de Minas Gerais/FAPEMIG [CBB APQ-01202-09, PPM-00296-11]; Brazilian National Research Council (CNPq); Programa PAPES V/FIOCRUZ; Centro de Pesquisas Rene Rachou (CPqRR/FIOCRUZ); Pro-Reitoria de Pesquisa/Universidade Federal de Minas Gerais; CBER; CNPq FX We thank Michele Silva de Matos, Weder Gomes de Oliveira, Jefferson Bernardes and Virgilio Gandra Martins for the technical support. This work was financially supported by Fundacao de Amparo a Pesquisa do Estado de Minas Gerais/FAPEMIG (Grant#CBB APQ-01202-09 and PPM-00296-11], Brazilian National Research Council (CNPq), Programa PAPES V/FIOCRUZ, Centro de Pesquisas Rene Rachou (CPqRR/FIOCRUZ) and Pro-Reitoria de Pesquisa/Universidade Federal de Minas Gerais and by CBER intramural funds. JAF, RCO, DB and RTF are supported by CNPq fellowships. The authors would like also to thank Dr. Robert Duncan and Dr. Ranadhir Dey for internal review of the paper. NR 54 TC 22 Z9 22 U1 1 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 3 PY 2013 VL 31 IS 14 BP 1785 EP 1792 DI 10.1016/j.vaccine.2013.01.048 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 124FW UT WOS:000317450200005 PM 23398933 ER PT J AU Marder, E Kirschke, D Robbins, D Dunn, J Jones, TF Racoosin, J Paulozzi, L Chang, A AF Marder, Ellyn Kirschke, David Robbins, Donna Dunn, John Jones, Timothy F. Racoosin, Judy Paulozzi, Leonard Chang, Art TI Thrombotic Thrombocytopenic Purpura (TTP)-Like Illness Associated With Intravenous Opana ER Abuse-Tennessee, 2012 (Reprinted from MMWR, vol 1, pg 1-4, 2013) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID ADAMTS13 C1 [Marder, Ellyn; Kirschke, David; Robbins, Donna; Dunn, John; Jones, Timothy F.] Tennessee Dept Hlth, Nashville, TN USA. [Racoosin, Judy] US FDA, Div Anesthesia Analgesia & Addict Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Paulozzi, Leonard] CDC, Div Unintent Injury Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA 30333 USA. [Chang, Art] CDC, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Kirschke, D (reprint author), Tennessee Dept Hlth, Nashville, TN USA. EM david.kirschke@tn.gov NR 10 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 3 PY 2013 VL 309 IS 13 BP 1338 EP 1340 DI 10.1001/jama.2013.357 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 117EC UT WOS:000316934500008 ER PT J AU Lee, JH Park, S Hyun, H Bordo, MW Oketokoun, R Nasr, KA Frangioni, JV Choi, HS AF Lee, Jeong Heon Park, Sunny Hyun, Hoon Bordo, Mark W. Oketokoun, Rafiou Nasr, Khaled A. Frangioni, John V. Choi, Hak Soo TI High-Throughput Screening of Small Molecule Ligands Targeted to Live Bacteria Surface SO ANALYTICAL CHEMISTRY LA English DT Article ID DECONVOLUTION MICROSCOPY; IDENTIFICATION; ASSAYS AB The discovery of small molecule ligands targeted to the surface of live pathogenic bacteria would enable an entirely new class of antibiotics. We report the development and validation of a microarray-based high-throughput screening platform for bacteria that exploits 300 mu m diameter chemical spots in a 1 in. x 3 in. nanolayered glass slide format. Using 24 model compounds and 4 different bacterial strains, we optimized the screening technology, including fluorophore-based optical deconvolution for automated scoring of affinity and cyan-magenta-yellow-key (CMYK) color-coding for scoring of both affinity and specificity. The latter provides a lossless, one-dimensional view of multidimensional data. By linking in silico analysis with cell binding affinity and specificity, we could also begin to identify the physicochemical factors that affect ligand performance. The technology we describe could form the foundation for developing new classes of antibiotics. C1 [Lee, Jeong Heon; Hyun, Hoon; Bordo, Mark W.; Oketokoun, Rafiou; Frangioni, John V.; Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Robot Chem Grp, Ctr Mol Imaging, Boston, MA 02215 USA. [Lee, Jeong Heon; Hyun, Hoon; Bordo, Mark W.; Oketokoun, Rafiou; Frangioni, John V.; Choi, Hak Soo] Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol Oncol, Boston, MA 02215 USA. [Frangioni, John V.] Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. [Park, Sunny] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nasr, Khaled A.] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA. RP Choi, HS (reprint author), BIDMC, Room SL-436A,330 Brookline Ave, Boston, MA 02215 USA. EM jfrangio@bidmc.harvard.edu; hchoi@bidmc.harvard.edu RI Choi, Hak Soo/C-9954-2011 FU Nehemias Gorin Foundation; National Institutes of Health; NCI BRP [R01-CA-115296]; NIBIB [R01-EB-010022, R01-EB-011523]; Dana Foundation Program in Brain and Immuno-Imaging FX We thank Alex Allardyce (ChemAxon, Budapest, Hungary), Marsha Paul (Caliper LS, Hopkinton, MA), Brian Stall (Bruker Daltonics, Billerica, MA), Rene Schena (ArrayIt Corp., Sunnyvale, CA), Colin Johnson (LAE Technologies, Barrie, Canada), and Yangsun Kim (HST, Newark, NJ) for technical support and many helpful discussions. We thank David Burrington, Jr. for editing and Eugenia Trabucchi for administrative assistance. This study was supported by a grant from the Nehemias Gorin Foundation and the following grants from the National Institutes of Health, NCI BRP grant #R01-CA-115296 (JVF), NIBIB grant #R01-EB-010022 (J.V.F. and H.S.C.), and NIBIB grant #R01-EB-011523 (H.S.C. and J.V.F.), and the Dana Foundation Program in Brain and Immuno-Imaging (H.S.C.). NR 22 TC 8 Z9 8 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 2 PY 2013 VL 85 IS 7 BP 3508 EP 3514 DI 10.1021/ac303199x PG 7 WC Chemistry, Analytical SC Chemistry GA 120MA UT WOS:000317173200010 PM 23461528 ER PT J AU Nelson, DE Jarman, DW Rehm, J Greenfield, TK Rey, G Kerr, WC Miller, P Shield, KD Ye, Y Naimi, TS AF Nelson, David E. Jarman, Dwayne W. Rehm, Juergen Greenfield, Thomas K. Rey, Gregoire Kerr, William C. Miller, Paige Shield, Kevin D. Ye, Yu Naimi, Timothy S. TI Alcohol-Attributable Cancer Deaths and Years of Potential Life Lost in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID CARDIOVASCULAR RISK-FACTORS; EPITHELIAL OVARIAN-CANCER; TELEPHONE SURVEY; BREAST-CANCER; METHODOLOGICAL ISSUES; ENDOMETRIAL CANCER; NONRESPONSE BIAS; PROSTATE-CANCER; POOLED ANALYSIS; RESPONSE RATES AB Objectives. Our goal was to provide current estimates of alcohol-attributable cancer mortality and years of potential life lost (YPLL) in the United States. Methods. We used 2 methods to calculate population-attributable fractions. We based relative risks on meta-analyses published since 2000, and adult alcohol consumption on data from the 2009 Alcohol Epidemiologic Data System, 2009 Behavioral Risk Factor Surveillance System, and 2009-2010 National Alcohol Survey. Results. Alcohol consumption resulted in an estimated 18 200 to 21 300 cancer deaths, or 3.2% to 3.7% of all US cancer deaths. The majority of alcohol-attributable female cancer deaths were from breast cancer (56% to 66%), whereas upper airway and esophageal cancer deaths were more common among men (53% to 71%). Alcohol-attributable cancers resulted in 17.0 to 19.1 YPLL for each death. Daily consumption of up to 20 grams of alcohol (<= 1.5 drinks) accounted for 26% to 35% of alcohol-attributable cancer deaths. Conclusions. Alcohol remains a major contributor to cancer mortality and YPLL. Higher consumption increases risk but there is no safe threshold for alcohol and cancer risk. Reducing alcohol consumption is an important and underemphasized cancer prevention strategy. C1 [Nelson, David E.; Miller, Paige] NCI, Bethesda, MD 20892 USA. [Jarman, Dwayne W.] US FDA, Detroit, MI USA. [Jarman, Dwayne W.] US PHS, Rockville, MD USA. [Rehm, Juergen; Shield, Kevin D.] Ctr Addict & Mental Hlth, Toronto, ON, Canada. [Greenfield, Thomas K.; Kerr, William C.; Ye, Yu] Inst Publ Hlth, Alcohol Res Grp, Emeryville, CA USA. [Rey, Gregoire] CepiDc, INSERM, Le Kremlin Bicetre, France. [Naimi, Timothy S.] Boston Univ, Med Ctr, Boston, MA USA. RP Nelson, DE (reprint author), 6120 Execut Blvd,Suite 150E, Bethesda, MD 20892 USA. EM nelsonde@mail.nih.gov OI /0000-0002-3108-4812 FU National Institute on Alcohol Abuse and Alcoholism(NIAAA Center) [P50 AA005595]; NIAAA [RO1-AA018377] FX Funding for the National Alcohol Survey and for T. K. Greenfield, W. C. Kerr, and Y. Ye was supported by the National Institute on Alcohol Abuse and Alcoholism(NIAAA Center grant P50 AA005595). T. S. Naimi's research was supported in part by NIAAA grant RO1-AA018377. NR 112 TC 62 Z9 62 U1 1 U2 17 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 EI 1541-0048 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2013 VL 103 IS 4 BP 641 EP 648 DI 10.2105/AJPH.2012.301199 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA AA0DU UT WOS:000330766100031 PM 23409916 ER PT J AU Keasling, AW Otter, RR Bailey, FC AF Keasling, A. W. Otter, R. R. Bailey, F. C. TI Phytotoxicity of Passiflora incarnata extracts on germination and growth of Hordeum vulgare and Raphanus sativus SO ALLELOPATHY JOURNAL LA English DT Article DE Barley; germination; isoschaftoside; lucenin-2; palmitic acid; Passiflora incarnata; Passionflower; radish; saponarin; vitexin ID NATURAL-PRODUCTS; HERBICIDE; PLANTS; L. AB Phytotoxic chemicals are of interest because they represent potentially novel pharmacophores possessing herbicidal activity that may target new molecular receptor sites. This study aimed to evaluate the phytotoxic activity of Passiflora incarnata extracts against the monocotyledonous and dicotyledonous indicator test species barley and radish. Continuous exposure to total aqueous extracts of P. incarnata inhibited the barley germination at the lowest tested concentration (1.25% w/v), whereas 10% w/v concentration was required for radish. Aqueous fractions from sequential-solvent partitioning showed reduced seed germination inhibitory activity in both test species relative to total aqueous extracts. A 14-day growth assay showed that 24 h pre-/post-germination exposure to total aqueous extracts had no effect on dry weights of either species. However, 47% leaf-bleaching was observed in the 24 h post-germination exposure in barley. GC-MS analysis of solvent extracts identified phytol and palmitic acid as the major components. LC-ESI-MS/MS analysis of aqueous fractions tentatively identified ten compounds: phenylalanine, leucine, and tryptophan, swertisin, vitexin, saponarin, isoschaftoside, orientin, lucenin-2, and eugenol. C1 [Keasling, A. W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Keasling, A. W.; Otter, R. R.; Bailey, F. C.] Middle Tennessee State Univ, Coll Basic & Appl Sci, Dept Biol, Murfreesboro, TN 37132 USA. RP Keasling, AW (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM awk2g@mtmail.mtsu.edu NR 21 TC 0 Z9 0 U1 3 U2 11 PU ALLELOPATHY JOURNAL PI ROHTAK PA INTERNATIONAL ALLELOPATHY FOUNDATION, 101, SECTOR 14, ROHTAK 124 001, HARYANA, INDIA SN 0971-4693 J9 ALLELOPATHY J JI Allelopathy J. PD APR PY 2013 VL 31 IS 2 BP 319 EP 331 PG 13 WC Agronomy SC Agriculture GA 221TY UT WOS:000324683600005 ER PT J AU Sulaiman, IM Torres, P Simpson, S Kerdahi, K Ortega, Y AF Sulaiman, Irshad M. Torres, Patricia Simpson, Steven Kerdahi, Khalil Ortega, Ynes TI Sequence Characterization of Heat Shock Protein Gene of Cyclospora cayetanensis Isolates from Nepal, Mexico, and Peru SO JOURNAL OF PARASITOLOGY LA English DT Article ID CYANOBACTERIUM-LIKE BODIES; MOLECULAR CHARACTERIZATION; CRYPTOSPORIDIUM PARASITES; BABESIA-GIBSONI; SP APICOMPLEXA; HSP70 GENE; HEAT-SHOCK-PROTEIN-70; ORGANISMS; PHYLOGENY; FAMILY AB We have described the development of a 2-step nested PCR protocol based on the characterization of the 70-kDa heat shock protein (HSP70) gene for rapid detection of the human-pathogenic Cyclospora cayetanensis parasite. We tested and validated these newly designed primer sets by PCR amplification followed by nucleotide sequencing of PCR-amplified HSP70 fragments belonging to 16 human C. cayetanensis isolates from 3 different endemic regions that include Nepal, Mexico, and Peru. No genetic polymorphism was observed among the isolates at the characterized regions of the HSP70 locus. This newly developed HSP70 gene-based nested PCR protocol provides another useful genetic marker for the rapid detection of C. cayetanensis in the future. C1 [Sulaiman, Irshad M.; Simpson, Steven; Kerdahi, Khalil] US FDA, Microbiol Sci Branch, Southeast Reg Lab, Atlanta, GA 30309 USA. [Torres, Patricia; Ortega, Ynes] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. RP Sulaiman, IM (reprint author), US FDA, Microbiol Sci Branch, Southeast Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM irshad.sulaiman@fda.hhs.gov FU Division of Field Sciences of FDA FX The findings and conclusions in this report are those of the authors and do not necessarily represent the views or official position of the FDA. The names of vendors or manufacturers are provided as examples of available product sources; inclusion does not imply endorsement of the vendors, manufacturers, or products by the FDA or the U.S. Department of Health and Human Services. This study was supported in part by funding from the Division of Field Sciences of FDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 6 Z9 7 U1 0 U2 1 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 2013 VL 99 IS 2 BP 379 EP 382 DI 10.1645/GE-3114.1 PG 4 WC Parasitology SC Parasitology GA 192XH UT WOS:000322520700036 PM 22924935 ER PT J AU Coleman, CN Blumenthal, DJ Casto, CA Alfant, M Simon, SL Remick, AL Gepford, HJ Bowman, T Telfer, JL Blumenthal, PM Noska, MA AF Coleman, C. Norman Blumenthal, Daniel J. Casto, Charles A. Alfant, Michael Simon, Steven L. Remick, Alan L. Gepford, Heather J. Bowman, Thomas Telfer, Jana L. Blumenthal, Pamela M. Noska, Michael A. TI Recovery and Resilience After a Nuclear Power Plant Disaster: A Medical Decision Model for Managing an Effective, Timely, and Balanced Response SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Article DE nuclear power plant; disaster resilience; disaster recovery; medical decision model ID CANCER-RISKS; HEALTH; JAPAN; FALLOUT AB Resilience after a nuclear power plant or other radiation emergency requires response and recovery activities that are appropriately safe, timely, effective, and well organized. Timely informed decisions must be made, and the logic behind them communicated during the evolution of the incident before the final outcome is known. Based on our experiences in Tokyo responding to the Fukushima Daiichi nuclear power plant crisis, we propose a real-time, medical decision model by which to make key health-related decisions that are central drivers to the overall incident management. Using this approach, on-site decision makers empowered to make interim decisions can act without undue delay using readily available and high-level scientific, medical, communication, and policy expertise. Ongoing assessment, consultation, and adaption to the changing conditions and additional information are additional key features. Given the central role of health and medical issues in all disasters, we propose that this medical decision model, which is compatible with the existing US National Response Framework structure, be considered for effective management of complex, large-scale, and large-consequence incidents. C1 [Coleman, C. Norman] NCI, Off Assistant Secretary Preparedness & Response, Radiat Res Program, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Blumenthal, Daniel J.; Remick, Alan L.] Natl Nucl Secur Adm, Dept Energy, Washington, DC USA. [Casto, Charles A.; Gepford, Heather J.] Nucl Regulatory Commiss, Rockville, MD USA. [Alfant, Michael] Amer Chamber Commerce Japan, Tokyo, Japan. [Bowman, Thomas] Ctr Dis Control & Prevent, Div Strateg Natl Stockpile, Atlanta, GA USA. [Telfer, Jana L.] Ctr Dis Control & Prevent, Agcy Tox Subst & Dis Registry, Atlanta, GA USA. [Blumenthal, Pamela M.] Dept Housing & Urban Dev, Washington, DC USA. [Noska, Michael A.] US FDA, Silver Spring, MD USA. RP Coleman, CN (reprint author), 9609 Med Ctr Dr,Room 3W102, Rockville, MD 20850 USA. EM ccoleman@mail.nih.gov NR 33 TC 3 Z9 3 U1 0 U2 23 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD APR PY 2013 VL 7 IS 2 BP 136 EP 145 DI 10.1017/dmp.2013.5 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 200AF UT WOS:000323037100009 PM 24618164 ER PT J AU Manson, JC Bishop, M Diack, AB Ritchie, D McCutcheon, S Blanco, RA Piccardo, P Ironside, J Will, R AF Manson, Jean C. Bishop, Matthew Diack, Abigail B. Ritchie, Diane McCutcheon, Sandra Blanco, Richard Alejo Piccardo, Pedro Ironside, James Will, Robert TI Variant CJD 17 years on SO PRION LA English DT Meeting Abstract C1 [Bishop, Matthew; Ritchie, Diane; Ironside, James; Will, Robert] Univ Edinburgh, Natl CJD Res & Surveillance Unit, Edinburgh, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 5 TC 0 Z9 0 U1 0 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-MAY PY 2013 VL 7 SU S BP 14 EP 14 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202LL UT WOS:000323217500033 ER PT J AU Cervenakova, L Yakovleva, O Vasilyeva, I De Castro, J Saa, P Kelleher-Andersson, J Piccardo, P AF Cervenakova, Larisa Yakovleva, Oksana Vasilyeva, Irina De Castro, Jorge Saa, Paula Kelleher-Andersson, Judith Piccardo, Pedro TI Addressing the transmissible spongiform encephalopathy TSE) infection in mice with a disrupted receptor-associated protein (RAP) gene SO PRION LA English DT Meeting Abstract C1 [Cervenakova, Larisa; Yakovleva, Oksana; Vasilyeva, Irina; De Castro, Jorge; Saa, Paula] Amer Red Cross, Holland Lab, Rockville, MD USA. [Kelleher-Andersson, Judith] Neuronascent Inc, Clarksville, MD USA. [Piccardo, Pedro] OBRR CBER FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-MAY PY 2013 VL 7 SU S BP 30 EP 30 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202LL UT WOS:000323217500067 ER PT J AU Diack, AB Cancellotti, E Mahal, S Somerville, R Brown, D Piccardo, P Weissmann, C Manson, JC AF Diack, Abigail B. Cancellotti, Enrico Mahal, Sukhvir Somerville, Robert Brown, Deborah Piccardo, Pedro Weissmann, Charles Manson, Jean C. TI Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties SO PRION LA English DT Meeting Abstract C1 [Diack, Abigail B.; Cancellotti, Enrico; Somerville, Robert; Brown, Deborah; Piccardo, Pedro; Manson, Jean C.] Roslin Inst, Easter Bush, England. [Diack, Abigail B.; Cancellotti, Enrico; Somerville, Robert; Brown, Deborah; Piccardo, Pedro; Manson, Jean C.] R D SVS, Easter Bush, England. [Mahal, Sukhvir; Weissmann, Charles] Scripps Florida, Dept Infectol, Jupiter, FL USA. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 J9 PRION JI Prion PD APR-MAY PY 2013 VL 7 SU S BP 85 EP 85 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 202LL UT WOS:000323217500193 ER PT J AU Ding, HL Fu, TJ Smith, MA AF Ding, Hongliu Fu, Tong-Jen Smith, Michelle A. TI Microbial Contamination in Sprouts: How Effective Is Seed Disinfection Treatment? SO JOURNAL OF FOOD SCIENCE LA English DT Article DE alfalfa; Escherichia coli O157: H7; food safety; pathogens; Salmonella; sprouts ID ESCHERICHIA-COLI O157-H7; MUNG BEAN-SEEDS; HIGH HYDROSTATIC-PRESSURE; ACIDIFIED SODIUM-CHLORITE; ALFALFA SEEDS; RADISH SEEDS; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; CHEMICAL TREATMENTS; KEEPING QUALITY AB Microbial contamination of sprouts by Salmonella and Escherichia coli O157 : H7 has been a common cause of foodborne diseases and a continuing challenge to the sprout industry. Seed disinfection treatment has been recommended as a major intervention step in a multihurdle approach to reduce the risk of illness associated with contaminated sprouts. U. S. Food and Drug Administration cited 20000 ppm calcium hypochlorite as an example treatment in its recommendation for seed treatment and this treatment has been considered the reference standard for seed disinfection treatment for over a decade. However, promising new disinfection treatments have emerged in recent years. In this study, we summarized published data and compared the efficacies of different disinfection methods in the reduction of microbial contamination on seeds. Our findings suggest that while biological interventions such as competitive exclusion and certain chemical treatments appear to be similar to 20000 ppm calcium hypochlorite for seed disinfection, physical methods especially high pressure may be more effective than the reference standard regardless of the type of bacteria or seed. The combination of 2 or more treatments, sequentially or simultaneously, may further improve disinfection results. Since treatments with high levels of chemical disinfectants, especially 20000 ppm calcium hypochlorite, can pose environmental and worker safety risks, alternative intervention approaches should be considered. Additional studies to confirm the greater efficacy of certain physical and combined seed disinfection treatments and to identify other effective management strategies are needed to further improve sprout safety. C1 [Ding, Hongliu] US FDA, Off Commissioner, Silver Spring, MD USA. [Ding, Hongliu; Fu, Tong-Jen] US FDA, Div Food Proc Sci & Technol, Bedford Pk, IL USA. [Smith, Michelle A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Ding, HL (reprint author), US FDA, Off Commissioner, Silver Spring, MD USA. EM Hongliu.Ding@fda.hhs.gov; Tongjen.Fu@fda.hhs.gov FU FDA Commissioner's Fellowship Program FX This work was supported by the FDA Commissioner's Fellowship Program. We thank Dr. Mary Lou Tortorello and Dr. Absar Alum for critically reading and editing this manuscript. NR 58 TC 15 Z9 17 U1 2 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD APR PY 2013 VL 78 IS 4 BP R495 EP R501 DI 10.1111/1750-3841.12064 PG 7 WC Food Science & Technology SC Food Science & Technology GA 167CT UT WOS:000320608900002 PM 23464679 ER PT J AU Singh, AK Sachdeva, A DeGrasse, JA Croley, TR Stanker, LH Hodge, D Sharma, SK AF Singh, Ajay K. Sachdeva, Amita DeGrasse, Jeffrey A. Croley, Timothy R. Stanker, Larry H. Hodge, David Sharma, Shashi K. TI Purification and Characterization of Neurotoxin Complex from a Dual Toxin Gene Containing Clostridium Botulinum Strain PS-5 SO PROTEIN JOURNAL LA English DT Article DE Botulism; Neurotoxin complex; Neurotoxin associated proteins; PCR; ELISA; Western blot; Endopeptidase activity ID INFANT BOTULISM; A(B) STRAINS; HA PROTEINS; SUBTYPE A5; HEMAGGLUTININ; EXPRESSION; PCR; ABSORPTION; DIVERSITY; COMPONENT AB Botulinum neurotoxins are produced as a toxin complex (TC) which consists of neurotoxin (NT) and neurotoxin associated proteins. The characterization of NT in its native state is an essential step for developing diagnostics and therapeutic countermeasures against botulism. The presence of NT genes was validated by PCR amplification of toxin specific fragments from genomic DNA of Clostridium botulinum strain PS-5 which indicated the presence of both serotype A and B genes on PS-5 genome. Further, TC was purified and characterized by Western blotting, Digoxin-enzyme linked immunosorbent assay, endopeptidase activity assay, and Liquid chromatography-Mass spectrometry. The data showed the presence of serotype A specific neurotoxin. Based on the analysis of neurotoxin genes and characterization of TC, PS-5 strain appears as a serotype A (B) strain of C. botulinum which produces only serotype A specific TC in the cell culture medium. C1 [Singh, Ajay K.; Sachdeva, Amita; Sharma, Shashi K.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [DeGrasse, Jeffrey A.; Croley, Timothy R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Stanker, Larry H.] ARS, Western Reg Res Ctr, USDA, Albany, CA 94170 USA. [Hodge, David] Dept Homeland Secur, Washington, DC 20528 USA. RP Singh, AK (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM ajay.singh@fda.hhs.gov; shashi.sharma@fda.hhs.gov RI DeGrasse, Jeffrey/J-1151-2014 OI DeGrasse, Jeffrey/0000-0003-3178-6301 FU Department of Homeland Security through Inter Agency Grant FX Authors thank Dr. Eric W. Brown for valuable discussions and advice. This work was supported by the Department of Homeland Security through Inter Agency Grant. The views or opinions presented in this article are those of the authors and should not be construed as an official view of the U.S. Food and Drug Administration. NR 41 TC 0 Z9 0 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1572-3887 EI 1573-4943 J9 PROTEIN J JI Protein J. PD APR PY 2013 VL 32 IS 4 BP 288 EP 296 DI 10.1007/s10930-013-9486-1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 180UV UT WOS:000321625200007 PM 23625059 ER PT J AU Wang, YP Lin, Z Liu, ZC Harris, S Kelly, R Zhang, J Ge, WG Chen, MJ Borlak, J Tong, WD AF Wang, Yuping Lin, Zhi Liu, Zhichao Harris, Stephen Kelly, Reagan Zhang, Jie Ge, Weigong Chen, Minjun Borlak, Juergen Tong, Weida TI A Unifying Ontology to Integrate Histological and Clinical Observations for Drug-Induced Liver Injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID AUTOIMMUNE HEPATITIS; DISEASE ONTOLOGY; ADVERSE EVENTS; FAILURE; HEPATOTOXICITY; NEVIRAPINE; FEATURES; DANAZOL; BIOPSY; TRANSPLANTATION AB Drug-induced liver injury (DILI) may present any morphologic characteristic of acute or chronic Liver disease with no standardized terminology in place. Defining Lexemes of DILI histopathology would allow the development of advanced knowledge discovery and data mining tools for across comparisons of publicly available information. For these purposes, a DILI ontology (DILIo) was developed by using the Unified Medical Language System tool and the standardized terminology of the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). The DILIo was entrained on findings of 114 US Food and Drug Administration approved drugs by extracting all clinically DILI-related histopathologic descriptions for 1082 liver biopsy samples, which were then analyzed using the Unified Medical Language System MetaMap and subsequently mapped to the SNOMED CT. The DILIo provides a standard means to describe and organize Liver injury induced by drugs, enabling comparative analysis of drugs within and across histopathologic terms. The analysis showed that flutamide, troglitazone, diclofenac, isoniazid, and tamoxifen were reported to have the most diverse histopathologic observations in liver biopsy. Necrosis, cholestasis, fatty degeneration, fibrosis, infiltrate, and hepatic necrosis were the most frequent terms used as descriptors of histopathologic features of DILI. In conclusion, DILI entrains different algorithms for an efficient meta-analysis of published findings for an improved understanding of mechanisms and clinical characteristics of DILI. C1 [Wang, Yuping; Lin, Zhi; Liu, Zhichao; Harris, Stephen; Kelly, Reagan; Zhang, Jie; Ge, Weigong; Chen, Minjun; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Bioinformat, Jefferson, AR 72079 USA. [Wang, Yuping; Lin, Zhi; Liu, Zhichao; Harris, Stephen; Kelly, Reagan; Zhang, Jie; Ge, Weigong; Chen, Minjun; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Biostat, Jefferson, AR 72079 USA. [Lin, Zhi] Natl Inst Food & Drug Control, Natl Ctr Safety Evaluat Drugs, Beijing, Peoples R China. [Borlak, Juergen] Hannover Med Sch, Ctr Pharmacol & Toxicol, Hannover, Germany. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Liu, Zhichao/C-4035-2011 FU FDA's Office of International Programs; FDA's Critical Path Initiative; Office of Women's Health; Chief Scientist Challenge grant; German Federal Ministry for Education and Research Virtual Liver Network initiative [031 6154]; ORISE Stipend of the FDA FX Z. Lin works at the National Center for Toxicological Research through the International Scientist Exchange Program sponsored by the FDA's Office of International Programs. The LTKB project is supported by the FDA's Critical Path Initiative, the Office of Women's Health, and a Chief Scientist Challenge grant. J.B. is supported by the German Federal Ministry for Education and Research Virtual Liver Network initiative (grant 031 6154) and is a recipient of an ORISE Stipend of the FDA. NR 46 TC 3 Z9 4 U1 1 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2013 VL 182 IS 4 BP 1180 EP 1187 DI 10.1016/j.ajpath.2012.12.033 PG 8 WC Pathology SC Pathology GA 165NY UT WOS:000320491800017 PM 23395088 ER PT J AU Andrews, KW Roseland, JM Middleton, A Solomon, A Palachuvattil, J Dang, PT Holden, JM Pehrsson, PR Dwyer, JT Bailey, RL Betz, JM Costello, RB Saldanha, LG Hardy, CJ Gahche, JJ Emenaker, NJ Douglass, L AF Andrews, K. W. Roseland, J. M. Middleton, A. Solomon, A. Palachuvattil, J. Dang, P. T. Holden, J. M. Pehrsson, P. R. Dwyer, J. T. Bailey, R. L. Betz, J. M. Costello, R. B. Saldanha, L. G. Hardy, C. J. Gahche, J. J. Emenaker, N. J. Douglass, L. TI Chemical analysis of omega-3 (n-3) fatty acid supplements for the Dietary Supplement Ingredient Database (DSID) SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Andrews, K. W.; Roseland, J. M.; Middleton, A.; Solomon, A.; Palachuvattil, J.; Dang, P. T.; Holden, J. M.; Pehrsson, P. R.] USDA, Nutrient Data Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. [Dwyer, J. T.; Bailey, R. L.; Betz, J. M.; Costello, R. B.; Saldanha, L. G.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Hardy, C. J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Gahche, J. J.] US Dept Hlth & Human Serv, Natl Ctr Hlth Stat, Ctr Dis Control, Hyattsville, MD USA. [Emenaker, N. J.] NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 242.8 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504129 ER PT J AU Dwyer, J Andrews, KW Bailey, RL Betz, JM Burt, VL Costello, RB Emenaker, NJ Gahche, JJ Hardy, CJ Pehrsson, PR Roseland, JM Saldanha, LG AF Dwyer, Johanna Andrews, Karen W. Bailey, Regan L. Betz, Joseph M. Burt, Vicki L. Costello, Rebecca B. Emenaker, Nancy J. Gahche, Jaime J. Hardy, Constance J. Pehrsson, Pamela R. Roseland, Janet M. Saldanha, Leila G. TI Progress in the Development of Federal Resources to Assess Dietary Supplement (DS) Exposures SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Dwyer, Johanna; Bailey, Regan L.; Betz, Joseph M.; Costello, Rebecca B.; Saldanha, Leila G.] ODS, NIH, Bethesda, MD USA. [Emenaker, Nancy J.] NCI, NIH, Bethesda, MD 20892 USA. [Andrews, Karen W.; Pehrsson, Pamela R.; Roseland, Janet M.] ARS, USDA, Beltsville, MD USA. [Burt, Vicki L.; Gahche, Jaime J.] CDC, NCHS, Hyattsville, MD USA. [Hardy, Constance J.] CFSAN, FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 242.3 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883503526 ER PT J AU He, G Zhang, W Chen, HZ Saliba, S Thorpe, C Rogers, E Hsie, SF AF He, Gui Zhang, Wei Chen, Huizhong Saliba, Sam Thorpe, Conner Rogers, Eugene Hsie, Shufeng TI Impacts of Silver Nanoparticles on Bacterial Multidrug Efflux Pump SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [He, Gui; Zhang, Wei; Saliba, Sam; Thorpe, Conner; Rogers, Eugene; Hsie, Shufeng] Univ Massachusetts, Lowell, MA USA. [Chen, Huizhong] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 575.12 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883504251 ER PT J AU Juan, WY Zhang, YT Kantor, M Ali, M AF Juan, WenYen Zhang, Yuanting Kantor, Mark Ali, Mir TI Perceptions and use of nutrition labeling information SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Juan, WenYen; Kantor, Mark] Ctr Food Safety & Appl Nutr, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Zhang, Yuanting] Ctr Food Safety & Appl Nutr, Off Analyt & Outreachietary Supplements, College Pk, MD USA. [Ali, Mir] US FDA, Off Regulat Policy & Social Sci, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1065.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860505378 ER PT J AU Knapton, A Herman, E Todd, J Estis, J Zhang, J AF Knapton, Alan Herman, Eugene Todd, John Estis, Joel Zhang, Jun TI An exploration of sunitinb-induced cardiotoxicity in male Sprague-Dawley rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Knapton, Alan; Herman, Eugene; Zhang, Jun] US FDA, Silver Spring, MD USA. [Todd, John; Estis, Joel] Singulex Inc, Alameda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 652.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883501633 ER PT J AU Kranz, S Dodd, K Juan, WY Johnson, LK Jahns, L AF Kranz, Sibylle Dodd, Kevin Juan, WenYen Johnson, Luann K. Jahns, Lisa TI Essential steps in the analysis of NHANES dietary data SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kranz, Sibylle] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Dodd, Kevin] NCI, Bethesda, MD 20892 USA. [Juan, WenYen] US FDA, College Pk, MD USA. [Johnson, Luann K.; Jahns, Lisa] USDA, Grand Forks, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 848.20 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505363 ER PT J AU Kranz, S Dodd, KW Juan, WY Johnson, LK AF Kranz, Sibylle Dodd, Kevin W. Juan, WenYen Johnson, LuAnn K. TI Comparison of main contributors to dietary fiber and whole grain in Americans' Diet: NHANES 2003-2010 SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Kranz, Sibylle] Purdue Univ, Dept Nutr Sci, W Lafayette, IN 47907 USA. [Dodd, Kevin W.] NCI, Rockville, MD USA. [Juan, WenYen] US FDA, College Pk, MD USA. [Johnson, LuAnn K.] USDA, Grand Forks, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 1065.11 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156YK UT WOS:000319860502609 ER PT J AU Noinaj, N Kuszak, A Gumbart, JC Lukacik, P Chang, HS Easley, N Lithgow, T Buchanan, SK AF Noinaj, Nicholas Kuszak, Adam Gumbart, J. C. Lukacik, Petra Chang, Hoshing Easley, Nicole Lithgow, Trevor Buchanan, Susan K. TI Structural insights into the role of BamA in the biogenesis of beta-barrel membrane proteins in Gram-negative bacteria SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP Amer Soc Pharmacol & Expt Therapeut (ASPET), British Pharmacol Soc (BPS), Amer Assoc Anatomists (AAA), Amer Physiol Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutr (ASN) C1 [Noinaj, Nicholas; Kuszak, Adam; Easley, Nicole; Buchanan, Susan K.] NIDDK, NIH, Bethesda, MD 20857 USA. [Gumbart, J. C.] Georgia Inst Technol, Atlanta, GA USA. [Lukacik, Petra] Diamond Light Source Ltd, Didcot, Oxon, England. [Chang, Hoshing] US FDA, Rockville, MD USA. [Lithgow, Trevor] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic, Australia. NR 0 TC 1 Z9 1 U1 0 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 APR PY 2013 VL 27 MA 1025.2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883500435 ER PT J AU Saldanha, LG Dwyer, JT Bailen, RA Chang, FF Andrews, KW Bailey, RL Betz, JM Burt, VL Costello, RB Emenaker, NJ Gahche, JJ Hardy, CJ Pehrsson, PR Roseland, JM AF Saldanha, Leila G. Dwyer, Johanna T. Bailen, Richard A. Chang, Florence F. Andrews, Karen W. Bailey, Regan L. Betz, Joseph M. Burt, Vicki L. Costello, Rebecca B. Emenaker, Nancy J. Gahche, Jaime J. Hardy, Constance J. Pehrsson, Pamela R. Roseland, Janet M. TI Dietary Supplement Label Database (DSLD) Will Capture Information from Dietary Supplement (DS) Labels SO FASEB JOURNAL LA English DT Meeting Abstract CT Joint Annual Meeting of the ASPET/BPS at Experimental Biology (EB) CY APR 20-24, 2013 CL Boston, MA SP ASPET, British Pharmacol Soc (BPS) C1 [Saldanha, Leila G.; Dwyer, Johanna T.; Bailen, Richard A.; Bailey, Regan L.; Betz, Joseph M.; Costello, Rebecca B.] NIH, ODS, Bethesda, MD 20892 USA. [Chang, Florence F.] NIH, Natl Lib Med, Bethesda, MD 20892 USA. [Emenaker, Nancy J.] NCI, NIH, Bethesda, MD 20892 USA. [Andrews, Karen W.; Pehrsson, Pamela R.; Roseland, Janet M.] ARS, USDA, Beltsville, MD USA. [Burt, Vicki L.; Gahche, Jaime J.] CDC, NCHS, Hyattsville, MD USA. [Hardy, Constance J.] US FDA, CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2013 VL 27 MA 848.1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157GG UT WOS:000319883505448 ER PT J AU Pacini, N Prearo, M Abete, MC Brizio, P Dorr, AJM Reimschuessel, R Andersen, W Gasco, L Righetti, M Elia, AC AF Pacini, Nicole Prearo, Marino Abete, Maria Cesarina Brizio, Paola Doerr, Ambrosius Josef Martin Reimschuessel, Renate Andersen, Wendy Gasco, Laura Righetti, Marzia Elia, Antonia Concetta TI Antioxidant Responses and Renal Crystal Formation in Rainbow Trout Treated with Melamine Administered Individually or in Combination with Cyanuric Acid SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID ONCORHYNCHUS-MYKISS; OXIDATIVE STRESS; DETOXIFYING RESPONSE; LIPID-PEROXIDATION; MASS-SPECTROMETRY; NRK-52E CELLS; ATRAZINE; GLUTATHIONE; TOXICITY; EXPOSURE AB In 2007 and 2008, renal stone formation and kidney damage in human infants were linked to consumption of melamine (MEL)-contaminated infant formula, as well as renal failure and death in pets due to pet food containing both MEL and cyanuric acid (CYA). The aim of this study was to examine the effects of MEL and CYA administered individually or in combination on concentrations of certain metabolites and enzyme activities that serve as markers for oxidative stress in kidney and liver of rainbow trout. In addition, the levels of muscle MEL and renal crystal formation were determined. Trout were fed MEL and/or CYA for 8 wk at 250, 500, or 1000 mg of each compound/kg in feed. Fish muscle residues of MEL exhibited a dose-response relationship. Coexposure of trout to MEL and CYA at the highest dose led to lower MEL residue concentrations in muscle compared to exposure to MEL alone. Renal MEL-CYA complexes were found in kidneys of fish treated with combined MEL and CYA. A dose response was evident with respect to both (1) number of trout displaying renal crystals and (2) number of crystals per fish. Changes in concentration of antioxidant parameters, such as glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase, were recorded in both tissues of MEL- and CYA-dosed trout. Lipid peroxidation was more pronounced in kidney than liver. Therefore, feed contaminated with both MEL and CYA could be problematic for fish, as MEL administered to trout, individually or in combination with CYA, may facilitate the onset of oxidative damage in trout. C1 [Pacini, Nicole; Doerr, Ambrosius Josef Martin; Elia, Antonia Concetta] Univ Perugia, Dept Cellular & Environm Biol, I-06123 Perugia, Italy. [Prearo, Marino; Righetti, Marzia] State Vet Inst, Fish Dis Lab, Turin, Italy. [Abete, Maria Cesarina; Brizio, Paola] State Vet Inst, CReAA, Natl Reference Ctr Surveillance & Monitoring Anim, Turin, Italy. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD USA. [Andersen, Wendy] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO USA. [Gasco, Laura] Univ Turin, Dept Zootech Sci, Turin, Italy. RP Elia, AC (reprint author), Univ Perugia, Dept Cellular & Environm Biol, I-06123 Perugia, Italy. EM elia@unipg.it RI Doerr, Ambrosius/G-9915-2014; Elia, Antonia/F-4646-2014; Abete, Maria Cesarina/J-8219-2016; OI Doerr, Ambrosius/0000-0002-2768-3783; Elia, Antonia/0000-0002-7750-6339; GASCO, Laura/0000-0002-1829-7936 FU Ministero della Salute (Ricerca Corrente, Italy) FX This study was financially supported by Ministero della Salute (Ricerca Corrente 2007, Italy). NR 57 TC 10 Z9 10 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 1 PY 2013 VL 76 IS 8 BP 491 EP 508 DI 10.1080/15287394.2013.785205 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 159YR UT WOS:000320083700002 PM 23721584 ER PT J AU Hart, ME Tsang, LH Deck, J Daily, ST Jones, RC Liu, HL Hu, HJ Hart, MJ Smeltzer, MS AF Hart, Mark E. Tsang, Laura H. Deck, Joanna Daily, Sonja T. Jones, Richard C. Liu, Huanli Hu, Haijing Hart, Morgan J. Smeltzer, Mark S. TI Hyaluronidase expression and biofilm involvement in Staphylococcus aureus UAMS-1 and its sarA, agr and sarA agr regulatory mutants SO MICROBIOLOGY-SGM LA English DT Article ID COMPLETE GENOME SEQUENCE; METHICILLIN-RESISTANT; CLOSTRIDIUM-PERFRINGENS; STREPTOCOCCUS-INTERMEDIUS; CHONDROITIN SULFATE; SIGMA(B) REGULON; GENE; VIRULENCE; GROWTH; LYASE AB In a previous study, two proteins identified as hyaluronidases were detected in spent media by MS and found to be in greater quantity in the sarA and sarA agr mutant strains when compared with the parent and agr mutant strains of Staphylococcus aureus UAMS-1. In the present study, spent media and total RNA were isolated from UAMS-1 and its regulatory mutants and analysed for hyaluronidase activity and steady-state hyaluronidase (hysA) RNA message levels. Hyaluronidase activity was observed throughout all time points examined regardless of the regulatory effects of sarA and agr but activity was always substantially higher in the sarA and sarA agr mutant strains than in the UAMS-1 parent and agr mutant strains. Northern analysis did not detect hysA message for either the UAMS-1 parent or the agr mutant strains at any time point examined, while steady-state hysA message levels were detected throughout growth for the sarA mutant strain, but only at exponential and early post-exponential growth for the sarA agr mutant strain. An in vitro biofilm plate assay, pre-coated with human plasma as a source of hyaluronic acid, demonstrated no significant increase in biofilm for a sarA mutant strain of S. aureus UAMS-1 defective in hyaluronidase activity when compared with the sarA mutant strain. These data indicate that, while hysA message levels and hyaluronidase activity are elevated in the sarA mutant strains of S. aureus UAMS-1, the increase in activity did not contribute to the biofilm-negative phenotype observed in the sarA mutant strain of S. aureus UAMS-1. C1 [Hart, Mark E.; Deck, Joanna; Liu, Huanli; Hu, Haijing] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Hart, Mark E.; Tsang, Laura H.; Daily, Sonja T.; Smeltzer, Mark S.] Univ Arkansas Med Sci, Dept Microbiol & Immunol, Little Rock, AR 72205 USA. [Jones, Richard C.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hart, Morgan J.] Ouachita Baptist Univ, Dept Biol, Arkadelphia, AR 71998 USA. RP Hart, ME (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM mark.hart@fda.hhs.gov FU National Center for Toxicological Research of the United States Food and Drug Administration [E0717501]; National Institute of Allergy and Infectious Disease [AI074087]; National Center for Toxicological Research FX This work was supported by the National Center for Toxicological Research of the United States Food and Drug Administration (protocol E0717501 awarded to M. E. H.) and by the National Institute of Allergy and Infectious Disease (grant AI074087 awarded to M. S. S.). Support to H. L. was provided by the Postdoctoral Research Program at the National Center for Toxicological Research, which is administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. We are indebted to Drs Carl Cerniglia, Steve Foley, Robin Stingley and Jon Blevins for careful evaluation of the manuscript. Special thanks to Paul Felton, Division of Personalized Nutrition and Medicine, for statistical evaluation. The views presented in this article do not necessarily reflect those of the United States Food and Drug Administration. NR 59 TC 4 Z9 5 U1 0 U2 10 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD APR PY 2013 VL 159 BP 782 EP 791 DI 10.1099/mic.0.065367-0 PN 4 PG 10 WC Microbiology SC Microbiology GA 154AR UT WOS:000319644400012 PM 23393148 ER PT J AU Bentayeb, K Ackerman, LK Lord, T Begley, TH AF Bentayeb, K. Ackerman, L. K. Lord, T. Begley, T. H. TI Non-visible print set-off of photoinitiators in food packaging: detection by ambient ionisation mass spectrometry SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE food packaging; ink; set-off; photoinitiator; DART; TOF-MS; ITX; benzophenone AB Direct analysis in real time coupled to time-of-flight mass spectrometry (DART/TOF-MS) was used to detect the non-visible set-off of photoinitiators on the food contact surface of three different packages. The samples were intentionally under-cured to provoke set-off. Twelve commercially available photoinitiators were included in the ink formulations including -amino-, morpholino, and -hydroxy benzophenones, thioxanthones, aryl-phosphine oxide and three polymeric versions of these. Major colours of the packages' prints were analysed, as well as the specific areas of the inner surface in contact with them. Larger quantities of photoinitiators were detected on the food contact areas in contact with the darker colours of the images. Speed-cure 7005 and 4-phenylbenzophenone were the compounds most susceptible to set-off in each of the samples by DART response. An identification protocol for unknown set-off compounds was tested, resulting in the set-off detection of diethylene glycol ethers, erucamide and acrylates, and confirmed by solvent extraction GC-MS analysis. Finally, DART/TOF-MS was scanned across transects of the food contact side of packages to map the presence of photoinitiators. Higher photoinitiator signals were observed in patterns corresponding to the printed image, suggesting DART/TOF-MS might image print set-off. C1 [Bentayeb, K.; Ackerman, L. K.; Begley, T. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Bentayeb, K.] Univ Zaragoza, Dept Analyt Chem, Zaragoza, Spain. [Lord, T.] Smithers Pira, Smithers Pira Testing Serv, Leatherhead, Surrey, England. RP Bentayeb, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM karimben@unizar.es RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 13 TC 15 Z9 16 U1 3 U2 26 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD APR 1 PY 2013 VL 30 IS 4 BP 750 EP 759 DI 10.1080/19440049.2012.762694 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 149LR UT WOS:000319321700017 PM 23421479 ER PT J AU Dharmasena, MN Hanisch, BW Wai, TT Kopecko, DJ AF Dharmasena, Madushini N. Hanisch, Brock W. Wai, Tint T. Kopecko, Dennis J. TI Stable expression of Shigella sonnei form I O-polysaccharide genes recombineered into the chromosome of live Salmonella oral vaccine vector Ty21a SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article DE Oral vaccine; Shigella sonnei; Bifunctional typhoid-shigellosis vaccine; Chromosomal recombineering ID ENTERICA SEROVAR PARATYPHI; ESCHERICHIA-COLI; TYPHOID VACCINE; BIVALENT VACCINE; ANTIGEN; PROTECTION; INFECTION; STRAIN; FEVER; IMMUNOGENICITY AB Live, attenuated Salmonella enterica serovar Typhi strain Ty21a, a licensed oral typhoid fever vaccine, has also been employed for use as a vector to deliver protective antigens of Shigella and other pathogens. Importantly, lipopolysaccharide (LPS) alone has been shown to be a potent antigen for specific protection against shigellosis. We reported previously the plasmid cloning of heterologous LPS biosynthetic genes and the expression in Ty21a of either S. sonnei or of S. dysenteriae 1 LPS's. The resulting plasmids encoding Shigella LPS's were reasonably stable for >50 generations of growth in nonselective media, but still contained an antibiotic resistance marker that is objectionable to vaccine regulatory authorities. Deletion of this antibiotic-resistance marker inexplicably resulted in significant plasmid instability. Thus, we sought a method to insert the large similar to 12 kb S. sonnei LPS gene region into the chromosome, that would allow for subsequent removal of a selectable marker and would result in 100% genetic stability. Toward this objective, we optimized an existing recombination method to mediate the insertion of a similar to 12 kb region encoding the S. sonnei LPS genes into the Ty21a genome in a region that is nonfunctional due to mutation. The resulting strain Ty21a-Ss simultaneously expresses both homologous Ty21a and heterologous S. sonnei O-antigens. This chromosomal insert was shown to be 100% genetically stable in vitro and in vivo. Moreover, Ty21a-Ss elicited strong dual anti-LPS serum immune responses and 100% protection in mice against a virulent S. sonnei challenge. This new vaccine candidate, absolutely stable for vaccine manufacture, should provide combined protection against enteric fevers due to Salmonella serovar Typhi as shown previously (and some Paratyphi infections) and against shigellosis due to S. sonnei. Published by Elsevier GmbH. C1 [Dharmasena, Madushini N.; Hanisch, Brock W.; Wai, Tint T.; Kopecko, Dennis J.] US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, HFM440,Bldg 29,Rm 420,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Dennis.Kopecko@fda.hhs.gov NR 38 TC 10 Z9 10 U1 1 U2 8 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 EI 1618-0607 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD APR PY 2013 VL 303 IS 3 BP 105 EP 113 DI 10.1016/j.ijmm.2013.01.001 PG 9 WC Microbiology; Virology SC Microbiology; Virology GA 151TG UT WOS:000319482500001 PM 23474241 ER PT J AU Jiang, W Lionberger, R Li, J Peng, Y Yu, L AF Jiang, W. Lionberger, R. Li, J. Peng, Y. Yu, L. TI Pharmaceutical Quality and Bioequivalence Assessment of Generic Mycophenolate Mofetil Tablets. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Jiang, W.; Lionberger, R.; Li, J.; Peng, Y.; Yu, L.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 161 EP 161 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240300419 ER PT J AU Nee, R Abbott, K Little, D Ramsey-Goldman, R Agodoa, L Hurst, F Jindal, R AF Nee, R. Abbott, K. Little, D. Ramsey-Goldman, R. Agodoa, L. Hurst, F. Jindal, R. TI Racial Differences and Income Disparities Are Associated with Worse Allograft and Death Outcomes in Kidney Transplant Recipients with Lupus Nephritis. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 13th American Transplant Congress (ATC) CY MAY 18-22, 2013 CL Seattle, WA C1 [Nee, R.; Abbott, K.; Little, D.; Jindal, R.] Walter Reed Natl Mil Med Ctr, Bethesda, MD USA. [Ramsey-Goldman, R.] Northwestern Univ, Chicago, IL 60611 USA. [Agodoa, L.] NIDDK, NIH, Bethesda, MD USA. [Hurst, F.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD APR PY 2013 VL 13 SU 5 SI SI BP 541 EP 541 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 134UL UT WOS:000318240301942 ER PT J AU Wear, KA AF Wear, Keith A. TI Estimation of fast and slow wave properties in cancellous bone using Prony's method and curve fitting SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BAND ULTRASOUND ATTENUATION; BAYESIAN PROBABILITY-THEORY; ANISOTROPIC POROUS-MEDIA; BIOT-ATTENBOROUGH MODEL; HUMAN TRABECULAR BONE; 2 LONGITUDINAL-WAVES; IN-VITRO; PHASE CANCELLATION; HUMAN CALCANEUS; TIME-DOMAIN AB The presence of two longitudinal waves in poroelastic media is predicted by Biot's theory and has been confirmed experimentally in through-transmission measurements in cancellous bone. Estimation of attenuation coefficients and velocities of the two waves is challenging when the two waves overlap in time. The modified least squares Prony's (MLSP) method in conjuction with curve-fitting (MLSP + CF) is tested using simulations based on published values for fast and slow wave attenuation coefficients and velocities in cancellous bone from several studies in bovine femur, human femur, and human calcaneus. The search algorithm is accelerated by exploiting correlations among search parameters. The performance of the algorithm is evaluated as a function of signal-to-noise ratio (SNR). For a typical experimental SNR (40 dB), the root-mean-square errors (RMSEs) for one example (human femur) with fast and slow waves separated by approximately half of a pulse duration were 1 m/s (slow wave velocity), 4 m/s (fast wave velocity), 0.4 dB/cm MHz (slow wave attenuation slope), and 1.7 dB/cm MHz (fast wave attenuation slope). The MLSP + CF method is fast (requiring less than 2 s at SNR -40 dB on a consumer-grade notebook computer) and is flexible with respect to the functional form of the parametric model for the transmission coefficient. The MLSP + CF method provides sufficient accuracy and precision for many applications such that experimental error is a greater limiting factor than estimation error. C1 US FDA, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62,Room 3108, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU FDA Office of Women's Health FX The author is grateful to Robert F. Wagner for discussions in the early 1990s regarding Prony's method for applications other than ultrasonic characterization of bone. The author is grateful for funding from the FDA Office of Women's Health. The mention of commercial products, their sources, 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 Department of Health and Human Services. NR 81 TC 8 Z9 8 U1 0 U2 8 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD APR PY 2013 VL 133 IS 4 BP 2490 EP 2501 DI 10.1121/1.4792935 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 139BB UT WOS:000318555300078 PM 23556613 ER PT J AU Cohen, MH Chen, HY Shord, S Fuchs, C He, K Zhao, H Sickafuse, S Keegan, P Pazdur, R AF Cohen, Martin H. Chen, Huanyu Shord, Stacy Fuchs, Chana He, Kun Zhao, Hong Sickafuse, Sharon Keegan, Patricia Pazdur, Richard TI Approval Summary: Cetuximab in Combination With Cisplatin or Carboplatin and 5-Fluorouracil for the First-Line Treatment of Patients With Recurrent Locoregional or Metastatic Squamous Cell Head and Neck Cancer SO ONCOLOGIST LA English DT Article DE Cetuximab; Erbitux; Head and neck cancer; Advanced disease ID GROWTH-FACTOR RECEPTOR; PLATINUM-BASED CHEMOTHERAPY; PHASE-II MULTICENTER; PLUS CETUXIMAB; ANTIBODY CETUXIMAB; CARCINOMA AB On November 7, 2011, the U.S. Food and Drug Administration approved cetuximab in combination with cisplatin or carboplatin and 5-fluorouracil for the first-line treatment of patients with recurrent locoregional or metastatic squamous cell head and neck cancer. Approval was based on a randomized study of 442 patients conducted outside the U. S. Cisplatin (100 mg/m(2) intravenously) or carboplatin (area under the curve 5 intravenously) on day 1 with 5-fluorouracil (1,000 mg/m(2)/day continuous intravenous infusion days 1-4) were administered every 3 weeks. Cetuximab, 400 mg/m(2) intravenously, was administered initially followed by cetuximab, 250 mg/m(2) intravenously weekly. After completion of six planned treatment courses, cetuximab patients without progression continued cetuximab 250 mg/m(2) weekly. The study used European Union (EU)-approved cetuximab rather than U. S.-approved cetuximab. U. S.-approved cetuximab provides approximately 28% higher exposure relative to EU-approved cetuximab in a pharmacokinetic comparability study in monkeys. Overall survival, the primary efficacy endpoint, was significantly improved in cetuximab-treated patients (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.64-0.98; p = .034, stratified log-rank test). Median survival times were 10.1 and 7.4 months, respectively. Progression-free survival (PFS) was also significantly improved in patients receiving cetuximab (HR: 0.57; 95% CI: 0.46-0.72; p < .0001). Median PFS times were 5.5 and 3.3 months, respectively. Response rates were 35.6% and 19.5% (odds ratio: 2.33; 95% CI: 1.50-3.60; p = .0001). Adverse reactions (>= 25%) from cetuximab plus chemotherapy treatment included nausea, anemia, vomiting, neutropenia, rash, asthenia, diarrhea, and anorexia. Conjunctivitis occurred in 10% of cetuximab patients. Other adverse reactions, sometimes severe, included infusion reactions, hypomagnesemia, hypocalcemia, and hypokalemia. The Oncologist 2013;18:460-466 C1 [Cohen, Martin H.; Chen, Huanyu; Shord, Stacy; Fuchs, Chana; He, Kun; Zhao, Hong; Sickafuse, Sharon; Keegan, Patricia; Pazdur, Richard] US FDA, Off Hematol Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 14 TC 17 Z9 17 U1 0 U2 10 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2013 VL 18 IS 4 BP 460 EP 466 DI 10.1634/theoncologist.2012-0458 PG 7 WC Oncology SC Oncology GA 136CB UT WOS:000318336200022 PM 23576486 ER PT J AU O'Neill, RT AF O'Neill, Robert T. TI Reflections on Professor Jerome Cornfield's contributions to the US Food and Drug Administration SO CLINICAL TRIALS LA English DT Editorial Material ID RAUWOLFIA DERIVATIVES; BREAST-CANCER C1 Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP O'Neill, RT (reprint author), Ctr Drug Evaluat & Res, FDA Bldg 21,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Robert.ONeill@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD APR PY 2013 VL 10 IS 2 BP 332 EP 336 DI 10.1177/1740774513477933 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 135CJ UT WOS:000318263300014 PM 23539111 ER PT J AU Clayton, JA Joseph, S AF Clayton, Janine Austin Joseph, Stephanie TI Why research sex differences and similarities? SO MEDICAL PHYSICS LA English DT Editorial Material C1 [Clayton, Janine Austin] NIH, Off Res Womens Hlth, Bethesda, MD 20892 USA. [Joseph, Stephanie] US FDA, Off Special Hlth Issues, Silver Spring, MD 20993 USA. RP Clayton, JA (reprint author), NIH, Off Res Womens Hlth, 6707 Democracy Blvd,Suite 400, Bethesda, MD 20892 USA. EM Janine.Clayton@nih.gov; Stephanie.Joseph@fda.hhs.gov NR 3 TC 2 Z9 2 U1 1 U2 1 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 APR PY 2013 VL 40 IS 4 AR 040403 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 130UP UT WOS:000317945900004 PM 23556868 ER PT J AU Smith, JK AF Smith, Jeffrey K. TI Regulatory Administrative Databases in FDA's Center for Biologics Evaluation and Research: Convergence Toward a Unified Database SO AAPS JOURNAL LA English DT Editorial Material DE database; FDA; managed review; PDUFA; regulatory workload; silos AB Regulatory administrative database systems within the Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research (CBER) are essential to supporting its core mission, as a regulatory agency. Such systems are used within FDA to manage information and processes surrounding the processing, review, and tracking of investigational and marketed product submissions. This is an area of increasing interest in the pharmaceutical industry and has been a topic at trade association conferences (Buckley 2012). Such databases in CBER are complex, not for the type or relevance of the data to any particular scientific discipline but because of the variety of regulatory submission types and processes the systems support using the data. Commonalities among different data domains of CBER's regulatory administrative databases are discussed. These commonalities have evolved enough to constitute real database convergence and provide a valuable asset for business process intelligence. Balancing review workload across staff, exploring areas of risk in review capacity, process improvement, and presenting a clear and comprehensive landscape of review obligations are just some of the opportunities of such intelligence. This convergence has been occurring in the presence of usual forces that tend to drive information technology (IT) systems development toward separate stovepipes and data silos. CBER has achieved a significant level of convergence through a gradual process, using a clear goal, agreed upon development practices, and transparency of database objects, rather than through a single, discrete project or IT vendor solution. This approach offers a path forward for FDA systems toward a unified database. C1 US FDA, Rockville, MD 20852 USA. RP Smith, JK (reprint author), US FDA, Rockville, MD 20852 USA. EM JeffreyK.Smith@fda.hhs.gov RI sebastianovitsch, stepan/G-8507-2013 NR 9 TC 0 Z9 0 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 388 EP 394 DI 10.1208/s12248-012-9448-0 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100010 PM 23269527 ER PT J AU Liu, J Jadhav, P Wang, YN Gobburu, J AF Liu, Jiang Jadhav, Pravin Wang, Yaning Gobburu, Jogarao TI Improper Selection of a Pre-specified Primary Dose-Response Analysis Delays Regulatory Drug Approval SO AAPS JOURNAL LA English DT Article DE dose-response; power; type I error AB Dose-response analysis is one of the accepted efficacy endpoints to establish effectiveness. The purpose of this research was to inform selection of an appropriate pre-specified primary dose-response analysis to demonstrate drug efficacy in a registration trial. The power and the type I error rate of the placebo-corrected (i.e., simply adjusting the observed treatment value by subtracting the placebo mean) and the placebo-anchored (i.e., including the placebo data as dose 0 in the regression) slope analyses were assessed based on regulatory submission data for two antihypertensive drugs and simulated data from hypothetical clinical trials. In the simulated hypothetical trials, the impact of different dosing strategies (i.e., the fixed dose versus the weight-based per kilogram dose), sample size, and scenarios governing the drug exposure-response relationship (e.g., E (max), ED (50) , and SD) was also evaluated. For each scenario, a total 300 replications were simulated. The placebo-anchored slope analysis is always more powerful to demonstrate effectiveness in all plausible scenarios. The difference between the placebo-anchored and the placebo-corrected analyses was maximum when the studied doses were too high. However, the dose-response analysis is not sensitive to the dosing strategies. Furthermore, the type I error rate of these two methods was also found to be comparable. The design of dose-response studies should carefully consider these results to justify the inclusion of placebo and the analysis method. The pharmaceutical industry and the regulatory agencies are equally responsible for using the appropriate methods of primary analysis and providing justification in the protocol. C1 [Liu, Jiang; Jadhav, Pravin; Wang, Yaning; Gobburu, Jogarao] US FDA, Div Pharmacometr, Off Clin Pharmacol, CDER, Silver Spring, MD 20993 USA. RP Liu, J (reprint author), US FDA, Div Pharmacometr, Off Clin Pharmacol, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jiang.liu@fda.hhs.gov NR 4 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 407 EP 414 DI 10.1208/s12248-012-9438-2 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100012 PM 23307587 ER PT J AU Bai, JPF Alekseyenko, AV Statnikov, A Wang, IM Wong, PH AF Bai, Jane P. F. Alekseyenko, Alexander V. Statnikov, Alexander Wang, I-Ming Wong, Peggy H. TI Strategic Applications of Gene Expression: From Drug Discovery/Development to Bedside SO AAPS JOURNAL LA English DT Review DE clinical molecular signatures; molecular signatures of disease; signature genes; target engagement; toxicological pathways ID YELLOW-FEVER VACCINE; HUMAN BREAST-CANCER; INDUCED HYPERLIPIDEMIA; TRANSPLANT RECIPIENTS; TARGET IDENTIFICATION; SIGNAL-TRANSDUCTION; MOLECULAR SUBTYPES; MYELOID-LEUKEMIA; MICROARRAY DATA; OSTEOARTHRITIS AB Gene expression is useful for identifying the molecular signature of a disease and for correlating a pharmacodynamic marker with the dose-dependent cellular responses to exposure of a drug. Gene expression offers utility to guide drug discovery by illustrating engagement of the desired cellular pathways/networks, as well as avoidance of acting on the toxicological pathways. Successful employment of gene-expression signatures in the later stages of drug development depends on their linkage to clinically meaningful phenotypic characteristics and requires a biologically meaningful mechanism combined with a stringent statistical rigor. Much of the success in clinical drug development is hinged on predefining the signature genes for their fitness for purposes of application. Specific examples are highlighted to illustrate the breadth and depth of the potential utility of gene-expression signatures in drug discovery and clinical development to targeted therapeutics at the bedside. C1 [Bai, Jane P. F.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20993 USA. [Alekseyenko, Alexander V.; Statnikov, Alexander] NYU, Ctr Hlth Informat & Bioinformat, Div Translat Med, Dept Med,Langone Med Ctr, New York, NY 10016 USA. [Wang, I-Ming] Merck Res Lab, Informat & Anal Dept, West Point, PA 19486 USA. [Wong, Peggy H.] Merck Res Labs, Rahway, NJ 07065 USA. RP Bai, JPF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20993 USA. EM jane.bai@fda.hhs.gov OI Alekseyenko, Alexander/0000-0002-5748-2085 FU NIH/NLM [1 R01 LM011179-01] FX Alexander Statnikov was supported in part by NIH/NLM grant 1 R01 LM011179-01. NR 98 TC 7 Z9 7 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 427 EP 437 DI 10.1208/s12248-012-9447-1 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100014 PM 23319288 ER PT J AU Bai, JPF Barrett, JS Burckart, GJ Meibohm, B Sachs, HC Yao, L AF Bai, Jane P. F. Barrett, Jeffrey S. Burckart, Gibert J. Meibohm, Bernd Sachs, Hari Cheryl Yao, Lynne TI Strategic Biomarkers for Drug Development in Treating Rare Diseases and Diseases in Neonates and Infants SO AAPS JOURNAL LA English DT Review DE biomarkers; infants; neonates; rare diseases ID SYSTEMIC CLEARANCE PATHWAYS; POPULATION PHARMACOKINETICS; PEDIATRIC-PATIENTS; PRETERM INFANTS; CHILDREN; ONTOGENY; EXPRESSION; PHARMACODYNAMICS; GLUCURONIDATION; DISPOSITION AB There are similar challenges in developing a product designed to treat patients with a rare disease and drugs to treat critically ill neonates and infants. Part of the challenge in developing such products as well as identifying the optimal dosing regimen for the treatment of young children arises from the complex interrelationship between developmental changes and changes in biomarkers responsive to drug therapy. These difficulties are further compounded by our lack of understanding of the key physiological factors that cause the differences in clinical responses between adults and neonates and infants. Regulatory efforts have succeeded in overcoming these challenges in many areas of pediatric and orphan drug development. Strategic applications of biomarkers and surrogate endpoints for the development and approval of a product used to treat an orphan disease will be highlighted with examples of approved products. Continued efforts are still needed to fill in our knowledge gap and to strategically link biomarkers and surrogate endpoints to clinical responses for rare diseases and diseases affecting neonates and infants. C1 [Bai, Jane P. F.; Burckart, Gibert J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Barrett, Jeffrey S.] Childrens Hosp Philadelphia, Pediat Pharmacol Res Unit, Philadelphia, PA 19104 USA. [Meibohm, Bernd] Univ Tennessee, Ctr Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. [Sachs, Hari Cheryl] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM jane.bai@fda.hhs.gov; lynne.yao@fda.hhs.gov NR 40 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 447 EP 454 DI 10.1208/s12248-013-9452-z PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100016 PM 23334978 ER PT J AU Weber, B Lee, SL Lionberger, R Li, BV Tsong, Y Hochhaus, G AF Weber, Benjamin Lee, Sau L. Lionberger, Robert Li, Bing V. Tsong, Yi Hochhaus, Guenther TI A Sensitivity Analysis of the Modified Chi-square Ratio Statistic for Equivalence Testing of Aerodynamic Particle Size Distribution SO AAPS JOURNAL LA English DT Article DE aerodynamic particle size distribution; bioequivalence; cascade impactor; modified Chi-square ratio statistic; orally inhaled drug products AB Demonstration of equivalence in aerodynamic particle size distribution (APSD) is one key component for establishing bioequivalence of orally inhaled drug products. We previously proposed a modified version of the Chi-square ratio statistic (mCSRS) for APSD equivalence testing and demonstrated that the median of the distribution of the mCSRS (MmCSRS) is a robust metric when test (T) and reference (R) cascade impactor (CI) profiles are identical. Here, we systematically evaluate the behavior of the MmCSRS when T and R CI profiles differ from each other in their mean deposition and variability on a single and multiple sites. All CI profiles were generated by Monte-Carlo simulations based upon modified actual CI data. Twenty thousand sets of 30 T and 30 R CI profiles were simulated for each scenario, and the behavior of the MmCSRS was correlated to metrics that characterize the difference between T and R product in mean deposition and variability. The two key findings were, first, that the MmCSRS is more sensitive to difference between T and R CI profiles on high deposition sites, and second, that a cut-off value for APSD equivalence testing based on the MmCSRS needs to be scaled on the variability of the R product. The former is considered as beneficial for equivalence testing of CI profiles as it decreases the likelihood of failing identical CI profiles by chance, in part, due to increasing analytical variability associated with lower deposition sites. The latter is expected to be important for consistently being able to discriminate equivalent from inequivalent CI profiles. C1 [Weber, Benjamin; Hochhaus, Guenther] Univ Florida, Coll Pharm, Dept Pharmaceut, Ctr Pharmacometr & Syst Pharmacol, Gainesville, FL 32610 USA. [Lee, Sau L.; Lionberger, Robert; Li, Bing V.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Tsong, Yi] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lee, SL (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Sau.Lee@fda.hhs.gov NR 10 TC 5 Z9 5 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 465 EP 476 DI 10.1208/s12248-013-9453-y PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100018 PM 23344791 ER PT J AU Sharkey, M AF Sharkey, Michele TI The Challenges of Assessing Osteoarthritis and Postoperative Pain in Dogs SO AAPS JOURNAL LA English DT Review DE pain assessment; veterinary pain scales ID QUALITY-OF-LIFE; PRESSURE WALKWAY SYSTEM; KINEMATIC GAIT ANALYSIS; GROUND REACTION FORCES; VISUAL ANALOG SCALE; SHORT-FORM; BEHAVIORAL PAIN; WESTERN-ONTARIO; CLINICAL PAIN; HIP-DYSPLASIA AB The challenge of measuring pain in veterinary medicine is compounded by the lack of fully validated, reliable methods to measure and assess pain in nonverbal patients. In human medicine, there are numerous, validated pain assessment tools (PATs) for assessing various, specific types of pain. The advances in human medicine pain management and numerous validated pain scales should serve as incentives and templates to facilitate similar advances in the development of validated PATs for use in dogs (and other species). The limited number of canine PATs constrains our ability to adequately and reliably assess pain. Improving the ability to quantify osteoarthritis and postoperative pain in dogs would enhance the development of analgesics for animals, advance the management of animal pain, facilitate the use of animal pain models in preclinical trials for human analgesics, and provide insight into the quantification of pain responses in humans who lack the ability to adequately communicate. This review describes the need for practical, valid, and reliable PATs for use in veterinary patients and discusses some currently available PATs commonly used to evaluate acute and chronic pain in dogs. C1 US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. RP Sharkey, M (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, HFV-114,7500 Standish Pl,MPN 2, Rockville, MD 20855 USA. EM michele.sharkey@fda.hhs.gov NR 92 TC 10 Z9 11 U1 6 U2 43 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD APR PY 2013 VL 15 IS 2 BP 598 EP 607 DI 10.1208/s12248-013-9467-5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 119YO UT WOS:000317136100032 PM 23456420 ER PT J AU Jarvis, KG Yan, QQ Grim, CJ Power, KA Franco, AA Hu, L Gopinath, G Sathyamoorthy, V Kotewicz, ML Kothary, MH Lee, C Sadowski, J Fanning, S Tall, BD AF Jarvis, Karen G. Yan, Qiong Q. Grim, Christopher J. Power, Karen A. Franco, Augusto A. Hu, Lan Gopinath, Gopal Sathyamoorthy, Venugopal Kotewicz, Michael L. Kothary, Mahendra H. Lee, Chloe Sadowski, Jennifer Fanning, Seamus Tall, Ben D. TI Identification and Characterization of Five New Molecular Serogroups of Cronobacter spp. SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID NEIGHBOR-JOINING METHOD; ANTIGEN GENE CLUSTERS; O-ANTIGENS; ESCHERICHIA-COLI; ENTEROBACTER-SAKAZAKII; TRANSPORTERS; SEROTYPE; GENOMES AB Cronobacter spp. (formerly Enterobacter sakazakii) is an emerging foodborne pathogen consisting of seven species including C. sakazakii, C. malonaticus, C. muytjensii, C. turicensis, C. dublinensis (with three subspecies, dublinensis, lausannensis, and lactaridi), C. universalis, and C. condimenti. To date, 12 Cronobacter serogroups have been identified. In this study, MboII restriction fragment length polymorphism patterns and DNA sequences of O-antigen gene clusters were used to identify novel serogroups of Cronobacter spp. Sequence analysis of the O-antigen regions, located between galF and gnd, of strains with distinct restriction fragment length polymorphism patterns revealed five unique gene clusters. These new O-antigen gene clusters were species specific and were termed C. turicensis O3, C. muytjensii O2, C. dublinensis O1, C. dublinensis O2, and C. universalis O1. Polymerase chain reaction assays were developed using primers specific to O-antigen processing genes and used to screen a collection of Cronobacter strains to determine the frequency of these newly identified serotypes. C1 [Jarvis, Karen G.; Grim, Christopher J.; Franco, Augusto A.; Hu, Lan; Gopinath, Gopal; Sathyamoorthy, Venugopal; Kotewicz, Michael L.; Kothary, Mahendra H.; Lee, Chloe; Sadowski, Jennifer; Tall, Ben D.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Jarvis, Karen G.; Grim, Christopher J.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Yan, Qiong Q.; Power, Karen A.; Fanning, Seamus] Univ Coll Dublin, Sch Publ Hlth Physiotherapy & Populat Sci, WHO Collaborating Ctr Res Reference & Training Cr, UCD Ctr Food Safety, Dublin 2, Ireland. RP Jarvis, KG (reprint author), US FDA, Lab 3412, MOD Facil 1, Virulence Mech Branch HFS 025,Div Virulence Asses, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM karen.jarvis@fda.hhs.gov OI Fanning, Seamus/0000-0002-1922-8836; Tall, Ben/0000-0003-0399-3629 FU Department of Energy FX We thank Atin R. Datta, Barbara A. McCardell, and Kevin Gaido, for reviewing this manuscript. K. G. Jarvis, L. Hu, and C. J. Grim are Oak Ridge Institute for Science and Education fellows and the authors wish to thank the Department of Energy for their support. NR 29 TC 17 Z9 18 U1 0 U2 21 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD APR PY 2013 VL 10 IS 4 BP 343 EP 352 DI 10.1089/fpd.2012.1344 PG 10 WC Food Science & Technology SC Food Science & Technology GA 122YB UT WOS:000317353400008 PM 23566272 ER PT J AU Gallagher, D Ebel, ED Gallagher, O LaBarre, D Williams, MS Golden, NJ Pouillot, R Dearfield, KL Kause, J AF Gallagher, Daniel Ebel, Eric D. Gallagher, Owen LaBarre, David Williams, Michael S. Golden, Neal J. Pouillot, Regis Dearfield, Kerry L. Kause, Janell TI Characterizing uncertainty when evaluating risk management metrics: Risk assessment modeling of Listeria monocytogenes contamination in ready-to-eat deli meats SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Performance objective; Appropriate level of protection; Dose response; Listeria; Risk metric ID FOOD SAFETY OBJECTIVES; DISTRIBUTIONS; TEMPERATURE AB This report illustrates how the uncertainty about food safety metrics may influence the selection of a performance objective (PO). To accomplish this goal, we developed a model concerning Listeria monocytogenes in ready-to-eat (RTE) deli meats. This application used a second order Monte Carlo model that simulates L. monocytogenes concentrations through a series of steps: the food-processing establishment transport, retail, the consumer's home and consumption. The model accounted for growth inhibitor use, retail cross contamination, and applied an FAO/WHO dose response model for evaluating the probability of illness. An appropriate level of protection (ALOP) risk metric was selected as the average risk of illness per serving across all consumed servings-per-annum and the model was used to solve for the corresponding performance objective (PO) risk metric as the maximum allowable L. monocytogenes concentration (cfu/g) at the processing establishment where regulatory monitoring would occur. Given uncertainty about model inputs, an uncertainty distribution of the PO was estimated. Additionally, we considered how RTE deli meats contaminated at levels above the PO would be handled by the industry using three alternative approaches. Points on the PO distribution represent the probability that - if the industry complies with a particular PO - the resulting risk-per-serving is less than or equal to the target ALOP. For example, assuming 1) a target ALOP of -6.41 log(10) risk of illness per serving, 2) industry concentrations above the PO that are re-distributed throughout the remaining concentration distribution and 3) no dose response uncertainty, establishment PO's of -4.98 and -4.39 log(10) cfu/g would be required for 90% and 75% confidence that the target ALOP is met, respectively. The PO concentrations from this example scenario are more stringent than the current typical monitoring level of an absence in 25 g (i.e. -1.40 log(10) cfu/g) or a stricter criteria of absence in 125 g (i.e., -2.1 log(10) cfu/g). This example, and others, demonstrates that a PO for L. monocytogenes would be far below any current monitoring capabilities. Furthermore, this work highlights the demands placed on risk managers and risk assessors when applying uncertain risk models to the current risk metric framework. (C) 2013 Elsevier B.V. All rights reserved. C1 [Gallagher, Daniel; Gallagher, Owen] Virginia Polytech Inst & State Univ, Dept Civil & Environm Engn, Blacksburg, VA 24061 USA. [Ebel, Eric D.; LaBarre, David; Williams, Michael S.; Golden, Neal J.; Dearfield, Kerry L.; Kause, Janell] US Food Safety & Inspect Serv, Off Publ Hlth Sci, USDA, Washington, DC 20250 USA. [Pouillot, Regis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Gallagher, D (reprint author), Virginia Tech, Dept Civil & Environm Engn, 409 Durham Hall, Blacksburg, VA 24061 USA. EM dang@vt.edu RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU Center for Food Safety and Applied Nutrition; NSF [CNS-0923386]; [G-3A94-P-08-0148] FX This work is a summary of work performed under contract AG-3A94-P-08-0148 for the Office of Public Health Science, Food Safety and Inspection Service, U.S. Department of Agriculture. This work was supported in part by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. This research utilized the Colorado State University ISTeC Cray HPC System supported by NSF grant CNS-0923386. NR 37 TC 8 Z9 8 U1 0 U2 37 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD APR 1 PY 2013 VL 162 IS 3 BP 266 EP 275 DI 10.1016/j.ijfoodmicro.2013.01.016 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 124FM UT WOS:000317449200009 PM 23454818 ER PT J AU Lau, HK Clotilde, LM Lin, AP Hartman, GL Lauzon, CR AF Lau, Henry K. Clotilde, Laurie M. Lin, Andrew P. Hartman, Gary L. Lauzon, Carol R. TI Comparison of IMS Platforms for Detecting and Recovering Escherichia coli O157 and Shigella flexneri in Foods SO JALA LA English DT Article DE immunomagnetic beads; detection; foodborne; Shigella; Escherichia coli O157 ID PCR ASSAY; SEPARATION AB Two automated platforms using immunomagnetic separation technology were compared for detecting and recovering Escherichia coli O157 in ground beef and sprouts and Shigella flexneri in green onions. The foods were inoculated with < 20 CFU/25 g and tested at 5 and 24 h postincubation. Immunomagnetic beads were mixed with food enrichments, processed through the Pathatrix Auto or KingFisher Flex, and tested by real-time PCR (qPCR) and recovery on selective agars. At 5 h, the Pathatrix Auto detected E. coli O157 in 90% and 60% of the ground beef and sprouts samples and S. flexneri in all of the green onion samples. It also recovered E. coli O157 in all the samples but could not recover S. flexneri in any of the green onion samples. In comparison, the KingFisher Flex detected E. coli O157 in 80% and 30% of the ground beef and sprouts samples and S. flexneri in all of the green onion samples. It also recovered E. coli O157 in 90% of the ground beef samples but none of the sprouts samples and S. flexneri in 20% of the green onion samples. At 24 h, both platforms detected and recovered the target bacteria in all of the samples. C1 [Lau, Henry K.; Clotilde, Laurie M.; Lin, Andrew P.; Hartman, Gary L.] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. [Lauzon, Carol R.] Calif State Univ Hayward, Hayward, CA 94542 USA. RP Lau, HK (reprint author), US FDA, San Francisco Dist Lab, 1431 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM henry.lau@fda.hhs.gov NR 8 TC 3 Z9 4 U1 3 U2 25 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2211-0682 J9 JALA-J LAB AUTOM JI JALA PD APR PY 2013 VL 18 IS 2 BP 178 EP 183 DI 10.1177/2211068212468583 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 125FE UT WOS:000317524200007 PM 23190790 ER PT J AU Laassri, M DiPiazza, A Bidzhieva, B Zagorodnyaya, T Chumakov, K AF Laassri, Majid DiPiazza, Anthony Bidzhieva, Bella Zagorodnyaya, Tatiana Chumakov, Konstantin TI Quantitative one-step RT-PCR assay for rapid and sensitive identification and titration of polioviruses in clinical specimens SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Real-time PCR; Quantitative PCR; Poliovirus surveillance; Poliovirus excretion; Shedding; Mucosal immunity; Titration ID DEOXYINOSINE RESIDUES; CODON DEGENERACY; STOOL SPECIMENS; MIXED-BASE; VACCINE; PRIMERS; HYBRIDIZATION; POSITIONS; SEROTYPE; STRAINS AB Rapid identification and quantitation of polioviruses in clinical specimens is important for surveillance and analysis of virus shedding by vaccine recipients, which could be used to assess the level of mucosal immunity. A quantitative one step RT-PCR was developed for identification and titration of all three poliovirus serotypes. The assay could be an alternative to the traditional procedure based on cell culture isolation and subsequent determination of poliovirus serotype and virus titration. The method is based on quantitative PCR performed with reverse transcription reaction in the same tube. The multiplex assay that quantifies all three serotypes of poliovirus was found to be highly specific, sensitive, and takes only one day to complete. Published by Elsevier B.V. C1 [Laassri, Majid; DiPiazza, Anthony; Bidzhieva, Bella; Zagorodnyaya, Tatiana; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laassri, M (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM majid.laassri@fda.hhs.gov NR 13 TC 3 Z9 3 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 2013 VL 189 IS 1 BP 7 EP 14 DI 10.1016/j.jviromet.2012.12.015 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 124HT UT WOS:000317455100002 PM 23305817 ER PT J AU Mokhtari, A Blancato, VS Repizo, GD Henry, C Pikis, A Bourand, A Alvarez, MD Immel, S Mechakra-Maza, A Hartke, A Thompson, J Magni, C Deutscher, J AF Mokhtari, Abdelhamid Blancato, Victor S. Repizo, Guillermo D. Henry, Celine Pikis, Andreas Bourand, Alexa de Fatima Alvarez, Maria Immel, Stefan Mechakra-Maza, Aicha Hartke, Axel Thompson, John Magni, Christian Deutscher, Josef TI Enterococcus faecalis utilizes maltose by connecting two incompatible metabolic routes via a novel maltose 6-phosphate phosphatase (MapP) SO MOLECULAR MICROBIOLOGY LA English DT Article ID GRAM-POSITIVE BACTERIA; FUSOBACTERIUM-MORTIFERUM ATCC-25557; BACILLUS-SUBTILIS; CATABOLITE REPRESSION; LACTOBACILLUS-CASEI; INDUCER EXCLUSION; KLEBSIELLA-PNEUMONIAE; LACTOCOCCUS-LACTIS; ESCHERICHIA-COLI; TRANSPORT AB Similar to Bacillus subtilis, Enterococcus faecalis transports and phosphorylates maltose via a phosphoenolpyruvate (PEP):maltose phosphotransferase system (PTS). The maltose-specific PTS permease is encoded by the malT gene. However, E.faecalis lacks a malA gene encoding a 6-phospho--glucosidase, which in B.subtilis hydrolyses maltose 6-P into glucose and glucose 6-P. Instead, an operon encoding a maltose phosphorylase (MalP), a phosphoglucomutase and a mutarotase starts upstream from malT. MalP was suggested to split maltose 6-P into glucose 1-P and glucose 6-P. However, purified MalP phosphorolyses maltose but not maltose 6-P. We discovered that the gene downstream from malT encodes a novel enzyme (MapP) that dephosphorylates maltose 6-P formed by the PTS. The resulting intracellular maltose is cleaved by MalP into glucose and glucose 1-P. Slow uptake of maltose probably via a maltodextrin ABC transporter allows poor growth for the mapP but not the malP mutant. Synthesis of MapP in a B.subtilis mutant accumulating maltose 6-P restored growth on maltose. MapP catalyses the dephosphorylation of intracellular maltose 6-P, and the resulting maltose is converted by the B.subtilis maltose phosphorylase into glucose and glucose 1-P. MapP therefore connects PTS-mediated maltose uptake to maltose phosphorylase-catalysed metabolism. Dephosphorylation assays with a wide variety of phospho-substrates revealed that MapP preferably dephosphorylates disaccharides containing an O--glycosyl linkage. C1 [Mokhtari, Abdelhamid; Henry, Celine; Bourand, Alexa; Deutscher, Josef] INRA, Microbiol Alimentat Serv Sante Humaine MICALIS, UMR1319, F-78350 Jouy En Josas, France. [Mokhtari, Abdelhamid; Henry, Celine; Bourand, Alexa; Deutscher, Josef] AgroParisTech, MICALIS, UMR1319, F-78350 Jouy En Josas, France. [Mokhtari, Abdelhamid; Mechakra-Maza, Aicha] Univ Mentouri, Fac Nat Sci & Life, Dept Biochem Microbiol, Lab Environm Biol, Constantine 25017, Algeria. [Blancato, Victor S.; Repizo, Guillermo D.; Magni, Christian] Univ Nacl Rosario, Inst Biol Mol & Celular Rosario IBR CONICET, Fac Ciencias Bioquim & Farmaceut, RA-2000 Rosario, Santa Fe, Argentina. [Blancato, Victor S.; Repizo, Guillermo D.; Magni, Christian] Univ Nacl Rosario, Dept Microbiol, Fac Ciencias Bioquim & Farmaceut, RA-2000 Rosario, Santa Fe, Argentina. [Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bourand, Alexa; Deutscher, Josef] CNRS, MICALIS, SNC9130, F-78350 Jouy En Josas, France. [de Fatima Alvarez, Maria] Univ Nacl Tucuman, Fac Bioquim Quim & Farm, Inst Super Invest Biol INSIBIO UNT CONICET, RA-4000 San Miguel De Tucuman, Argentina. [de Fatima Alvarez, Maria] Univ Nacl Tucuman, Fac Bioquim Quim & Farm, Dept Biol Desarrollo, RA-4000 San Miguel De Tucuman, Argentina. [Immel, Stefan] Tech Univ Darmstadt, Inst Organ Chem, D-64287 Darmstadt, Germany. [Hartke, Axel] Univ Caen Basse Normandie, EA4655, Stress Virulence U2RM, F-14032 Caen, France. [Thompson, John] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Deutscher, J (reprint author), INRA, Microbiol Alimentat Serv Sante Humaine MICALIS, UMR1319, F-78350 Jouy En Josas, France. EM josef.deutscher@grignon.inra.fr OI Blancato, Victor/0000-0003-3945-2859 FU MinCyt/ECOS-Sud programme [A09B03]; Agencia Nacional de Promocion y Tecnologica (AN-PCyT, Argentina) [2010-1828, 2008-1562]; NIDCR, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland [20892] FX We thank Tarek Msadek and Dusko Ehrlich for vectors pAC7 and pMUTIN respectively, and Eliane Milohanic for providing us with a plasmid containing the promoter and Shine-Dalgarno box of B. subtilis ptsH. We are grateful to Isabelle Rince for technical assistance during construction of the mapP mutant. This work was supported by grants from the MinCyt/ECOS-Sud programme (Action No. A09B03) (C. M and J.D), the Agencia Nacional de Promocion y Tecnologica (AN-PCyT, contract 2010-1828 and 2008-1562; Argentina) (C. M.), and the Intramural Research Program of the NIDCR, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892 (J.T.). G. R. is a fellow researcher of CONICET (Argentina), and V. B and C. M. are Career Investigators of CONICET (Argentina). NR 47 TC 5 Z9 7 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2013 VL 88 IS 2 BP 234 EP 253 DI 10.1111/mmi.12183 PG 20 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 126CG UT WOS:000317588300003 PM 23490043 ER PT J AU Tebbens, RJD Pallansch, MA Chumakov, KM Halsey, NA Hovi, T Minor, PD Modlin, JF Patriarca, PA Sutter, RW Wright, PF Wassilak, SGF Cochi, SL Kim, JH Thompson, KM AF Tebbens, Radboud J. Duintjer Pallansch, Mark A. Chumakov, Konstantin M. Halsey, Neal A. Hovi, Tapani Minor, Philip D. Modlin, John F. Patriarca, Peter A. Sutter, Roland W. Wright, Peter F. Wassilak, Steven G. F. Cochi, Stephen L. Kim, Jong-Hoon Thompson, Kimberly M. TI Expert Review on Poliovirus Immunity and Transmission SO RISK ANALYSIS LA English DT Review DE Dynamic modeling; polio eradication; risk management ID ORAL POLIOMYELITIS VACCINE; ENTERIC VIRUS INFECTIONS; ANTIBODY-RESPONSE; MUCOSAL IMMUNITY; IMMUNIZATION SCHEDULES; UNITED-STATES; NATURAL IMMUNITY; CONTROLLED-TRIAL; LIVE VIRUS; NEUTRALIZING ANTIBODIES AB Successfully managing risks to achieve wild polioviruses (WPVs) eradication and address the complexities of oral poliovirus vaccine (OPV) cessation to stop all cases of paralytic poliomyelitis depends strongly on our collective understanding of poliovirus immunity and transmission. With increased shifting from OPV to inactivated poliovirus vaccine (IPV), numerous risk management choices motivate the need to understand the tradeoffs and uncertainties and to develop models to help inform decisions. The U.S. Centers for Disease Control and Prevention hosted a meeting of international experts in April 2010 to review the available literature relevant to poliovirus immunity and transmission. This expert review evaluates 66 OPV challenge studies and other evidence to support the development of quantitative models of poliovirus transmission and potential outbreaks. This review focuses on characterization of immunity as a function of exposure history in terms of susceptibility to excretion, duration of excretion, and concentration of excreted virus. We also discuss the evidence of waning of host immunity to poliovirus transmission, the relationship between the concentration of poliovirus excreted and infectiousness, the importance of different transmission routes, and the differences in transmissibility between OPV and WPV. We discuss the limitations of the available evidence for use in polio risk models, and conclude that despite the relatively large number of studies on immunity, very limited data exist to directly support quantification of model inputs related to transmission. Given the limitations in the evidence, we identify the need for expert input to derive quantitative model inputs from the existing data. C1 [Tebbens, Radboud J. Duintjer; Kim, Jong-Hoon; Thompson, Kimberly M.] Kid Risk Inc, Orlando, FL 32832 USA. [Pallansch, Mark A.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Halsey, Neal A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Hovi, Tapani] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Minor, Philip D.] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Potters Bar, Herts, England. [Modlin, John F.; Wright, Peter F.] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. [Patriarca, Peter A.] Biol Consulting Grp Inc, Bethesda, MD USA. [Sutter, Roland W.] WHO, Polio Eradicat Initiat, CH-1211 Geneva, Switzerland. [Wassilak, Steven G. F.; Cochi, Stephen L.] Ctr Dis Control & Prevent, Ctr Global Hlth, Global Immunizat Div, Atlanta, GA USA. RP Tebbens, RJD (reprint author), Kid Risk Inc, 10524 Moss Pk Rd Ste 204-364, Orlando, FL 32832 USA. EM rdt@kidrisk.org FU U.S. Centers for Disease Control and Prevention (CDC) [200-2010-M-33379] FX We thank the U.S. Centers for Disease Control and Prevention (CDC) for its support of the work described in this article by hosting the expert meeting mentioned in the article and providing financial support to Kid Risk, Inc. under Contract 200-2010-M-33379. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the World Health Organization. We thank Drs. Walter Dowdle, Olen Kew, and Walter Orenstein for helpful comments. NR 145 TC 33 Z9 34 U1 3 U2 40 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 2013 VL 33 IS 4 BP 544 EP 605 DI 10.1111/j.1539-6924.2012.01864.x PG 62 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 122DG UT WOS:000317295900003 ER PT J AU Tebbens, RJD Pallansch, MA Chumakov, KM Halsey, NA Hovi, T Minor, PD Modlin, JF Patriarca, PA Sutter, RW Wright, PF Wassilak, SGF Cochi, SL Kim, JH Thompson, KM AF Tebbens, Radboud J. Duintjer Pallansch, Mark A. Chumakov, Konstantin M. Halsey, Neal A. Hovi, Tapani Minor, Philip D. Modlin, John F. Patriarca, Peter A. Sutter, Roland W. Wright, Peter F. Wassilak, Steven G. F. Cochi, Stephen L. Kim, Jong-Hoon Thompson, Kimberly M. TI Review and Assessment of Poliovirus Immunity and Transmission: Synthesis of Knowledge Gaps and Identification of Research Needs SO RISK ANALYSIS LA English DT Article DE Dynamic modeling; expert judgment; polio eradication ID VACCINE-DERIVED POLIOVIRUS; EXPERT JUDGMENT; SENSITIVITY ANALYSES; CONTROLLED-TRIAL; GLOBAL POLICIES; OPV CESSATION; DOUBLE-BLIND; POLIOMYELITIS; ERADICATION; MANAGEMENT AB With the intensifying global efforts to eradicate wild polioviruses, policymakers face complex decisions related to achieving eradication and managing posteradication risks. These decisions and the expanding use of inactivated poliovirus vaccine (IPV) trigger renewed interest in poliovirus immunity, particularly the role of mucosal immunity in the transmission of polioviruses. Sustained high population immunity to poliovirus transmission represents a key prerequisite to eradication, but poliovirus immunity and transmission remain poorly understood despite decades of studies. In April 2010, the U.S. Centers for Disease Control and Prevention convened an international group of experts on poliovirus immunology and virology to review the literature relevant for modeling poliovirus transmission, develop a consensus about related uncertainties, and identify research needs. This article synthesizes the quantitative assessments and research needs identified during the process. Limitations in the evidence from oral poliovirus vaccine (OPV) challenge studies and other relevant data led to differences in expert assessments, indicating the need for additional data, particularly in several priority areas for research: (1) the ability of IPV-induced immunity to prevent or reduce excretion and affect transmission, (2) the impact of waning immunity on the probability and extent of poliovirus excretion, (3) the relationship between the concentration of poliovirus excreted and infectiousness to others in different settings, and (4) the relative role of fecal-oral versus oropharyngeal transmission. This assessment of current knowledge supports the immediate conduct of additional studies to address the gaps. C1 [Tebbens, Radboud J. Duintjer; Kim, Jong-Hoon; Thompson, Kimberly M.] Kid Risk Inc, Orlando, FL 32832 USA. [Pallansch, Mark A.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Halsey, Neal A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Hovi, Tapani] Natl Inst Hlth & Welf THL, Helsinki, Finland. [Minor, Philip D.] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Potters Bar, Herts, England. [Modlin, John F.; Wright, Peter F.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. [Patriarca, Peter A.] Biol Consulting Grp Inc, Bethesda, MD USA. [Sutter, Roland W.] WHO, Polio Eradicat Initiat, CH-1211 Geneva, Switzerland. [Wassilak, Steven G. F.; Cochi, Stephen L.] Ctr Dis Control & Prevent, Global Immunizat Div, Ctr Global Hlth, Atlanta, GA USA. [Thompson, Kimberly M.] Univ Cent Florida, Coll Med, Orlando, FL 32816 USA. RP Tebbens, RJD (reprint author), Kid Risk Inc, 10524 Moss Pk Rd,Ste 204-364, Orlando, FL 32832 USA. EM rdt@kidrisk.org FU U.S. Centers for Disease Control and Prevention (CDC) [200-2010-M-33379, 200-2010-M-35172] FX We thank the U.S. Centers for Disease Control and Prevention (CDC) for its support of the work described in this article by hosting the expert meeting mentioned in the article and providing financial support to Kid Risk, Inc. under Contracts 200-2010-M-33379 and 200-2010-M-35172. The contents of this article are solely the responsibility of the authors and do not necessarily represent the official views of the CDC or the World Health Organization. We thank Drs. Walter Dowdle, Olen Kew, and Walter Orenstein for helpful comments. NR 60 TC 32 Z9 32 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 2013 VL 33 IS 4 BP 606 EP 646 DI 10.1111/risa.12031 PG 41 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 122DG UT WOS:000317295900004 ER PT J AU Zhi, L Chi, X Gelderman, MP Vostal, JG AF Zhi, Li Chi, Xuan Gelderman, Monique P. Vostal, Jaroslav G. TI Activation of platelet protein kinase C by ultraviolet light B mediates platelet transfusionrelated acute lung injury in a two-event animal model SO TRANSFUSION LA English DT Article ID GLYCOPROTEIN IIB/IIIA; MOUSE MODEL; CALDAG-GEFI; SAFETY; TRIAL; THROMBOSIS; ABCIXIMAB; REDUCTION; PATHWAYS; BLOCKADE AB BACKGROUND: We recently reported that infusion of ultraviolet light B (UVB)-exposed human platelets (HPs) can be the second event that mediates acute lung injury (ALI) in a two-event mouse model of transfusion-related acute lung injury (mTRALI). We have now identified changes in HPs induced by UVB light and responses of the recipient animal that mediate the mTRALI. STUDY DESIGN AND METHODS: Effects of UVB on HPs were monitored by flow cytometry and aggregation. HPs exposed to UVB, with or without inhibitors to specific biochemical pathways, were infused into lipopolysaccharide (LPS)-primed severe combined immunodeficient (SCID) mice. ALI was monitored by protein elevations in bronchoalveolar lavage fluid (BALF). RESULTS: UVB increased fibrinogen binding and potentiated HP aggregation. Infusion of UVB HPs into LPS-primed SCID mice led to macrophage inflammatory protein 2 (MIP-2) elevations in plasma and BALF and resulted in ALI. Protein kinase C (PKC) inhibitors prevented UVB-induced HP changes in vitro and reduced MIP-2 elevation and mTRALI in vivo. Blocking of fibrinogen binding to HP IIb3 with c7E3 monoclonal antibody prevented mTRALI. MIP-2 elevation in vivo in response to UVB HPs was essential for ALI since blocking of MIP-2 receptor in vivo prevented mTRALI. CONCLUSION: PKC signaling mediates UVB-induced HP fibrinogen binding and aggregation in vitro. The host animal responds to an infusion of UVB HPs by MIP-2 elevation that mediates downstream mTRALI. Elucidation of molecular mechanisms in UVB HPmediated mTRALI may provide insight into pulmonary adverse events reported with UV-irradiated pathogen-reduced platelets. C1 [Zhi, Li; Chi, Xuan; Gelderman, Monique P.; Vostal, Jaroslav G.] US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res,OBRR, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res,OBRR, Bldg 29,Room 321,HFM 335,8800 Rockville Pike, Bethesda, MD 20892 USA. EM jaroslav.vostal@fda.hhs.gov FU US Department of Energy; US Food and Drug Administration FX The authors thank the NIH blood bank for collection of apheresis PLTs. This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through and interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 37 TC 9 Z9 9 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2013 VL 53 IS 4 BP 722 EP 731 DI 10.1111/j.1537-2995.2012.03811.x PG 10 WC Hematology SC Hematology GA 123DI UT WOS:000317368200008 PM 22853798 ER PT J AU Sager, P Heilbraun, J Turner, JR Gintant, G Geiger, MJ Kowey, PR Mansoor, GA Mendzelevski, B Michelson, EL Stockbridge, N Weber, MA White, WB AF Sager, Philip Heilbraun, Jeffrey Turner, J. Rick Gintant, Gary Geiger, Mary J. Kowey, Peter R. Mansoor, George A. Mendzelevski, Boaz Michelson, Eric L. Stockbridge, Norman Weber, Michael A. White, William B. TI Assessment of drug-induced increases in blood pressure during drug development: Report from the Cardiac Safety Research Consortium SO AMERICAN HEART JOURNAL LA English DT Article ID HEART-ASSOCIATION COUNCIL; TYPE-2 DIABETES-MELLITUS; CARDIOVASCULAR EVENTS; INDUCED HYPERTENSION; EUROPEAN-SOCIETY; CLINICAL-TRIALS; HOME; METAANALYSIS; PREVENTION; DISEASE AB This White Paper, prepared by members of the Cardiac Safety Research Consortium, discusses several important issues regarding the evaluation of blood pressure (BP) responses to drugs being developed for indications not of a direct cardiovascular (CV) nature. A wide range of drugs are associated with off-target BP increases, and both scientific attention and regulatory attention to this topic are increasing. The article provides a detailed summary of scientific discussions at a Cardiac Safety Research Consortium-sponsored Think Tank held on July 18, 2012, with the intention of moving toward consensus on how to most informatively collect and analyze BP data throughout clinical drug development to prospectively identify unacceptable CV risk and evaluate the benefit-risk relationship. The overall focus in on non-CV drugs, although many of the points also pertain to CV drugs. Brief consideration of how clinical assessment can be informed by nonclinical investigation is also outlined. These discussions present current thinking and suggestions for furthering our knowledge and understanding of off-target drug-induced BP increases and do not represent regulatory guidance. (Am Heart J 2013;165:477-88.) C1 [Sager, Philip] Sager Expert Consulting, Cardiac Safety Res Consortium, San Francisco, CA USA. [Heilbraun, Jeffrey] CoreLab Partners, Princeton, NJ USA. [Turner, J. Rick] Quintiles, Durham, NC USA. [Gintant, Gary] Abbvie Inc, Chicago, IL USA. [Geiger, Mary J.] Relypsa, Santa Clara, CA USA. [Kowey, Peter R.] Main Line Hlth, Lankenau Inst Med Res, Wynnewood, PA USA. [Kowey, Peter R.] Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. [Mansoor, George A.] Merck Sharp & Dohme Ltd, Whitehouse Stn, NJ USA. [Mendzelevski, Boaz] CoreLab Partners, London, England. [Michelson, Eric L.] AstraZeneca LP, Wilmington, DE USA. [Stockbridge, Norman] FDA, Div Cardiovasc & Renal Drug Prod, Silver Spring, MD USA. [Weber, Michael A.] SUNY Downstate Coll Med, Brooklyn, NY USA. [White, William B.] Univ Connecticut, Sch Med, Farmington, CT 06030 USA. RP White, WB (reprint author), Univ Connecticut, Sch Med Farmington, Calhoun Cardiol Ctr, Div Hypertens & Clin Pharmacol, Farmington, CT 06030 USA. EM wwhite@nso1.uchc.edu FU National Institutes of Health (National Institute of Aging, National Institute of Drug Abuse) FX William B. White, MD, has declared no stock ownership and is not a member of any speakers' bureaus. He received research funding from the National Institutes of Health (National Institute of Aging, National Institute of Drug Abuse). He is a safety consultant (member of DSMB, CV end point committee, or advisory board) to Ardea Biosciences; Astra-Zeneca; Astellas, Inc; Bristol-Myers Squibb; Dendreon; Forest Research Institute; Nycomed-Takeda; Palatin Technologies; Roche, Inc; Shire Pharmaceuticals; Takeda Global Research and Development; and Teva Pharmaceutical Industries. He is the president of the American Society of Hypertension from 2012 to 2014. Philip T. Sager, MD, has a stock ownership in Merck, Aegerion. He is not a member of any speakers' bureaus and has declared no research funding. He is a safety consultant (member of DSMB, CV end point committee, consultant, or advisory board) to Shire Pharmaceuticals, PolyMedix, Pfizer, Theravance, Lilly, Milestone, Medtronic, Aerpio, Array, SK Science, Zalicus, Elan, Sanofi, and BioMarin. He is a member of FDA Cardiovascular and Renal Drugs Advisory Committee and Executive Committee Member, CSRC. J. Rick Turner, PhD, is the senior scientific director of Clinical Communications, Quintiles. He is not a member of any speakers' bureaus. He has declared no stock ownership, research funding, or consulting job (outside consulting as part of his regular full-time employment at Quintiles). Dr Turner has disclosed that he is a full-time employee of the CRO Quintiles. Their Cardiac Safety Services division already does, or is shortly to, start offering ABPM services to the biopharmaceutical industry in the specific context of assessing drug-induced off-target BP responses. Jeffrey Heilbraun, MS, is the director of Strategic Development, CoreLab Partners, Inc. He is not a member of any speakers' bureaus. He has declared no stock ownership, research funding, or consulting job. He is a full-time employee of the CRO CoreLab Partners, Inc; Cardiac Safety Services division provides BP monitoring services (including ABPM) services to the biopharmaceutical industry. Peter R. Kowey, MD, is the chairman of the Cardiology, Lankenau Institute for Medical Research, Main Line Health and Jefferson Medical College. He has a stock ownership in Cardionet. He is not a member of any speakers' bureaus. He is a consultant to Ardea, AZ, Astellas, BMS, Dendreon, Theravance, Forest, Nycomed, Takeda, Palatin, Roche, Shire, Teva, J&J, Merck, Novartis, BI, Daiichi, Gilead, Lilly, Sanofi, Pfizer, and GSK. Norman Stockbridge, MD, PhD, is employed by the FDA, Silver Springs, MD and has no disclosures or potential conflicts of interest. Michael A. Weber, MD, if a professor of medicine of the State University of New York Downstate College of Medicine. He has declared no stock ownership. He is a member of the following speakers' bureaus: Daiichi Sankyo, Forest Pharmaceuticals, Novartis, and Takeda Pharmaceuticals. He is a consultant to Boehringer-Ingelheim, Daiichi Sankyo, Forest Pharmaceuticals, and Takeda Pharmaceuticals. Gary Gintant, PhD, if an employee of Abbvie, Inc, Chicago, IL. Mary Jane Geiger, MD, PhD, is an employee of Relypsa Pharmaceuticals, San Francisco, CA. She has declared a stock ownership in Eli Lilly Pharmaceuticals, Inc. George Mansoor, MD, is an employee and shareholder of Merck Inc. Boaz Mendzelevski, MD, is an employee of CoreLab Partners, Inc. Eric Michelson, MD is an employee and owns stock in AstraZeneca. NR 53 TC 15 Z9 16 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2013 VL 165 IS 4 BP 477 EP 488 DI 10.1016/j.ahj.2013.01.002 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120PV UT WOS:000317184300008 PM 23537963 ER PT J AU Nada, A Gintant, GA Kleiman, R Gutstein, DE Gottfridsson, C Michelson, EL Strnadova, C Killeen, M Geiger, MJ Fiszman, ML Koplowitz, LP Carlson, GF Rodriguez, I Sager, PT AF Nada, Adel Gintant, Gary A. Kleiman, Robert Gutstein, David E. Gottfridsson, Christer Michelson, Eric L. Strnadova, Colette Killeen, Matthew Geiger, Mary Jane Fiszman, Monica L. Koplowitz, Luana Pesco Carlson, Glenn F. Rodriguez, Ignacio Sager, Philip T. TI The evaluation and management of drug effects on cardiac conduction (PR and QRS Intervals) in clinical development SO AMERICAN HEART JOURNAL LA English DT Article ID BUNDLE-BRANCH BLOCK; HEART-ASSOCIATION ELECTROCARDIOGRAPHY; FOR-COMPUTERIZED-ELECTROCARDIOLOGY; TRICYCLIC ANTIDEPRESSANT OVERDOSE; 1ST-DEGREE ATRIOVENTRICULAR-BLOCK; OF-CARDIOLOGY-FOUNDATION; HEALTHY MALE-VOLUNTEERS; INTRAVENTRICULAR-CONDUCTION; PROGNOSTIC-SIGNIFICANCE; VENTRICULAR CONDUCTION AB Recent advances in electrocardiographic monitoring and waveform analysis have significantly improved the ability to detect drug-induced changes in cardiac repolarization manifested as changes in the QT/corrected QT interval. These advances have also improved the ability to detect drug-induced changes in cardiac conduction. This White Paper summarizes current opinion, reached by consensus among experts at the Cardiac Safety Research Consortium, on the assessment of electrocardiogram-based safety measurements of the PR and QRS intervals, representing atrioventricular and ventricular conduction, respectively, during drug development. (Am Heart J 2013;165:489-500.) C1 [Nada, Adel] Baxter Healthcare Corp, Deerfield, IL 60015 USA. [Gintant, Gary A.] AbbVie, N Chicago, IL USA. [Kleiman, Robert] ERT, Philadelphia, PA USA. [Gutstein, David E.] Merck Sharp & Dohme Corp, Whitehouse Stn, NJ USA. [Gottfridsson, Christer] AstraZeneca R&D, Molndal, Sweden. [Michelson, Eric L.; Carlson, Glenn F.] AstraZeneca LP, Wilmington, DE USA. [Strnadova, Colette] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Killeen, Matthew] Decis Resources, Boston, MA USA. [Geiger, Mary Jane] Relypsa Inc, Redwood City, CA USA. [Fiszman, Monica L.] US FDA, Silver Spring, MD USA. [Koplowitz, Luana Pesco] Duck Flats Pharma, Elbridge, NY USA. [Rodriguez, Ignacio] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Sager, Philip T.] SagConsulting Experts, San Francisco, CA USA. RP Nada, A (reprint author), Baxter Healthcare Corp, New Therapeut Dev, Cardiovasc Cellular Therapies, 1 Baxter Pkwy, Deerfield, IL 60015 USA. EM adel_nada@baxter.com NR 68 TC 14 Z9 14 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD APR PY 2013 VL 165 IS 4 BP 489 EP 500 DI 10.1016/j.ahj.2013.01.011 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 120PV UT WOS:000317184300009 PM 23537964 ER PT J AU Shi, Q Yang, X Mendrick, DL AF Shi, Qiang Yang, Xi Mendrick, Donna L. TI Hopes and challenges in using miRNAs as translational biomarkers for drug-induced liver injury SO BIOMARKERS IN MEDICINE LA English DT Review DE acetaminophen; biomarker; DILI; drug-induced liver injury; hepatotoxicity; miRNA ID CIRCULATING MICRORNAS; GENE-EXPRESSION; CAUSALITY ASSESSMENT; HEPATOTOXICITY; DISEASE; CANCER; IDENTIFICATION; PROFILES; TOXICITY; FAILURE AB There is a need for better biomarkers of drug-induced liver injury (DILI) to guide risk assessment and patient management. Over the past 3 years, both animal and clinical studies have provided proof-of-concept data showing that a subset of miRNAs appear to offer unique advantages over the conventional DILI biomarkers, such as enhanced sensitivity and specificity, reduced inter-individual variations, the potential to differentiate lethal and nonlethal liver injury, and the ability to reflect the patterns and even the etiology of liver injury. Notably, many studies have demonstrated that level of miR-122, a liver-enriched miRNA accounting for approximately 70% of total hepatic miRNAs, was increased many fold in the blood when DILI occurred. However, currently available data are predominantly based on animal models and not human samples. Due to the lack of a standard quantification method for miRNAs and confirmatory studies using a comprehensive list of drugs and patients, the true value of all reported miRNA biomarkers remains to be carefully assessed. An outstanding challenge is to examine if miRNAs are also useful for idiosyncratic DILI, which constitutes the major part of clinical DILI cases but generally cannot be recapitulated in traditional animal models or in clinical trials (the latter due to its relative rarity). C1 [Shi, Qiang; Yang, Xi; Mendrick, Donna L.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, Q (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM qiang.shi@fda.hhs.gov RI Qiang, Shi/E-6266-2012 FU US FDA's Chief Scientist's Challenge Grants program FX This study is supported by the US FDA's Chief Scientist's Challenge Grants program. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 48 TC 12 Z9 13 U1 1 U2 20 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD APR PY 2013 VL 7 IS 2 BP 307 EP 315 DI 10.2217/BMM.13.9 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 120FA UT WOS:000317155000022 PM 23547824 ER PT J AU Serrano, K AF Serrano, Katherine TI FDA Supports Standardized Reporting and Analysis on CGM Devices SO DIABETES TECHNOLOGY & THERAPEUTICS LA English DT Letter C1 US FDA, Div Chem & Toxicol Devices, Off Vitro Diagnost, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Serrano, K (reprint author), US FDA, Div Chem & Toxicol Devices, Off Vitro Diagnost, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 66,Room 5646, Silver Spring, MD 20993 USA. EM Katherine.Serrano@fda.hhs.gov NR 1 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1520-9156 J9 DIABETES TECHNOL THE JI Diabetes Technol. Ther. PD APR PY 2013 VL 15 IS 4 BP 348 EP 348 DI 10.1089/dia.2013.8313 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 122VX UT WOS:000317347400013 PM 23565642 ER PT J AU Kumar, S Zheng, H Sangweme, DT Mahajan, B Kozakai, Y Pham, PT Morin, MJ Locke, E Kumar, N AF Kumar, Sanjai Zheng, Hong Sangweme, Davison T. Mahajan, Babita Kozakai, Yukiko Pham, Phuong T. Morin, Merribeth J. Locke, Emily Kumar, Nirbhay TI A chemiluminescent-western blot assay for quantitative detection of Plasmodium falciparum circumsporozoite protein SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE Plasmodium falciparum; Circumsporozoite protein; Chemiluminescent-western blot; IOD ID HUMAN MALARIA PARASITES; MONOCLONAL-ANTIBODIES; VACCINE; SPOROZOITES; IMMUNOGENICITY; EFFICACY; ANTIGEN; VIVAX AB Highly sensitive and reliable assays based on the quantitation of immunologically relevant component(s) in recombinant or whole parasite-based vaccines would facilitate pre-clinical and clinical phases and the monitoring of malaria vaccine deployment. Here we report a laboratory-grade Western Blot assay for quantitative detection of Plasmodium falciparum circumsporozoite protein (PfCSP) in P. falciparum sporozoite (PfSPZ) and in recombinant (rPfCSP) product. This assay is based on the immuno-reactivity of an anti-P. falciparum CSP monoclonal antibody (mAb 2A10) with the NANP-repeat units on PfCSP. The antigen-antibody complex is detected by reaction with a commercially obtained chemiluminescence-linked Immunodetection system. The linear range for detecting the recombinant P. falciparum CSP (rPfCSP) in this assay is 3-12 pg (R-2 = 0.9399). The range for detecting the day 15 salivary-gland PfSPZ is between 0.0625 and 1 parasite (R-2 = 0.9448) and approximately 10.0 pg of PfCSP was detected on each sporozoite. The assay was highly reproducible in measuring the PfCSP on PfSPZ. The inter-assay Coefficient of Variation (CV%) was 10.31% while the intra-assay CV% on three different days was 6.05%, 2.03% and 1.42% respectively. These results suggest that this ECL-WB assay is highly sensitive and robust with a low degree of inter-assay and intra-assay variations. To our knowledge, this is the most sensitive immunoassay for the detection of a recombinant or native malarial protein and may have a wider range of applications including the quantification of immunological component(s) in a vaccine formulation, determination of the antigenic integrity in adjuvanted-vaccine and in stability studies. In addition, this assay can be applied to measure the mosquito infectivity in malaria transmission areas and to determine the effects of intervention measures on malaria transmission. Published by Elsevier B.V. C1 [Kumar, Sanjai; Zheng, Hong; Mahajan, Babita; Kozakai, Yukiko; Pham, Phuong T.] US FDA, Lab Emerging Pathogens, DETTD, CBER, Rockville, MD 20852 USA. [Sangweme, Davison T.; Kumar, Nirbhay] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Morin, Merribeth J.; Locke, Emily] PATH Malaria Vaccine Initiat, Washington, DC 20001 USA. RP Kumar, S (reprint author), US FDA, Lab Emerging Pathogens, DETTD, CBER, 1401 Rockville Pike HFM 313, Rockville, MD 20852 USA. EM Sanjai.kumar@fda.hhs.gov FU PATH Malaria Vaccine Initiative FX We thank the PATH Malaria Vaccine Initiative for providing the financial support for this study. NR 23 TC 5 Z9 5 U1 0 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR PY 2013 VL 390 IS 1-2 BP 99 EP 105 DI 10.1016/j.jim.2013.02.001 PG 7 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 123IB UT WOS:000317380500012 PM 23399449 ER PT J AU Bekisz, J Sato, Y Johnson, C Husain, SR Puri, RK Zoon, KC AF Bekisz, Joseph Sato, Yuki Johnson, Chase Husain, Syed R. Puri, Raj K. Zoon, Kathryn C. TI Immunomodulatory Effects of Interferons in Malignancies SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Review ID TRAIL-INDUCED APOPTOSIS; OVARIAN-CANCER CELLS; ACTIVATED MACROPHAGES; IFN-ALPHA; ADOPTIVE IMMUNOTHERAPY; TUMORICIDAL ACTIVITY; BLOOD MONOCYTES; IN-VITRO; PHASE-I; GAMMA AB Investigation of the antitumor and immunomodulatory activities of interferon (IFN) began shortly after the cytokine was discovered in 1957. Early work showed a direct correlation between administration of IFN and inhibition of symptoms associated with virally induced leukemia in mice as well as an increase in their survival time. Subsequent studies with purified IFNs confirmed the direct and indirect stimulation of immune cells, resulting in antitumor activities of IFN. Clinically, IFN-alphas (alpha s) have been shown to have activity against a variety of tumors. Initially, the U.S. Food and Drug Administration licensed 2 recombinant IFN-alpha s for the treatment of hairy-cell leukemia and then later for several other cancers. The success rate seen with IFNs and certain tumors has been varied. Unfortunately, some neoplasms show no response to IFN. Monocytes/macrophages play an important role in cancer progression. Monocytes in combination with IFN may be an important therapy for several cancers. This article focuses on the role of IFN and monocytes alone or in combination in affecting malignancies. C1 [Bekisz, Joseph; Johnson, Chase; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. [Sato, Yuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Zoon, KC (reprint author), NIAID, Div Intramural Res, NIH, Bldg 33,Rm 2N09G2,33 North Dr, Bethesda, MD 20892 USA. EM kzoon@niaid.nih.gov NR 50 TC 19 Z9 19 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 2013 VL 33 IS 4 SI SI BP 154 EP 161 DI 10.1089/jir.2012.0167 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 124KY UT WOS:000317463400003 PM 23570381 ER PT J AU Graham, DJ Williams, JR Hsueh, YH Calia, K Levenson, M Pinheiro, SP MaCurdy, TE Shih, D Worrall, C Kelman, JA AF Graham, David J. Williams, James R. Hsueh, Ya-Hui Calia, Katlyn Levenson, Mark Pinheiro, Simone P. MaCurdy, Thomas E. Shih, David Worrall, Chris Kelman, Jeffrey A. TI Cardiovascular and mortality risks in Parkinson's disease patients treated with entacapone SO MOVEMENT DISORDERS LA English DT Article DE entacapone; Parkinson's disease; acute myocardial infarction; stroke; mortality ID ACUTE MYOCARDIAL-INFARCTION; POSITIVE PREDICTIVE-VALUE; ADMINISTRATIVE DATA; CODING ACCURACY; DEATH; COHORT; STROKE; DIAGNOSIS; SURVIVAL; ONTARIO AB The controlled trial Stalevo Reduction in Dyskinesia Evaluation in Parkinson's Disease (STRIDE-PD) reported an unexpected increase in acute myocardial infarction (AMI) with entacapone use in patients with Parkinson's disease (PD). The authors investigated whether entacapone increased cardiovascular and mortality risk compared with the use of a non-levodopa dopamine agonist (DA) or a selective monoamine oxidase type-B inhibitor (MAOBI). Using national Medicare data, a new-user cohort of elderly patients with PD treated with entacapone was propensity score (PS) matched with new users of either DA or MAOBI. The PS model included variables for sociodemographics, cardiovascular disease, medications, prior PD treatment, and comorbidities. Cox proportional hazards regression was used to compare on-therapy time to event for AMI, stroke, and death with DA-MAOBI as a reference. Study cohorts included 8681 entacapone-treated and 17,362 DA-MAOBI-treated initators who were followed for 2569 and 5385 person-years, respectively. Cohorts were closely balanced for all covariates. During follow-up, there were 106 AMIs, 89 strokes, and 201 deaths. The hazard ratio (HR) and 95% confidence interval (CI) associated with entacapone use was 0.86 (95% CI, 0.571.30) for AMI, 0.85 (95% CI, 0.541.35) for stroke, and 0.79 (95% CI, 0.581.07) for death. The risk was unchanged for treatment of6 months' and>6 months' duration and was unaffected by adjustment for time-varying levodopa use during follow-up. The risk of each endpoint was not differentially affected by diabetes, ischemic heart disease, or kidney failure status. However, the risk of stroke was modified by the presence (HR, 2.09; 95% CI, 0.984.45) or absence (HR, 0.51; 95% CI, 0.270.95) of advanced PD-related morbidities (P value for interaction=0.004). Entacapone was not associated with an increased risk of AMI, stroke, or death in elderly patients with PD. (c) 2013 Movement Disorder Society C1 [Graham, David J.; Williams, James R.; Pinheiro, Simone P.; Shih, David] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hsueh, Ya-Hui; Levenson, Mark] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Calia, Katlyn; MaCurdy, Thomas E.] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Dept Econ, Palo Alto, CA 94304 USA. [Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicare Serv, Washington, DC USA. [Worrall, Chris; Kelman, Jeffrey A.] Ctr Medicaid Serv, Washington, DC USA. RP Graham, DJ (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4314, Silver Spring, MD 20993 USA. EM david.graham1@fda.hhs.gov FU Centers for Medicare & Medicaid Services (CMS); Food and Drug Administration (FDA) under an intra-agency agreement FX This study was funded by the Centers for Medicare & Medicaid Services (CMS) and the Food and Drug Administration (FDA) under an intra-agency agreement. NR 28 TC 4 Z9 4 U1 0 U2 8 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2013 VL 28 IS 4 BP 490 EP 497 DI 10.1002/mds.25351 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 123CO UT WOS:000317366100018 PM 23443994 ER PT J AU Hong, HX Jawaid, A Wang, J Catalano, J Fox, JC Hawkins, TB AF Hong, Huixiao Jawaid, Ansar Wang, Jian Catalano, Jennifer Fox, Jayne C. Hawkins, Troy B. TI Combining genetic variations in CYP2C9 and VKORC1 with clinical factors for warfarin dosing determination improved clinical effectiveness SO PHARMACOGENOMICS LA English DT Editorial Material ID POLYMORPHISM; TRIAL C1 [Hong, Huixiao] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jawaid, Ansar; Fox, Jayne C.] AstraZeneca, Personalised Healthcare & Biomarkers, Macclesfield SK10 4TG, Cheshire, England. [Wang, Jian] Eli Lilly & Co, Lilly Corp Ctr, Res Informat, Indianapolis, IN 46285 USA. [Catalano, Jennifer] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Hawkins, Troy B.] Eli Lilly & Co, Lilly Corp Ctr, Tailored Therapeut, Indianapolis, IN 46285 USA. RP Hong, HX (reprint author), US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huixiao.hong@fda.hhs.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2013 VL 14 IS 5 BP 459 EP 460 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 120NP UT WOS:000317177700007 PM 23556443 ER PT J AU Li, J Ulitzky, L Silberstein, E Taylor, DR Viscidi, R AF Li, Jie Ulitzky, Laura Silberstein, Erica Taylor, Deborah R. Viscidi, Raphael TI Immunogenicity and Protection Efficacy of Monomeric and Trimeric Recombinant SARS Coronavirus Spike Protein Subunit Vaccine Candidates SO VIRAL IMMUNOLOGY LA English DT Article ID ACUTE-RESPIRATORY-SYNDROME; TRANSMISSIBLE GASTROENTERITIS VIRUS; NEUTRALIZING ANTIBODIES; GLYCOPROTEIN; COV; MICE; S2; DOMAIN; IDENTIFICATION; IMMUNITY AB Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease, and an effective vaccine is not available. In this study, we compared the immunogenicity and protection efficacy of recombinant proteins corresponding to different domains of the SARS-coronavirus spike protein. Trimeric recombinant proteins were created by fusing the foldon domain derived from T4 bacteriophage to the carboxy-termini of individual domains of the spike protein. While the full-length ectodomain (S) of the spike protein, the full-length ectodomain fused to foldon (S-foldon), the S1 domain (S1), S1-foldon, and the S2 domain(S2) antigens all elicited comparable antibody titers as measured by ELISA, S-foldon induced a significantly higher titer of neutralizing antibody and S2 protein did not elicit virus neutralizing antibodies. When tested in a mouse virus replication model, all the mice vaccinated with the S1, S1-foldon, S, or S-foldon were completely protected. C1 [Li, Jie; Viscidi, Raphael] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. [Li, Jie; Ulitzky, Laura; Silberstein, Erica; Taylor, Deborah R.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Viscidi, R (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, 600 N Wolfe St, Baltimore, MD 21287 USA. EM rviscidi1@jhmi.edu FU National Institutes of Health [RO1-AI064372 (RPV)]; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported by grant RO1-AI064372 (RPV) from the National Institutes of Health. J. Li was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 25 TC 6 Z9 6 U1 0 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD APR PY 2013 VL 26 IS 2 BP 126 EP 132 DI 10.1089/vim.2012.0076 PG 7 WC Immunology; Virology SC Immunology; Virology GA 124OH UT WOS:000317473600002 PM 23573979 ER PT J AU Zheng, J Allard, S Reynolds, S Millner, P Arce, G Blodgett, RJ Brown, EW AF Zheng, Jie Allard, Sarah Reynolds, Sara Millner, Patricia Arce, Gabriela Blodgett, Robert J. Brown, Eric W. TI Colonization and Internalization of Salmonella enterica in Tomato Plants SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID IRRIGATION WATER; UNITED-STATES; SEROVAR TYPHIMURIUM; ESCHERICHIA-COLI; SOIL; CONTAMINATION; NEWPORT; GROWTH; SURVEILLANCE; PERSISTENCE AB The consumption of fresh tomatoes has been linked to numerous food-borne outbreaks involving various serovars of Salmonella enterica. Recent advances in our understanding of plant-microbe interactions have shown that human enteric pathogenic bacteria, including S. enterica, are adapted to survive in the plant environment. In this study, tomato plants (Solanum lycopersicum cv. Micro-Tom) grown in sandy loam soil from Virginia's eastern shore (VES) were inoculated with S. enterica serovars to evaluate plausible internalization routes and to determine if there is any niche fitness for certain serovars. Both infested soil and contaminated blossoms can lead to low internal levels of fruit contamination with Salmonella. Salmonella serovars demonstrated a great ability to survive in environments under tomato cultivation, not only in soil but also on different parts of the tomato plant. Of the five serovars investigated, Salmonella enterica serovars Newport and Javiana were dominant in sandy loam soil, while Salmonella enterica serovars Montevideo and Newport were more prevalent on leaves and blossoms. It was also observed that Salmonella enterica serovar Typhimurium had a poor rate of survival in all the plant parts examined here, suggesting that post-harvest contamination routes are more likely in S. Typhimurium contamination of tomato fruit. Conversely, S. Newport was the most prevalent serovar recovered in both the tomato rhizosphere and phyllosphere. Plants that were recently transplanted (within 3 days) had an increase in observable internalized bacteria, suggesting that plants were more susceptible to internalization right after transplant. These findings suggest that the particular Salmonella serovar and the growth stage of the plant were important factors for internalization through the root system. C1 [Zheng, Jie; Allard, Sarah; Arce, Gabriela; Blodgett, Robert J.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Allard, Sarah; Reynolds, Sara] ARS, Environm Microbial & Food Safety Lab, USDA, Beltsville, MD USA. RP Zheng, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM jie.zheng@fda.hhs.gov NR 34 TC 21 Z9 21 U1 1 U2 53 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2013 VL 79 IS 8 BP 2494 EP 2502 DI 10.1128/AEM.03704-12 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 117LZ UT WOS:000316956200001 PM 23377940 ER PT J AU Cieslak, J Ausin, C Grajkowski, A Beaucage, SL AF Cieslak, Jacek Ausin, Cristina Grajkowski, Andrzej Beaucage, Serge L. TI The 2-Cyano-2,2-dimethylethanimine-N-oxymethyl Group for the 2 '-Hydroxyl Protection of Ribonucleosides in the Solid-Phase Synthesis of RNA Sequences SO CHEMISTRY-A EUROPEAN JOURNAL LA English DT Article DE phosphoramidite monomers; protecting groups; RNA deprotection; RNA synthesis; solid-phase synthesis ID CHEMICAL-SYNTHESIS; OLIGORIBONUCLEOTIDES; IDENTIFICATION; INTERFERENCE AB The reaction of 2-cyano-2-methyl propanal with 2-O-aminooxymethylribonucleosides leads to stable and yet reversible 2-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl)ribonucleosides. Following N-protection of the nucleobases, 5-dimethoxytritylation and 3-phosphitylation, the resulting 2-protected ribonucleoside phosphoramidite monomers are employed in the solid-phase synthesis of three chimeric RNA sequences, each differing in their ratios of purine/pyrimidine. When the activation of phosphoramidite monomers is performed in the presence of 5-benzylthio-1H-tetrazole, coupling efficiencies averaging 99% are obtained within 180s. Upon completion of the RNA-chain assemblies, removal of the nucleobase and phosphate protecting groups and release of the sequences from the solid support are carried out under standard basic conditions, whereas the cleavage of 2-O-(2-cyano-2,2-dimethylethanimine-N-oxymethyl) protective groups is effected (without releasing RNA alkylating side-products) by treatment with tetra-n-butylammonium fluoride (0.5m) in dry DMSO over a period of 2448h at 55 degrees C. Characterization of the fully deprotected RNA sequences by polyacrylamide gel electrophoresis (PAGE), enzymatic hydrolysis, and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry confirmed the identity and quality of these sequences. Thus, the use of 2-O-aminooxymethylribonucleosides in the design of new 2-hydroxyl protecting groups is a powerful approach to the development of a straightforward, efficient, and cost-effective method for the chemical synthesis of high-quality RNA sequences in the framework of RNA interference applications. C1 [Cieslak, Jacek; Ausin, Cristina; Grajkowski, Andrzej; Beaucage, Serge L.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM serge.beaucage@fda.hhs.gov NR 33 TC 3 Z9 3 U1 2 U2 18 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 0947-6539 J9 CHEM-EUR J JI Chem.-Eur. J. PD APR PY 2013 VL 19 IS 14 BP 4623 EP 4632 DI 10.1002/chem.201204235 PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 112WM UT WOS:000316625000030 PM 23417977 ER PT J AU Coelho, SG Zmudzka, BZ Yin, LL Miller, SA Yamaguchi, Y Tadokoro, T Hearing, VJ Beer, JZ AF Coelho, Sergio G. Zmudzka, Barbara Z. Yin, Lanlan Miller, Sharon A. Yamaguchi, Yuji Tadokoro, Taketsugu Hearing, Vincent J. Beer, Janusz Z. TI Non-invasive diffuse reflectance measurements of cutaneous melanin content can predict human sensitivity to ultraviolet radiation SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE DNA damage; erythema; melanin; race/ethnicity ultraviolet radiation ID MAST-CELLS; ANGIOGENIC FACTORS; TUMOR ENVIRONMENT; SCHWANN-CELLS; NEUROFIBROMATOSIS; EXPRESSION; NF1; MICROENVIRONMENT; NF1(+/-); GAP AB The diversity of human skin phenotypes and the ubiquitous exposure to ultraviolet radiation (UVR) underscore the need for a non-invasive tool to predict an individual's UVR sensitivity. We analysed correlations between UVR sensitivity, melanin content, diffuse reflectance spectroscopy (DR) and UVR-induced DNA damage in the skin of subjects from three racial/ethnic groups: Asian, Black or African American and White. UVR sensitivity was determined by evaluating each subject's response to one minimal erythemal dose (MED) of UVR one day after the exposure. Melanin content was measured using DR and by densitometric analysis of Fontana-Masson staining (FM) in skin biopsies taken from unexposed areas. An individual's UVR sensitivity based on MED was highly correlated with melanin content measured by DR and by FM. Therefore, a predictive model for the non-invasive determination of UVR sensitivity using DR was developed. The MED precision was further improved when we took race/ethnicity into consideration. The use of DR serves as a tool for predicting UVR sensitivity in humans that should be invaluable for determining appropriate UVR doses for therapeutic, diagnostic and/or cosmetic devices. C1 [Coelho, Sergio G.; Yin, Lanlan; Yamaguchi, Yuji; Tadokoro, Taketsugu; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Zmudzka, Barbara Z.; Miller, Sharon A.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Coelho, SG (reprint author), NIH, Pigment Cell Biol Sect, Cell Biol Lab, Bldg 37 Rm 2132, Bethesda, MD 20892 USA. EM coelhos@mail.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. We also thank Dr. Nikiforos Kollias for valuable comments and suggestions for improving the manuscript. The mention of commercial products, their sources or their use in connection with material reported herein is not to be construed as either an actual or an implied endorsement of such products by the Department of Health and Human Services. NR 21 TC 7 Z9 8 U1 1 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD APR PY 2013 VL 22 IS 4 BP 266 EP 271 DI 10.1111/exd.12116 PG 6 WC Dermatology SC Dermatology GA 115PS UT WOS:000316825000006 PM 23528212 ER PT J AU Bird, ST Hartzema, AG Etminan, M Brophy, JM Delaney, JAC AF Bird, Steven T. Hartzema, Abraham G. Etminan, Mahyar Brophy, James M. Delaney, Joseph. A. C. TI Polycystic ovary syndrome and combined oral contraceptive use: a comparison of clinical practice in the United States to treatment guidelines SO GYNECOLOGICAL ENDOCRINOLOGY LA English DT Article DE Drug utilization; oral contraceptives; polycystic ovary syndrome ID WOMENS HEALTH-ASPECTS; SYNDROME PCOS; DROSPIRENONE; CONSENSUS; SAFETY; RISK AB The October 2010 ESHRE/ASRM polycystic ovary syndrome (PCOS) workshop concluded: (1) all combined oral contraceptives (COC) appear to have equal efficacy for PCOS, (2) addition of antiandrogens (spironolactone) to COCs has little treatment benefit and (3) metformin does not improve the live-birth rate and should only be used with impaired glucose tolerance. We compared these guidelines to current practice in the United States IMS claims-database. Time-series analyses were conducted by calendar-year in women with PCOS to evaluate prescribing preferences for COCs, concomitant use of spironolactone, and utilization of metformin. Trends were analyzed with linear regression. Our cohort included 1.6 million women taking COCs, 46 780 with a PCOS claim. Drospirenone utilization increased by 1.52% (SE:0.48%, p=0.007) per-year more in women with PCOS (4.16%, SE:0.45%, p < 0.001) than in women without PCOS (2.64%, SE:0.17%, p < 0.001)). Concomitant use of drospirenone and spironolactone was common (14.26%) and increased by 0.75% (SE:0.15%, p = 0.002) per-year. Although plasma glucose tests were unavailable, women with PCOS were more likely to take metformin than have a diabetes claim (45.8% versus 15.2%, p < 0.001), indicating some women likely receive metformin solely for PCOS. Our data suggests further attention is needed to medication management of PCOS to bridge the gap between guidelines and practice. C1 [Bird, Steven T.; Hartzema, Abraham G.; Delaney, Joseph. A. C.] Univ Florida, Coll Pharm & Epidemiol, Gainesville, FL USA. [Bird, Steven T.] US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Off Management,CDER Acad Collaborat Program, Silver Spring, MD USA. [Etminan, Mahyar] Univ British Columbia, Pharmaceut Outcomes Programme, Vancouver, BC V5Z 1M9, Canada. [Brophy, James M.] McGill Univ, Royal Victoria Hosp, Montreal, PQ H3A 1A1, Canada. RP Bird, ST (reprint author), US FDA, Dept Hlth & Human Serv, Ctr Drug Evaluat & Res, Off Management,CDER Acad Collaborat Program, Silver Spring, MD USA. EM bird.steven@gmail.com FU McGill University Health Center; Fonds de la Recherche en Sante du Quebec; Ministere de la Sante et des Services Sociaux; AHRQ; National Institute of Health FX This work was supported by an unrestricted operating grant funded in part by the McGill University Health Center, Fonds de la Recherche en Sante du Quebec, and the Ministere de la Sante et des Services Sociaux. Dr Brophy is a physician scientist who receives peer review financial support from le Fonds de la Recherche en Sante du Quebec. Dr Delaney receives peer review financial support from AHRQ. Dr Hartzema holds a grant from the National Institute of Health and is the PI for the Observational Medical Outcomes Partnership (OMOP), a private-public partnership designed to help improve drug safety monitoring. NR 15 TC 3 Z9 4 U1 0 U2 7 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0951-3590 J9 GYNECOL ENDOCRINOL JI Gynecol. Endocrinol. PD APR PY 2013 VL 29 IS 4 BP 365 EP 369 DI 10.3109/09513590.2012.743007 PG 5 WC Endocrinology & Metabolism; Obstetrics & Gynecology SC Endocrinology & Metabolism; Obstetrics & Gynecology GA 117AV UT WOS:000316925400021 PM 23311996 ER PT J AU Jiang, L Wang, F Han, F Prinyawiwatkul, W No, HK Ge, B AF Jiang, L. Wang, F. Han, F. Prinyawiwatkul, W. No, H. K. Ge, B. TI Evaluation of diffusion and dilution methods to determine the antimicrobial activity of water-soluble chitosan derivatives SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE agar dilution; antimicrobial activity; broth microdilution; chitosan; disc diffusion ID ANTIBACTERIAL ACTIVITY; AGAR DILUTION; PLANT-EXTRACTS; CAMPYLOBACTER-JEJUNI; VIBRIO-VULNIFICUS; ESCHERICHIA-COLI; MOLECULAR-WEIGHT; RAW OYSTERS; SUSCEPTIBILITY; PRESERVATION AB Aims Chitosan has gained wide applications in the food industry and biomedical field owing to its biodegradability, biocompatibility, nontoxicity and its antimicrobial activity against a wide spectrum of micro-organisms. However, the methods used to investigate antimicrobial effects of chitosan vary considerably among studies, making comparisons difficult. Methods and Results One diffusion (disc diffusion) and two dilution (agar dilution and broth microdilution) methods commonly used in clinical laboratories to assess microbial susceptibility/resistance to antimicrobial agents were comparatively used to determine the antimicrobial activity of two water-soluble chitosan derivatives (molecular weights of 43 and 67kDa) against 31 representative foodborne pathogens. When tested at 1 center dot 6% for the 43-kDa chitosan and 3 center dot 2% for the 67-kDa chitosan, by disc diffusion, approximately 10- to 11-mm-diameter inhibition zones were observed for all of the bacterial groups, except for Salmonella tested for the 67-kDa chitosan where no inhibition zone was observed. By agar dilution and broth microdilution, the minimal inhibitory concentration (MIC) values varied largely dependent upon the molecular weight of chitosan, bacterial genus/species and the testing method. The agreement between MIC values obtained by the two methods was poor, with broth microdilution generally having lower MIC values than agar dilution. Regardless of the testing method, Salmonella strains were the least susceptible among Gram-negative strains for both chitosans, followed by Escherichia coli and Vibrio. Conclusions Besides chitosan's molecular weight and bacterial genus/species, the antimicrobial activity of chitosan was also influenced largely by the susceptibility testing method used. Significance and Impact of the Study This is the first study that comparatively evaluated these diffusion and dilution methods, particularly two quantitative methods (agar dilution and broth microdilution), to assess the antimicrobial activity of two water-soluble chitosans against a large number of foodborne pathogens. The study highlights the need for standardized methods to be used in evaluating chitosan's antimicrobial properties in future studies. C1 [Jiang, L.; Wang, F.; Han, F.; Prinyawiwatkul, W.; Ge, B.] Louisiana State Univ, Ctr Agr, Dept Food Sci, Baton Rouge, LA 70803 USA. [No, H. K.] Catholic Univ Daegu, Dept Food Sci & Technol, Hayang, South Korea. RP Ge, B (reprint author), US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM beilei.ge@fda.hhs.gov RI Wang, Fei/J-4353-2014 FU Aquaculture Special Grant from the US Department of Agriculture FX This study was supported in part by an Aquaculture Special Grant from the US Department of Agriculture. NR 40 TC 8 Z9 8 U1 0 U2 46 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD APR PY 2013 VL 114 IS 4 BP 956 EP 963 DI 10.1111/jam.12111 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 112DK UT WOS:000316572200004 PM 23279192 ER PT J AU Vyas, D Moallem, U Teter, BB Fardin-Kia, ARK Erdman, RA AF Vyas, D. Moallem, U. Teter, B. B. Fardin-Kia, A. R. K. Erdman, R. A. TI Milk fat responses to butterfat infusion during conjugated linoleic acid-induced milk fat depression in lactating dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE milk fat; de novo synthesis; fatty acid; dairy cow ID MAMMARY EPITHELIAL-CELLS; LIPOGENIC GENE NETWORKS; LIPID-SYNTHESIS; INTRAVENOUS INFUSIONS; RUMINAL FERMENTATION; ABOMASAL INFUSION; CHAIN-LENGTH; COCONUT OIL; CIS-12 CLA; TRANS-10 AB During diet-induced milk fat depression (MFD), the short and medium-chain fatty acids (SMCFA), which are synthesized de novo in the mammary gland, are reduced to a much greater extent than the long-chain fatty acids (LCFA) that originate from the circulation. Our hypothesis was that increased availability of SMCFA might rescue conjugated linoleic acid (CLA)-induced MFD in lactating dairy cows. To test that hypothesis, 4 rumen-fistulated lactating Holstein cows (128 +/- 23 d in milk) were used in a 4 x 4 Latin square design with 3-wk experimental periods. Treatments were applied during the last 2 wk of each period and included 3x daily abomasal infusion of a total of (1) 230 g/d of LCFA (blend of 59% cocoa butter, 36% olive oil, and 5% palm oil); (2) 420 g/d of butterfat (BF); (3) 230 g/d of LCFA with 27 g/d of CLA (LC-CLA), containing 10 g/d of trans-10,cis-12 CLA; and (4) 420 g/d of butterfat with 27 g/d of CLA (BF-CLA). Butterfat provided 50% of C16 (115 g/d) and similar amounts of C18 FA as found in LCFA, such that the difference between the BF and LCFA treatments was 190 g/d of SMCFA. No treatment effects were observed for DMI or milk yield. Milk fat content was reduced by 41 and 32%, whereas milk fat yield was reduced by 41 and 38% with LC-CLA and BF-CLA, respectively, compared with their respective controls. Abomasal infusion of CLA reduced de novo synthesized fatty acid (DNFA; SMCFA and 50% C16:0) concentration, whereas DNFA tended to be greater with BF infusion. An interaction was observed between SMCFA and CLA as the increased availability of SMCFA reduced stearoyl-CoA-desaturase-1 gene expression, whereas it tended to reduce lipoprotein lipase (LPL), 1-acylglycerol-3-phosphate O-acyltransferase 6 (AGPAT-6), sterol regulatory element-binding protein cleavage-activating protein (SCAP), and peroxisome proliferator-activated receptor gamma (PPAR-gamma) gene expression in the presence of CLA. The mRNA expression of genes involved in de novo fatty acid synthesis [acetyl-coenzyme A carboxylase alpha (ACACA) and fatty acid synthase (FASN)], fatty acid uptake (LPL), and triglyceride synthesis [AGPAT-6 and diacylglycerol O-acyltransferase 1 (DGAT-1)] along with protein abundance of the ACC and FASN were reduced with CLA. However, the increased availability of SMCFA had no effect on lipogenic gene expression except for LPL, whose expression was increased with BF infusion. The nutritional manipulation by increasing the intestinal availability of SMCFA was not sufficient to rescue CLA-induced MFD. C1 [Vyas, D.; Teter, B. B.; Erdman, R. A.] Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. [Moallem, U.] Agr Res Org, Volcani Ctr, Inst Anim Sci, Dept Ruminant Sci, IL-50250 Bet Dagan, Israel. [Fardin-Kia, A. R. K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Erdman, RA (reprint author), Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. EM erdman@umd.edu OI Vyas, Diwakar/0000-0002-7657-0267 NR 42 TC 6 Z9 6 U1 1 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD APR PY 2013 VL 96 IS 4 BP 2387 EP 2399 DI 10.3168/jds.2012-5861 PG 13 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 114VW UT WOS:000316772000043 PM 23415539 ER PT J AU Inn, KGW Johnson, CM Oldham, W Jerome, S Tandon, L Schaaff, T Jones, R Mackney, D MacKill, P Palmer, B Smith, D LaMont, S Griggs, J AF Inn, Kenneth G. W. Johnson, C. Martin, Jr. Oldham, Warren Jerome, Simon Tandon, Lav Schaaff, Thomas Jones, Robert Mackney, Daniel MacKill, Pam Palmer, Brett Smith, Donna LaMont, Stephen Griggs, John TI The urgent requirement for new radioanalytical certified reference materials for nuclear safeguards, forensics, and consequence management SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Reference materials; Metrology; Nuclear; Safeguards; Post-detonation; Detecting technologies; Consequence management AB A multi-agency workshop was held from 25 to 27 August 2009, at the National Institute of Standards and Technology (NIST), to identify and prioritize the development of radioanalytical Certified Reference Materials (CRMs, generally provided by National Metrology Institutes; Standard Reference Materials, a CRM issued by NIST) for field and laboratory nuclear measurement methods to be used to assess the consequences of a domestic or international nuclear event. Without these CRMs, policy makers concerned with detecting proliferation and trafficking of nuclear materials, attribution and retribution following a nuclear event, and public health consequences of a nuclear event would have difficulty making decisions based on analytical data that would stand up to scientific, public, and judicial scrutiny. The workshop concentrated on three areas: post-incident Improvised Nuclear Device (IND) nuclear forensics, safeguard materials characterization, and consequence management for an IND or a Radiological Dispersion Device detonation scenario. The workshop identified specific CRM requirements to fulfill the needs for these three measurement communities. Of highest priority are: (1) isotope dilution mass spectrometry standards, specifically U-233, Np-236g, Pu-244, and Am-243, used for quantitative analysis of the respective elements that are in critically short supply and in urgent need of replenishment and certification; (2) CRMs that are urgently needed for post-detonation debris analysis of actinides and fission fragments, and (3) CRMs used for destructive and nondestructive analyses for safeguards measurements, and radioisotopes of interest in environmental matrices. C1 [Inn, Kenneth G. W.] NIST, Gaithersburg, MD 20899 USA. [Johnson, C. Martin, Jr.] USAF, San Antonio, TX USA. [Oldham, Warren; Tandon, Lav; Smith, Donna; LaMont, Stephen] Los Alamos Natl Lab, Los Alamos, NM USA. [Jerome, Simon] Natl Phys Lab, London, England. [Schaaff, Thomas] Y12 Natl Secur Complex, Oak Ridge, TN USA. [Jones, Robert] Ctr Dis Control & Prevent, NCEH, Atlanta, GA USA. [Mackney, Daniel; Griggs, John] US EPA, NAREL, Montgomery, AL USA. [MacKill, Pam] US FDA, WEAC, Winchester, MA USA. [Palmer, Brett] Navarro Res & Engn Inc, Oak Ridge, TN USA. RP Inn, KGW (reprint author), NIST, 100 Bur Dr,MS 8462, Gaithersburg, MD 20899 USA. EM kenneth.inn@nist.gov OI Oldham, Warren/0000-0002-0997-2653 NR 19 TC 12 Z9 12 U1 2 U2 32 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2013 VL 296 IS 1 BP 5 EP 22 DI 10.1007/s10967-012-1972-y PG 18 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 112CM UT WOS:000316569600003 ER PT J AU Anderson, DL Cunningham, WC AF Anderson, David L. Cunningham, William C. TI Analysis of FDA in-house food reference materials with anticoincidence INAA SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE In-house reference materials; Swordfish; Cocoa powder; INAA AB In-house reference material (IRM) cocoa powder (CCP) has been in use at US Food and Drug Administration laboratories for about 15 years. A single lot of commercial material was originally characterized for 32 elements by several laboratories and five techniques. A unique approach for basis weight determination based upon ambient relative humidity was developed for CCP, eliminating the need for dry weight determinations. The CCP Reference Sheet is updated by incorporating new results approximately every 5 years. The last update occurred in 2006. As part of an effort to revalidate and update values for CCP, anticoincidence instrumental neutron activation analysis (INAA) was used to determine mass fractions for 16 of the originally characterized elements, as well as to provide information on 16 other elements. Results were in very good agreement with 2006 Reference Sheet values. A new candidate IRM, fresh-frozen swordfish (FFSF) powder, was produced by adding inorganic As, Cd, Cr, Hg, Pb, Sb, and Se to liquid nitrogen-frozen commercial swordfish filets which were then homogenized. Portions of FFSF were analyzed by INAA to provide mass fraction and homogeneity information for As, Cd, Cr, Hg, Sb, and Se as well as for eight other elements occurring naturally in the material. Non-homogeneities were a parts per thousand currency sign2.5 % for As, Br, Cd, and Cs, and a parts per thousand currency sign1.8 % for Cr, Hg, Rb, Sb, and Se. Certified reference materials DORM-3 Fish Protein powder and fresh-frozen SRM 1947 Lake Michigan Fish Tissue were analyzed as controls. C1 [Anderson, David L.; Cunningham, William C.] US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 13 TC 0 Z9 1 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2013 VL 296 IS 1 BP 175 EP 180 DI 10.1007/s10967-012-1931-7 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 112CM UT WOS:000316569600028 ER PT J AU Anderson, DL AF Anderson, David L. TI INAA study of Hg, Se, As, and Br irradiation losses from l-cysteine treated and untreated reference materials SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Hg; Se; As; Br; INAA; Procedural losses; L-cysteine treatment ID NEUTRON-ACTIVATION ANALYSIS; BIOLOGICAL-MATERIALS; ELEMENTS; MERCURY; FISH AB U. S. Food and Drug Administration in-house reference material (RM) Cocoa Powder and National Institute of Standards and Technology Standard RMs (SRMs) 1515 apple leaves, 1547 peach leaves, 1571 orchard leaves, 1566a oyster tissue, and 1568a rice flour were co-irradiated together with polyethylene blanks and analyzed for Hg and Se by anticoincidence instrumental neutron activation analysis. The three botanical SRM portions showed a combined Hg recovery of 70 % while the other portions showed a combined Hg recovery of 169 %, indicating that volatile Hg was lost from botanical SRMs and absorbed by the other irradiated portions. Total Hg recovery for all portions was 82 %. Se results showed no evidence of cross-contamination and all results agreed with certified and known values. National Research Council of Canada Certified RMs DOLT-3 dogfish liver, TORT-2 lobster hepatopancreas, and DORM-3 fish protein were separately analyzed either with no treatment or after treatment with l-cysteine solutions followed by drying over magnesium perchlorate. Each set of portions was co-irradiated with polyethylene and treated filter blanks. Analysis of all components of each treated portion irradiation package showed that essentially all Hg was retained within the package. Treated DOLT-3 portions (inorganic Hg content 53 %) showed a tenfold improvement with 99 % Hg retention. Hg retention for DORM-3 (7 % inorganic Hg) was 85 % (a twofold improvement) while retention for TORT-2 (44 % inorganic Hg), was 94 %, similar to that for untreated portions (96 %). Small irradiation losses (a parts per thousand currency sign0.5 %) of volatile species of Se, As, and Br were observed. C1 US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 16 TC 0 Z9 1 U1 2 U2 11 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2013 VL 296 IS 1 BP 181 EP 185 DI 10.1007/s10967-012-1929-1 PG 5 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 112CM UT WOS:000316569600029 ER PT J AU Anderson, DL AF Anderson, David L. TI Anticoincidence INAA capabilities for analysis of FDA Total Diet Study seafoods SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article DE Anticoincidence INAA; Total Diet Study; Seafoods; Ag; U; Sediment content ID NEUTRON-ACTIVATION ANALYSIS; SPECTROMETRY; URANIUM AB Anticoincidence instrumental neutron activation analysis was used to analyze three portions each of five fresh-weight FDA Total Diet Study seafoods from 3 Market Basket collections for fiscal years 2006-2008. Portions were treated with l-cysteine solutions to enhance retention of Hg during irradiation then dried at room temperature over magnesium perchlorate. Results or limits of detection were obtained for 33 elements. In general, results agreed with those available from FDA's Kansas city field laboratory (KAN-DO). Of three shrimp composites analyzed, one showed mass fractions of Ag, Fe, rare earths, U, Th, and Mo significantly higher (up to a factor of 10) than the other two shrimp composites. The same shrimp composite showed a lower Hg result (about 50 % after accounting for any irradiation loss) compared to the KAN-DO value. This may represent a drying loss. There were other indications of Hg loss during the drying process. SRM 1947 Lake Michigan Fish Tissue, run as a control, yielded an INAA Hg mass fraction 20 % lower (corrected for irradiation losses) than the certified value, similar to the difference between the INAA (0.171 mg/kg Hg) and KAN-DO (0.211 mg/kg Hg) results for a TDS canned tuna composite. Because previous studies showed that l-cysteine effectively sequesters inorganic Hg, these discrepancies likely represent methyl mercury loss. INAA results for As, Fe, Rb, and Se were in good agreement with SRM 1947 certified values. C1 US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Div Bioanalyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@fda.hhs.gov NR 16 TC 0 Z9 0 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 EI 1588-2780 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD APR PY 2013 VL 296 IS 1 BP 187 EP 194 DI 10.1007/s10967-012-1930-8 PG 8 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 112CM UT WOS:000316569600030 ER PT J AU Shin, EC Park, SH Nascimbeni, M Major, M Caggiari, L de Re, V Feinstone, SM Rice, CM Rehermann, B AF Shin, Eui-Cheol Park, Su-Hyung Nascimbeni, Michelina Major, Marian Caggiari, Laura de Re, Valli Feinstone, Stephen M. Rice, Charles M. Rehermann, Barbara TI The Frequency of CD127(+) Hepatitis C Virus (HCV)-Specific T Cells but Not the Expression of Exhaustion Markers Predicts the Outcome of Acute HCV Infection SO JOURNAL OF VIROLOGY LA English DT Article ID PD-1 EXPRESSION; VIRAL PERSISTENCE; FUNCTIONAL RESTORATION; PROGRAMMED DEATH-1; CD8 RESPONSES; PHENOTYPE; BLOCKADE; LYMPHOCYTES; DYSFUNCTION; CHIMPANZEES AB T cells are exhausted and overexpress inhibitory molecules in chronic hepatitis C virus (HCV) infection. It is unclear whether this is the cause or consequence of HCV persistence. By studying serial blood and liver samples of chimpanzees during acute infection, we demonstrate that the early expression of the memory precursor marker CD127 on HCV-specific T cells, but not the expression of inhibitory molecules on those T cells or their ligands in the liver, predicts the outcome of acute infection. C1 [Shin, Eui-Cheol; Park, Su-Hyung; Nascimbeni, Michelina; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD USA. [Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Lab Immunol & Infect Dis, Taejon 305701, South Korea. [Major, Marian; Feinstone, Stephen M.] US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. [Caggiari, Laura; de Re, Valli] IRCCS, Natl Canc Inst, CRO Ctr Riferimento Oncol, Expt & Clin Pharmacol Unit, Aviano, PN, Italy. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, Bethesda, MD USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011; Park, Su-Hyung/N-3514-2014 FU NIDDK, NIH; [AIRC-10266]; Associazione Italiana per la Ricerca sul Cancro FX This work was supported by grant AIRC-10266 to V. D. R. and by the NIDDK, NIH, intramural research program. NR 35 TC 17 Z9 21 U1 1 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 APR PY 2013 VL 87 IS 8 BP 4772 EP 4777 DI 10.1128/JVI.03122-12 PG 6 WC Virology SC Virology GA 113MC UT WOS:000316671000059 PM 23388706 ER PT J AU Boulanger, A Chen, Q Hinton, DM Stibitz, S AF Boulanger, Alice Chen, Qing Hinton, Deborah M. Stibitz, Scott TI In vivo phosphorylation dynamics of the Bordetella pertussis virulence-controlling response regulator BvgA SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; RNA-POLYMERASE; DNA-BINDING; BACILLUS-SUBTILIS; FHAB GENE; ACTIVATION; TRANSCRIPTION; MUTATIONS; EXPRESSION; PROMOTER AB We have used protein electrophoresis through polyacrylamide gels derivatized with the proprietary ligand Phos-tag to separate the response regulator BvgA from its phosphorylated counterpart BvgA approximate to P. This approach has allowed us to readily ascertain the degree of phosphorylation of BvgA in in vitro reactions, or in crude lysates of Bordetella pertussis grown under varying laboratory conditions. We have used this technique to examine the kinetics of BvgA phosphorylation after shift of B.pertussis cultures from non-permissive to permissive conditions, or of its dephosphorylation following a shift from permissive to non-permissive conditions. Our results provide the first direct evidence that levels of BvgA approximate to Pin vivo correspond temporally to the expression of early and late BvgA-regulated virulence genes. We have also examined a number of other aspects of BvgA function predicted from previous studies and by analogy with other two-component response regulators. These include the site of BvgA phosphorylation, the exclusive role of the cognate BvgS sensor kinase in its phosphorylation in Bordetella pertussis, and the effect of the T194M mutation on phosphorylation. We also detected the phosphorylation of a small but consistent fraction of BvgA purified after expression in Escherichia coli. C1 [Boulanger, Alice; Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA. [Chen, Qing; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM stibitz@helix.nih.gov FU Intramural Research Program of the NIH, NIDDK FX The authors thank A. Battesti, L. Knipling, T. James, S. Jha, L. Abell and J. Kassis for helpful discussions, Ilana Cohen for technical assistance and J. P. Castaing for the construction of pET21a+ D54N. This research was supported in part by the Intramural Research Program of the NIH, NIDDK. NR 49 TC 19 Z9 20 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2013 VL 88 IS 1 BP 156 EP 172 DI 10.1111/mmi.12177 PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 115KW UT WOS:000316812100012 PM 23489959 ER PT J AU Xu, ZL Qiu, Q Tian, J Smith, JS Conenello, GM Morita, T Byrnes, AP AF Xu, Zhili Qiu, Qi Tian, Jie Smith, Jeffrey S. Conenello, Gina M. Morita, Takashi Byrnes, Andrew P. TI Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement SO NATURE MEDICINE LA English DT Article ID GENE-TRANSFER; HUMAN-SERUM; IN-VIVO; TRANSGENE EXPRESSION; SCAVENGER RECEPTORS; INNATE IMMUNITY; KUPFFER CELLS; VECTORS; BINDING; HEXON AB Adenovirus type 5 (Ad5) specifically binds coagulation factor X (FX), and FX is normally essential for intravenously injected Ad5 vectors to transduce the liver. We demonstrate that the ability of FX to enhance liver transduction by Ad5 vectors is due to an unexpected ability of FX to protect Ad5 from attack by the classical complement pathway. In vitro, naive mouse serum neutralized Ad5 when FX was blocked from binding Ad5. This neutralization was mediated by natural IgM and the classical complement pathway. In vivo, FX was essential for Ad5 vectors to transduce the livers of wild-type mice, but FX was not required for liver transduction in mice that lack antibodies, C1q or C4. We conclude that Ad5 recruits FX as a defense against complement and that the sensitivity of Ad5 to inactivation by complement must be taken into account when designing vectors for systemic gene therapy. C1 [Xu, Zhili; Qiu, Qi; Tian, Jie; Smith, Jeffrey S.; Conenello, Gina M.; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Morita, Takashi] Meiji Pharmaceut Univ, Dept Biochem, Tokyo, Japan. RP Byrnes, AP (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM andrew.byrnes@fda.hhs.gov OI Byrnes, Andrew/0000-0003-1135-2629 FU US Food and Drug Administration (FDA); Oak Ridge Institute for Science and Education FX Funding was provided by the US Food and Drug Administration (FDA), including the FDA's Critical Path program. This project was supported in part by fellowships administered by the Oak Ridge Institute for Science and Education. We thank M. Barry (Mayo Clinic) for providing vectors, H. Mizuguchi (Osaka University) for providing plasmid pAdHM4-CMVL1 and M. Diamond (Washington University) for providing C1qa-/- mice. We thank M. Shlomchik (Yale University), S. Epstein (FDA) and J. Misplon (FDA) for providing JHD and mIg Tg mice. We thank the Center for Biologics Evaluation and Research animal facility staff for outstanding support. We thank S. Epstein, C. Kimchi-Sarfaty, G. Price and C. Wiethoff for helpful discussions or comments on the manuscript. NR 54 TC 52 Z9 52 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2013 VL 19 IS 4 BP 452 EP + DI 10.1038/nm.3107 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 119PF UT WOS:000317109100030 PM 23524342 ER PT J AU Snyder, KM Reaman, G Avant, D Pazdur, R AF Snyder, Kristen M. Reaman, Gregory Avant, Debbie Pazdur, Richard TI The Impact of the Written Request Process on Drug Development in Childhood Cancer SO PEDIATRIC BLOOD & CANCER LA English DT Article DE Best Pharmaceuticals for Children Act; FDA Modernization Act; pediatric cancer treatment; Pediatric Drug Development; Written Request ID GASTROINTESTINAL STROMAL TUMORS; INITIATIVES; CHILDREN; KIT AB Purpose. The Food and Drug Administration (FDA) Modernization Act, enacted in 1997, created a pediatric exclusivity incentive allowing sponsors to qualify for an additional 6 months of marketing exclusivity after satisfying the requirements outlined in the Written Request (WR). This review evaluates the impact of the WR mechanism on the development of oncology drugs in children. Methods. A search of the FDA document archiving, reporting, and regulatory tracking system was performed for January 1, 2000 to December 31, 2010. Drugs were identified and pediatric-specific labeling information was obtained from Drugs@fda.gov and FDA Pediatric Labeling Changes Table. Results. Fifty WRs have been issued for oncology drugs. Pediatric studies have been submitted for 14 drugs. Thirteen received pediatric exclusivity. As of December 31, 2010, labeling changes have been made for 11 drugs. Three drugs were approved for pediatric use. Conclusion. WRs have provided a mechanism to promote the study of drugs in pediatric malignancies. Information from studies resulting from the WRs regarding safety, pharmacokinetics, and tolerability of oncology drugs has been incorporated into pediatric labeling for 11/14 of the drugs. Earlier communication and collaboration between the FDA, National Cancer Institute, clinical investigators, and commercial sponsors are envisioned to facilitate the identification and prioritization of emerging new drugs of interest for WR consideration. Since this is the only regulatory mechanism, resulting from specific legislative initiatives relevant to cancer drug development for children, efforts to enhance its impact on increasing drug approval for pediatric cancer indications are warranted. Pediatr Blood Cancer 2013;60:531-537. (C) 2013 Wiley Periodicals, Inc. C1 [Snyder, Kristen M.; Reaman, Gregory; Pazdur, Richard] US FDA, Off Hematol & Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20901 USA. [Avant, Debbie] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20901 USA. RP Reaman, G (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2202, Silver Spring, MD 20901 USA. EM gregory.reaman@fda.hhs.gov NR 9 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2013 VL 60 IS 4 BP 531 EP 537 DI 10.1002/pbc.24346 PG 7 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 108KI UT WOS:000316291400003 PM 23335552 ER PT J AU Ray, WA Murray, KT Kawai, V Graham, DJ Cooper, WO Hall, K Stein, CM AF Ray, Wayne A. Murray, Katherine T. Kawai, Vivian Graham, David J. Cooper, William O. Hall, Kathi Stein, Charles Michael TI Propoxyphene and the risk of out-of-hospital death SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pharmacoepidemiology; propoxyphene; cardiovascular; sudden death ID SUDDEN CARDIAC DEATH; UNITED-STATES; CO-PROXAMOL; CHANNEL BLOCKADE; CLINICAL-TRIALS; OVERDOSE; MORTALITY; THERAPY; PHARMACOEPIDEMIOLOGY; NORPROPOXYPHENE AB Purpose The opioid analgesic propoxyphene was withdrawn from the US market in 2010, motivated by concerns regarding fatality in overdose and adverse cardiac effects, including prolongation of the QT interval. These concerns were based on case reports, summary vital statistics, and surrogate endpoint studies. Methods Using the linked Tennessee Medicaid database (19922007), we conducted a retrospective cohort study that compared risk of sudden cardiac, medication toxicity, and total out-of-hospital death for propoxyphene users with that for comparable nonusers of any prescribed opioid analgesic and users of hydrocodone, an opioid with similar indications. Cohort members had 1873500 propoxyphene prescriptions, 1873500 matched nonuser control periods, and 936750 matched hydrocodone prescriptions. Results Current propoxyphene users had no increased risk for sudden cardiac death (versus nonusers: hazard ratio [HR]=1.00 [0.811.23]; versus current hydrocodone users: HR=0.91 [0.681.21]) but did have increased risk for medication toxicity deaths (versus nonusers: HR=1.85 [1.073.19], p=0.027; versus current hydrocodone users: HR=2.10 [0.875.10], p=0.100). Because toxicity deaths were a small proportion of study deaths, total out-of-hospital mortality differed by less than 10% between the study groups and was not significantly elevated for propoxyphene (versus nonusers: HR=1.09 [0.951.25]; versus current hydrocodone users: HR=1.06 [0.871.29] ). Conclusions Our findings support the concern that propoxyphene has greater toxicity in overdose but do not provide evidence that it increases the risk of sudden cardiac death. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Ray, Wayne A.; Hall, Kathi] Dept Prevent Med, Div Pharmacoepidemiol, Nashville, TN USA. [Murray, Katherine T.] Vanderbilt Univ, Dept Med & Pharmacol, Div Cardiol, Sch Med, Nashville, TN USA. [Stein, Charles Michael] Vanderbilt Univ, Dept Med & Pharmacol, Div Rheumatol, Sch Med, Nashville, TN USA. [Murray, Katherine T.; Kawai, Vivian; Stein, Charles Michael] Vanderbilt Univ, Dept Med & Pharmacol, Div Clin Pharmacol, Sch Med, Nashville, TN USA. [Cooper, William O.] Vanderbilt Univ, Dept Pediat, Sch Med, Nashville, TN USA. [Graham, David J.] US FDA, Silver Spring, MD USA. RP Ray, WA (reprint author), Village Vanderbilt, Div Pharmacoepidemiol, Dept Prevent Med, Suite 2600,1501 21st Ave South, Nashville, TN 37212 USA. EM wayne.ray@vanderbilt.edu FU Food and Drug Administration [HHSF223201000011I]; National Heart, Lung, and Blood Institute [HL081707]; National Institute for Arthritis and Musculoskeletal and Skin Diseases [P60AR056116] FX This study was supported in part by a contract from the Food and Drug Administration (HHSF223201000011I) and grants from the National Heart, Lung, and Blood Institute (HL081707) and the National Institute for Arthritis and Musculoskeletal and Skin Diseases (P60AR056116). The views expressed are the authors' and not necessarily those of the Food and Drug Administration. NR 47 TC 8 Z9 8 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD APR PY 2013 VL 22 IS 4 BP 403 EP 412 DI 10.1002/pds.3411 PG 10 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 118FM UT WOS:000317009200008 PM 23408551 ER PT J AU Toh, S Li, Q Cheetham, TC Cooper, WO Davis, RL Dublin, S Hammad, TA Li, DK Pawloski, PA Pinheiro, SP Raebel, MA Scott, PE Smith, DH Bobo, WV Lawrence, JM Dashevsky, I Haffenreffer, K Avalos, LA Andrade, SE AF Toh, Sengwee Li, Qian Cheetham, T. Craig Cooper, William O. Davis, Robert L. Dublin, Sascha Hammad, Tarek A. Li, De-Kun Pawloski, Pamala A. Pinheiro, Simone P. Raebel, Marsha A. Scott, Pamela E. Smith, David H. Bobo, William V. Lawrence, Jean M. Dashevsky, Inna Haffenreffer, Katherine Avalos, Lyndsay A. Andrade, Susan E. TI Prevalence and trends in the use of antipsychotic medications during pregnancy in the U.S., 2001-2007: a population-based study of 585,615 deliveries SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Article DE Antipsychotics; Database; Pregnancy; Prevalence ID ATYPICAL ANTIPSYCHOTICS; BIPOLAR DISORDER; BIRTH-WEIGHT; MANAGEMENT; SCHIZOPHRENIA; EXPOSURE; PSYCHOTROPICS; OUTCOMES; RISKS; AGE AB This study aims to estimate the prevalence of and temporal trends in prenatal antipsychotic medication use within a cohort of pregnant women in the U.S. We identified live born deliveries to women aged 15-45 years in 2001-2007 from 11 U.S. health plans participating in the Medication Exposure in Pregnancy Risk Evaluation Program. We ascertained prenatal exposure to antipsychotics from health plan pharmacy dispensing files, gestational age from linked infant birth certificate files, and ICD-9-CM diagnosis codes from health plan claims files. We calculated the prevalence of prenatal use of atypical and typical antipsychotics according to year of delivery, trimester of pregnancy, and mental health diagnosis. Among 585,615 qualifying deliveries, 4,223 (0.72 %) were to women who received an atypical antipsychotic and 548 (0.09 %) were to women receiving a typical antipsychotic any time from 60 days before pregnancy through delivery. There was a 2.5-fold increase in atypical antipsychotic use during the study period, from 0.33 % (95 % confidence interval: 0.29 %, 0.37 %) in 2001 to 0.82 % (0.76 %, 0.88 %) in 2007, while the use of typical antipsychotics remained stable. Depression was the most common mental health diagnosis among deliveries to women with atypical antipsychotic use (63 %), followed by bipolar disorder (43 %) and schizophrenia (13 %). The number and proportion of pregnancies exposed to atypical antipsychotics has increased dramatically in recent years. Studies are needed to examine the comparative safety and effectiveness of these medications relative to other therapeutic options in pregnancy. C1 [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA 02215 USA. [Toh, Sengwee; Dashevsky, Inna; Haffenreffer, Katherine] Harvard Pilgrim Hlth Care Inst, Boston, MA 02215 USA. [Li, Qian] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. [Cheetham, T. Craig] Kaiser Permanente, Pharm Analyt Serv, Downey, CA USA. [Cooper, William O.] Vanderbilt Univ, Sch Med, Dept Pediat & Prevent Med, Nashville, TN 37212 USA. [Davis, Robert L.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA. [Dublin, Sascha] Grp Hlth Res Inst, Seattle, WA USA. [Hammad, Tarek A.; Pinheiro, Simone P.; Scott, Pamela E.] Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Li, De-Kun; Avalos, Lyndsay A.] Kaiser Permanente Northern Calif, Div Res, Oakland, CA USA. [Pawloski, Pamala A.] HealthPartners Res Fdn, Bloomington, MN USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Smith, David H.] Kaiser Permanente Northwest, Ctr Hlth Res, Portland, OR USA. [Bobo, William V.] Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37212 USA. [Lawrence, Jean M.] Kaiser Permanente Southern Calif, Dept Res & Evaluat, Pasadena, CA USA. [Andrade, Susan E.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Worcester, MA USA. RP Toh, S (reprint author), Harvard Univ, Sch Med, Dept Populat Med, 133 Brookline Ave 6th Floor, Boston, MA 02215 USA. EM darrentoh@post.harvard.edu RI Toh, Sengwee/D-7567-2017 OI Toh, Sengwee/0000-0002-5160-0810 FU U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Silver Spring, MD, USA) [HHSF223200510012C, HHSF223200510009C, HHSF223200510008C]; National Institute on Aging [K23AG028954]; National Institute of Mental Health [K23MH087747]; GlaxoSmithKline FX This study was supported through funding from contracts HHSF223200510012C, HHSF223200510009C, and HHSF223200510008C from the U.S. Food and Drug Administration (Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research, Silver Spring, MD, USA). Dr. Dublin was supported by National Institute on Aging grant K23AG028954, Dr. Bobo was supported by National Institute of Mental Health grant K23MH087747. Dr. Andrade has received research funding from GlaxoSmithKline, a manufacturer of an antipsychotic medication, in the past 12 months for a project unrelated to antipsychotic medication use. The views expressed in this paper are those of the authors and are not intended to convey official U.S. Food and Drug Administration policy or guidance. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Aging, National Institute of Mental Health, or the National Institutes of Health. NR 35 TC 29 Z9 29 U1 3 U2 20 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD APR PY 2013 VL 16 IS 2 BP 149 EP 157 DI 10.1007/s00737-013-0330-6 PG 9 WC Psychiatry SC Psychiatry GA 106LX UT WOS:000316146300009 PM 23389622 ER PT J AU Prabhakara, R Foreman, O De Pascalis, R Lee, GM Plaut, RD Kim, SY Stibitz, S Elkins, KL Merkel, TJ AF Prabhakara, Ranjani Foreman, Oded De Pascalis, Roberto Lee, Gloria M. Plaut, Roger D. Kim, Stanley Y. Stibitz, Scott Elkins, Karen L. Merkel, Tod J. TI Epicutaneous Model of Community-Acquired Staphylococcus aureus Skin Infections SO INFECTION AND IMMUNITY LA English DT Article ID SITE-DIRECTED MUTAGENESIS; SOFT-TISSUE INFECTIONS; METHICILLIN-RESISTANT; CUTANEOUS INFECTION; ALPHA-HEMOLYSIN; HOST-DEFENSE; MURINE MODEL; MOUSE MODEL; SPIDER BITE; VIRULENCE AB Staphylococcus aureus is one of the most common etiological agents of community-acquired skin and soft tissue infection (SSTI). Although the majority of S. aureus community-acquired SSTIs are uncomplicated and self-clearing in nature, some percentage of these cases progress into life-threatening invasive infections. Current animal models of S. aureus SSTI suffer from two drawbacks: these models are a better representation of hospital-acquired SSTI than community-acquired SSTI, and they involve methods that are difficult to replicate. For these reasons, we sought to develop a murine model of community-acquired methicillin-resistant S. aureus SSTI (CA-MRSA SSTI) that can be consistently reproduced with a high degree of precision. We utilized this model to begin to characterize the host immune response to this type of infection. We infected mice via epicutaneous challenge of the skin on the outer ear pinna using Morrow-Brown allergy test needles coated in S. aureus USA300. When mice were challenged in this model, they developed small, purulent, self-clearing lesions with predictable areas of inflammation that mimicked a human infection. CFU in the ear pinna peaked at day 7 before dropping by day 14. The T(h)1 and T(h)17 cytokines gamma interferon (IFN-gamma), interleukin-12 (IL-12) p70, tumor necrosis factor alpha (TNF-alpha), IL-17A, IL-6, and IL-21 were all significantly increased in the draining lymph node of infected mice, and there was neutrophil recruitment to the infection site. In vivo neutrophil depletion demonstrated that neutrophils play a protective role in preventing bacterial dissemination and fatal invasive infection. C1 [Prabhakara, Ranjani; De Pascalis, Roberto; Lee, Gloria M.; Plaut, Roger D.; Kim, Stanley Y.; Stibitz, Scott; Elkins, Karen L.; Merkel, Tod J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Foreman, Oded] Jackson Lab, Sacramento, CA USA. RP Merkel, TJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM tod.merkel@fda.hhs.gov RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X FU NIH [N01-AI-95359]; NIAID FX Strain NRS384 was obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA), supported under NIAID, NIH contract no. N01-AI-95359. NR 54 TC 16 Z9 16 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2013 VL 81 IS 4 BP 1306 EP 1315 DI 10.1128/IAI.01304-12 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108RM UT WOS:000316313700027 PM 23381997 ER PT J AU Kasser, MJ AF Kasser, Michael J. TI Regulation of UHMWPE biomaterials in total hip arthroplasty SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE polyethylene (UHMWPE); hip prosthesis; arthroplasty; joint replacement ID MOLECULAR-WEIGHT POLYETHYLENE; CROSS-LINKING; FATIGUE RESISTANCE; ALPHA-TOCOPHEROL; WEAR; STERILIZATION; OXIDATION; IMPLANTS AB This manuscript provides a brief history of the development of ultrahigh molecular weight polyethylene (UHWMPE) biomaterials and how the U.S. Food and Drug Administration (FDA) regulates medical devices. The flowchart used to decide whether a device is medium or high risk, known as the 510(k) flowchart, is illustrated by taking several examples through the flowchart. In order to demonstrate how changes to UHWMPE material used in the acetabular liners of total hips have been regulated, two major modifications to UHMWPE, highly crosslinked polyethylene and Vitamin E polyethylene, are taken through the flowchart. This manuscript describes the testing that has been provided to demonstrate safety and effectiveness of these modifications, as well as an explanation why the testing was supplied to the FDA. (c) 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 101B: 400406, 2013. C1 US FDA, Orthoped Joint Devices Branch, Off Device Evaluat, Silver Spring, MD 20993 USA. RP Kasser, MJ (reprint author), US FDA, Orthoped Joint Devices Branch, Off Device Evaluat, Silver Spring, MD 20993 USA. EM michael.kasser@fda.hhs.gov NR 18 TC 2 Z9 4 U1 2 U2 31 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2013 VL 101B IS 3 BP 400 EP 406 DI 10.1002/jbm.b.32809 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 112DY UT WOS:000316573600002 PM 22987363 ER PT J AU Younis, IR Laughren, TP Wang, YN Mathis, M Gobburu, JV AF Younis, Islam Rasem Laughren, Thomas P. Wang, Yaning Mathis, Mitchell Gobburu, Jogarao V. TI An Integrated Approach for Establishing Dosing Recommendations Paliperidone for the Treatment of Adolescent Schizophrenia SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE dosing recommendations; exposure-response; paliperidone; adolescents; schizophrenia ID EXTENDED-RELEASE TABLETS; DOUBLE-BLIND; RISPERIDONE; SAFETY; MULTICENTER; HALOPERIDOL; EFFICACY; 6-WEEK AB The Food and Drug Administration recently approved Invega for the treatment of schizophrenia in adolescents 12 to 17 years. If dosing recommendations for this population would have been based only on the results of the single efficacy trial included in this program, paliperidone dosing in adolescents might have been limited to 3 mg/d in adolescents less than 51 kg and to 6 mg/d in adolescents greater than or equal to 51 kg. This article provides an illustration of a more integrated approach to arrive at dosing recommendation that included practical considerations, modeling and simulation of data from the clinical trial, and the totality of evidence for both paliperidone and the parent drug, risperidone. On the basis of this integrated approach, the agency approved a starting dose of 3 mg/d in both adolescent weight groups and subsequent dosing in a range of 3 to 6 mg/d for adolescents less than 51 kg and 3 to 12 mg/d for adolescents greater than 51 kg, although the 3-mg dose was not evaluated in the greater than or equal to 51-kg group. C1 [Younis, Islam Rasem; Wang, Yaning] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Laughren, Thomas P.; Mathis, Mitchell] US FDA, Div Psychiat Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Gobburu, Jogarao V.] Univ Maryland, Sch Pharm, Inst Translat Med, Baltimore, MD 21201 USA. [Gobburu, Jogarao V.] Univ Maryland, Sch Med, Inst Translat Med, Baltimore, MD 21201 USA. RP Younis, IR (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10993 New Hampshire Ave,Bldg 51, Silver Spring, MD 20993 USA. EM islam.younis@fda.hhs.gov NR 10 TC 3 Z9 3 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2013 VL 33 IS 2 BP 152 EP 156 DI 10.1097/JCP.0b013e31828393a8 PG 5 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 108NX UT WOS:000316303700002 PM 23422374 ER PT J AU Kaushal, S Gervais, B Lute, S Eroraha, A Faustino, P Brorson, K Hussong, D AF Kaushal, Simran Gervais, Brandi Lute, Scott Eroraha, Ajiri Faustino, Patrick Brorson, Kurt Hussong, David TI Evidence for grow-through penetration of 0.2-mu m-pore-size filters by Serratia marcescens and Brevundimonas diminuta SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Filtration; Serratia marcescens; Brevundimonas diminuta; Pharmaceutical product sterility ID MEMBRANE-FILTER; INFILTRATION; PSEUDOFLAVA; ABILITY; SIZE AB We find that both Brevundimonas diminuta and Serratia marcescens can grow through sterilizing grade filter membranes of different membrane polymer compositions. Although this passage does not occur on a consistent basis, generation of "grow-through positive" results indicate that grow-through can occur stochastically at basal levels. This observation argues that the following risk mitigation strategies during pharmaceutical aseptic processing are warranted: minimization of processing times, and monitoring, minimizing and characterizing pre-filter bioburden. C1 [Kaushal, Simran; Gervais, Brandi; Lute, Scott; Eroraha, Ajiri; Faustino, Patrick; Brorson, Kurt; Hussong, David] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Gervais, Brandi] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. [Eroraha, Ajiri] Notre Dame Univ Maryland, Baltimore, MD 21210 USA. RP Brorson, K (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov FU CDER's Regulatory Science Research program [10-40, 12-39] FX This work was funded in part by a grant from CDER's Regulatory Science Research program (grants 10-40 and 12-39). The authors thank Laurie Graham and Mansoor Khan for careful review of this manuscript. NR 12 TC 1 Z9 1 U1 1 U2 10 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD APR PY 2013 VL 40 IS 3-4 BP 327 EP 334 DI 10.1007/s10295-013-1232-3 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 107PE UT WOS:000316229600007 PM 23385852 ER PT J AU Koturbash, I Melnyk, S James, SJ Beland, FA Pogribny, IP AF Koturbash, Igor Melnyk, Stepan James, S. Jill Beland, Frederick A. Pogribny, Igor P. TI Role of epigenetic and miR-22 and miR-29b alterations in the downregulation of Mat1a and Mthfr genes in early preneoplastic livers in rats induced by 2-acetylaminofluorene SO MOLECULAR CARCINOGENESIS LA English DT Article DE hepatocarcinogenesis; epigenetics; microRNA ID HUMAN HEPATOCELLULAR-CARCINOMA; ABERRANT DNA METHYLATION; PROMOTER METHYLATION; HISTONE H3; METHIONINE METABOLISM; S-ADENOSYLMETHIONINE; CANCER; EXPRESSION; HYPERMETHYLATION; ASSOCIATION AB Carcinogenesis is a multistep sequential process of clonal expansion of initiated cells associated with the accumulation of multiple cancer-specific heritable phenotypes. The acquisition of these heritable cancer-specific alterations may be triggered by mutational and/or non-mutational changes in the genome that affect the regulation of gene expression. Currently, cancer-specific epigenetically mediated changes in gene expression are regarded as driving events in tumorigenesis. In the present study, we investigated the role of gene-specific expression changes in the mechanism of rat hepatocarcinogenesis induced by the complete hepatocarcinogen 2-acetylaminofluorene (2-AAF). The results of the present study demonstrate significant alterations in gene expression, especially of Mat1a and Mthfr genes, during early stages of rat 2-AAF-induced liver carcinogenesis. Both of these genes were downregulated in the livers of 2-AAF-treated male rats. Inhibition of Mat1a expression was associated with an increase in histone H3 lysine 27 trimethylation and a decrease in histone H3 lysine 18 acetylation at the gene promoter/first exon region. Additionally, we demonstrate for the first time a critical contribution of miR-22 and miR-29b microRNAs in the inhibition of Mat1a and Mthfr gene expression during 2-AAF-induced rat hepatocarcinogenesis. The downregulation of Mat1a and Mthfr genes was accompanied by marked functional alterations in one-carbon metabolism. The results of the present study suggest that downregulation of the Mat1a and Mthfr genes may be one of the main driver events that promote liver carcinogenesis by causing a profound accumulation of subsequent epigenetic abnormalities during progression of the carcinogenic process. (c) 2011 Wiley Periodicals, Inc. C1 [Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Melnyk, Stepan; James, S. Jill] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 51 TC 13 Z9 15 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 2013 VL 52 IS 4 BP 318 EP 327 DI 10.1002/mc.21861 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 112CQ UT WOS:000316570000008 PM 22213190 ER PT J AU Kurasawa, JH Shestopal, SA Jha, NK Ovanesov, MV Lee, TK Sarafanov, AG AF Kurasawa, James H. Shestopal, Svetlana A. Jha, Naveen K. Ovanesov, Mikhail V. Lee, Timothy K. Sarafanov, Andrey G. TI Insect cell-based expression and characterization of a single-chain variable antibody fragment directed against blood coagulation factor VIII SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Expression; Baculovirus system; Single-chain variable fragment; Factor VIII; Hemophilia A ID HIGH-LEVEL EXPRESSION; ESCHERICHIA-COLI; IN-VITRO; FV ANTIBODIES; TISSUE FACTOR; PURIFICATION; PROTEINS; DOMAINS; SYSTEMS; SCFV AB A recombinant single-chain variable antibody fragment (scFv) KM33 was previously described as a ligand that can inhibit the function of blood coagulation factor VIII (FVIII). This scFv was previously derived from an individual with anti-FVIII antibodies manifested in FVIII functional deficiency (Hemophilia A) and expressed in bacteria. In the present work, we describe an alternative approach for fast and easy production of KM33 in insect cells (Spodoptera frugiperda). The KM33 gene was codon-optimized and expressed in secreted form using a baculovirus system. The protein was isolated using metal-affinity and size-exclusion chromatography to purity of about 96% and yield of 0.4-1.2 mg per 120 mL of culture, based on several independent expression experiments. In a binding assay using surface plasmon resonance, the insect cell-derived KM33 (iKM33) was qualified as a high-affinity ligand for FVIII. Epitope specificity of iKM33 on FVIII (C1 domain) was confirmed by testing the binding with a relevant mutant of FVIII. In several FVIII functional tests (factor Xa generation, APTT clotting, thrombin generation and video microscopy clot growth assays), iKM33 strongly inhibited FVIII activity in accordance with the clinical effect of the parental antibody. Therefore, the expressed protein was concluded to be fully functional and applicable in various assays with FVIII. Published by Elsevier Inc. C1 [Kurasawa, James H.; Shestopal, Svetlana A.; Jha, Naveen K.; Ovanesov, Mikhail V.; Lee, Timothy K.; Sarafanov, Andrey G.] US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. RP Sarafanov, AG (reprint author), US FDA, CBER, OBRR, DH, 1401 Rockville Pike HFM-340, Rockville, MD 20852 USA. EM Andrey.Sarafanov@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration FX This work was supported by funds from the Center for Biologics Evaluation and Research (CBER) of the U.S. Food and Drug Administration and also by an appointment to the Research Participation Program at the CBER administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We are thankful to our colleagues from CBER, Drs. Michael Kennedy and Malgorzata Norton for support in the SPR-based experiments and Laura Wood for help in the manuscript preparation. NR 42 TC 6 Z9 6 U1 1 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2013 VL 88 IS 2 BP 201 EP 206 DI 10.1016/j.pep.2012.12.008 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 111RH UT WOS:000316537900005 PM 23306063 ER PT J AU Chen, G Wang, C Shi, LM Qu, XF Chen, JW Yang, JM Shi, CP Chen, L Zhou, PY Ning, BT Tong, WD Shi, TL AF Chen, Geng Wang, Charles Shi, Leming Qu, Xiongfei Chen, Jiwei Yang, Jianmin Shi, Caiping Chen, Long Zhou, Peiying Ning, Baitang Tong, Weida Shi, Tieliu TI Incorporating the human gene annotations in different databases significantly improved transcriptomic and genetic analyses SO RNA LA English DT Article DE RNA-seq; short-read mapping; gene expression quantification; differential expression calling; genetics ID RNA-SEQ; HUMAN GENOME; EXPRESSION; REVEALS; SEQUENCES; QUANTIFICATION; PROJECT; CANCER AB Human gene annotation is crucial for conducting transcriptomic and genetic studies; however, the impacts of human gene annotations in diverse databases on related studies have been less evaluated. To enable full use of various human annotation resources and better understand the human transcriptome, here we systematically compare the human annotations present in RefSeq, Ensembl (GENCODE), and AceView on diverse transcriptomic and genetic analyses. We found that the human gene annotations in the three databases are far from complete. Although Ensembl and AceView annotated more genes than RefSeq, more than 15,800 genes from Ensembl (or AceView) are within the intergenic and intronic regions of AceView (or Ensembl) annotation. The human transcriptome annotations in RefSeq, Ensembl, and AceView had distinct effects on short-read mapping, gene and isoform expression profiling, and differential expression calling. Furthermore, our findings indicate that the integrated annotation of these databases can obtain a more complete gene set and significantly enhance those transcriptomic analyses. We also observed that many more known SNPs were located within genes annotated in Ensembl and AceView than in RefSeq. In particular, 1033 of 3041 trait/disease-associated SNPs involved in about 200 human traits/diseases that were previously reported to be in RefSeq intergenic regions could be relocated within Ensembl and AceView genes. Our findings illustrate that a more complete transcriptome generated by incorporating human gene annotations in diverse databases can strikingly improve the overall results of transcriptomic and genetic studies. C1 [Chen, Geng; Qu, Xiongfei; Chen, Jiwei; Yang, Jianmin; Shi, Caiping; Chen, Long; Zhou, Peiying; Shi, Tieliu] E China Normal Univ, Ctr Bioinformat & Computat Biol, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China. [Chen, Geng; Qu, Xiongfei; Chen, Jiwei; Yang, Jianmin; Shi, Caiping; Chen, Long; Zhou, Peiying; Shi, Tieliu] E China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China. [Wang, Charles] City Hope Comprehens Canc Ctr, Funct Genom Core, Beckman Res Inst, Duarte, CA 91010 USA. [Shi, Leming; Ning, Baitang; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, TL (reprint author), E China Normal Univ, Ctr Bioinformat & Computat Biol, Shanghai Key Lab Regulatory Biol, Inst Biomed Sci, Shanghai 200241, Peoples R China. EM tieliushi01@gmail.com FU National 973 Key Basic Research Program [2010CB945401, 2012CB910400]; National Natural Science Foundation of China [31240038, 31071162, 31000590]; Science and Technology Commission of Shanghai Municipality [11DZ2260300]; Graduate School of East China Normal University FX We thank Pengzhan Hu for her assistance in drawing some figures. We are also grateful to Dr. Keely Walker at City of Hope for her help in reviewing the manuscript. This work was supported by the National 973 Key Basic Research Program (Grant Nos. 2010CB945401 and 2012CB910400), the National Natural Science Foundation of China (Grant No. 31240038, 31071162, and 31000590), the Science and Technology Commission of Shanghai Municipality (11DZ2260300), and the Graduate School of East China Normal University. NR 45 TC 9 Z9 10 U1 0 U2 21 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1355-8382 EI 1469-9001 J9 RNA JI RNA PD APR PY 2013 VL 19 IS 4 BP 479 EP 489 DI 10.1261/rna.037473.112 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 108XH UT WOS:000316329100007 PM 23431329 ER PT J AU Ferguson, SA Sarkar, S Schmued, LC AF Ferguson, Sherry A. Sarkar, Sumit Schmued, Larry C. TI Longitudinal behavioral changes in the APP/PS1 transgenic Alzheimer's Disease model SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE APP/PS1; Transgenic; Water maze; Alzheimer's Disease; Longitudinal; Male ID MORRIS WATER MAZE; APPSWE/PS1DE9 MOUSE MODEL; MEMORY DEFICITS; AMYLOID-BETA; SPATIAL MEMORY; EXPLORATORY ACTIVITY; MICE; PERFORMANCE; DEPOSITION; BRAIN AB The APP/PS1 double transgenic mouse is an Alzheimer's Disease-like model. However, cognitive deficits measured at one age do not necessarily indicate age-related progressions. Further, results of the most widely used behavioral assessment, water maze performance, are generally limited to 1-2 endpoints. Here, male APP/PS1 and noncarrier wildtypes (n = 11/group) were assessed at 7-15 months of age for water maze, open field, and motor coordination performance. Body weights and motor coordination were comparable for both groups throughout. Beginning at approximately 9 months of age, the transgenic group exhibited hypoactivity in the open field which continued throughout. Latency to locate the platform and swim path length were longer in the transgenic group; however, these appeared to be more related to increased floating and thigmotactic behavior and only partially related to a cognitive impairment. Age-related decrements in performance were not substantial; however, substantial plaque numbers were measured in six representative 16-month-old transgenic mice. The stability of water maze performance may be related to the longitudinal testing and repetitive experience, which previous research has demonstrated can confer beneficial effects on behavior and plaque deposition in transgenic Alzheimer's Disease models [1]. These results emphasize the importance of measuring multiple water maze endpoints and demonstrate the feasibility of longitudinal assessments in this model. Published by Elsevier B.V. C1 [Ferguson, Sherry A.; Sarkar, Sumit; Schmued, Larry C.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU National Center for Toxicological Research/FDA [07272] FX This work was supported by the National Center for Toxicological Research/FDA (Protocol #07272). NR 56 TC 10 Z9 12 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 1 PY 2013 VL 242 BP 125 EP 134 DI 10.1016/j.bbr.2012.12.055 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 099XV UT WOS:000315660100016 PM 23295401 ER PT J AU Ke, AB Nallani, SC Zhao, P Rostami-Hodjegan, A Isoherranen, N Unadkat, JD AF Ke, Alice Ban Nallani, Srikanth C. Zhao, Ping Rostami-Hodjegan, Amin Isoherranen, Nina Unadkat, Jashvant D. TI A Physiologically Based Pharmacokinetic Model to Predict Disposition of CYP2D6 and CYP1A2 Metabolized Drugs in Pregnant Women SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID SPARTEINE OXIDATION POLYMORPHISM; ACTIVITY IN-VIVO; METOPROLOL METABOLISM; PARALLEL PATHWAYS; BLOOD-PRESSURE; VITRO DATA; CLONIDINE; DEXTROMETHORPHAN; THEOPHYLLINE; PAROXETINE AB Conducting pharmacokinetic (PK) studies in pregnant women is challenging. Therefore, we asked if a physiologically based pharmacokinetic (PBPK) model could be used to evaluate different dosing regimens for pregnant women. We refined and verified our previously published pregnancy PBPK model by incorporating cytochrome P450 CYP1A2 suppression (based on caffeine PK) and CYP2D6 induction (based on metoprolol PK) into the model. This model accounts for gestational age-dependent changes in maternal physiology and hepatic CYP3A activity. For verification, the disposition of CYP1A2-metabolized drug theophylline (THEO) and CYP2D6-metabolized drugs paroxetine (PAR), dextromethorphan (DEX), and clonidine (CLO) during pregnancy was predicted. Our PBPK model successfully predicted THEO disposition during the third trimester (T-3). Predicted mean postpartum to third trimester (PP:T-3) ratios of THEO area under the curve (AUC), maximum plasma concentration, and minimum plasma concentration were 0.76, 0.95, and 0.66 versus observed values 0.75, 0.89, and 0.72, respectively. The predicted mean PAR steady-state plasma concentration (Css) ratio (PP: T-3) was 7.1 versus the observed value 3.7. Predicted mean DEX urinary ratio (UR) (PP: T-3) was 2.9 versus the observed value 1.9. Predicted mean CLO AUC ratio (PP: T-3) was 2.2 versus the observed value 1.7. Sensitivity analysis suggested that a 100% induction of CYP2D6 during T-3 was required to recover the observed PP: T-3 ratios of PAR Css, DEX UR, and CLO AUC. Based on these data, it is prudent to conclude that the magnitude of hepatic CYP2D6 induction during T3 ranges from 100 to 200%. Our PBPK model can predict the disposition of CYP1A2, 2D6, and 3A drugs during pregnancy. C1 [Ke, Alice Ban; Isoherranen, Nina; Unadkat, Jashvant D.] Univ Washington, Dept Pharmaceut, Seattle, WA 98195 USA. [Ke, Alice Ban; Nallani, Srikanth C.; Zhao, Ping] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. [Rostami-Hodjegan, Amin] Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester, Lancs, England. [Rostami-Hodjegan, Amin] Simcyp Ltd, Sheffield, S Yorkshire, England. RP Unadkat, JD (reprint author), Univ Washington, Dept Pharmaceut, Box 357610, Seattle, WA 98195 USA. EM jash@u.washington.edu FU Food and Drug Administration Office of Women's Health; Simcyp Limited (now part of Certara); National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [U10HD047892] FX This work was supported by the Food and Drug Administration Office of Women's Health and a visiting fellowship from Simcyp Limited (now part of Certara). The clonidine pharmacokinetics study in pregnancy was supported in part by a grant from the National Institutes of Health Eunice Kennedy Shriver National Institute of Child Health and Human Development [Grant U10HD047892]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Eunice Kennedy Shriver National Institute of Child Health and Human Development or the National Institutes of Health. NR 67 TC 16 Z9 19 U1 1 U2 21 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2013 VL 41 IS 4 BP 801 EP 813 DI 10.1124/dmd.112.050161 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 105XM UT WOS:000316106000016 PM 23355638 ER PT J AU Petrochenko, PE Scarel, G Hyde, GK Parsons, GN Skoog, SA Zhang, Q Goering, PL Narayan, RJ AF Petrochenko, Peter E. Scarel, Giovanna Hyde, G. Kevin Parsons, Gregory N. Skoog, Shelby A. Zhang, Qin Goering, Peter L. Narayan, Roger J. TI Prevention of Ultraviolet (UV)-Induced Surface Damage and Cytotoxicity of Polyethersulfone Using Atomic Layer Deposition (ALD) Titanium Dioxide SO JOM LA English DT Article ID HOLLOW-FIBER MEMBRANES; ULTRAFILTRATION MEMBRANE; TIO2 NANOPARTICLES; THIN-FILMS; PHOTODEGRADATION; POLYSULFONE; POLYMERS; CELLS; TEMPERATURE; IRRADIATION AB Nanostructured surfaces are finding use in several medical applications, including tissue scaffolds and wound dressings. These surfaces are frequently manufactured from biocompatible polymers that are susceptible to ultraviolet (UV) damage. Polyethersulfone (PES) is a biocompatible polymer that undergoes oxidation and degradation when exposed to ultraviolet (UV) light. A uniform TiO2 coating can protect PES during exposure to UV sources (e.g., germicidal lamps and sunlight). The goal of this study was to determine whether atomic layer deposition (ALD) can successfully be used to grow TiO2 onto PES, protect it from UV irradiation, and reduce macrophage in vitro cytotoxicity. TiO2 was ALD-coated onto PES at 21 nm thickness. Uncoated PES exposed to UV for 30 min visibly changed color, whereas TiO2-coated PES showed no color change, indicating limited degradation. Macrophages exposed to UV-treated PES for 48 h showed reduced cell viability (via MTT assay) to 18% of control. In contrast, the cell viability for UV-treated TiO2-coated PES was 90% of control. Non-UV treated PES showed no decrease in cell viability. The results indicate that ALD of TiO2 thin films is a useful technique to protect polymers from UV damage and to retain low cytotoxicity to macrophages and other types of cells that are involved in wound healing. TiO2- coated PES membranes also have potential use in direct methanol fuel cells and in wastewater treatment membranes. C1 [Petrochenko, Peter E.; Skoog, Shelby A.; Zhang, Qin; Goering, Peter L.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Petrochenko, Peter E.; Skoog, Shelby A.; Narayan, Roger J.] Univ N Carolina, Joint Dept Biomed Engn, Raleigh, NC USA. [Petrochenko, Peter E.; Skoog, Shelby A.; Narayan, Roger J.] N Carolina State Univ, Raleigh, NC 27695 USA. [Scarel, Giovanna; Hyde, G. Kevin; Parsons, Gregory N.] N Carolina State Univ, Dept Chem & Biomol Engn, Raleigh, NC 27695 USA. RP Petrochenko, PE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM peter_petrochenko@med.unc.edu RI Narayan, Roger/J-2789-2013; Parsons, Gregory/O-9762-2014 OI Narayan, Roger/0000-0002-4876-9869; Parsons, Gregory/0000-0002-0048-5859 FU NSF [1041375] FX Peter E. Petrochenko is supported in part by a NSF Award #1041375. NR 43 TC 7 Z9 7 U1 2 U2 54 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1047-4838 EI 1543-1851 J9 JOM-US JI JOM PD APR PY 2013 VL 65 IS 4 BP 550 EP 556 DI 10.1007/s11837-013-0565-8 PG 7 WC Materials Science, Multidisciplinary; Metallurgy & Metallurgical Engineering; Mineralogy; Mining & Mineral Processing SC Materials Science; Metallurgy & Metallurgical Engineering; Mineralogy; Mining & Mineral Processing GA 105NO UT WOS:000316078500014 ER PT J AU Yang, YS Bykadi, S Carlin, AS Shah, RB Yu, LX Khan, MA AF Yang, Yongsheng Bykadi, Srikant Carlin, Alan S. Shah, Rakhi B. Yu, Lawrence X. Khan, Mansoor A. TI Comparative evaluation of the in vitro efficacy of lanthanum carbonate chewable tablets SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE analysis; bioavailability; bioequivalence; chromatography; in vitro models; kinetics; pharmacokinetics ID CHRONIC-RENAL-FAILURE; CHRONIC KIDNEY-DISEASE; PHOSPHATE BINDER; CALCIUM-CARBONATE; DIALYSIS PATIENTS; HYPERPHOSPHATEMIA; SEVELAMER; PHOSPHORUS; ABSORPTION; MEAL AB The aims of this study were to systematically evaluate the effects of pH levels, phosphate concentrations, and tablet integrity on the phosphate binding profiles of lanthanum carbonate chewable tablets, and to compare the in vitro phosphate binding efficacy of one reference and two test products of lanthanum carbonate chewable tablets. Langmuir equation was utilized to calculate the binding constants k1 and k2. The phosphate binding to the tablets of lanthanum carbonate product was pH dependent, with a faster binding rate at low pH. The crushed tablets bind phosphate more rapid. Compared with the whole tablets, the kinetic binding profiles from the crushed tablets were less variable under all conditions for both test and reference products. The phosphate level has a significant impact on the phosphate binding for both whole and crushed tablets under all pH conditions, with more binding at higher phosphate concentration. The phosphate binding profiles displayed significant difference among the products. For a crushed tablet, the phosphate binding to lanthanum reached equilibrium within 8 h under all conditions. The 90% confidence interval for the k2 ratio (test/reference) was well within the 80%125% under all pH conditions. However, the k1 ratio varies from 54% to 144%. (c) 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:13701381, 2013 C1 [Yang, Yongsheng; Bykadi, Srikant; Carlin, Alan S.; Shah, Rakhi B.; Khan, Mansoor A.] US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. [Yu, Lawrence X.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Rockville, MD 20855 USA. RP Yang, YS (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. EM yongsheng.yang@fda.hhs.gov NR 33 TC 3 Z9 3 U1 3 U2 50 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD APR PY 2013 VL 102 IS 4 BP 1370 EP 1381 DI 10.1002/jps.23454 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 100SV UT WOS:000315723700020 PM 23334989 ER PT J AU Khare, R Hillestad, ML Xu, ZL Byrnes, AP Barry, MA AF Khare, Reeti Hillestad, Matthew L. Xu, Zhili Byrnes, Andrew P. Barry, Michael A. TI Circulating Antibodies and Macrophages as Modulators of Adenovirus Pharmacology SO JOURNAL OF VIROLOGY LA English DT Article ID SCAVENGER RECEPTORS; KUPFFER CELLS; IN-VIVO; GENE-TRANSFER; LIVER; COMPLEMENT; INFECTION; THERAPY; HEXON; SEQUESTRATION AB Adenovirus serotype 5 (Ad5) naturally infects the liver after intravenous injection, making it a candidate for hepatocyte-directed gene transfer. While Ad5 can be efficient, most of the dose is destroyed by liver Kupffer cells before it can reach hepatocytes. In contrast, Ad5 bearing the hexon from Ad6 (Ad5/6) evades Kupffer cells. While Ad5/6 dramatically increases hepatocyte transduction in BALB/c mice, it has surprisingly little effect on C57BL/6 mice. To determine the source of this strain-specific difference, the roles of Kupffer cells, liver sinusoidal endothelial cells (LSECs), hepatocytes, scavenger receptors, clotting factors, and immunoglobulins were analyzed. The numbers of Kupffer cells and LSECs, the level of clotting factor X, and hepatocyte infectibility did not differ between different strains of mice. In contrast, high levels of immunoglobulins correlated negatively with Ad5 liver transduction in different mouse strains. Removal of immunoglobulins by use of Rag-deficient mice restored Ad5 transduction to maximal levels. Removal of Kupffer cells by predosing or by testing in colony-stimulating factor knockout mice restored Ad5 transduction in the presence of immunoglobulins. Partial reconstitution of IgM in Rag mice resulted in significant reductions in liver transduction by Ad5 but not by Ad5/6. These data suggest a role for IgM-mediated clearance of Ad5 via Kupffer cells and may explain the mechanism by which Ad5/6 evades these cells. These mechanisms may play a vital role in Ad pharmacology in animals and in humans. C1 [Khare, Reeti; Hillestad, Matthew L.; Barry, Michael A.] Mayo Clin, Dept Med, Div Infect Dis, Rochester, MN 55905 USA. [Barry, Michael A.] Mayo Clin, Dept Immunol, Rochester, MN USA. [Barry, Michael A.] Mayo Clin, Dept Mol Med, Rochester, MN USA. [Xu, Zhili; Byrnes, Andrew P.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Barry, MA (reprint author), Mayo Clin, Dept Med, Div Infect Dis, Rochester, MN 55905 USA. EM mab@mayo.edu RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 FU NCI [5P30 CA15083-37]; NIH [R01-CA136945]; Mayo Clinic Liver Regenerative Medicine Program; Kidney Disease Research Training Program at Mayo Clinic; [T32-DK00703] FX We thank the Mayo Clinic Cancer Center TACMA shared resource, which provided immunohistological services that are supported in part by NCI grant 5P30 CA15083-37. This work was supported by a grant to M.A.B. from the NIH (R01-CA136945) and by funding from the Mayo Clinic Liver Regenerative Medicine Program. M.L.H. was supported by grant T32-DK00703, Kidney Disease Research Training Program at Mayo Clinic. NR 28 TC 13 Z9 13 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2013 VL 87 IS 7 BP 3678 EP 3686 DI 10.1128/JVI.01392-12 PG 9 WC Virology SC Virology GA 103ZC UT WOS:000315957100006 PM 23325678 ER PT J AU Martinez, O Johnson, JC Honko, A Yen, B Shabman, RS Hensley, LE Olinger, GG Basler, CF AF Martinez, Osvaldo Johnson, Joshua C. Honko, Anna Yen, Benjamin Shabman, Reed S. Hensley, Lisa E. Olinger, Gene G. Basler, Christopher F. TI Ebola Virus Exploits a Monocyte Differentiation Program To Promote Its Entry SO JOURNAL OF VIROLOGY LA English DT Article ID LAKE-VICTORIA-MARBURGVIRUS; HUMAN DENDRITIC CELLS; NIEMANN-PICK C1; HEMORRHAGIC-FEVER; DC-SIGN; MACROPHAGE DIFFERENTIATION; ZAIRE-EBOLAVIRUS; BLOOD MONOCYTES; MUCIN DOMAIN; VIRAL ENTRY AB Antigen-presenting cells (APCs) are critical targets of Ebola virus (EBOV) infection in vivo. However, the susceptibility of monocytes to infection is controversial. Studies indicate productive monocyte infection, and yet monocytes are also reported to be resistant to EBOV GP-mediated entry. In contrast, monocyte-derived macrophages and dendritic cells are permissive for both EBOV entry and replication. Here, freshly isolated monocytes are demonstrated to indeed be refractory to EBOV entry. However, EBOV binds monocytes, and delayed entry occurs during monocyte differentiation. Cultured monocytes spontaneously downregulate the expression of viral entry restriction factors such as interferon-inducible transmembrane proteins, while upregulating the expression of critical EBOV entry factors cathepsin B and NPC1. Moreover, these processes are accelerated by EBOV infection. Finally, ectopic expression of NPC1 is sufficient to rescue entry into an undifferentiated, normally nonpermissive monocytic cell line. These results define the molecular basis for infection of APCs and suggest means to limit APC infection. C1 [Martinez, Osvaldo; Yen, Benjamin; Shabman, Reed S.; Basler, Christopher F.] Icahn Sch Med Mt Sinai, New York, NY USA. [Johnson, Joshua C.; Honko, Anna; Olinger, Gene G.] USA, Med Res Inst Infect Dis, Ft Detrick, MD USA. [Hensley, Lisa E.] US FDA, Med Countermeasures Initiat, OCS, OCET, Silver Spring, MD USA. RP Basler, CF (reprint author), Icahn Sch Med Mt Sinai, New York, NY USA. EM chris.basler@mssm.edu OI Olinger, Gene/0000-0001-7338-0292; Johnson, Joshua/0000-0002-5677-3841; Martinez, Osvaldo/0000-0001-7335-4342; Honko, Anna/0000-0001-9165-148X; Shabman, Reed/0000-0003-3272-3484 FU National Institutes of Health [R01AI059536, R21AI097568, AI057158]; U.S. Army [W81XWH-10-1-0683]; NIH [5F32AI084453-02] FX This study was supported in part by National Institutes of Health grants R01AI059536, R21AI097568, and AI057158 (Northeast Biodefense Center-Lipkin), U.S. Army grant W81XWH-10-1-0683 to C.F.B., and NIH fellowship 5F32AI084453-02 to R.S.S. NR 79 TC 15 Z9 15 U1 0 U2 27 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2013 VL 87 IS 7 BP 3801 EP 3814 DI 10.1128/JVI.02695-12 PG 14 WC Virology SC Virology GA 103ZC UT WOS:000315957100018 PM 23345511 ER PT J AU Parsons, BL Myers, MB AF Parsons, Barbara L. Myers, Meagan B. TI Personalized Cancer Treatment and the Myth of KRAS Wild-type Colon Tumors SO DISCOVERY MEDICINE LA English DT Article ID METASTATIC COLORECTAL-CANCER; RAS MUTATIONS; COST-EFFECTIVENESS; CETUXIMAB; CELLS; CHEMOTHERAPY; PANITUMUMAB; RESISTANCE; BRAF; PCR AB The impact of KRAS mutations on the efficacy of therapies that target the epidermal growth factor receptor (EGFR) is a major, ongoing area of oncology research, aimed at identifying the best possible treatments for individual colon cancer patients. Because patients with KRAS mutant colorectal tumors rarely respond to anti-EGFR monoclonal antibodies, testing is required to confirm the patient's tumor is KRAS wild-type before utilizing these therapies. Despite being studied for more than 30 years, new information continues to develop regarding KRAS and its role in colon carcinogenesis. This information must be integrated into the development of effective colon cancer treatment strategies. This review will summarize recent evidence that most, if not all, colon tumors encompass at least a subpopulation of KRAS mutant cells, meaning tumors characterized as KRAS wild-type are in most cases tumors with relatively low KRAS mutant tumor cell content. Recent studies support the hypothesis that relapse in advanced colorectal patients treated with EGFR-targeted monoclonal antibody therapy involves the outgrowth of previously undetected KRAS mutant tumor cell populations. Studies investigating the effects of oxidative stress on Ras signaling suggest that the frequent presence of minor KRAS mutant tumor cell populations may be a consequence of hypoxic conditions within tumors, which produce a negative selection against KRAS mutant cells in polyclonal tumors. Thus, the literature and current practices for characterizing tumor KRAS mutation don't accurately reflect the nature of colon tumor KRAS mutation, even though an accurate understanding is critical for identifying the best strategies for intervention. C1 [Parsons, Barbara L.; Myers, Meagan B.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov NR 55 TC 20 Z9 20 U1 0 U2 0 PU DISCOVERY MEDICINE PI TIMONIUM PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA SN 1539-6509 EI 1944-7930 J9 DISCOV MED JI Discov. Med. PD APR PY 2013 VL 15 IS 83 BP 259 EP 267 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 202DX UT WOS:000323194800007 PM 23636143 ER PT J AU Singh, P Foley, SL Nayak, R Kwon, YM AF Singh, Pallavi Foley, Steven L. Nayak, Rajesh Kwon, Young Min TI Massively parallel sequencing of enriched target amplicons for high-resolution genotyping of Salmonella serovars SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE Multilocus sequence typing; Next generation sequencing; Target capturing; Strain typing; Salmonella ID ENTERICA SEROVARS; AMPLIFICATION; TYPHIMURIUM; GENES AB With next generation sequencing (NGS) technology, it is now possible to carry out in-depth, large-scale sequencing projects, such as whole genome sequencing, in a fast and inexpensive manner. However, often it is more practical and convenient to sequence and analyze multiple, smaller regions of the bacterial genome to gain valuable information about an organism. One such application is genotyping of bacterial strains by multilocus sequence typing (MLST) that involves PCR and sequencing analysis of typically 7 housekeeping genes. Recently, we described a novel MLST method, called MLST-seq that combines a PCR-based target enrichment method and NGS technology to simultaneously analyze numerous target gene sequences, thereby improving the resolution and high-throughput capacity of current MLST approaches. However, the performance of the MLST-seq method was hampered from a substantial bias in target enrichment step. In this study, we used an improved target enrichment method using hairpin selectors to amplify 21 target genes simultaneously from each of 41 Salmonella strains. The resulting amplicons tagged with strain-specific barcodes were pooled and sequenced en masse by 454 pyrosequencing. Analysis of sequence data from 38 Salmonella strains using combinations of 3, 7 and 14 target genes resulted in 23, 32 and 37 distinct allelic profiles, respectively. These results demonstrated that MLST-seq with an increased number of target genes is an efficient way to improve discrimination among closely-related strains of Salmonella. With the rapidly increasing sequencing capacity of NGS technologies combined with further improvements in target capturing methods, MLST-seq could become a promising approach to perform high-resolution strain typing of a large collection of Salmonella, and likely other genera in a labor- and cost-efficient manner in the future. (C) 2012 Elsevier Ltd. All rights reserved. C1 [Singh, Pallavi; Kwon, Young Min] Univ Arkansas, Cell & Mol Biol Program, Fayetteville, AR 72701 USA. [Foley, Steven L.; Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kwon, Young Min] Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. RP Kwon, YM (reprint author), Univ Arkansas, Dept Poultry Sci, 1260 W Maple St, Fayetteville, AR 72701 USA. EM ykwon@uark.edu OI Singh, Pallavi/0000-0002-0283-7459 FU USDA Food Safety Consortium grant FX This project has been supported by the USDA Food Safety Consortium grant. NR 13 TC 5 Z9 6 U1 0 U2 46 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 2013 VL 27 IS 2 BP 80 EP 85 DI 10.1016/j.mcp.2012.11.004 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 084RK UT WOS:000314556600002 PM 23201627 ER PT J AU Wright, DJ Earnhardt, JN Perry, R Bailey, S Komm, B Minck, DR Cukierski, MA AF Wright, David J. Earnhardt, J. Nicole Perry, Richard Bailey, Steven Komm, Barry Minck, Daniel R. Cukierski, Mark A. TI Carcinogenicity and hormone studies with the tissue-selective estrogen receptor modulator bazadoxifene SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID ANTERIOR-PITUITARY GLAND; LUTEINIZING-HORMONE; PROLACTIN LEVELS; GRANULOSA-CELLS; MAMMARY-TUMORS; OVARIAN-CANCER; RATS; MICE; TUMORIGENESIS; KEOXIFENE AB Bazedoxifene Acetate (BZA) is a selective estrogen receptor modulator (SERM) that is approved for the prevention and/or treatment of osteoporosis in postmenopausal women. To assess for carcinogenic potential, BZA was administered ad libitum in the diet to rats for 2 years. BZA caused an increase in benign ovarian tumors in female rats and decreased incidences of mammary tumors (females) and pituitary tumors (males and females). In addition, BZA provided a significant survival benefit at all dosages tested, which correlated with a significant reduction in pituitary and mammary gland tumors and decreased body weight gain (both genders). Additional studies were subsequently conducted in rats and monkeys to further explore the mechanisms likely responsible for the observed effects. Results from studies in hypophysectomized and chemically castrated female rats indicated that BZA did not directly stimulate formation of ovarian cysts, but an intact pituitary was required for cyst formation. Further, BZA increased estradiol concentrations in rats and monkeys. In monkeys, BZA increased concentrations of luteinizing hormone (LH) after onset of treatment and prohibited the preovulatory surge of LH until after cessation of treatment. These hormonal changes suggest that BZA inhibited both the positive and negative feedback effects of estrogen on gonadotropins and the resulting increase in LH caused formation and persistence of ovarian cysts, which eventually transformed into benign ovarian granulosa cell tumors in the rat carcinogenicity study. These results also suggest that the reductions in pituitary and mammary gland tumors were attributed to BZA-related antagonism of endogenous estrogens at the estrogen receptors. J. Cell. Physiol. 228: 724733, 2013. (c) 2012 Wiley Periodicals, Inc. C1 [Wright, David J.; Perry, Richard; Bailey, Steven; Cukierski, Mark A.] Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA. [Earnhardt, J. Nicole] Pfizer, Pharmacokinet Dynam & Metab, La Jolla, CA USA. [Komm, Barry] Pfizer, Med Affairs, Collegeville, PA USA. [Minck, Daniel R.] US FDA, Div Metab & Endocrinol Prod, Silver Spring, MD USA. RP Wright, DJ (reprint author), Pfizer Inc, Drug Safety Res & Dev, Groton, CT 06340 USA. EM david.wright@pfizer.com NR 53 TC 3 Z9 3 U1 0 U2 34 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 2013 VL 228 IS 4 BP 724 EP 733 DI 10.1002/jcp.24219 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 062TN UT WOS:000312945500010 PM 22949219 ER PT J AU McKibben, L AF McKibben, Linda TI Efficacy of tetravalent dengue vaccine in Thai schoolchildren SO LANCET LA English DT Letter C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20901 USA. RP McKibben, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20901 USA. EM linda.mckibben@fda.hhs.gov NR 5 TC 1 Z9 1 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD MAR 30 PY 2013 VL 381 IS 9872 BP 1094 EP 1094 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 122WL UT WOS:000317348900019 PM 23540848 ER PT J AU Dmitrienko, A D'Agostino, RB Huque, MF AF Dmitrienko, Alex D'Agostino, Ralph B., Sr. Huque, Mohammad F. TI Key multiplicity issues in clinical drug development SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; multiple comparisons; type I error rate control; mltiple testing procedures; gatekeeping procedures ID CLOSED-TESTING PROCEDURES; SIMULTANEOUS CONFIDENCE-REGIONS; POINT ADJUSTMENT METHODS; SECONDARY END-POINTS; GATEKEEPING PROCEDURES; BONFERRONI PROCEDURE; TRIAL APPLICATIONS; STRATEGIES; HOCHBERG; PLACEBO AB Much progress has been made over the past decade with the development of novel methods for addressing increasingly more complex multiplicity problems arising in confirmatory Phase III clinical trials. This includes traditional problems with a single source of multiplicity, for example, analysis of multiple endpoints or doseplacebo contrasts. In addition, more advanced problems with several sources of multiplicity have attracted attention in clinical drug development. These problems include two or more families of objectives such as multiple endpoints evaluated at multiple dose levels or in multiple patient populations. This paper provides a review of concepts that play a central role in defining and solving multiplicity problems (error rate definitions) and introduces main classes of multiple testing procedures widely used in clinical trials (nonparametric, semiparametric, and parametric procedures). The paper also presents recent advances in multiplicity research, including gatekeeping procedures for clinical trials with multiple sets of objectives. The concepts and methods introduced in the paper are illustrated using several case studies on the basis of real clinical trials. Software implementation of commonly used multiple testing and gatekeeping procedures is discussed. Copyright (c) 2012 John Wiley & Sons, Ltd. C1 [Dmitrienko, Alex] Quintiles Inc, Durham, NC 27703 USA. [D'Agostino, Ralph B., Sr.] Boston Univ, Boston, MA 02215 USA. [Huque, Mohammad F.] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD USA. RP Dmitrienko, A (reprint author), Quintiles Inc, 4820 Emperor Blvd, Durham, NC 27703 USA. EM alex.dmitrienko@quintiles.com NR 62 TC 16 Z9 16 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD MAR 30 PY 2013 VL 32 IS 7 BP 1079 EP 1111 DI 10.1002/sim.5642 PG 33 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 107IX UT WOS:000316210800001 PM 23044723 ER PT J AU Jia, YP Wood, F Buehler, PW Alayash, AI AF Jia, Yiping Wood, Francine Buehler, Paul W. Alayash, Abdu I. TI Haptoglobin Preferentially Binds beta but Not alpha Subunits Cross-Linked Hemoglobin Tetramers with Minimal Effects on Ligand and Redox Reactions SO PLOS ONE LA English DT Article ID OXYGEN-BINDING; AUTOCATALYTIC OXIDATION; CHAINS; NITRITE; COMPLEX; MECHANISM; PEROXIDE; OXYHEMOGLOBIN; INTERMEDIATE; DECREASES AB Human hemoglobin (Hb) and haptoglobin (Hp) exhibit an extremely high affinity for each other, and the dissociation of Hb tetramers into dimers is generally believed to be a prerequisite for complex formation. We have investigated Hp interactions with native Hb, alpha alpha, and beta beta cross-linked Hb (alpha alpha XLHb and beta beta XLHb, respectively), and rapid kinetics of Hb ligand binding as well as the redox reactivity in the presence of and absence of Hp. The quaternary conformation of beta beta subunit cross-linking results in a higher binding affinity than that of alpha alpha subunit cross-linked Hb. However, beta beta cross-linked Hb exhibits a four fold slower association rate constant than the reaction rate of unmodified Hb with Hp. The Hp contact regions in the Hb dimer interfaces appear to be more readily exposed in beta beta XLHb than alpha alpha XLHb. In addition, apart from the functional changes caused by chemical modifications, Hp binding does not induce appreciable effects on the ligand binding and redox reactions of beta beta XLHb. Our findings may therefore be relevant to the design of safer Hb-based oxygen therapeutics by utilizing this preferential binding of beta beta XLHb to Hp. This may ultimately provide a safe oxidative inactivation and clearance pathway for chemically modified Hbs in circulation. C1 [Jia, Yiping; Wood, Francine; Buehler, Paul W.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Jia, YP (reprint author), US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM yiping.jia@fda.hhs.gov FU National Institutes of Health (NIH) [HL 110900]; U.S. Food and Drug Administration (MODSCI); H.H.S. Medical Counter Measures Grant FX This work was supported in part by National Institutes of Health (NIH) grant HL 110900 (AIA), the U.S. Food and Drug Administration (MODSCI 2011) (AIA), and H.H.S. Medical Counter Measures Grant (PWB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 4 Z9 4 U1 0 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 29 PY 2013 VL 8 IS 3 AR e59841 DI 10.1371/journal.pone.0059841 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121SG UT WOS:000317263900032 PM 23555800 ER PT J AU Kozauer, N Katz, R AF Kozauer, Nicholas Katz, Russell TI Regulatory Innovation and Drug Development for Early-Stage Alzheimer's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MILD COGNITIVE IMPAIRMENT C1 [Kozauer, Nicholas; Katz, Russell] US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Kozauer, N (reprint author), US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 90 Z9 92 U1 2 U2 15 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 28 PY 2013 VL 368 IS 13 BP 1169 EP 1171 DI 10.1056/NEJMp1302513 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 116FU UT WOS:000316869000001 PM 23484795 ER PT J AU Inacio, MCS Ake, CF Paxton, EW Khatod, M Wang, CL Gross, TP Kaczmarek, RG Marinac-Dabic, D Sedrakyan, A AF Inacio, Maria C. S. Ake, Christopher F. Paxton, Elizabeth W. Khatod, Monti Wang, Cunlin Gross, Thomas P. Kaczmarek, Ronald G. Marinac-Dabic, Danica Sedrakyan, Art TI Sex and Risk of Hip Implant Failure Assessing Total Hip Arthroplasty Outcomes in the United States SO JAMA INTERNAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; TOTAL JOINT; FEMORAL-HEAD; REPLACEMENT; REVISION; POPULATION; SURGERY; INFECTION; REGISTER; GENDER AB Importance: The role of sex in relationship to implant failure after total hip arthroplasty (THA) is important for patient management and device innovation. Objective: To evaluate the association of sex with short-term risk of THA revision after adjusting for patient, implant, surgery, surgeon, and hospital confounders. Design and Setting: A prospective cohort of patients enrolled in a total joint replacement registry from April 1, 2001, through December 31, 2010. Participants: Patients undergoing primary, elective, unilateral THA. Main Outcome Measures: Failure of THA, defined as revision procedure for (1) any reason, (2) septic reason, or (3) aseptic reason after the index procedure. Results: A total of 35 140 THAs with 3.0 years of median follow-up were identified. Women constituted 57.5% of the study sample, and the mean (SD) patient age was 65.7 (11.6) years. A higher proportion of women received 28-mm femoral heads (28.2% vs 13.1%) and had metal on highly cross-linked polyethylene-bearing surfaces (60.6% vs 53.7%) than men. Men had a higher proportion of 36-mm or larger heads (55.4% vs 32.8%) and metal on metal-bearing surfaces (19.4% vs 9.6%). At 5-year follow-up, implant survival was 97.4% (95% CI, 97.2%97.6%). Device survival for men (97.7%; 95% CI, 97.4%98.0%) vs women (97.1%; 95% CI, 96.8%-97.4%) was significantly different (P=.01). After adjustments, the hazards ratios for women were 1.29 (95% CI, 1.11-1.51) for all-cause revision, 1.32 (95% CI, 1.10-1.58) for aseptic revision, and 1.17 (95% CI, 0.81-1.68) for septic revision. Conclusions: After considering patient-, surgery-, surgeon-, volume-, and implant-specific risk factors, women had a 29% higher risk of implant failure than men after THA in this community-based sample. C1 [Inacio, Maria C. S.; Ake, Christopher F.; Paxton, Elizabeth W.] So Calif Permanente Med Grp, Surg Outcomes & Anal Dept, San Diego, CA 92108 USA. [Khatod, Monti] So Calif Permanente Med Grp, Dept Orthopaed Surg, West Los Angeles, CA USA. [Wang, Cunlin; Gross, Thomas P.; Kaczmarek, Ronald G.; Marinac-Dabic, Danica] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Sedrakyan, Art] Cornell Univ, Weill Med Coll, New York, NY USA. RP Inacio, MCS (reprint author), So Calif Permanente Med Grp, Surg Outcomes & Anal Dept, 8954 Rio San Diego Dr,Ste 406, San Diego, CA 92108 USA. EM maria.cs.inacio@kp.org OI Inacio, Maria/0000-0001-8261-2665 FU Division of Epidemiology, Office of Surveillance and Biometrics, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland [HHSF22200860493P] FX This study was funded by contract HHSF22200860493P from the Division of Epidemiology, Office of Surveillance and Biometrics, Center for Devices and Radiological Health, US Food and Drug Administration, Silver Spring, Maryland. NR 40 TC 18 Z9 18 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6106 J9 JAMA INTERN MED JI JAMA Intern. Med. PD MAR 25 PY 2013 VL 173 IS 6 BP 435 EP 441 DI 10.1001/jamainternmed.2013.3271 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 154NA UT WOS:000319681400009 PM 23420484 ER PT J AU Graber, N Stavinsky, F Hoffman, R Button, J Clark, N Martin, S Robertson, A Hustedt, J AF Graber, Nathan Stavinsky, Faina Hoffman, Robert Button, Jessica Clark, Nancy Martin, Scott Robertson, Alison Hustedt, John TI Ciguatera Fish Poisoning-New York City, 2010-2011 (Reprinted from vol 4, pg 61, 2013) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Graber, Nathan; Stavinsky, Faina; Hoffman, Robert; Button, Jessica; Clark, Nancy] New York City Dept Hlth & Mental Hyg, New York, NY USA. [Martin, Scott] SUNY Stony Brook, Sch Med, Stony Brook, NY 11794 USA. [Robertson, Alison] US FDA, Rockville, MD 20857 USA. [Hustedt, John] CDC, Publ Hlth Prevent Svc, Atlanta, GA 30333 USA. RP Hustedt, J (reprint author), CDC, Publ Hlth Prevent Svc, Atlanta, GA 30333 USA. EM johnhustedt@gmail.com NR 1 TC 1 Z9 1 U1 0 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 20 PY 2013 VL 309 IS 11 BP 1102 EP 1104 DI 10.1001/jama.2013.1523 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 108FF UT WOS:000316276500008 ER PT J AU Yu, PP Pisitkun, T Wang, GH Wang, R Katagiri, Y Gucek, M Knepper, MA Geller, HM AF Yu, Panpan Pisitkun, Trairak Wang, Guanghui Wang, Rong Katagiri, Yasuhiro Gucek, Marjan Knepper, Mark A. Geller, Herbert M. TI Global Analysis of Neuronal Phosphoproteome Regulation by Chondroitin Sulfate Proteoglycans SO PLOS ONE LA English DT Article ID SPINAL-CORD-INJURY; EXTRACELLULAR-MATRIX; NEURITE OUTGROWTH; INHIBITORY-ACTIVITY; CANCER-CELLS; AXON GROWTH; GLIAL SCAR; PHOSPHORYLATION; REGENERATION; GUIDANCE AB Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix which mediate inhibition of axonal regeneration after injury to the central nervous system (CNS). Several neuronal receptors for CSPGs have recently been identified; however, the signaling pathways by which CSPGs restrict axonal growth are still largely unknown. In this study, we applied quantitative phosphoproteomics to investigate the global changes in protein phosphorylation induced by CSPGs in primary neurons. In combination with isobaric Tags for Relative and Absolute Quantitation (iTRAQ) labeling, strong cation exchange chromatography (SCX) fractionation, immobilized metal affinity chromatography (IMAC) and LC-MS/MS, we identified and quantified 2214 unique phosphopeptides corresponding to 1118 phosphoproteins, with 118 changing significantly in abundance with CSPG treatment. The proteins that were regulated by CSPGs included key components of synaptic vesicle trafficking, axon guidance mediated by semaphorins, integrin signaling, cadherin signaling and EGF receptor signaling pathways. A significant number of the regulated proteins are cytoskeletal and related proteins that have been implicated in regulating neurite growth. Another highly represented protein category regulated by CSPGs is nucleic acid binding proteins involved in RNA post-transcriptional regulation. Together, by screening the overall phosphoproteome changes induced by CSPGs, this data expand our understanding of CSPG signaling, which provides new insights into development of strategies for overcoming CSPG inhibition and promoting axonal regeneration after CNS injury. C1 [Yu, Panpan; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Pisitkun, Trairak; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Wang, Guanghui; Gucek, Marjan] NHLBI, Prote Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA. [Wang, Rong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Geller, HM (reprint author), NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Div Intramural Res,NIH, Bldg 10, Bethesda, MD 20892 USA. EM geller@helix.nih.gov RI Yu, Panpan/A-4962-2013; OI Pisitkun, Trairak/0000-0001-6677-2271; Geller, Herbert/0000-0002-7048-6144 FU National Heart, Lung, and Blood Institute (NHLBI) Intramural Program FX This research was entirely funded through the National Heart, Lung, and Blood Institute (NHLBI) Intramural Program. There were no external funding sources for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 9 Z9 9 U1 1 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 18 PY 2013 VL 8 IS 3 AR e59285 DI 10.1371/journal.pone.0059285 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 109ZS UT WOS:000316411600054 PM 23527152 ER PT J AU Thompson, J Pikis, A Rich, J Hall, BG Withers, SG AF Thompson, John Pikis, Andreas Rich, Jamie Hall, Barry G. Withers, Stephen G. TI alpha-Galacturonidase(s): A new class of Family 4 glycoside hydrolases with strict specificity and a unique CHEV active site motif SO FEBS LETTERS LA English DT Article DE Glycoside hydrolase Family 4; alpha-Galacturonidase; LplD; CAZy database; Phylogenetic; pNP-alpha-D-galactopyranosiduronic acid; Bacillus subtilis ID PHOSPHO-ALPHA-GLUCOSIDASE; THERMOTOGA-MARITIMA; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; THERMOPHILIC BACTERIUM; GALACTOSIDASE; HYDROLYSIS; MECHANISM; 6-PHOSPHO-ALPHA-GLUCOSIDASE; ELIMINATION AB The catalytic activity of the Family 4 glycosidase LplD protein, whose active site motif is CHEV, is unknown despite its crystal structure having been determined in 2008. Here we identify that activity as being an alpha-galacturonidase whose natural substrate is probably alpha-1,4-di-galacturonate (GalUA(2)). Phylogenetic analysis shows that LplD belongs to a monophyletic clade of CHEV Family 4 enzymes, of which four other members are also shown to be galacturonidases. Family GH 4 enzymes catalyze the cleavage of the glycosidic bond, via a non-canonical redox-assisted mechanism that contrasts with Koshland's double-displacement mechanism. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies. C1 [Thompson, John; Pikis, Andreas] NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. [Pikis, Andreas] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Rich, Jamie; Withers, Stephen G.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. [Hall, Barry G.] Bellingham Res Inst, Bellingham, WA 98229 USA. RP Thompson, J (reprint author), NIDCR, Microbial Biochem & Genet Sect, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA. EM jthompson@dir.nidcr.nih.gov FU National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD; Natural Sciences and Engineering Research Council of Canada FX We thank Ricardo Dreyfuss for assistance with photography and computer graphics. This investigation was supported by the Intramural Research Program (IRP) of the National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD and by the Natural Sciences and Engineering Research Council of Canada. NR 33 TC 2 Z9 6 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 18 PY 2013 VL 587 IS 6 BP 799 EP 803 DI 10.1016/j.febslet.2013.02.004 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 103VK UT WOS:000315947400041 PM 23416295 ER PT J AU Liu, YT Flynn, TJ Ferguson, MS Hoagland, EM AF Liu, Yitong Flynn, Thomas J. Ferguson, Martine S. Hoagland, Erica M. TI Use of the Combination Index to determine interactions between plant-derived phenolic acids on hepatotoxicity endpoints in human and rat hepatoma cells SO PHYTOMEDICINE LA English DT Article DE Hepatotoxicity; Dietary phenolic acids; Mixtures; Interactions; Species differences ID ROSMARINIC ACID; DIETARY-INTAKE; METABOLISM; INDUCTION; SYNERGISM; ANTIOXIDANT; POLYPHENOLS; PREDICTION; EXTRACT; MODEL AB The beneficial or adverse effects of isolated phytochemicals are not always concordant with effects of the botanical dietary supplements from which they were derived. This disparity could be due to interactions between the various phytochemicals present in the whole plant. The phenolic acids, rosmarinic acid (RA), caffeic acid (CA) and ferulic acid (FA) are widely present in foods and dietary supplements, and they are assumed to exert various beneficial biological effects. However, there is little data on the potential biological interactions of these three phenolic acids which commonly occur together and are linked metabolically. In the present study, liver toxicity of the three phenolic acids was assessed on the three compounds singly and in various binary and one ternary combinations. A series of in vitro endpoints relevant to liver toxicity were evaluated in both a human (HepG2/C3A) and rat (MH1C1) hepatocyte cell line. The Combination Index (CI) was calculated for each endpoint from both the concentration responses of the single compounds and the responses of the various binary and ternary mixtures. Both synergistic and antagonistic interactions were observed for some endpoints and some combinations of test agents. Interactions were most prevalent in measures of oxidative stress and cytochrome P450 activities in both cell types. There was only a 53% concordance between the rat and human cells which may be suggestive of species differences. The data suggest an approach for better characterizing the beneficial or adverse effects of complex botanical products through evaluation of interactions between individual phytochemical components. Published by Elsevier GmbH. C1 [Liu, Yitong; Flynn, Thomas J.; Hoagland, Erica M.] US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Ferguson, Martine S.] US FDA, Div Publ Hlth & Biostat, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Liu, Yitong] Oak Ridge Inst Sci & Educ, Oak Ridge, TN 37831 USA. RP Flynn, TJ (reprint author), US FDA, MOD Labs 1, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM thomas.flynn@fda.hhs.gov RI Liu, Yitong/H-2213-2011; OI Liu, Yitong/0000-0002-4300-4349; Flynn, Thomas/0000-0002-7248-0643 NR 31 TC 7 Z9 8 U1 0 U2 10 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PD MAR 15 PY 2013 VL 20 IS 5 BP 461 EP 468 DI 10.1016/j.phymed.2012.12.013 PG 8 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 125IZ UT WOS:000317534800012 PM 23380082 ER PT J AU Yakes, BJ Papafragkou, E Conrad, SM Neill, JD Ridpath, JF Burkhardt, W Kulka, M DeGrasse, SL AF Yakes, Betsy Jean Papafragkou, Efstathia Conrad, Stephen M. Neill, John D. Ridpath, Julia F. Burkhardt, William, III Kulka, Michael DeGrasse, Stacey L. TI Surface plasmon resonance biosensor for detection of feline calicivirus, a surrogate for norovirus SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Intact virus; Norovirus; Surface plasmon resonance; Biosensor; Foodborne; Shellfish ID NORWALK-LIKE VIRUSES; UNITED-STATES; HUMAN PATHOGENS; HIGH-THROUGHPUT; FOOD-SAFETY; OYSTERS; INACTIVATION; SHELLFISH; ASSAY; SPR AB The human noroviruses are the most common non-bacterial cause of gastroenteritis and are responsible for as much as 50% of all gastroenteritis outbreaks worldwide. Norovirus (NoV), a single stranded RNA virus, is highly contagious with an infectious dose of less than 100 viral particles. While techniques exist for the identification of NoV, the lack of a reliable cell culture system, NoV genetic variability, and time-consuming sample preparation steps required to isolate the virus (or its genome) prior to molecular based methods has hindered rapid virus detection. To better protect the public from virus-contaminated food and enable better detection in clinical and environmental samples, sensitive and selective methods with simple sample preparation are needed. Surface plasmon resonance (SPR) biosensors represent an emerging detection platform, and this approach has been applied to the rapid detection of foodbome small molecule toxins, protein toxins, and bacteria. This analytical technique, however, has yet to be fully investigated for rapid virus detection, especially for intact viral particles extracted from food matrices. For this study, the culturable, non-human pathogen feline calicivirus (FCV), which has similar morphology and is genetically related to NoV, was chosen as a surrogate virus for designing and evaluating an SPR assay. An antibody-based assay was performed by first immobilizing anti-FCV to an SPR chip surface and then directly measuring virus binding and subsequent secondary antibody binding. The resulting biosensor directly detected intact FCV particles with limits of detection of approximately 10(4) TCID50 FCV/mL from purified cell culture lysates. In addition, intact virus detection in FCV-spiked oyster matrix was possible when using a simple extraction procedure and employing a secondary antibody to FCV for quantitation. The results from these preliminary studies show promise for the development of a rapid assay for detecting intact viruses, such as NoV, using an SPR biosensor. While the current level of sensitivity achieved with this SPR biosensor may be more applicable to virus detection in clinical specimens, broader application and increased sensitivity of this method for foodbome viruses may be achieved when performed in conjunction with efficient virus extraction and concentration methods. Published by Elsevier B.V. C1 [Yakes, Betsy Jean; Conrad, Stephen M.; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Papafragkou, Efstathia; Kulka, Michael] US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. [Neill, John D.; Ridpath, Julia F.] USDA, Natl Anim Dis Ctr, Ruminant Dis & Immunol Res Unit, Ames, IA 50010 USA. [Burkhardt, William, III] US FDA, Ctr Food Safety & Appl Nutr, Off Food Safety, Dauphin Isl, AL 36528 USA. RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov; efstathia.papafragkou@fda.hhs.gov; stephen.conrad@fda.hhs.gov; john.neill@ars.usda.gov; julia.ridpath@ars.usda.gov; william.burkhardt@fda.hhs.gov; michael.kulka@fda.hhs.gov; stacey.degrasse@fda.hhs.gov RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 NR 53 TC 6 Z9 6 U1 3 U2 61 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 15 PY 2013 VL 162 IS 2 BP 152 EP 158 DI 10.1016/j.ijfoodmicro.2013.01.011 PG 7 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 115UK UT WOS:000316837200005 PM 23416550 ER PT J AU Ryan, PB Madigan, D Stang, PE Overhage, JM Racoosin, JA Hartzema, AG AF Ryan, Patrick B. Madigan, David Stang, Paul E. Overhage, J. Marc Racoosin, Judith A. Hartzema, Abraham G. TI Response to Comment on 'Empirical assessment of methods for risk identification in healthcare data' SO STATISTICS IN MEDICINE LA English DT Article C1 [Ryan, Patrick B.; Stang, Paul E.] Janssen Res & Dev, Titusville, NJ 08560 USA. [Ryan, Patrick B.; Madigan, David; Stang, Paul E.; Overhage, J. Marc; Racoosin, Judith A.; Hartzema, Abraham G.] NIH, Observat Med Outcomes Partnership Fdn, Bethesda, MD 20892 USA. [Ryan, Patrick B.] Univ N Carolina, UNC Eshelman Sch Pharm, Chapel Hill, NC USA. [Madigan, David] Columbia Univ, Dept Stat, New York, NY USA. [Overhage, J. Marc] Regenstrief Inst Hlth Care, Indianapolis, IN USA. [Overhage, J. Marc] Indiana Univ Sch Med, Indianapolis, IN USA. [Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hartzema, Abraham G.] Univ Florida, Coll Pharm, Gainesville, FL USA. RP Ryan, PB (reprint author), Janssen Res & Dev, 1125 Trenton Harbourton Rd,POB 200,MS K304, Titusville, NJ 08560 USA. EM ryan@omop.org NR 3 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2013 VL 32 IS 6 BP 1075 EP 1077 DI 10.1002/sim.5725 PG 3 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 092BT UT WOS:000315094500015 PM 23413215 ER PT J AU Borrego, F AF Borrego, Francisco TI The CD300 molecules: an emerging family of regulators of the immune system SO BLOOD LA English DT Review ID IMMUNOGLOBULIN-LIKE RECEPTOR; INHIBITORY RECEPTOR; DENDRITIC CELLS; MYELOID CELLS; CMRF-35-LIKE MOLECULE-1; ACTIVATING RECEPTOR; IRP60 CD300A; MAST-CELLS; FCR-GAMMA; NK CELLS AB The CD300 family of molecules modulates a broad and diverse array of immune cell processes via their paired activating and inhibitory receptor functions. The description that CD300 molecules are able to recognize lipids, such as extracellular ceramide, phosphatidylserine, and phosphatidylethanolamine, that are exposed on the outer leaflet of the plasma membrane of dead and activated cells has opened a new field of research. Through their binding to lipids and other ligands, this family of receptors is poised to have a significant role in complex biological processes and in the host response to severe pathological conditions. Indeed, published data have demonstrated their participation in the pathogenesis of several disease states. Moreover, this family of receptors has great potential as targets for diagnosis and therapeutic purposes in infectious diseases, allergies, cancer, and other pathological situations. For instance, one member of the family, CD300a, has been studied as a possible biomarker. Here, a review is provided on the cellular distribution of the human and mouse families of receptors, the stimuli that regulate their expression, their ability to tune leukocyte function and immune responses, their signaling pathways, ligand recognition, and their clinical relevance. C1 [Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bldg 29B,Room 3NN18,29 Lincoln Dr,HFD 123, Bethesda, MD 20892 USA. EM francisco.borrego@fda.hhs.gov FU intramural program of the Food and Drug Administration FX This work was funded by the intramural program of the Food and Drug Administration. NR 100 TC 44 Z9 44 U1 2 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD MAR 14 PY 2013 VL 121 IS 11 BP 1951 EP 1960 DI 10.1182/blood-2012-09-435057 PG 10 WC Hematology SC Hematology GA 182PR UT WOS:000321756700011 PM 23293083 ER PT J AU Zou, W Chen, HC Hise, KB Tang, HL Foley, SL Meehan, J Lin, WJ Nayak, R Xu, JS Fang, H Chen, JJ AF Zou, Wen Chen, Hung-Chia Hise, Kelley B. Tang, Hailin Foley, Steven L. Meehan, Joe Lin, Wei-Jiun Nayak, Rajesh Xu, Joshua Fang, Hong Chen, James J. TI Meta-Analysis of Pulsed-Field Gel Electrophoresis Fingerprints Based on a Constructed Salmonella Database SO PLOS ONE LA English DT Article ID ENTERICA SEROVAR ENTERITIDIS; DRAFT GENOME SEQUENCES; TANDEM REPEAT ANALYSIS; MICROARRAY ANALYSIS; UNITED-STATES; SEROTYPES; IDENTIFICATION; TYPHIMURIUM; STRAINS; DISCRIMINATION AB A database was constructed consisting of 45,923 Salmonella pulsed-field gel electrophoresis (PFGE) patterns. The patterns, randomly selected from all submissions to CDC PulseNet during 2005 to 2010, included the 20 most frequent serotypes and 12 less frequent serotypes. Meta-analysis was applied to all of the PFGE patterns in the database. In the range of 20 to 1100 kb, serotype Enteritidis averaged the fewest bands at 12 bands and Paratyphi A the most with 19, with most serotypes in the 13215 range among the 32 serptypes. The 10 most frequent bands for each of the 32 serotypes were sorted and distinguished, and the results were in concordance with those from distance matrix and two-way hierarchical cluster analyses of the patterns in the database. The hierarchical cluster analysis divided the 32 serotypes into three major groups according to dissimilarity measures, and revealed for the first time the similarities among the PFGE patterns of serotype Saintpaul to serotypes Typhimurium, Typhimurium var. 5-, and I 4,[5], 12:i:-; of serotype Hadar to serotype Infantis; and of serotype Muenchen to serotype Newport. The results of the meta-analysis indicated that the pattern similarities/dissimilarities determined the serotype discrimination of PFGE method, and that the possible PFGE markers may have utility for serotype identification. The presence of distinct, serotype specific patterns may provide useful information to aid in the distribution of serotypes in the population and potentially reduce the need for laborious analyses, such as traditional serotyping. C1 [Zou, Wen; Chen, Hung-Chia; Meehan, Joe; Xu, Joshua; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Chen, Hung-Chia] China Med Univ, Granduate Inst Biostat, Taichung, Taiwan. [Chen, Hung-Chia] China Med Univ, Ctr Biostat, Taichung, Taiwan. [Hise, Kelley B.] Ctr Dis Control & Prevent CDC, PulseNet Database Unit, Enter Dis Lab Branch, Div Foodborne Waterborne & Environm Dis,Natl Ctr, Atlanta, GA USA. [Foley, Steven L.; Nayak, Rajesh] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Lin, Wei-Jiun] Feng Chia Univ, Dept Appl Math, Taichung 40724, Taiwan. [Fang, Hong] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. RP Zou, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. EM wen.zou@fda.hhs.gov FU Food Protection Plan of FDA FX This work was funded by Food Protection Plan of FDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 9 Z9 9 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 14 PY 2013 VL 8 IS 3 AR e59224 DI 10.1371/journal.pone.0059224 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 109YM UT WOS:000316407400099 PM 23516614 ER PT J AU Turnipseed, SB Romano, J AF Turnipseed, Sherri B. Romano, Joe TI The 49th Annual Florida Pesticide Residue Workshop SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Editorial Material AB The papers in this special issue of Journal of Agricultural and Food Chemistry were originally presented at the 49th annual Florida Pesticide Residue Workshop (FPRW). The FPRW is an annual meeting for scientists specializing in trace level analysis of pesticides, veterinary drug residues, and other chemical contaminants in food, animal feed, and environmental samples. C1 [Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Romano, Joe] Waters Corp, Food & Environm Business Operat, Milford, MA 01757 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. EM Sherri.Turnipseed@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 13 PY 2013 VL 61 IS 10 BP 2291 EP 2292 DI 10.1021/jf304585r PG 2 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 107TO UT WOS:000316243900001 PM 23282283 ER PT J AU Kaewsuya, P Brewer, WE Wong, J Morgan, SL AF Kaewsuya, Pakritsadang Brewer, William E. Wong, Jon Morgan, Stephen L. TI Automated QuEChERS Tips for Analysis of Pesticide Residues in Fruits and Vegetables by GC-MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE QuEChERS; pesticides; GC-MS; DPX ID LIQUID-LIQUID-EXTRACTION; TANDEM MASS-SPECTROMETRY; MULTIRESIDUE METHOD AB This paper reports the development of an automated method of QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) using pipet tips fitted with filtration screens and containing primary-secondary amine, magnesium sulfate, and graphitized carbon black. These tips are referred to as "QuEChERS Tips". Using loosely contained sorbent, dispersive solid phase extraction (dSPE) cleanup was performed with the QuEChERS Tips and automation. The main advantage of the QuEChERS Tips is that they are readily automated because this dSPE method does not require centrifugation. High recoveries (70-117%) and good reproducibilities (<12%) are shown for over 200 pesticides using automated QuEChERS Tips and GC-MS in various sample matrices. C1 [Kaewsuya, Pakritsadang; Brewer, William E.; Morgan, Stephen L.] Univ S Carolina, Dept Chem & Biochem, Columbia, SC 29208 USA. [Wong, Jon] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Brewer, WE (reprint author), Univ S Carolina, Dept Chem & Biochem, 631 Sumter St, Columbia, SC 29208 USA. EM brewer@sc.edu OI Morgan, Stephen L./0000-0001-5091-3148 NR 25 TC 18 Z9 19 U1 2 U2 52 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 EI 1520-5118 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 13 PY 2013 VL 61 IS 10 BP 2299 EP 2314 DI 10.1021/jf304648h PG 16 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 107TO UT WOS:000316243900003 PM 23331058 ER PT J AU Chamkasem, N Ollis, LW Harmon, T Lee, S Mercer, G AF Chamkasem, Narong Ollis, Lisa W. Harmon, Tiffany Lee, Sookwang Mercer, Greg TI Analysis of 136 Pesticides in Avocado Using a Modified QuEChERS Method with LC-MS/MS and GC-MS/MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE triple quadrupole; tandem mass spectrometry; liquid chromatography; gas chromatography; pesticide residue analysis; avocado; QuEChERS ID GAS CHROMATOGRAPHY/MASS SPECTROMETRY; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; MULTIRESIDUE ANALYSIS; RESIDUE ANALYSIS; OLIVE OIL; MATRICES; PRODUCE; CLEANUP AB A simple and high-throughput screening method for the analysis of 136 pesticides in avocado (Persea americana) by LC-(+)-ESI-MS/MS and GC-MS/MS is presented. A modified QuEChERS sample preparation method was developed to improve the extraction recovery of highly lipophilic pesticides. Extracts from minced avocados after acetonitrile (MeCN) extraction were directly injected to LC-MS/MS, whereas other GC-amenable compounds were treated with the modified QuEChERS procedure for GC-MS/MS analysis. The average recoveries for 79 pesticides quantified by LC-MS/MS at 10, 50, and 200 ng/g fortifying levels were 86.1% or better (with maximum RSD at 9.2%), whereas GC-MS/MS analysis demonstrated 70.2% or better (RSD < 18%) for average recovery from 57 compounds at the same spike levels. The application of LC- and GC-MS/MS combined with the improved extraction procedures led to the current method, which can quantitate these pesticides even if they are present in avocados below the targeted action level by FDA. This method demonstrated the improved recovery of several challenging lipophilic pesticides in highly fat-rich avocados. C1 [Chamkasem, Narong; Ollis, Lisa W.; Harmon, Tiffany; Lee, Sookwang] US FDA, Southeast Reg Lab, Atlanta, GA 30309 USA. [Mercer, Greg] US FDA, Pacific Reg Lab Northwest, Bothell, WA 98021 USA. RP Chamkasem, N (reprint author), US FDA, Southeast Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM narong.chamkasem@fda.hhs.gov NR 20 TC 29 Z9 35 U1 5 U2 72 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 13 PY 2013 VL 61 IS 10 BP 2315 EP 2329 DI 10.1021/jf304191c PG 15 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 107TO UT WOS:000316243900004 PM 23362971 ER PT J AU Lohne, JJ Andersen, WC Casey, CR Turnipseed, SB Madson, MR AF Lohne, Jack J. Andersen, Wendy C. Casey, Christine R. Turnipseed, Sherri B. Madson, Mark R. TI Analysis of Stilbene Residues in Aquacultured Finfish Using LC-MS/MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE stilbenes; fish; aquaculture; LC-MS/MS ID TANDEM MASS-SPECTROMETRY; GAS-CHROMATOGRAPHIC DETERMINATION; LIQUID-CHROMATOGRAPHY; ANABOLIC-STEROIDS; DIETHYLSTILBESTROL; GROWTH; HORMONES; TISSUES; CATTLE; WATER AB This analytical method was developed for the determination of three stilbene residues, diethylstilbestrol (DES), dienestrol (DEN), and hexestrol (HEX), in edible tissues of finfish including catfish, salmon, trout, and tilapia. Fortified fish samples were extracted with acetonitrile and further cleaned up using silica solid phase extraction columns. Stilbene residues were separated from matrix components by reversed phase high-performance liquid chromatography on a C8 column and analyzed using a tandem mass spectrometer with negative electrospray ionization. The overall average residue recoveries using post-fortified matrix-matched calibrants were 119, 99, and 104% with %RSDs of 18, 11, and 15% for DEN, DES, and HEX, respectively. Method detection limits of DEN, DES, and HEX in each matrix were found to be at or below 0.21 ng/g, and the limit of quantification averaged 0.3 ng/g and ranged from 0.18 to 0.65 ng/g for all analytes in all matrices. C1 [Lohne, Jack J.; Andersen, Wendy C.; Turnipseed, Sherri B.; Madson, Mark R.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Casey, Christine R.; Madson, Mark R.] US FDA, Denver Lab, Denver, CO 80225 USA. RP Lohne, JJ (reprint author), US FDA, Anim Drugs Res Ctr, Denver Fed Ctr Bldg 20,West 6th Ave & Kipling Blv, Denver, CO 80225 USA. EM jack.lohne@fda.hhs.gov NR 37 TC 6 Z9 6 U1 3 U2 38 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 13 PY 2013 VL 61 IS 10 BP 2364 EP 2370 DI 10.1021/jf3045878 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 107TO UT WOS:000316243900009 PM 23379635 ER PT J AU Al-Taher, F Banaszewski, K Jackson, L Zweigenbaum, J Ryu, D Cappozzo, J AF Al-Taher, Fadwa Banaszewski, Katie Jackson, Lauren Zweigenbaum, Jerry Ryu, Dojin Cappozzo, Jack TI Rapid Method for the Determination of Multiple Mycotoxins in Wines and Beers by LC-MS/MS Using a Stable Isotope Dilution Assay SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE multiple mycotoxins; beer; wine; internal standard; LC-MS/MS ID TANDEM MASS-SPECTROMETRY; OCHRATOXIN-A; GRAPE-JUICE; RISK AB A "dilute and shoot" method for the liquid chromatography-tandem mass spectrometric (LC-MS/MS) determination of multiple mycotoxins (aflatoxins B1, B2, G1, G2, ochratoxin A (OTA), fumonisins (F) B1 and B2, zearalenone, deoxynivalenol, T-2 toxin, and HT-2 toxin) in wines and beers has been developed and validated. Separation was accomplished using ultrahigh-performance liquid chromatography (UHPLC) with <10 min analysis time. Mycotoxins were detected by dynamic multiple reaction monitoring (MRM) in positive electrospray ionization mode. Due to matrix effects, C-13-uniformly labeled mycotoxins were added to the sample extracts prior to LC-MS/MS analysis. With external calibration, recoveries were 18-148% for white wines, 15-118% for red wines, and 20-125% for beers, at three spiking levels. The C-13-labeled internal standards compensated for matrix effects effectively, with overall recoveries of 94-112% for white wines, 80-137% for red wines, and 61-131% for beers, with greater recoveries for FB1 and FB2, at three spiking levels. The relative standard deviation was <20% for all analytes in the wines and beers. This method was applied to a USDA-funded nationwide survey of domestic and imported wines and beers for the determination of OTA and extended to include other mycotoxins. C1 [Al-Taher, Fadwa; Banaszewski, Katie; Cappozzo, Jack] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Jackson, Lauren] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Zweigenbaum, Jerry] Agilent Technol, Wilmington, DE 19898 USA. [Ryu, Dojin] Univ Idaho, Sch Food Sci, Moscow, ID 83844 USA. RP Cappozzo, J (reprint author), IIT, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM jcappozz@iit.edu FU National Institute of Food and Agriculture, U.S. Department of Agriculture [2011-67005-30018] FX This project is supported in part by the National Institute of Food and Agriculture, U.S. Department of Agriculture, under Agreement 2011-67005-30018. NR 22 TC 31 Z9 32 U1 6 U2 89 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR 13 PY 2013 VL 61 IS 10 BP 2378 EP 2384 DI 10.1021/jf304729f PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 107TO UT WOS:000316243900011 PM 23256627 ER PT J AU Plaut, RD Mocca, CP Prabhakara, R Merkel, TJ Stibitz, S AF Plaut, Roger D. Mocca, Christopher P. Prabhakara, Ranjani Merkel, Tod J. Stibitz, Scott TI Stably Luminescent Staphylococcus aureus Clinical Strains for Use in Bioluminescent Imaging SO PLOS ONE LA English DT Article ID METHICILLIN-RESISTANT; MOUSE MODEL; IN-VIVO; VIRULENCE; SEQUENCE; GENOME; GENE; REPLACEMENT; EVOLUTION; INFECTION AB In vivo bioluminescent imaging permits the visualization of bacteria in live animals, allowing researchers to monitor, both temporally and spatially, the progression of infection in each animal. We sought to engineer stably luminescent clinical strains of Staphylococcus aureus, with the goal of using such strains in mouse models. The gram-positive shuttle vector pMAD was used as the backbone for an integration plasmid. A chloramphenicol resistance gene, a modified lux operon from Photorhabdus luminescens, and approximately 650 bp of homology to the chromosome of the USA300 S. aureus strain NRS384 were added, generating plasmid pRP1195. Electroporation into strain RN4220 followed by temperature shift led to integration of pRP1195 into the chromosome. The integrated plasmid was transferred to clinical strains by phage transduction. Luminescent strains displayed no in vitro growth defects. Moreover, luminescence was stable in vitro after three rounds of subculture over 48 hours of growth in the absence of antibiotics. Mice were infected with a luminescent strain of NRS384 in skin and intravenous models. In a mouse skin model, luminescent bacteria were present in lesions that formed and cleared over the course of several days, and in an intravenous model, bacteria inoculated in the mouse tail vein were observed spreading to multiple tissues. No statistically significant difference in virulence was observed between NRS384 and the luminescent strain in either infection model. These preliminary data suggest that this luminescent USA300 strain is suitable for use in mouse models. Similar strains were engineered using other sequenced clinical strains. Because these strains are stably luminescent, they should prove useful in animal models of infection. C1 [Plaut, Roger D.; Mocca, Christopher P.; Prabhakara, Ranjani; Merkel, Tod J.; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Plaut, RD (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM Roger.Plaut@fda.hhs.gov RI Plaut, Roger/B-2340-2013 OI Plaut, Roger/0000-0002-0883-972X FU Food and Drug Administration Medical Countermeasures Initiative; National Institute of Allergy and Infectious Diseases/National Institutes of Health [HHSN272200700055C] FX Stanley Kim was supported by the Food and Drug Administration Medical Countermeasures Initiative. Strain NRS384 was obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA; www.narsa.net) Program, supported under National Institute of Allergy and Infectious Diseases/National Institutes of Health Contract No. HHSN272200700055C. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 22 TC 13 Z9 13 U1 1 U2 24 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 12 PY 2013 VL 8 IS 3 AR e59232 DI 10.1371/journal.pone.0059232 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 107WV UT WOS:000316252500075 PM 23555002 ER PT J AU Vitelli, A Quirion, MR Lo, CY Misplon, JA Grabowska, AK Pierantoni, A Ammendola, V Price, GE Soboleski, MR Cortese, R Colloca, S Nicosia, A Epstein, SL AF Vitelli, Alessandra Quirion, Mary R. Lo, Chia-Yun Misplon, Julia A. Grabowska, Agnieszka K. Pierantoni, Angiolo Ammendola, Virginia Price, Graeme E. Soboleski, Mark R. Cortese, Riccardo Colloca, Stefano Nicosia, Alfredo Epstein, Suzanne L. TI Vaccination to Conserved Influenza Antigens in Mice Using a Novel Simian Adenovirus Vector, PanAd3, Derived from the Bonobo Pan paniscus SO PLOS ONE LA English DT Article ID CD8(+) T-CELLS; A VIRUSES; NEUTRALIZING ANTIBODIES; GENE-TRANSFER; NUCLEOPROTEIN; LYMPHOCYTES; IMMUNOGENICITY; IMMUNITY; DNA; EFFICACY AB Among approximately 1000 adenoviruses from chimpanzees and bonobos studied recently, the Pan Adenovirus type 3 (PanAd3, isolated from a bonobo, Pan paniscus) has one of the best profiles for a vaccine vector, combining potent transgene immunogenicity with minimal pre-existing immunity in the human population. In this study, we inserted into a replication defective PanAd3 a transgene expressing a fusion protein of conserved influenza antigens nucleoprotein (NP) and matrix 1 (M1). We then studied antibody and T cell responses as well as protection from challenge infection in a mouse model. A single intranasal administration of PanAd3-NPM1 vaccine induced strong antibody and T cell responses, and protected against high dose lethal influenza virus challenge. Thus PanAd3 is a promising candidate vector for vaccines, including universal influenza vaccines. C1 [Quirion, Mary R.; Lo, Chia-Yun; Misplon, Julia A.; Price, Graeme E.; Soboleski, Mark R.; Epstein, Suzanne L.] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Therapy & Immunogen Branch, Bethesda, MD 20892 USA. [Vitelli, Alessandra; Grabowska, Agnieszka K.; Pierantoni, Angiolo; Ammendola, Virginia; Cortese, Riccardo; Colloca, Stefano; Nicosia, Alfredo] Okairos, Rome, Italy. [Nicosia, Alfredo] Ctr Ingn Genet & Biotecnol Avanzate CEINGE, Naples, Italy. [Nicosia, Alfredo] Univ Naples Federico II, Dept Biochem & Med Biotechnol, Naples, Italy. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Gene Therapy & Immunogen Branch, Bethesda, MD 20892 USA. EM suzanne.epstein@fda.hhs.gov FU Okairos; CBER, FDA FX Research funding was provided by Okairos and by CBER, FDA. Authors from Okairos are employees of and/or shareholders in Okairos, which is developing vectored vaccines for malaria and other diseases. All decisions concerning study design, data collection and analysis, decision to publish, and preparation of the manuscript were those of the authors, with concurrence of all authors. NR 47 TC 19 Z9 21 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 11 PY 2013 VL 8 IS 3 AR e55435 DI 10.1371/journal.pone.0055435 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 107WI UT WOS:000316251100002 PM 23536756 ER PT J AU Chen, L Bonson, KR AF Chen, Ling Bonson, Katherine R. TI An Equivalence Test for the Comparison Between a Test Drug and Placebo in Human Abuse Potential Studies SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Crossover design; Drug abuse potential studies; Equivalence margin; Meta-analysis ID LIABILITY ASSESSMENT AB Statistical methodologies for human abuse potential studies are rarely evaluated. Human abuse potential studies assess whether test drugs produce positive and negative subjective responses on abuse-related measures using volunteers with histories of recreational drug use. These studies typically have a randomized, double-blind, placebo- and positive-controlled crossover design with at least four treatments: placebo, at least two doses of a test drug, and at least one dose of a positive control drug (a drug with known abuse potential). This article proposes a new test for assessing whether a test drug produces data indicative of abuse potential when compared to placebo. C1 [Chen, Ling] US FDA, Div Biometr 6, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Bonson, Katherine R.] US FDA, Off Ctr Director, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chen, L (reprint author), 10903 New Hampshire Ave,Bld 21,RM 4644, Silver Spring, MD 20903 USA. EM ling.chen@fda.hhs.gov FU Regulatory Science Review (RSR) Enhancement Program FX This research is supported by the 2009 and 2010 Regulatory Science Review (RSR) Enhancement Program. The authors thank the summer intern, Bing Fan, Department of Statistics/ Biostatistics, Rutgers University, for his help on organizing datasets, and the ORISE Research Fellow, Junqing Wu, Department of Statistics, University of California-Santa Barbara, for his help on the simulation for the distribution of (delta) over cap. The authors thank Drs. Stella G. Machado, Michael Klein, and Silvia Calderon for their helpful comments and support. NR 17 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD MAR 11 PY 2013 VL 23 IS 2 BP 294 EP 306 DI 10.1080/10543406.2011.616972 PG 13 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 100GD UT WOS:000315684500002 PM 23437940 ER PT J AU Lin, L Hedayat, AS Tang, YQ AF Lin, Lawrence Hedayat, A. S. Tang, Yuqing TI A Comparison Model for Measuring Individual Agreement SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Individual bioequivalence; Intraintra ratio; Mean squared deviation; Totalintra ratio ID CONCORDANCE CORRELATION-COEFFICIENT; TOTAL DEVIATION INDEX; WEIGHTED KAPPA; EVALUATE REPRODUCIBILITY; VARIANCE-COMPONENTS; BIOEQUIVALENCE; OBSERVERS AB This article proposes a general comparison model for assessing individual agreement of k 2 raters evaluating n subjects with m 2 replicated readings. Users can explore total-rater agreement relative to intrarater agreement where any subset of the k raters can be selected in the numerator and denominator. Users are also allowed to compare intrarater agreement among selected raters. Based on the ratio of mean squared deviations (MSDs), two comparative agreement indices, totalintra ratio (TIR) and intraintra ratio (IIR), are proposed. The TIR is a noninferiority assessment such that the differences of individual readings from different raters cannot be inferior by a prespecified margin to the differences of the replicated readings within raters. TIR can be used whether a reference exists or not. The method used by the Food and Drug Administration (FDA) for evaluating individual bioequivalence under relative scale becomes the special case of our approach. The IIR is a classical assessment such that the precision of selected raters can be better than; equal to; or worse than that of other raters. The estimation and statistical inference of TIR and IIR are obtained through GEE methodology. C1 [Lin, Lawrence] Baxter Healthcare Co, Round Lake, IL USA. [Lin, Lawrence; Hedayat, A. S.] Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60680 USA. [Tang, Yuqing] US FDA, Silver Spring, MD USA. RP Lin, L (reprint author), 1589 Triton St, Carlsbad, CA 92011 USA. EM equeilin@gmail.com FU National Science Foundation [DMS-0603761, DMS-0904125] FX This research was primarily sponsored by the National Science Foundation, grants DMS-0603761 and DMS-0904125. The views expressed in this article are the author's personal views and not necessarily of the U.S. Food and Drug Administration. NR 32 TC 1 Z9 1 U1 1 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PD MAR 11 PY 2013 VL 23 IS 2 BP 322 EP 345 DI 10.1080/10543406.2011.616970 PG 24 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 100GD UT WOS:000315684500004 PM 23437942 ER PT J AU Adams, LV Craig, SR Mmbaga, EJ Naburi, H Lahey, T Nutt, CT Kisenge, R Noel, GJ Spielberg, SP AF Adams, Lisa V. Craig, Sienna R. Mmbaga, Elia John Naburi, Helga Lahey, Timothy Nutt, Cameron T. Kisenge, Rodrick Noel, Gary J. Spielberg, Stephen P. TI Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences SO PLOS ONE LA English DT Article ID DEVELOPING-WORLD; PHARMACOLOGY; INITIATIVES; FORMULATION; ADHERENCE; HEALTH AB Objective: The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. Patients and Methods: We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Results: Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. Conclusions: There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under-or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings. C1 [Adams, Lisa V.; Lahey, Timothy] Audrey & Theodor Geisel Sch Med Dartmouth, Hanover, NH USA. [Craig, Sienna R.] Dartmouth Coll, Hanover, NH 03755 USA. [Mmbaga, Elia John; Naburi, Helga; Kisenge, Rodrick] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Nutt, Cameron T.] Dartmouth Ctr Hlth Care Delivery Sci, Hanover, NH USA. [Noel, Gary J.] Inst Pediat Innovat, Cambridge, MA USA. [Noel, Gary J.] Weill Cornell Med Coll, New York, NY USA. [Noel, Gary J.] AstraZeneca, Waltham, MA USA. [Spielberg, Stephen P.] US FDA, Washington, DC 20204 USA. RP Adams, LV (reprint author), Audrey & Theodor Geisel Sch Med Dartmouth, Hanover, NH USA. EM Lisa.V.Adams@Dartmouth.edu FU World Health Organization (WHO), Better Medicines for Children project FX This research was supported by a grant from the World Health Organization (WHO) as part of the Better Medicines for Children project. The funders had no role in the data collection, decision to publish, or preparation of the manuscript. Technical advice on the study design and data analysis was provided by appropriate experts at WHO. The named authors alone are responsible for the views expressed in this publication. NR 28 TC 8 Z9 8 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 6 PY 2013 VL 8 IS 3 AR e58303 DI 10.1371/journal.pone.0058303 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 117EP UT WOS:000316936100102 PM 23484012 ER PT J AU Cancellotti, E Mahal, SP Somerville, R Diack, A Brown, D Piccardo, P Weissmann, C Manson, JC AF Cancellotti, Enrico Mahal, Sukhvir P. Somerville, Robert Diack, Abigail Brown, Deborah Piccardo, Pedro Weissmann, Charles Manson, Jean C. TI Post-translational changes to PrP alter transmissible spongiform encephalopathy strain properties SO EMBO JOURNAL LA English DT Article DE glycosylation; phenotypic change; prion; transmissible spongiform encephalopathy ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE INCUBATION-TIME; HUMAN PRION DISEASES; CELL PANEL ASSAY; MOLECULAR-BASIS; PHENOTYPIC VARIABILITY; AGENT STRAINS; MOUSE SCRAPIE; VARIANT CJD; PROTEIN AB The agents responsible for transmissible spongiform encephalopathies (TSEs), or prion diseases, contain as a major component PrPSc, an abnormal conformer of the host glycoprotein PrPC. TSE agents are distinguished by differences in phenotypic properties in the host, which nevertheless can contain PrPSc with the same amino-acid sequence. If PrP alone carries information defining strain properties, these must be encoded by post-translational events. Here we investigated whether the glycosylation status of host PrP affects TSE strain characteristics. We inoculated wild-type mice with three TSE strains passaged through transgenic mice with PrP devoid of glycans at the first, second or both N-glycosylation sites. We compared the infectious properties of the emerging isolates with TSE strains passaged in wild-type mice by in vivo strain typing and by the standard scrapie cell assay in vitro. Strain-specific characteristics of the 79A TSE strain changed when PrPSc was devoid of one or both glycans. Thus infectious properties of a TSE strain can be altered by post-translational changes to PrP which we propose result in the selection of mutant TSE strains. The EMBO Journal (2013) 32, 756-769. doi:10.1038/emboj.2013.6; published online: 8 February 2013 C1 [Cancellotti, Enrico; Somerville, Robert; Diack, Abigail; Brown, Deborah; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Div Neurobiol, Easter Bush EH25 9RG, Midlothian, Scotland. [Cancellotti, Enrico; Somerville, Robert; Diack, Abigail; Brown, Deborah; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, Royal Dick Sch Vet Studies, Easter Bush EH25 9RG, Midlothian, Scotland. [Mahal, Sukhvir P.; Weissmann, Charles] Scripps Florida, Dept Infectol, Jupiter, FL USA. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Manson, JC (reprint author), Univ Edinburgh, Roslin Inst, Div Neurobiol, Easter Bush EH25 9RG, Midlothian, Scotland. EM jean.manson@roslin.ed.ac.uk FU Roslin Institute Strategic Grant; BBSRC; National Institutes of Health [NIH-NIAID Y1-A1-4893-02, 1RO1NSO59543, 1RO1NS067214]; Food and Drugs Administration [FDA 224-05-1307]; Alafi Family Foundation FX The work in Edinburgh was supported by a Roslin Institute Strategic Grant funding from the BBSRC. PP was supported by funding from the National Institutes of Health: NIH-NIAID Y1-A1-4893-02 and the Food and Drugs Administration: FDA 224-05-1307. The work in TSRI Florida was supported by grants from the National Institutes of Health 1RO1NSO59543, 1RO1NS067214 and from the Alafi Family Foundation to CW. We thank Dorothy Kisielewski for mouse genotyping, Aileen Boyle for the excellent work on lesion profile analysis, and Anne Coghill, Sandra Mack and Gillian McGregor for assistance with the pathology analysis. Irene McConnell, Val Thompson, Simon Cumming, Leanne Frame and Kris Hogan for the breeding, care, injections and the clinical scoring of the mice. We are very grateful to Dr Andreas Lengeling for critical reading of the manuscript. 8H4 and 7A12 antibodies were kindly provided by Dr Man-Sun Sy (Case Western Reserve University) and the BH1 antibody by Dr Sandra McCutcheon (The Roslin Institute). 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. NR 69 TC 24 Z9 24 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 6 PY 2013 VL 32 IS 5 BP 756 EP 769 DI 10.1038/emboj.2013.6 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 110TE UT WOS:000316468000015 PM 23395905 ER PT J AU Seaworth, BJ Field, K Flood, J Saliba, J Mase, SR Cronin, A Shah, N Jereb, J Chorba, T AF Seaworth, Barbara J. Field, Kim Flood, Jennifer Saliba, Jouhayna Mase, Sundari R. Cronin, Ann Shah, Neha Jereb, John Chorba, Terence TI Interruptions in Supplies of Second-Line Antituberculosis Drugs-United States, 2005-2012 (Reprinted from MMWR, vol 2, pg 23-26, 2013) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Seaworth, Barbara J.] Univ Texas Hlth Sci Ctr, San Antonio, TX USA. [Field, Kim] San Diego Cty TB Control Program, San Diego, CA USA. [Saliba, Jouhayna] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Mase, Sundari R.; Cronin, Ann; Shah, Neha; Jereb, John; Chorba, Terence] CDC, Div TB Eliminat, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA 30333 USA. RP Mase, SR (reprint author), CDC, Div TB Eliminat, Natl Ctr HIV Viral Hepatitis STD & TB Prevent, Atlanta, GA 30333 USA. EM smase@cdc.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 6 PY 2013 VL 309 IS 9 BP 866 EP 868 DI 10.1001/jama.2013.691 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 099PC UT WOS:000315632700009 ER PT J AU Bowyer, JF Patterson, TA Saini, UT Hanig, JP Thomas, M Camacho, L George, NI Chen, JJ AF Bowyer, John F. Patterson, Tucker A. Saini, Upasana T. Hanig, Joseph P. Thomas, Monzy Camacho, Luisa George, Nysia I. Chen, James J. TI Comparison of the global gene expression of choroid plexus and meninges and associated vasculature under control conditions and after pronounced hyperthermia or amphetamine toxicity SO BMC GENOMICS LA English DT Article DE Gene expression; Meninges; Cerebral vasculature; Choroid plexus; Cerebrospinal fluid; Amphetamines; Hyperthermia ID BLOOD-BRAIN-BARRIER; CEREBROSPINAL-FLUID; NEURONAL DEGENERATION; SUBSTITUTED AMPHETAMINES; METHAMPHETAMINE ABUSE; C57BL/6J MOUSE; STROKE; NEUROTOXICITY; TEMPERATURE; HEMORRHAGE AB Background: The meninges (arachnoid and pial membranes) and associated vasculature (MAV) and choroid plexus are important in maintaining cerebrospinal fluid (CSF) generation and flow. MAV vasculature was previously observed to be adversely affected by environmentally-induced hyperthermia (EIH) and more so by a neurotoxic amphetamine (AMPH) exposure. Herein, microarray and RT-PCR analysis was used to compare the gene expression profiles between choroid plexus and MAV under control conditions and at 3 hours and 1 day after EIH or AMPH exposure. Since AMPH and EIH are so disruptive to vasculature, genes related to vasculature integrity and function were of interest. Results: Our data shows that, under control conditions, many of the genes with relatively high expression in both the MAV and choroid plexus are also abundant in many epithelial tissues. These genes function in transport of water, ions, and solutes, and likely play a role in CSF regulation. Most genes that help form the blood-brain barrier (BBB) and tight junctions were also highly expressed in MAV but not in choroid plexus. In MAV, exposure to EIH and more so to AMPH decreased the expression of BBB-related genes such as Sox18, Ocln, and Cldn5, but they were much less affected in the choroid plexus. There was a correlation between the genes related to reactive oxidative stress and damage that were significantly altered in the MAV and choroid plexus after either EIH or AMPH. However, AMPH (at 3 hr) significantly affected about 5 times as many genes as EIH in the MAV, while in the choroid plexus EIH affected more genes than AMPH. Several unique genes that are not specifically related to vascular damage increased to a much greater extent after AMPH compared to EIH in the MAV (Lbp, Reg3a, Reg3b, Slc15a1, Sct and Fst) and choroid plexus (Bmp4, Dio2 and Lbp). Conclusions: Our study indicates that the disruption of choroid plexus function and damage produced by AMPH and EIH is significant, but the changes may not be as pronounced as they are in the MAV, particularly for AMPH. Expression profiles in the MAV and choroid plexus differed to some extent and differences were not restricted to vascular related genes. C1 [Bowyer, John F.; Patterson, Tucker A.; Saini, Upasana T.; Thomas, Monzy] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Camacho, Luisa] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [George, Nysia I.; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Bowyer, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM john.bowyer@fda.hhs.gov FU Oak Ridge Institute for Science and Education; National Center for Toxicological Research/U.S. Food and Drug Administration FX Also, the expertise of Nathan Crabtree in additional Ingenuity Pathway Analysis of gene expression in the choroid plexus is acknowledged. He is a student of the UALR/UAMS Bioinformatics Graduate Program and funded through the Oak Ridge Institute for Science and Education administered through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration.; This research was funded by the National Center for Toxicological Research/U.S. Food and Drug Administration and supported by a fellowship (Monzy Thomas) from the Oak Ridge Institute for Science and Education. NR 68 TC 8 Z9 8 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 5 PY 2013 VL 14 AR 147 DI 10.1186/1471-2164-14-147 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 109WZ UT WOS:000316402400001 PM 23497014 ER PT J AU Mans, DJ Callahan, RJ Dunn, JD Gryniewicz-Ruzicka, CM AF Mans, Daniel J. Callahan, Rebecca J. Dunn, Jamie D. Gryniewicz-Ruzicka, Connie M. TI Rapid-screening detection of acetildenafils, sildenafils and avanafil by ion mobility spectrometry SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Ion mobility spectrometry; Acetildenafils; Sildenafils; Avanafil ID HERBAL DIETARY-SUPPLEMENT; SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; LC-ESI-MS; STRUCTURE ELUCIDATION; ERECTILE DYSFUNCTION; STRUCTURAL ELUCIDATION; ENHANCEMENT PRODUCTS; DESIGNER DRUG AB Ion mobility spectrometry was used as a rapid screening tool for the detection of acetildenafils, sildenafils and avanafil within adulterated herbal supplement matrices. Acetildenafils show a tendency for partial fragmentation during the desorption/ionization process affording two peaks in the ion mobility spectrum in addition to the intact compound. The fragmentation appears to occur a to the carbonyl group along the C-N bond attaching the piperazine moiety, producing a common fragment (K-o = 1.0280 cm(2) V-1 s(-1)) along with the respective piperazine fragment. The sildenafils and avanafil afford one molecular ion peak per compound. Published by Elsevier B.V. C1 [Mans, Daniel J.; Callahan, Rebecca J.; Dunn, Jamie D.; Gryniewicz-Ruzicka, Connie M.] US FDA, CDER Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Mans, DJ (reprint author), US FDA, CDER Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM Daniel.Mans@fda.hhs.gov FU Center for Drug Evaluation and Research FX This project was supported in part by an appointment to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration (RJC). NR 43 TC 8 Z9 12 U1 2 U2 55 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 EI 1873-264X J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAR 5 PY 2013 VL 75 BP 153 EP 157 DI 10.1016/j.jpba.2012.11.031 PG 5 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 081OW UT WOS:000314332500020 PM 23262416 ER PT J AU Woodcock, J AF Woodcock, Janet TI Comparative effectiveness research and the regulation of drugs, biologics and devices SO JOURNAL OF COMPARATIVE EFFECTIVENESS RESEARCH LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM janet.woodcock@fda.hhs.gov NR 5 TC 4 Z9 4 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 2042-6305 EI 2042-6313 J9 J COMP EFFECT RES JI J. Comp. Eff. Res. PD MAR PY 2013 VL 2 IS 2 BP 95 EP 97 DI 10.2217/CER.13.9 PG 3 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 299CN UT WOS:000330372700001 PM 24236548 ER PT J AU Jacobs, AC Hatfield, KP AF Jacobs, A. C. Hatfield, K. P. TI History of Chronic Toxicity and Animal Carcinogenicity Studies for Pharmaceuticals SO VETERINARY PATHOLOGY LA English DT Article DE carcinogenicity tests; historical aspects; oral contraceptives; pharmaceutical preparations; policy ID DEPOT-MEDROXYPROGESTERONE ACETATE; CONTRACEPTIVE STEROIDS; BREAST-CANCER; REQUIREMENTS; GUIDELINES; FDA; PROGESTOGENS; SAFETY; DRUGS AB During the 20th century, as drug products were being developed to treat both known and emerging human diseases and conditions, determining the safety of these new chemicals became of increasing importance and necessity. For a time, the safety of use in human populations was of question, let alone whether the drug product was truly effective. As such, US and international regulatory agencies have played a major role in establishing standardized testing to evaluate the safety and efficacy of drug products. Pharmacologic and toxicologic evaluation of a new drug in animals is an important part of the pharmaceutical development process prior to its first-time use in humans, as well as its potential chronic use in affected populations. Just as both science and technology have evolved over the past century and further, so have the guidelines that have been put forth to adequately and efficiently evaluate the toxicity of new drugs and their subsequent safety in humans. This review summarizes the historical highlights of the conduct of drug safety evaluations in animals, particularly with regard to chronic toxicity and carcinogenicity assessments, and how we have progressed to our current standards and protocols to ensure safe use of drug products in human populations. C1 [Jacobs, A. C.; Hatfield, K. P.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Jacobs, AC (reprint author), US FDA, CDER OND, Silver Spring, MD 20993 USA. EM abigail.jacobs@fda.hhs.gov NR 56 TC 14 Z9 15 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0300-9858 EI 1544-2217 J9 VET PATHOL JI Vet. Pathol. PD MAR PY 2013 VL 50 IS 2 BP 324 EP 333 DI 10.1177/0300985812450727 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 298AO UT WOS:000330296500017 PM 22700852 ER PT J AU Chen, YH Dennis, SB Hartnett, E Paoli, G Pouillot, R Ruthman, T Wilson, M AF Chen, Yuhuan Dennis, Sherri B. Hartnett, Emma Paoli, Greg Pouillot, Regis Ruthman, Todd Wilson, Margaret TI FDA-iRISK-A Comparative Risk Assessment System for Evaluating and Ranking Food-Hazard Pairs: Case Studies on Microbial Hazards SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES; PEANUT BUTTER; SALMONELLA; PRODUCE; MELON; TOOL AB Stakeholders in the system of food safety, in particular federal agencies, need evidence-based, transparent, and rigorous approaches to estimate and compare the risk of foodborne illness from microbial and chemical hazards and the public health impact of interventions. FDA-iRISK (referred to here as iRISK), a Web-based quantitative risk assessment system, was developed to meet this need. The modeling tool enables users to assess, compare, and rank the risks posed by multiple food-hazard pairs at all stages of the food supply system, from primary production, through manufacturing and processing, to retail distribution and, ultimately, to the consumer. Using standard data entry templates, built-in mathematical functions, and Monte Carlo simulation techniques, iRISK integrates data and assumptions from seven components: the food, the hazard, the population of consumers, process models describing the introduction and fate of the hazard up to the point of consumption, consumption patterns, dose-response curves, and health effects. Beyond risk ranking, iRISK enables users to estimate and compare the impact of interventions and control measures on public health risk. iRISK provides estimates of the impact of proposed interventions in various ways, including changes in the mean risk of illness and burden of disease metrics, such as losses in disability-adjusted life years. Case studies for Listeria monocytogenes and Salmonella were developed to demonstrate the application of iRISK for the estimation of risks and the impact of interventions for microbial hazards. iRISK was made available to the public at http://irisk.foodrisk.org in October 2012. C1 [Chen, Yuhuan; Dennis, Sherri B.; Pouillot, Regis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hartnett, Emma; Paoli, Greg; Ruthman, Todd; Wilson, Margaret] Risk Sci Int Inc, Ottawa, ON K1N 7G2, Canada. RP Dennis, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sherri.dennis@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 FU Research Participation Program at the Center for Food Safety and Applied Nutrition; U.S. Department of Energy; U.S. Food and Drug Administration FX The authors thank the many experts who provided invaluable input and critiques to assist the development of the iRISK system, including members of the IFT expert panel, RTI, and external peer reviewers. This work was supported in part by appointments (R. Pouillot) to the Research Participation Program at the Center for Food Safety and Applied Nutrition, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 43 TC 15 Z9 16 U1 3 U2 35 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2013 VL 76 IS 3 BP 376 EP 385 DI 10.4315/0362-028X.JFP-12-372 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240EV UT WOS:000326078600001 PM 23462073 ER PT J AU Patazca, E Morrissey, TR Loeza, V Reddy, NR Skinner, GE Larkin, JW AF Patazca, Eduardo Morrissey, Travis R. Loeza, Viviana Reddy, N. Rukma Skinner, Guy E. Larkin, John W. TI Effect of Packaging Systems and Pressure Fluids on Inactivation of Clostridium botulinum Spores by Combined High Pressure and Thermal Processing SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BACILLUS-AMYLOLIQUEFACIENS SPORES; TEMPERATURE; ENDOSPORES; KINETICS; HEAT AB Several studies have been published on the inactivation of bacterial spores by using high pressure processing in combination with heat. None of the studies investigated the effect of the packaging system or the pressurizing fluid on spore inactivation. The objective of this study was to select and validate an appropriate packaging system and pressure transfer fluid for inactivation of Clostridium botulinum spores by using high pressure processing in combination with thermal processing. Inactivation of spores packaged in three packaging systems (plastic pouches, cryovials, and transfer pipettes) was measured in two pressure test systems (laboratory-scale and pilot-scale) at 700 MPa and >105 degrees C. Total destruction (>6.6-log reduction) of the spores packaged in the graduated tube part of transfer pipettes was obtained after processing for up to 10 min at 118 degrees C and 700 MPa in both pressure test systems, compared with the spores packaged either in plastic pouches or cryovials. Reduction of spores packaged in plastic pouches was lowest (<4.8 log) for both pressure test systems when processed at the same conditions (i.e., 700 MPa and 118 degrees C). Within the pilot-scale pressure system, increasing the process temperature from 118 to 121 degrees C at 700 MPa for 10 min resulted in only a small increase in spore reduction (<5.1 log) for spores packaged in plastic pouches, whereas there were no recoverable spores for either of the other two packaging systems. Use of plastic pouches for packaging spores in inactivation kinetic studies could lead to erroneous conclusions about the effect of high pressure in combination with heat. BioGlycol is the pressure-heat transfer fluid of choice, as compared with Duratherm oil, to maximize the temperature response rate during pressurization within the laboratory-scale pressure test system. C1 [Patazca, Eduardo; Loeza, Viviana] IIT, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Morrissey, Travis R.; Reddy, N. Rukma; Skinner, Guy E.; Larkin, John W.] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Reddy, NR (reprint author), US FDA, Inst Food Safety & Hlth, 6502 South Archer Rd, Bedford Pk, IL 60501 USA. EM rukma.reddy@fda.hhs.gov FU U.S. Food and Drug Administration FX We acknowledge the assistance of Kenneth Boettcher in operating of the laboratory-scale and pilot-scale pressure test systems. The work was supported by a grant from the U.S. Food and Drug Administration to the Institute for Food Safety and Health at the Illinois Institute of Technology. NR 15 TC 8 Z9 8 U1 3 U2 25 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2013 VL 76 IS 3 BP 448 EP 455 DI 10.4315/0362-028X.JFP-12-181 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240EV UT WOS:000326078600010 PM 23462082 ER PT J AU Birbari, W Bunning, VK Dessai, U Dole, R Engeljohn, D Garrett, S Glass, K Golden, D Grooters, SV Hardin, M Hoover, D Johnson, L Knabel, S Natrajan, N Ruple, A Tauxe, R Whitaker, R Zink, D AF Birbari, Wafa Bunning, V. Kelly Dessai, Uday Dole, Robert Engeljohn, Daniel Garrett, Spencer Glass, Kathleen Golden, David Grooters, Susan Vaughn Hardin, Margaret Hoover, Dallas Johnson, Lee Knabel, Stephen Natrajan, Nandini Ruple, Angela Tauxe, Robert Whitaker, Robert Zink, Donald CA Natl Advisory Comm Microbiol TI Expedited Response to the Questions Posed by the United States Department of Agriculture Agricultural Marketing Service To Support Ground Beef Purchase for the Federal Food and Nutrition Assistance Programs SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; MEAT; POULTRY C1 [Glass, Kathleen] Univ Wisconsin, Madison, WI 53706 USA. [Golden, David] Univ Tennessee, Knoxville, TN 37996 USA. [Hoover, Dallas] Univ Delaware, Newark, DE 19716 USA. [Knabel, Stephen] Penn State Univ, University Pk, PA 16802 USA. [Ruple, Angela] US Dept Commerce, Natl Seafood Inspect Lab, Washington, DC 20230 USA. [Tauxe, Robert] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30329 USA. [Zink, Donald] US FDA, US Dept HHS, CFSAN, Rockville, MD 20857 USA. NR 34 TC 1 Z9 1 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2013 VL 76 IS 3 BP 523 EP 537 DI 10.4315/0362-028X.JFP-12-453 PG 15 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 240EV UT WOS:000326078600020 ER PT J AU Murthy, A Bartocci, E Fenton, FH Glimm, J Gray, RA Cherry, EM Smolka, SA Grosu, R AF Murthy, Abhishek Bartocci, Ezio Fenton, Flavio H. Glimm, James Gray, Richard A. Cherry, Elizabeth M. Smolka, Scott A. Grosu, Radu TI Curvature Analysis of Cardiac Excitation Wavefronts SO IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS LA English DT Article DE Cardiac excitation waves; isopotentials; Bezier curves; curvature; cardiac arrhythmia and fibrillation ID MODEL; MEDIA; ELECTROPHYSIOLOGY; REPOLARIZATION; PROPAGATION; SIMULATION; MYOCYTES; TISSUE; ROLES AB We present the Spiral Classification Algorithm (SCA), a fast and accurate algorithm for classifying electrical spiral waves and their associated breakup in cardiac tissues. The classification performed by SCA is an essential component of the detection and analysis of various cardiac arrhythmic disorders, including ventricular tachycardia and fibrillation. Given a digitized frame of a propagating wave, SCA constructs a highly accurate representation of the front and the back of the wave, piecewise interpolates this representation with cubic splines, and subjects the result to an accurate curvature analysis. This analysis is more comprehensive than methods based on spiral-tip tracking, as it considers the entire wave front and back. To increase the smoothness of the resulting symbolic representation, the SCA uses weighted overlapping of adjacent segments which increases the smoothness at join points. SCA has been applied to a number of representative types of spiral waves, and, for each type, a distinct curvature evolution in time (signature) has been identified. Distinct signatures have also been identified for spiral breakup. These results represent a significant first step in automatically determining parameter ranges for which a computational cardiac-cell network accurately reproduces a particular kind of cardiac arrhythmia, such as ventricular fibrillation. C1 [Murthy, Abhishek; Smolka, Scott A.] SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. [Bartocci, Ezio] Vienna Univ Technol, Inst Comp Engn, Fac Informat, A-1040 Vienna, Austria. [Fenton, Flavio H.] Cornell Univ, Dept Biomed Sci, Ithaca, NY 14850 USA. [Glimm, James] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Gray, Richard A.] US FDA, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Cherry, Elizabeth M.] Cornell Univ, Dept Biomed Sci, Coll Vet Med, Ithaca, NY 14853 USA. [Grosu, Radu] Vienna Univ Technol, Fac Informat, Inst Comp Engn, Dependable Syst Grp, A-1040 Vienna, Austria. RP Murthy, A (reprint author), SUNY Stony Brook, Dept Comp Sci, Stony Brook, NY 11794 USA. EM amurthy@cs.sunysb.edu; ezio.bartocci@tuwien.ac.at; flavio.h.fenton@cornell.edu; glimm@ams.sunysb.edu; Richard.Gray@fda.hhs.gov; elizabeth.m.cherry@cornell.edu; sas@cs.stonybrook.edu; radu.grosu@tuwien.ac.at RI Gray, Richard/F-3916-2015; OI Gray, Richard/0000-0003-2798-6378; Bartocci, Ezio/0000-0002-8004-6601 FU NSF [CCF-0926190] FX This research was performed under the US National Science Foundation (NSF) Expeditions project on Computational Modeling and Analysis for Complex Systems (CMACS) funded by the grant: NSF CCF-0926190 (http://cmacs.cs.cmu.edu). NR 28 TC 2 Z9 2 U1 0 U2 4 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1314 USA SN 1545-5963 J9 IEEE ACM T COMPUT BI JI IEEE-ACM Trans. Comput. Biol. Bioinform. PD MAR-APR PY 2013 VL 10 IS 2 BP 323 EP 336 DI 10.1109/TCBB.2012.125 PG 14 WC Biochemical Research Methods; Computer Science, Interdisciplinary Applications; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Biochemistry & Molecular Biology; Computer Science; Mathematics GA 206FM UT WOS:000323504100007 PM 23929858 ER PT J AU Sun, JC Beger, RD Schnackenberg, LK AF Sun, Jinchun Beger, Richard D. Schnackenberg, Laura K. TI Metabolomics as a tool for personalizing medicine: 2012 update SO PERSONALIZED MEDICINE LA English DT Review DE biomarkers; metabolomics; personalized medicine; pharmacogenetics; pharmacometabolomics ID MAGNETIC-RESONANCE SPECTROSCOPY; MILD COGNITIVE IMPAIRMENT; GENOME-WIDE ASSOCIATION; PROTON MR SPECTROSCOPY; ALZHEIMERS-DISEASE; CHINESE MEDICINE; BREAST-CANCER; RHEUMATOID-ARTHRITIS; DRUG-METABOLISM; INBORN-ERRORS AB Numerous factors in conjunction with an individual's genetic make up will determine predisposition to disease, adverse or beneficial effects of drug treatment or therapy, and disease progression. A major limitation of current clinical measures is that the disease phenotype, which is comprised of the genotype and other environmental factors, is underestimated. Rather, each disease is treated similarly even though the disease process is highly complex. Methods that evaluate the interaction of genotype and environmental factors would likely be a better indicator of patients' response to medical treatments. The omics technologies, specifically metabolomics, will play a major role in the movement towards personalized medicine. Metabolomics is phenotype driven and should provide better clinical biomarkers. Furthermore, recent studies have shown that associations between genetic variants and downstream metabolite changes can provide a unique description of an individual's genotype and phenotype, which will further enhance the movement towards personalized medicine. C1 [Sun, Jinchun; Beger, Richard D.; Schnackenberg, Laura K.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM laura.schnackenberg@fda.hhs.org NR 80 TC 10 Z9 10 U1 6 U2 49 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAR PY 2013 VL 10 IS 2 BP 149 EP 161 DI 10.2217/PME.13.8 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 105BO UT WOS:000316040800010 ER PT J AU Parsons, BL Myers, MB AF Parsons, Barbara L. Myers, Meagan B. TI KRAS mutant tumor subpopulations can subvert durable responses to personalized cancer treatments SO PERSONALIZED MEDICINE LA English DT Article DE ACB-PCR; carcinogenesis; colorectal cancer; epidermal growth factor receptor; mutation detection; non-small-cell lung cancer; oncogene; personalized medicine; polyclonal tumor origin; reactive oxygen species ID CELL LUNG-CANCER; METASTATIC COLORECTAL-CANCER; TYROSINE KINASE INHIBITORS; KIRSTEN RAS MUTATIONS; ACQUIRED-RESISTANCE; PHASE-III; CLINICAL-IMPLICATIONS; EGFR; ERLOTINIB; THERAPY AB KRAS mutations in colorectal and lung cancers predict failure to respond to therapies that target the EGFR. Significant percentages of patients with KRAS wild-type tumors also fail to respond to these therapies. Relapse occurs in patients with KRAS wild-type and mutant tumors, with moderately longer progression-free survival in patients with KRAS wild-type tumors. Colon and lung tumors frequently carry KRAS mutant tumor subpopulations not detected by DNA sequencing. This suggests detected and undetected KRAS mutant subpopulations in colon and lung tumors are undermining the efficacy of anti-EGFR therapies. Therefore, consideration should be given to combining therapies that target KRAS mutant cells with those that downregulate EGFR signaling. As tumors are frequently polyclonal in origin and comprised of distinct clonal populations carrying complementing genetic and/or epigenetic lesions, preclinical models that assess the efficacy of combination therapies in the context of heterogeneous tumor cell populations will be essential for progress in this area. C1 [Parsons, Barbara L.; Myers, Meagan B.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov FU Intramural FDA HHS [FD999999] NR 57 TC 6 Z9 6 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD MAR PY 2013 VL 10 IS 2 BP 191 EP 199 DI 10.2217/PME.13.1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 105BO UT WOS:000316040800014 PM 27867401 ER PT J AU Potnis, PA Dutta, DK Wood, SC AF Potnis, Pushya A. Dutta, Debargh K. Wood, Steven C. TI Toll-like receptor 4 signaling pathway mediates proinflammatory immune response to cobalt-alloy particles SO CELLULAR IMMUNOLOGY LA English DT Article DE Metal-on-metal hips; Co-alloy particles; TLR4 signaling; Cytokines; Periprosthetic osteolysis ID HIP RESURFACING ARTHROPLASTY; ORTHOPEDIC WEAR PARTICLES; METAL-ION CONCENTRATIONS; IN-VITRO; LYMPHOCYTE-REACTIVITY; IMPLANT; DEBRIS; CHROMIUM; BLOOD; CELLS AB Metal orthopedic implant debris-induced osteolysis of hip bone is a major problem in patients with prosthetic-hips. Although macrophages are the principal targets for implant-wear debris, the receptor(s) and mechanisms underlying these responses are not fully elucidated. We examined whether the TLR4 pathway mediates immune response to metal-on-metal (MoM) implant-generated wear particles. Human monocytes (THP-1) were exposed to Co-alloy particles at increasing particle:cell ratio for 24 h. Challenge with particles caused up-regulation of IL-1 beta, TNF-alpha and IL-8, and mediated degradation of cytosolic I-kappa B and nuclear translocation of NF-kappa B. Blocking antibodies against TLR4 or gene silencing of MyD88 and IRAK-1 prevented particle-induced I-kappa B/NF-kappa B activation response and markedly inhibited IL-8 release. Particle-mediated IL-8 response was not observed in TLR4-negative HEK293T cells; whereas transfection-based TLR4-overexpression in HEK293T enabled particle-sensitivity, as observed by I-kappa B degradation and IL-8 expression in response to particles. Results demonstrate that Co-alloy particles trigger immune response via the TLR4-MyD88-dependent signaling pathway. Published by Elsevier Inc. C1 [Potnis, Pushya A.; Dutta, Debargh K.; Wood, Steven C.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Potnis, PA (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM pushya.potnis@fda.hhs.gov RI Dutta, Debargh/J-6086-2015 OI Dutta, Debargh/0000-0003-1517-0670 FU Office of Science and Engineering Laboratories (OSEL), Center for Devices and Radiological Health (CDRH), Food and Drug Administration (FDA) FX This work is supported by funds provided by the Office of Science and Engineering Laboratories (OSEL), Center for Devices and Radiological Health (CDRH), Food and Drug Administration (FDA). The authors would like to sincerely thank Dr. Belay Tesfamariam for his valuable input and proof reading the manuscript. NR 47 TC 24 Z9 24 U1 0 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD MAR PY 2013 VL 282 IS 1 BP 53 EP 65 DI 10.1016/j.cellimm.2013.04.003 PG 13 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 170DA UT WOS:000320828900008 PM 23680697 ER PT J AU Zhang, L Yan, BJ Gong, XC Yu, LX Qu, HB AF Zhang, Lei Yan, Binjun Gong, Xingchu Yu, Lawrence X. Qu, Haibin TI Application of Quality by Design to the Process Development of Botanical Drug Products: A Case Study SO AAPS PHARMSCITECH LA English DT Article DE botanical drug products; design of experiments (DOE); design space; ethanol precipitation; quality by design (QbD) ID ETHANOL PRECIPITATION; ALCOHOL PRECIPITATION; WATER; MANUFACTURE; SOLUBILITY; CHEMISTRY; MIXTURES; TANSHEN; DANSHEN; SUGARS AB This paper was designed to assess the value of quality by design (QbD) to improve the manufacturing process understanding of botanical drug products. Ethanol precipitation, a widely used unit operation in the manufacture of botanical drug products was employed to illustrate the use of QbD, taking the process of danshen (the dry root of Salvia miltiorrhiza Bunge) as an example. The recovery of four active pharmaceutical ingredients (APIs) and the removal of saccharides were used to represent the performance of ethanol precipitation. Potentially critical variables, including density of concentrate, ethanol consumption, and settling temperature were identified through risk assessment methods. Design of experiments (DOE) was used to evaluate the effects of the potentially critical factors on the performance of ethanol precipitation. It was observed that higher density of concentrate leads to higher removal of saccharides, but results in lower recovery of APIs. With the rise of ethanol consumption, the recovery of different APIs behaves in different ways. A potential design space of ethanol precipitation operation was established through DOE studies. The results in this work facilitate the enhanced understanding of the relationships between multiple factors (material attributes and process parameters) and the performance of ethanol precipitation. This case study demonstrated that QbD is a powerful tool to develop manufacturing process of botanical drug products. C1 [Zhang, Lei; Yan, Binjun; Gong, Xingchu; Qu, Haibin] Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China. [Yu, Lawrence X.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Qu, HB (reprint author), Zhejiang Univ, Pharmaceut Informat Inst, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China. EM quhb@zju.edu.cn RI Yu, Lawrence/L-6280-2016; OI Yan, Binjun/0000-0003-3509-0686 FU China International Science and Technology Cooperation Project [2010DFB33630]; Zhejiang Provincial Natural Science Foundation of China [LQ12H29004] FX This work was financially supported by the China International Science and Technology Cooperation Project (2010DFB33630) and Zhejiang Provincial Natural Science Foundation of China (LQ12H29004). NR 34 TC 15 Z9 18 U1 0 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2013 VL 14 IS 1 BP 277 EP 286 DI 10.1208/s12249-012-9919-8 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156CL UT WOS:000319798100032 PM 23297167 ER PT J AU Croley, TR White, KD Wong, J Callahan, JH Musser, SM Antler, M Lashin, V McGibbon, GA AF Croley, Timothy R. White, Kevin D. Wong, Jon Callahan, John H. Musser, Steven M. Antler, Margaret Lashin, Vitaly McGibbon, Graham A. TI Combining targeted and nontargeted data analysis for liquid chromatography/high-resolution mass spectrometric analyses SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Automatic data processing; High-resolution mass spectrometry; Nontargeted analysis ID IDENTIFICATION; EXTRACTION; DATABASES; PRODUCTS; DRUGS; FOOD; MS AB Increasing importation of food and the diversity of potential contaminants have necessitated more analytical testing of these foods. Historically, mass spectrometric methods for testing foods were confined to monitoring selected ions (SIM or MRM), achieving sensitivity by focusing on targeted ion signals. A limiting factor in this approach is that any contaminants not included on the target list are not typically identified and retrospective data mining is limited. A potential solution is to utilize high-resolution MS to acquire accurate mass full-scan data. Based on the instrumental resolution, these data can be correlated to the actual mass of a contaminant, which would allow for identification of both target compounds and compounds that are not on a target list (nontargets). The focus of this research was to develop software algorithms to provide rapid and accurate data processing of LC/MS data to identify both targeted and nontargeted analytes. Software from a commercial vendor was developed to process LC/MS data and the results were compared to an alternate, vendor-supplied solution. The commercial software performed well and demonstrated the potential for a fully automated processing solution. C1 [Croley, Timothy R.; White, Kevin D.; Wong, Jon; Callahan, John H.; Musser, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Antler, Margaret; Lashin, Vitaly; McGibbon, Graham A.] Adv Chem Dev Inc, Toronto, ON, Canada. RP Croley, TR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-707,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM timothy.croley@fda.hhs.gov NR 19 TC 2 Z9 2 U1 1 U2 17 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY SN 1615-9306 EI 1615-9314 J9 J SEP SCI JI J. Sep. Sci. PD MAR PY 2013 VL 36 IS 5 BP 971 EP 979 DI 10.1002/jssc.201200348 PG 9 WC Chemistry, Analytical SC Chemistry GA 156ZI UT WOS:000319863600020 PM 23371431 ER PT J AU Grim, CJ Kozlova, EV Sha, J Fitts, EC van Lier, CJ Kirtley, ML Joseph, SJ Read, TD Burd, EM Tall, BD Joseph, SW Horneman, AJ Chopra, AK Shak, JR AF Grim, Christopher J. Kozlova, Elena V. Sha, Jian Fitts, Eric C. van Lier, Christina J. Kirtley, Michelle L. Joseph, Sandeep J. Read, Timothy D. Burd, Eileen M. Tall, Ben D. Joseph, Sam W. Horneman, Amy J. Chopra, Ashok K. Shak, Joshua R. TI Characterization of Aeromonas hydrophila Wound Pathotypes by Comparative Genomic and Functional Analyses of Virulence Genes SO MBIO LA English DT Article ID III SECRETION SYSTEM; N-ACYLHOMOSERINE LACTONES; IN-VIVO VIRULENCE; BIOFILM FORMATION; CLINICAL ISOLATE; CYTOTOXIC ENTEROTOXIN; GENUS AEROMONAS; VIBRIO-PARAHAEMOLYTICUS; NECROTIZING FASCIITIS; SWARMING MOTILITY AB Aeromonas hydrophila has increasingly been implicated as a virulent and antibiotic-resistant etiologic agent in various human diseases. In a previously published case report, we described a subject with a polymicrobial wound infection that included a persistent and aggressive strain of A. hydrophila (E1), as well as a more antibiotic-resistant strain of A. hydrophila (E2). To better understand the differences between pathogenic and environmental strains of A. hydrophila, we conducted comparative genomic and functional analyses of virulence-associated genes of these two wound isolates (E1 and E2), the environmental type strain A. hydrophila ATCC 7966(T), and four other isolates belonging to A. aquariorum, A. veronii, A. salmonicida, and A. caviae. Full-genome sequencing of strains E1 and E2 revealed extensive differences between the two and strain ATCC 7966(T). The more persistent wound infection strain, E1, harbored coding sequences for a cytotoxic enterotoxin (Act), a type 3 secretion system (T3SS), flagella, hemolysins, and a homolog of exotoxin A found in Pseudomonas aeruginosa. Corresponding phenotypic analyses with A. hydrophila ATCC 7966(T) and SSU as reference strains demonstrated the functionality of these virulence genes, with strain E1 displaying enhanced swimming and swarming motility, lateral flagella on electron microscopy, the presence of T3SS effector AexU, and enhanced lethality in a mouse model of Aeromonas infection. By combining sequence-based analysis and functional assays, we characterized an A. hydrophila pathotype, exemplified by strain E1, that exhibited increased virulence in a mouse model of infection, likely because of encapsulation, enhanced motility, toxin secretion, and cellular toxicity. IMPORTANCE Aeromonas hydrophila is a common aquatic bacterium that has increasingly been implicated in serious human infections. While many determinants of virulence have been identified in Aeromonas, rapid identification of pathogenic versus nonpathogenic strains remains a challenge for this genus, as it is for other opportunistic pathogens. This paper demonstrates, by using whole-genome sequencing of clinical Aeromonas strains, followed by corresponding virulence assays, that comparative genomics can be used to identify a virulent subtype of A. hydrophila that is aggressive during human infection and more lethal in a mouse model of infection. This aggressive pathotype contained genes for toxin production, toxin secretion, and bacterial motility that likely enabled its pathogenicity. Our results highlight the potential of whole-genome sequencing to transform microbial diagnostics; with further advances in rapid sequencing and annotation, genomic analysis will be able to provide timely information on the identities and virulence potential of clinically isolated microorganisms. C1 [Grim, Christopher J.; Tall, Ben D.] US FDA, Laurel, MD USA. [Kozlova, Elena V.; Sha, Jian; Fitts, Eric C.; van Lier, Christina J.; Kirtley, Michelle L.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Joseph, Sandeep J.; Read, Timothy D.; Burd, Eileen M.; Shak, Joshua R.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA. [Burd, Eileen M.] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. [Joseph, Sam W.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Joseph, Sam W.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Horneman, Amy J.] VA Maryland Hlth Care Syst, Pathol Serv, Baltimore, MD USA. [Horneman, Amy J.] VA Maryland Hlth Care Syst, Lab Med Serv, Baltimore, MD USA. RP Shak, JR (reprint author), Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA 30322 USA. EM achopra@utmb.edu; jshak@emory.edu OI Tall, Ben/0000-0003-0399-3629 FU Molecules to Mankind Program; Medical Scientist Training Program at Emory University; Dr. Leon Bromberg Professorship, University of Texas Medical Branch; Oak Ridge Associated Universities FX J.R.S. acknowledges the financial support of the Molecules to Mankind Program and the Medical Scientist Training Program at Emory University. A.K.C. acknowledges funds from his Dr. Leon Bromberg Professorship, University of Texas Medical Branch, to conduct portions of these studies. C.J.G. acknowledges financial support from Oak Ridge Associated Universities. NR 78 TC 20 Z9 21 U1 1 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 2150-7511 J9 MBIO JI mBio PD MAR-APR PY 2013 VL 4 IS 2 AR e00064-13 DI 10.1128/mBio.00064-13 PG 13 WC Microbiology SC Microbiology GA 137JI UT WOS:000318431500010 PM 23611906 ER PT J AU Sprenger, K Nickerson, D Meeker-O'Connell, A Morrison, BW AF Sprenger, Kenneth Nickerson, David Meeker-O'Connell, Ann Morrison, Briggs W. TI Quality by Design in Clinical Trials: A Collaborative Pilot With FDA SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE clinical trials; quality planning; quality by design; FDA; integrated quality management plan ID ASSURANCE; COSTS AB The quality of a clinical trial can be assessed by whether the trial meets the needs of its various customers, as well as by its freedom from critical deficiencies or errors. In order to ensure the quality of a clinical trial, it is therefore important to conduct quality planning in parallel with the process to design and prior to the conduct of the trial. Quality planning consists of prospectively establishing quality goals and developing the products and processes required to deliver a quality trial. This article describes the quality planning process conducted by a pharmaceutical sponsor for a clinical trial and the pilot review of the resulting integrated quality management plan by the FDA. This pilot demonstrates the usefulness of this process to enable alignment between sponsors and regulators concerning quality in clinical trials. C1 [Sprenger, Kenneth; Nickerson, David] Pfizer Inc, Groton, CT 06340 USA. [Meeker-O'Connell, Ann] US FDA, Off Sci Invest, Silver Spring, MD USA. [Morrison, Briggs W.] AstraZeneca, Wilmington, DE USA. RP Nickerson, D (reprint author), Pfizer Inc, MS 8260-2249,445 Eastern Point Rd, Groton, CT 06340 USA. EM David.F.Nickerson@Pfizer.com NR 10 TC 1 Z9 2 U1 2 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2013 VL 47 IS 2 BP 161 EP 166 DI 10.1177/0092861512458909 PG 6 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DZ UT WOS:000318342900003 ER PT J AU Zhang, JJ Chen, HY He, K Tang, SH Justice, R Keegan, P Pazdur, R Sridhara, R AF Zhang, Jenny J. Chen, Huanyu He, Kun Tang, Shenghui Justice, Robert Keegan, Patricia Pazdur, Richard Sridhara, Rajeshwari TI Evaluation of Blinded Independent Central Review of Tumor Progression in Oncology Clinical Trials: A Meta-analysis SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Review DE blinded independent central review (BICR); progression-free survival (PFS); bias; meta-analysis ID FREE SURVIVAL; RECOMMENDATIONS; OUTCOMES AB Use of blinded independent central review (BICR) has become more common in oncology phase 3 trials as progression-free survival (PFS) has been increasingly used as an endpoint for regulatory approval. Since PFS is primarily a radiographic endpoint, BICR has been implemented to assess and reduce potential bias in the local evaluation (LE) of PFS. Recent publications note an agreement between LE and BICR of the ultimate reported PFS treatment effect, which questions the need for costly and time-consuming complete-case BICR of PFS. A meta-analysis was conducted to systematically evaluate the relationship between BICR-and LE-assessed PFS based on FDA's regulatory experience from 2005 to present. Our results support the claim that a complete review of all radiographs by BICR may not be necessary for oncology trials, and alternative methods should be explored to evaluate bias. One potential alternative is to use BICR as an audit tool to detect evaluation bias in LE assessments. C1 [Zhang, Jenny J.; Chen, Huanyu; He, Kun; Tang, Shenghui; Sridhara, Rajeshwari] US FDA, Div Biometr 5, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Justice, Robert; Keegan, Patricia; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Hematol & Oncol Prod, Silver Spring, MD USA. RP Sridhara, R (reprint author), US FDA, Div Biometr 5, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM rajeshwari.sridhara@fda.hhs.gov NR 12 TC 9 Z9 9 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2013 VL 47 IS 2 BP 167 EP 174 DI 10.1177/0092861512459733 PG 8 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DZ UT WOS:000318342900004 ER PT J AU Wu, K Schmelz, LS Doshi, SM AF Wu, Kimberly Schmelz, Laura Smith Doshi, Sara M. TI Medical Information Specialists: Benchmarks in Practice SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE medical information; drug information; medical communication; best practices; benchmark ID PHARMACEUTICAL-INDUSTRY AB A gap exists for global benchmarking data on medical information specialists across the pharmaceutical industry. As such, the purpose of this study was to benchmark the practices and training of medical information specialists in the pharmaceutical industry. Results collected will be used to identify training and background of current medical information specialists as well as to describe current medical information-related responsibilities. A 23-item, electronic survey instrument was sent to individuals with an interest in or association with medical communications, medical information, and/or medical science liaisons through the DIA database. A total of 61 complete and 29 incomplete responses were received. Results indicated that similarities exist in medical information specialists' positions regarding organization and reporting structure, job requirements and credentials, core responsibilities, and even identified challenges. These findings may help medical information specialist organizations better compare their own practices with those of other groups in the pharmaceutical industry. C1 [Wu, Kimberly] US FDA, Silver Spring, MD 20993 USA. [Wu, Kimberly] Purdue Univ, W Lafayette, IN 47907 USA. [Wu, Kimberly] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Schmelz, Laura Smith] Kowa Pharmaceut Amer Inc, Indianapolis, IN USA. [Doshi, Sara M.] Eli Lilly & Co, Global Med Commun Med Informat, Indianapolis, IN 46285 USA. RP Wu, K (reprint author), US FDA, 10001 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kimberly.wu@fda.hhs.gov NR 7 TC 1 Z9 1 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2013 VL 47 IS 2 BP 190 EP 197 DI 10.1177/2168479012461442 PG 8 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DZ UT WOS:000318342900007 ER PT J AU Dang, QY Zhang, J AF Dang, Qianyu Zhang, Joanne TI Validation of QT Interval Correction Methods When a Drug Changes Heart Rate SO THERAPEUTIC INNOVATION & REGULATORY SCIENCE LA English DT Article DE QT interval correction; QT-RR correction validation; drug-induced heart rate change; mixed effects model; drug blood concentration ID PROLONGATION AB The QT interval is correlated with heart rate; therefore, the QT interval is usually corrected by heart rate when drug-induced QT effect is studied. Currently, there are many correction methods that use either fixed or data-driven approaches. The effectiveness of correction methods depends on many factors and varies from study to study. Statistical validation and comparisons need to be performed to determine the most appropriate correction method for each study. We examined different validation methods and explored a new approach to use when the testing drug changes heart rate. C1 [Dang, Qianyu; Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Dang, QY (reprint author), US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM qianyu.dang@fda.hhs.gov NR 12 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 2168-4790 J9 THER INNOV REGUL SCI JI Ther. Innov. Regul. Sci. PD MAR PY 2013 VL 47 IS 2 BP 256 EP 260 DI 10.1177/2168479012467018 PG 5 WC Medical Informatics; Pharmacology & Pharmacy SC Medical Informatics; Pharmacology & Pharmacy GA 136DZ UT WOS:000318342900017 ER PT J AU Courtney, B Sherman, S Penn, M AF Courtney, Brooke Sherman, Susan Penn, Matthew TI Federal Legal Preparedness Tools for Facilitating Medical Countermeasure Use during Public Health Emergencies SO JOURNAL OF LAW MEDICINE & ETHICS LA English DT Article AB Preparing for and responding to public health emergencies involving medical countermeasures (MCMs) raise often complex legal challenges and questions among response stakeholders at the local, state, and federal levels. This includes concerns about emergency legal authorities, liability, emergency use of regulated medical products, and regulations that might enhance or hinder public health response goals. In this article, lawyers from the U.S. Department of Health and Human Services' (HHS) Office of the General Counsel (OGC), Centers for Disease Control and Prevention (CDC), and Food and Drug Administration (FDA) discuss federal legal tools that are critical to enhancing MCM legal preparedness for public health emergencies, with an emphasis on the legal mechanisms that can be used to facilitate the emergency use of countermeasures. Specifically, the authors describe the Public Readiness and Emergency Preparedness (PREP) Act and Emergency Use Authorization (EUA) authority, outlining the conditions under which these tools can be utilized and providing examples of how they have supported both pre-event (e.g., doxycycline mass dispensing preparedness for anthrax) and intra-event (e.g., 2009 H1N1 influenza pandemic response) activities. C1 [Courtney, Brooke] US FDA, Rockville, MD 20857 USA. NR 23 TC 8 Z9 8 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1073-1105 J9 J LAW MED ETHICS JI J. Law Med. Ethics PD SPR PY 2013 VL 41 SU 1 SI SI BP 22 EP 27 DI 10.1111/jlme.12033 PG 6 WC Ethics; Law; Medical Ethics; Medicine, Legal SC Social Sciences - Other Topics; Government & Law; Medical Ethics; Legal Medicine GA 130JF UT WOS:000317910100005 PM 23590735 ER PT J AU Zaslavsky, BG AF Zaslavsky, Boris G. TI Bayesian Hypothesis Testing in Two-Arm Trials with Dichotomous Outcomes SO BIOMETRICS LA English DT Article DE Credible limits; Hypothesis testing; Markov Chain Monte Carlo method; Posterior distribution; p-Value ID SAMPLE-SIZE DETERMINATION; CLINICAL-TRIALS; FREQUENTIST EVIDENCE; P-VALUES; HEMOPHILIA; PROPORTIONS; INHIBITORS; OPINION AB This article is motivated by an interest in comparing inferences made when using a Bayesian or frequentist statistical approach. The article addresses the study of one-sided superiority and noninferiority Bayesian tests. These tests are stated in terms of the posterior probability that the null hypothesis is true for the binomial distribution and in terms of one-sided credible limits. We restrict our considerations to conjugate beta priors with integer parameters. Under this assumption, the posterior probabilities of tested hypotheses can be transformed into the frequentist probabilities of Bernoulli trials with an adjusted number of events and population sizes. The method resembles a standard frequentist problem formulation. By using an appropriate choice of prior parameters, the posterior probabilities of the null hypothesis can be made smaller or larger than the p-values of frequentist tests. C1 US FDA, CBER HFM 219, Rockville, MD 20852 USA. RP Zaslavsky, BG (reprint author), US FDA, CBER HFM 219, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Boris.Zaslavsky@FDA.HHS.gov NR 42 TC 2 Z9 2 U1 1 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X EI 1541-0420 J9 BIOMETRICS JI Biometrics PD MAR PY 2013 VL 69 IS 1 BP 157 EP 163 DI 10.1111/j.1541-0420.2012.01806.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 122FM UT WOS:000317303500017 PM 23002906 ER PT J AU Wu, K Shepherd, J Jackson, S Chew, C AF Wu, Kimberly Shepherd, Jennifer Jackson, Steven Chew, Catherine TI FDA Drug Safety Podcasts: Resources for drug information SO JOURNAL OF THE AMERICAN PHARMACISTS ASSOCIATION LA English DT Article DE Podcasts; drug safety; drug information; Food and Drug Administration; social media ID SOCIAL MEDIA AB Objective: To describe a Web-based drug information service provided by the Food and Drug Administration (FDA) to increase the reach of Drug Safety Communications to pharmacists and other health professionals. Setting: The Division of Drug Information (DDI) within the FDA Center for Drug Evaluation and Research (CDER), Office of Communications, Silver Spring, MD, between January 2010 and April 2012. Practice description: DDI provides drug information services regarding human drug products and expert advice and guidance on all aspects of CDER activities. Customers include consumers, health professionals, regulated industry, insurance companies, academia, law enforcement, and other government agencies (national and international). Practice innovation: Use of audio podcasts to disseminate timely drug safety information targeted toward pharmacists and other health professionals. Results: Since 2010, DDI has recorded and published 119 FDA Drug Safety Podcasts that have reached more than 620,000 individuals. Conclusion: FDA Drug Safety Podcasts serve as portable and convenient options for pharmacists to stay current on the latest drug safety information. Pharmacists are encouraged to explore incorporating Web-based technologies, such as audio podcasts, into their practices. C1 [Wu, Kimberly] Purdue Univ, Coll Pharm, Indianapolis, IN USA. [Wu, Kimberly] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Wu, Kimberly] US FDA, Silver Spring, MD 20993 USA. [Shepherd, Jennifer; Chew, Catherine] US PHS, Silver Spring, MD USA. [Shepherd, Jennifer; Jackson, Steven; Chew, Catherine] US FDA, Div Drug Informat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wu, K (reprint author), US FDA, 10001 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kimberly.wu@fda.hhs.gov NR 17 TC 1 Z9 1 U1 0 U2 7 PU AMER PHARMACEUTICAL ASSOC PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 1544-3191 J9 J AM PHARM ASSOC JI J. Am. Pharm. Assoc. PD MAR-APR PY 2013 VL 53 IS 2 BP 188 EP 192 DI 10.1331/JAPhA.2013.12120 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 126TU UT WOS:000317644900015 PM 23571627 ER PT J AU Zimmermann, M Trumbo, PR AF Zimmermann, Michael Trumbo, Paula R. TI Iodine SO ADVANCES IN NUTRITION LA English DT Editorial Material C1 [Zimmermann, Michael] Swiss Fed Inst Technol, Human Nutr Lab, ICCIDD Global Network, Zurich, Switzerland. [Trumbo, Paula R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Zimmermann, M (reprint author), Swiss Fed Inst Technol, Human Nutr Lab, ICCIDD Global Network, Zurich, Switzerland. EM michael.zimmermann@hest.ethz.ch RI Zimmermann, Michael/C-3062-2016 NR 7 TC 1 Z9 1 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 2161-8313 J9 ADV NUTR JI Adv. Nutr. PD MAR PY 2013 VL 4 IS 2 BP 262 EP 264 DI 10.3945/an.113.003665 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 120HJ UT WOS:000317161100015 PM 23493543 ER PT J AU Chen, XL Rohrig, E Stansly, PA AF Chen, Xulin Rohrig, Eric Stansly, Philip A. TI CARBON DIOXIDE ANESTHESIA OF TAMARIXIA RADIATA (HYMENOPTERA: EULOPHIDAE) PARASITOID OF DIAPHORINA CITRI (HEMIPTERA: PSYLLIDAE) SO FLORIDA ENTOMOLOGIST LA English DT Editorial Material ID QUARANTINE AB Carbon dioxide anesthesia is a convenient tool for manipulating insects, but can cause deleterious side effects. In this case, a 5 min exposure of Tamarixia radiata adults to 100% CO2 concentration caused a knockdown of about 4 min, significantly reduced survivorship and fecundity, but did not affect the sex ratio of progeny from treated adults. Future research will focus on using less concentrated doses or shorter exposure times to inactivate the wasps in order to improve survival and fecundity. C1 [Chen, Xulin; Stansly, Philip A.] Univ Florida, IFAS, Southwest Florida Res & Educ Ctr, Immokalee, FL 34142 USA. [Rohrig, Eric] Methods Dev & Biol Control, FDACS, Div Plant Ind, Gainesville, FL 32608 USA. RP Stansly, PA (reprint author), Univ Florida, IFAS, Southwest Florida Res & Educ Ctr, Immokalee, FL 34142 USA. EM pstansly@ufl.edu NR 14 TC 3 Z9 3 U1 0 U2 18 PU FLORIDA ENTOMOLOGICAL SOC PI LUTZ PA 16125 E LAKE BURRELL DR, LUTZ, FL 33548 USA SN 0015-4040 J9 FLA ENTOMOL JI Fla. Entomol. PD MAR PY 2013 VL 96 IS 1 BP 246 EP 248 PG 3 WC Entomology SC Entomology GA 123HO UT WOS:000317379200036 ER PT J AU Dominguez-Castillo, RI Verma, A Amador-Molina, JC Sirota, L Arciniega, JL AF Dominguez-Castillo, Rocio I. Verma, Anita Amador-Molina, Juan C. Sirota, Lev Arciniega, Juan L. TI Ability of ELISA and a toxin neutralization assay to detect changes in immunogenicity of a recombinant Bacillus anthracis protective antigen vaccine upon storage SO BIOLOGICALS LA English DT Article DE rPA-based anthrax vaccine; ELISA; TNA; Potency test ID POTENCY TEST; MICE; VALIDATION AB We examined the capability of a mouse immunogenicity assay to detect improper storage of a recombinant protective antigen (rPA)-based anthrax vaccine formulated with an aluminum adjuvant, using ELISA and a toxin neutralization assay (TNA) to measure the antibody response to rPA. The vaccine was stored at 4 degrees C, room temperature (RT) or 37 degrees C for one, four and eight weeks and used for immunization, along with freshly prepared vaccine. Results showed that, contrary to ELISA, TNA is suitable to detect a loss of immunogenicity of the rPA vaccine following its exposure to RI for a period of eight weeks and to 37 degrees C for a period as short as 1 week. Published by Elsevier Ltd on behalf of The International Alliance for Biological Standardization. C1 [Dominguez-Castillo, Rocio I.; Verma, Anita; Amador-Molina, Juan C.; Sirota, Lev; Arciniega, Juan L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Arciniega, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Mail Code HFM-443, Rockville, MD 20852 USA. EM juan.arciniega@fda.hhs.gov FU Biomedical Advanced Research Development Authority (BARDA); U.S. Department of Energy; U.S. Food and Drug Administration FX This project was supported in part by the Biomedical Advanced Research Development Authority (BARDA) and for an appointment (JC A-M) to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax PA, recombinant from Bacillus anthracis, NR-140 and from E. coli, NR-164; anthrax LF, recombinant from Bacillus anthracis, NR-142; and J774A.1 monocyte/macrophage (mouse) working cell bank, NR-28. NR 20 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2013 VL 41 IS 2 BP 111 EP 114 DI 10.1016/j.biologicals.2012.10.002 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 115WX UT WOS:000316843700009 PM 23137818 ER PT J AU Mastelic, B Lewis, DJM Golding, H Gust, I Sheets, R Lambert, PH AF Mastelic, Beatris Lewis, David J. M. Golding, Hana Gust, Ian Sheets, Rebecca Lambert, Paul-Henri TI Potential use of inflammation and early immunological event biomarkers in assessing vaccine safety SO BIOLOGICALS LA English DT Article DE Vaccine; Biomarkers; Vaccine safety ID MONOCYTE ACTIVATION TEST; HUMAN SERUM-ALBUMIN; WHOLE-BLOOD ASSAY; IN-WATER EMULSION; CD4(+) T-CELLS; NALP3 INFLAMMASOME; DENDRITIC CELLS; INTERNATIONAL VALIDATION; BYSTANDER ACTIVATION; AUTOIMMUNE-DISEASES AB Highly effective vaccines have traditionally been designed in a rather empirical way, often with incomplete understanding of their mode of action. Full assessment of efficacy and reactogenicity takes time and, as a result, vaccine introduction to the market is usually slow and expensive. In addition, in rare cases, unacceptable reactogenicity may only become apparent after years of development or even widespread use. However, recent advances in cell biology and immunology offer a range of new technologies and systems for identifying biological responses or "biomarkers" that could possibly be used to evaluate and predict efficacy and safety during vaccine development and post-marketing surveillance. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the potential use of biomarkers to assess vaccine safety which was held in Baltimore, Maryland, USA, from 10 to 11 May 2012 and organized by the International Association for Biologicals (JABS). The conference focused particularly on determining which biomarkers might relate to vaccine efficacy and reactogenicity and whether our knowledge base was sufficiently robust at this time for the data to be used for decision-making. More information on the conference output can be found on the JABS website, http://www.iabs.org/. C1 [Mastelic, Beatris; Lambert, Paul-Henri] Univ Geneva, WHO, Ctr Vaccinol & Neonatal Immunol, CMU, CH-1211 Geneva 4, Switzerland. [Lewis, David J. M.] Univ Surrey, Clin Res Ctr, Guildford GU2 7XP, Surrey, England. [Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. [Gust, Ian] Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3010, Australia. [Sheets, Rebecca] NIAID, CAPT, US PHS, NIH, Bethesda, MD 20892 USA. RP Lambert, PH (reprint author), Univ Geneva, WHO, Ctr Vaccinol & Neonatal Immunol, CMU, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM paul.lambert@unige.ch OI Lewis, David JM/0000-0003-3105-9075 FU GlaxoSmithKline Biologicals; Sanofi Pasteur; Novartis; IMI; Pfizer; CSL FX We thank Betty Dodet (Dodet Bioscience) for her skillful help in the preparation of this report. This workshop was made possible by unrestricted educational grants from GlaxoSmithKline Biologicals, Sanofi Pasteur, Novartis, IMI, Pfizer and CSL. NR 72 TC 8 Z9 8 U1 1 U2 10 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2013 VL 41 IS 2 BP 115 EP 124 DI 10.1016/j.biologicals.2012.10.005 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 115WX UT WOS:000316843700010 PM 23194656 ER PT J AU Bonhoeffer, J Black, S Izurieta, H Zuber, P Sturkenboom, M AF Bonhoeffer, Jan Black, Steve Izurieta, Hector Zuber, Patrick Sturkenboom, Miriam TI Current status and future directions of post-marketing vaccine safety monitoring with focus on USA and Europe (vol 40, pg 393, 2012) SO BIOLOGICALS LA English DT Correction C1 [Bonhoeffer, Jan] Brighton Collaborat Fdn, CH-4031 Basel, Switzerland. [Bonhoeffer, Jan] Univ Childrens Hosp Basel, Basel, Switzerland. [Black, Steve] Cincinnati Childrens Hosp, Cincinnati, OH USA. [Izurieta, Hector] US FDA, Rockville, MD 20857 USA. [Zuber, Patrick] WHO, CH-1211 Geneva, Switzerland. [Sturkenboom, Miriam] Erasmus MC, Rotterdam, Netherlands. RP Bonhoeffer, J (reprint author), Brighton Collaborat Fdn, CH-4031 Basel, Switzerland. EM j.bonhoeffer@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014 NR 1 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2013 VL 41 IS 2 BP 128 EP 128 DI 10.1016/j.biologicals.2012.11.002 PG 1 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 115WX UT WOS:000316843700012 ER PT J AU Sapsford, KE Algar, WR Berti, L Gemmill, KB Casey, BJ Oh, E Stewart, MH Medintz, IL AF Sapsford, Kim E. Algar, W. Russ Berti, Lorenzo Gemmill, Kelly Boeneman Casey, Brendan J. Oh, Eunkeu Stewart, Michael H. Medintz, Igor L. TI Functionalizing Nanoparticles with Biological Molecules: Developing Chemistries that Facilitate Nanotechnology SO CHEMICAL REVIEWS LA English DT Review ID IRON-OXIDE NANOPARTICLES; SOLID LIPID NANOPARTICLES; WALLED CARBON NANOTUBES; RESONANCE ENERGY-TRANSFER; MESOPOROUS SILICA NANOPARTICLES; CALCIUM-PHOSPHATE NANOPARTICLES; COWPEA MOSAIC-VIRUS; DRUG-DELIVERY SYSTEMS; SEMICONDUCTOR QUANTUM DOTS; HISTIDINE-TAGGED PROTEINS C1 [Sapsford, Kim E.; Casey, Brendan J.] US FDA, Div Biol, Dept Chem & Mat Sci, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Gemmill, Kelly Boeneman; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn Code 6900, Washington, DC 20375 USA. [Oh, Eunkeu; Stewart, Michael H.] USN, Res Lab, Div Opt Sci Code 5611, Washington, DC 20375 USA. [Algar, W. Russ] George Mason Univ, Coll Sci, Fairfax, VA 22030 USA. [Berti, Lorenzo] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Sacramento, CA 95817 USA. [Oh, Eunkeu] Sotera Def Solut, Crofton, MD 21114 USA. RP Medintz, IL (reprint author), USN, Res Lab, Ctr Bio Mol Sci & Engn Code 6900, Washington, DC 20375 USA. EM Igor.medintz@nrl.navy.mil FU NRL; NRL NSI; ONR; DARPA; DTRA-JSTO MIPR [B112582M]; Natural Sciences and Engineering Research Council of Canada (NSERC); Susan G. Komen for the Cure; Division of Biology, FDA; Critical Path Initiative FX The authors thank Dr. Melissa Massey for helpful comments on the manuscript. The authors acknowledge NRL, NRL NSI, ONR, DARPA, and DTRA-JSTO MIPR No. B112582M for financial support. W.R.A. is grateful to the Natural Sciences and Engineering Research Council of Canada (NSERC) for a postdoctoral fellowship. L.B. acknowledges Susan G. Komen for the Cure for supporting his research through a Career Catalyst Award. K.E.S. acknowledges the Division of Biology, FDA, and the Critical Path Initiative for financial support. K.E.S thanks Dr. T. Umbreit and Dr. K. S. Phillips for their comments and review of this manuscript. This paper reflects the current thinking and experience of the authors. The mention of commercial products, their sources, 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 Department of Health and Human Services. NR 2075 TC 413 Z9 416 U1 121 U2 1392 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2665 EI 1520-6890 J9 CHEM REV JI Chem. Rev. PD MAR PY 2013 VL 113 IS 3 BP 1904 EP 2074 DI 10.1021/cr300143v PG 171 WC Chemistry, Multidisciplinary SC Chemistry GA 107TL UT WOS:000316243600015 PM 23432378 ER PT J AU Xia, QS Yin, JJ Zhao, Y Wu, YS Wang, YQ Ma, L Chen, SJ Sun, X Fu, PP Yu, HT AF Xia, Qingsu Yin, Jun-Jie Zhao, Yuewei Wu, Yuh-Sen Wang, Yu-Qui Ma, Liang Chen, Shoujun Sun, Xin Fu, Peter P. Yu, Hongtao TI UVA Photoirradiation of Nitro-Polycyclic Aromatic Hydrocarbons-Induction of Reactive Oxygen Species and Formation of Lipid Peroxides SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH LA English DT Article DE nitro-polycyclic aromatic hydrocarbons; photoiradiation; UVA light; reactive oxygen species; lipid peroxidation ID DIRECT-ACTING MUTAGENICITY; SINGLET OXYGEN; BACTERIAL MUTAGENICITY; RETINYL PALMITATE; GROUP ORIENTATION; DNA-DAMAGE; SUBSTITUENT; METABOLISM; RADICALS; PHOTOTOXICITY AB Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are a class of genotoxic environmental contaminants. We have long been interested in determining the mechanisms by which nitro-PAHs induce genotoxicity. Although the metabolic activation of nitro-PAHs leading to toxicological activities has been well studied, the photo-induced activation of nitro-PAHs has seldom been reported. In this paper, we report photo-induced lipid peroxidation by 19 nitro-PAHs. The results indicated that all but two of the nitro-PAHs can induce lipid peroxidation. Mechanistic studies suggest that lipid peroxidation by nitro-PAHs is mediated by free radicals generated in the reaction. There was no structural correlation between the nitro-PAHs and their ability to induce lipid peroxidation upon UVA irradiation, or between the HOMO-LUMO gap and the ability to cause lipid peroxidation. Most of the nitro-PAHs are less potent in terms of causing lipid peroxidation than their parent PAHs. The lack of correlation is attributed to the complex photophysics and photochemistry of the nitro-PAHs and the yield of reactive oxygen species (ROS) and other factors. C1 [Xia, Qingsu; Zhao, Yuewei; Wang, Yu-Qui; Ma, Liang; Chen, Shoujun; Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Wu, Yuh-Sen] Hung Kuang Univ, Taichung 443, Taiwan. [Sun, Xin] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poisoning Control, Beijing 100050, Peoples R China. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM qingsu.xia@fda.hhs.gov; Junjie.yin@fda.hhs.gov; ywzhao98@gmail.com; ycwu@sunrise.hkc.edu.tw; yqqwang@yahoo.com; liang.ma@fda.hhs.gov; schen@syntapharma.com; Xinsun10@sina.com; peter.fu@fda.hhs.gov; yu@jsums.edu RI Yin, Jun Jie /E-5619-2014 NR 51 TC 6 Z9 6 U1 2 U2 28 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1660-4601 J9 INT J ENV RES PUB HE JI Int. J. Environ. Res. Public Health PD MAR PY 2013 VL 10 IS 3 BP 1062 EP 1084 DI 10.3390/ijerph10031062 PG 23 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 112QS UT WOS:000316608200023 PM 23493032 ER PT J AU Sun, HH Bastings, E Temeck, J Smith, PB Men, A Tandon, V Murphy, D Rodriguez, W AF Sun, Haihao Bastings, Eric Temeck, Jean Smith, P. Brian Men, Angela Tandon, Veneeta Murphy, Dianne Rodriguez, William TI Migraine Therapeutics in Adolescents SO JAMA PEDIATRICS LA English DT Article ID SUMATRIPTAN NASAL SPRAY; PLACEBO-CONTROLLED TRIAL; RIZATRIPTAN 5 MG; DOUBLE-BLIND; RANDOMIZED-TRIAL; OPEN-LABEL; ZOLMITRIPTAN; EFFICACY; CHILDREN; PHARMACOKINETICS AB Objectives: To conduct a systematic review and analysis of trial data submitted to the US Food and Drug Administration (FDA) to identify possible causes for the failure of pediatric trials of triptans for treatment of migraines. Data Source: The FDA website for drug information and published literature. Study Selection: All pediatric efficacy and pharmacokinetics trial data of drugs used for abortive treatment of migraine submitted to the FDA from January 1, 1999, through December 31, 2011. Main Outcome Measures: Patient demographic baseline characteristics, inclusion and exclusion criteria, trial designs, efficacy end points, and pharmacokinetic profiles were analyzed and compared across drug products. Results: We analyzed data for sumatriptan succinate nasal spray and zolmitriptan, eletriptan hydrobromide, almotriptan malate, and rizatriptan benzoate tablets. Seven efficacy trials had a randomized, double-blinded, placebo-controlled, parallel-group trial design. In 4 trials, patients were required to have a history of migraine attacks lasting at least 4 hours. High response rates for placebo were observed in all trials, with pain relief at 2 hours ranging from 53% to 57.5%. Nonrandomization of patients with an early placebo response design was used in the rizatriptan trial in 2011. Compared with the rizatriptan trial conducted in 1999, the 2011 rizatriptan trial reduced the placebo response rate by 6% for headache freedom at the 2-hour posttreatment end point owing to study design. The pharmacokinetic profiles between adolescents and adults were statistically similar. Conclusions: High placebo response rates are consistent across all trials and may represent the principal challenge in pediatric trials of drugs for abortive treatment of migraine. Enrichment with selection of subjects with long-lasting migraine attacks is not sufficient to overcome high placebo response rates. Another enrichment strategy, the nonrandomization of patients with an early placebo response, successfully reduces the high placebo response rate for rizatriptan and is a trial design that should be considered for future pediatric trials of abortive migraine therapeutics. JAMA Pediatr. 2013;167(3):243-249. Published online January 28, 2013. doi:10.1001/jamapediatrics.2013.872 C1 [Sun, Haihao; Bastings, Eric; Temeck, Jean; Men, Angela; Tandon, Veneeta; Murphy, Dianne; Rodriguez, William] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. [Sun, Haihao; Bastings, Eric; Temeck, Jean; Men, Angela; Tandon, Veneeta; Murphy, Dianne; Rodriguez, William] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Smith, P. Brian] Duke Univ, Med Ctr, Dept Pediat, Duke Clin Res Inst, Durham, NC 27710 USA. RP Rodriguez, W (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM william.rodriguez@fda.hhs.gov RI Smith, Phillip/I-5565-2014 NR 25 TC 21 Z9 21 U1 0 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 2168-6203 J9 JAMA PEDIATR JI JAMA Pediatr. PD MAR PY 2013 VL 167 IS 3 BP 243 EP 249 DI 10.1001/jamapediatrics.2013.872 PG 7 WC Pediatrics SC Pediatrics GA 115GB UT WOS:000316799500006 PM 23359002 ER PT J AU Zhao, L Ji, P Li, ZH Roy, P Sahajwalla, CG AF Zhao, Liang Ji, Ping Li, Zhihong Roy, Partha Sahajwalla, Chandrahas G. TI The Antibody Drug Absorption Following Subcutaneous or Intramuscular Administration and Its Mathematical Description by Coupling Physiologically Based Absorption Process with the Conventional Compartment Pharmacokinetic Model SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE absorption; bioavailability; monoclonal antibody; pharmacokinetics; physiologically based pharmacokinetic model ID MONOCLONAL-ANTIBODY; POPULATION PHARMACOKINETICS; LYMPHATIC ABSORPTION; IMMUNOGLOBULIN-G; RESIDENCE TIME; SOLID TUMORS; PBPK MODEL; TRANSPORT; FCRN; PHARMACODYNAMICS AB The main objective of this paper is to propose a quantitative model to describe the absorption process for monoclonal antibody (mAb) following subcutaneous (SC) or intramuscular (IM) administration. A hybrid model was established by coupling the physiologically based absorption process with a conventional pharmacokinetic-pharmacodynamic (PK-PD) or PK model associated with intravenous infusion. Key physiological parameters evaluated include the volume distribution before systemic absorption, mAb drug clearance during lymphatic transport, the neonatal Fc receptor (FcRn) capacity, the intrinsic drug clearance via lysosomal proteolytic process, and the lymphatic flow rate. Sensitivity analyses were performed to identify those physiological parameters significantly impacting time to peak concentration (T-max) or drug bioavailability. Simulation results showed that lymphatic flow rate is the only influential factor to T-max. Lymphatic transit time and drug clearance during lymphatic transport are most influential to bioavailability but not identifiable in their effects. Bioavailability is positively related to the lymphatic flow only at its low range (i.e., at <0.5-fold of the selected value of 0.043 mL/min). The rest of physiological parameters only have marginal effects on either drug bioavailability or T-max. Finally, simulation results confirmed lymphatic transport as the major route of mAb delivery. C1 [Zhao, Liang; Ji, Ping; Li, Zhihong; Roy, Partha; Sahajwalla, Chandrahas G.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhao, L (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM liang.zhao@fda.hhs.gov NR 43 TC 13 Z9 13 U1 1 U2 16 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 2013 VL 53 IS 3 BP 314 EP 325 DI 10.1002/jcph.4 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 116WV UT WOS:000316914900009 PM 23426855 ER PT J AU Ho, MW Tu, WZ Ghosh, P Tiwari, RC AF Ho, Man-Wai Tu, Wanzhu Ghosh, Pulak Tiwari, Ram C. TI A Nested Dirichlet Process Analysis of Cluster Randomized Trial Data With Application in Geriatric Care Assessment SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Clustered data; Random effects distribution; Treatment effect ID LINEAR MIXED-MODEL; CONSORT STATEMENT; OLDER PATIENTS; REVISED RECOMMENDATIONS; MEDICARE BENEFICIARIES; NONPARAMETRIC PROBLEMS; FUNCTIONAL OUTCOMES; MIXING DISTRIBUTION; BAYESIAN-ANALYSIS; QUALITY AB In cluster randomized trials, patients seen by the same physician are randomized to the same treatment arm as a group. Besides the natural clustering of patients due to cluster/group randomization, interactions between an individual patient and the attending physician within the group could just as well influence patient care outcomes. Despite the intuitive relevance of these interactions to treatment assessment, few studies have thus far examined their influences. Whether and to what extent these interactions affect assessment of the treatment effect remains unexplored. In fact, few statistical models provide ready accommodation for such interactions. In this research, we propose a general modeling framework based on the nested Dirichlet process (nDP) for assessing treatment effect in cluster randomized trials. The proposed methodology explicitly accounts for physician patient interactions by assuming that the interactions follow unspecified group-specific distributions from an nDP. In addition to accounting for physician patient interactions, the model has greatly enhanced the flexibility of traditional mixed effect models by allowing for nonnormally distributed random effects, thus, alleviating concerns about mixed effect misspecification and sidestepping verification of distributional assumptions on random effects. At the same time, the model retains the mixed models' ability to make inferences on fixed effects. The proposed method is easily extendable to more complicated hierarchical clustering structures. We introduce the method in the context of a real cluster randomized trial. A comprehensive simulation study was conducted to assess the operating characteristics of the proposed nDP model. C1 [Ho, Man-Wai] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117546, Singapore. [Tu, Wanzhu] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Management & Informat Sci, Bangalore 560076, Karnataka, India. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ho, MW (reprint author), Natl Univ Singapore, Dept Stat & Appl Probabil, 6 Sci Dr 2, Singapore 117546, Singapore. EM stahmw@nus.edu.sg; wutu1@exchange.iu.edu; pulakghosh@gmail.com; Ram.Tiwari@fda.hhs.gov FU Ministry of Education's AcRF Tier 1 funding from Republic of Singapore [R-155-000-103-112]; National Institutes of Health, USA [RO1 HL095086]; DST grant from the Government of India [SR?S4/MS:648/10] FX This research was supported by the Ministry of Education's AcRF Tier 1 funding (WBS number: R-155-000-103-112) from Republic of Singapore, and partially supported by grant RO1 HL095086 from the National Institutes of Health, USA. The third author (P. G.) acknowledges the support of the DST grant (#SR?S4/MS:648/10) from the Government of India. The authors thank the Editor, the Associate Editor, and the anonymous reviewers for their many constructive suggestions in improving the quality of this article. NR 57 TC 2 Z9 2 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD MAR PY 2013 VL 108 IS 501 BP 48 EP 68 DI 10.1080/01621459.2012.734164 PG 21 WC Statistics & Probability SC Mathematics GA 113EB UT WOS:000316648200005 ER PT J AU Mirams, GR Arthurs, CJ Bernabeu, MO Bordas, R Cooper, J Corrias, A Davit, Y Dunn, SJ Fletcher, AG Harvey, DG Marsh, ME Osborne, JM Pathmanathan, P Pitt-Francis, J Southern, J Zemzemi, N Gavaghan, DJ AF Mirams, Gary R. Arthurs, Christopher J. Bernabeu, Miguel O. Bordas, Rafel Cooper, Jonathan Corrias, Alberto Davit, Yohan Dunn, Sara-Jane Fletcher, Alexander G. Harvey, Daniel G. Marsh, Megan E. Osborne, James M. Pathmanathan, Pras Pitt-Francis, Joe Southern, James Zemzemi, Nejib Gavaghan, David J. TI Chaste: An Open Source C plus plus Library for Computational Physiology and Biology SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID CELLULAR ELECTROPHYSIOLOGY MODELS; CARDIAC ELECTROPHYSIOLOGY; TISSUE ELECTROPHYSIOLOGY; MONOCLONAL CONVERSION; BIDOMAIN EQUATIONS; MARKUP LANGUAGE; COLONIC CRYPT; STEM-CELLS; SIMULATION; REPOLARIZATION AB Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high-performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to 're-invent the wheel' with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials. C1 [Mirams, Gary R.; Arthurs, Christopher J.; Bordas, Rafel; Cooper, Jonathan; Harvey, Daniel G.; Osborne, James M.; Pathmanathan, Pras; Pitt-Francis, Joe; Gavaghan, David J.] Univ Oxford, Dept Comp Sci, Oxford, England. [Bernabeu, Miguel O.] UCL, CoMPLEX, London, England. [Bernabeu, Miguel O.] UCL, Ctr Computat Sci, London, England. [Corrias, Alberto] Natl Univ Singapore, Dept Bioengn, Singapore 117548, Singapore. [Davit, Yohan] Univ Oxford, Math Inst, Oxford Ctr Collaborat Appl Math, Oxford, England. [Dunn, Sara-Jane] Microsoft Res, Sci Computat Lab, Cambridge, England. [Fletcher, Alexander G.] Univ Oxford, Math Inst, Ctr Math Biol, Oxford, England. [Marsh, Megan E.] Univ Saskatchewan, Dept Math & Stat, Saskatoon, SK, Canada. [Pathmanathan, Pras] US FDA, Silver Spring, MD USA. [Southern, James] Fujitsu Labs Europe, London, England. [Zemzemi, Nejib] INRIA Bordeaux Sud Ouest, CARMEN Project, Talence, France. RP Mirams, GR (reprint author), Univ Oxford, Dept Comp Sci, Oxford, England. EM gary.mirams@cs.ox.ac.uk RI Bernabeu, Miguel/K-3288-2012; Mirams, Gary/B-6653-2008; Arthurs, Christopher/A-2494-2014 OI Mirams, Gary/0000-0002-4569-4312; Arthurs, Christopher/0000-0002-0448-6146 FU GlaxoSmithKline; EPSRC e-Science pilot project in Integrative Biology [GR/S72023/01]; EPSRC, Software for High Performance Computing project [EP/F011628/1]; European Commission, Prediction of Drug Impact in Cardiac Toxicity (preDiCT), Framework 7 grant [DG-INFSO 224381]; European Commission, Virtual Physiological Network of Excellence (VPH-NoE), Framework 7 grant [DG-INFSO 223920]; Science: EPSRC and Microsoft Research, Cambridge [EP/I017909/1]; BBSRC [BB/D020190/1]; Life Sciences Interface and Systems Biology Doctoral Training Centres; Systems Approaches to Biomedical Science Industrial Doctorate Centre [EP/E501605/1, EP/G50029/1, EP/G037280/1]; King Abdullah University of Science and Technology (KAUST) [KUK-C1-013-04] FX This work was funded by: GlaxoSmithKline Grants and Affiliates Award to GRM and DJG; EPSRC e-Science pilot project in Integrative Biology (GR/S72023/01); EPSRC, Software for High Performance Computing project (EP/F011628/1); European Commission, Prediction of Drug Impact in Cardiac Toxicity (preDiCT), Framework 7 grant (DG-INFSO 224381); European Commission, Virtual Physiological Network of Excellence (VPH-NoE), Framework 7 grant (DG-INFSO 223920); 2020 Science: EPSRC and Microsoft Research, Cambridge through grant EP/I017909/1 (www.2020science.net); BBSRC grant to Oxford Centre for Integrative Systems Biology (BB/D020190/1); The Life Sciences Interface and Systems Biology Doctoral Training Centres, and the Systems Approaches to Biomedical Science Industrial Doctorate Centre (EP/E501605/1, EP/G50029/1 and EP/G037280/1). This publication was also based on work supported in part by Award No. KUK-C1-013-04, made by King Abdullah University of Science and Technology (KAUST). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 74 TC 76 Z9 77 U1 1 U2 27 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2013 VL 9 IS 3 AR e1002970 DI 10.1371/journal.pcbi.1002970 PG 8 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 116EA UT WOS:000316864200041 PM 23516352 ER PT J AU Hong, HX Zhang, WQ Shen, J Su, ZQ Ning, BT Han, T Perkins, R Shi, LM Tong, WD AF Hong HuiXiao Zhang WenQian Shen Jie Su ZhenQiang Ning BaiTang Han Tao Perkins, Roger Shi LeMing Tong WeiDa TI Critical role of bioinformatics in translating huge amounts of next-generation sequencing data into personalized medicine (vol 56, pg 110, 2013) SO SCIENCE CHINA-LIFE SCIENCES LA English DT Correction C1 [Hong HuiXiao; Shen Jie; Su ZhenQiang; Perkins, Roger; Shi LeMing; Tong WeiDa] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. [Zhang WenQian] Beijing Genom Inst, Shenzhen 518083, Peoples R China. [Ning BaiTang; Han Tao] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. NR 1 TC 0 Z9 0 U1 0 U2 7 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD MAR PY 2013 VL 56 IS 3 BP 291 EP 291 DI 10.1007/s11427-013-4457-5 PG 1 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 114NA UT WOS:000316747000014 ER PT J AU Guo, YL Shi, LM Hong, HX Su, ZQ Fuscoe, J Ning, BT AF Guo YongLi Shi LeMing Hong HuiXiao Su ZhenQiang Fuscoe, James Ning BaiTang TI Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine (vol 56, pg 119, 2013) SO SCIENCE CHINA-LIFE SCIENCES LA English DT Correction C1 [Guo YongLi; Fuscoe, James; Ning BaiTang] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Shi LeMing; Hong HuiXiao; Su ZhenQiang] US FDA, Natl Ctr Toxicol Res, Div Bioinformat & Biostat, Jefferson, AR 72079 USA. RP Guo, YL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU SCIENCE PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1674-7305 J9 SCI CHINA LIFE SCI JI Sci. China-Life Sci. PD MAR PY 2013 VL 56 IS 3 BP 292 EP 292 DI 10.1007/s11427-013-4456-6 PG 1 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 114NA UT WOS:000316747000015 ER PT J AU Smith, ER Modric, S AF Smith, Emily R. Modric, Sanja TI Regulatory Considerations for the Approval of Analgesic Drugs for Cattle in the United States SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article DE Analgesics; Nonsteroidal anti-inflammatory drugs; Cattle; Pain; Regulatory ID PLASMA-CONCENTRATIONS; SUBSTANCE-P; CALVES; PAIN; CASTRATION; CORTISOL; ACCELEROMETERS; MELOXICAM; BEHAVIOR; BULLS AB Continuous life-cycle management of veterinary drugs by the Food and Drug Administration Center for Veterinary Medicine (CVM) ensures that safe and effective approved animal drugs are available for use in the United States. This article summarizes basic requirements for the approval of new animal drugs, with a specific focus on the approval of analgesic drugs for use in cattle. CVM encourages drug companies to use innovative approaches to demonstrate the effectiveness of analgesic drugs for cattle. There is an obvious need for continued research into the development of new animal drugs for the control of pain in cattle. C1 [Smith, Emily R.; Modric, Sanja] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Smith, ER (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl, Rockville, MD 20855 USA. EM emily.smith2@fda.hhs.gov NR 17 TC 6 Z9 6 U1 0 U2 15 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 2013 VL 29 IS 1 BP 1 EP + DI 10.1016/j.cvfa.2012.11.009 PG 11 WC Veterinary Sciences SC Veterinary Sciences GA 114VN UT WOS:000316771000002 PM 23438396 ER PT J AU Huang, Y Labiner-Wolfe, J Huang, H Choiniere, CJ Fein, SB AF Huang, Yi Labiner-Wolfe, Judith Huang, Hui Choiniere, Conrad J. Fein, Sara B. TI Association of Health Profession and Direct-to-Consumer Marketing with Infant Formula Choice and Switching SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article DE formula feeding; formula marketing; formula switching; health profession marketing; longitudinal analysis with time-varying covariates ID FEEDING PATTERNS; PACKS; MILK AB Background Infant formula is marketed by health professionals and directly to consumers. Formula marketing has been shown to reduce breastfeeding, but the relation with switching formulas has not been studied. Willingness to switch formula can enable families to spend less on formula. Methods Data are from the Infant Feeding Practices Study II, a United States national longitudinal study. Mothers were asked about media exposure to formula information during pregnancy, receiving formula samples or coupons at hospital discharge, reasons for their formula choice at infant age 1month, and formula switching at infant ages 2, 5, 7, and 9months. Analysis included 1,700 mothers who fed formula at infant age 1month; it used logistic regression and longitudinal data analysis methods to evaluate the association between marketing and formula choice and switching. Results Most mothers were exposed to both types of formula marketing. Mothers who received a sample of formula from the hospital at birth were more likely to use the hospital formula 1month later. Mothers who chose formula at 1month because their doctor recommended it were less likely to switch formula than those who chose in response to direct-to-consumer marketing. Mothers who chose a formula because it was used in the hospital were less likely to switch if they had not been exposed to Internet web-based formula information when pregnant or if they received a formula sample in the mail. Conclusions Marketing formula through health professionals may decrease mothers' willingness to switch formula. (BIRTH 40:1 March 2013) C1 [Huang, Yi] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Labiner-Wolfe, Judith] Dept Hlth & Human Serv, Off Womens Hlth, Washington, DC USA. [Choiniere, Conrad J.] US FDA, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Huang, Y (reprint author), Univ Maryland Baltimore Cty, Dept Math & Stat, 1000 Hilltop Circle, Baltimore, MD 21250 USA. NR 22 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD MAR PY 2013 VL 40 IS 1 BP 24 EP 31 DI 10.1111/birt.12025 PG 8 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 108AO UT WOS:000316263200004 PM 24635421 ER PT J AU Stockbridge, N Morganroth, J Shah, RR Garnett, C AF Stockbridge, Norman Morganroth, Joel Shah, Rashmi R. Garnett, Christine TI Dealing with Global Safety Issues Was the Response to QT-Liability of Non-Cardiac Drugs Well Coordinated? SO DRUG SAFETY LA English DT Review ID TORSADES-DE-POINTES; RISK-MANAGEMENT PROGRAM; CARDIAC REPOLARIZATION; INTERVAL PROLONGATION; POSITIVE CONTROL; CLINICAL-TRIALS; THOROUGH QT; IN-VITRO; LONG QT; CISAPRIDE AB Drug-induced torsade de pointes (TdP) is a potentially fatal iatrogenic entity. Its reporting rate in association with non-cardiac drugs increased exponentially from the early 1990s and was associated with an increasing number of new non-cardiac drugs whose proarrhythmic liability was not appreciated pre-marketing. This epidemic provoked a comprehensive global response from drug regulators, drug developers and academia, which resulted in stabilization of the reporting rate of TdP. This commentary reviews the chronology and nature of, and the reasons for, this response, examines its adequacy, and proposes future strategies for dealing with such iatrogenic epidemics more effectively. It is concluded that the response was piecemeal and lacked direction. No one entity was responsible, with the result that important contributions from regulators, industry and academia lacked coordination. While the process of dealing with QT crisis seemed to have worked reasonably well in this instance, it does not seem wise to expect the next crisis in drug development to be managed as well. Future crises will need better management and the challenge is to implement a system set up to respond globally and efficiently to a perceived drug-related hazard. In this regard, we discuss the roles of new tools the legislation has provided to the regulators and the value of an integrated expert assessment of all pre-approval data that may signal a potential safety issue in the postmarketing period. We also discuss the roles of other bodies such as the WHO Collaborating Centre for International Drug Monitoring, CIOMS and the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). C1 [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Morganroth, Joel] ERes Technol, Philadelphia, PA 19103 USA. [Shah, Rashmi R.] Rashmi Shah Consultancy Ltd, Gerrards Cross, England. [Garnett, Christine] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Morganroth, J (reprint author), ERes Technol, 1818 Market St 1000, Philadelphia, PA 19103 USA. EM jmorganroth@ert.com NR 74 TC 44 Z9 45 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PD MAR PY 2013 VL 36 IS 3 BP 167 EP 182 DI 10.1007/s40264-013-0016-z PG 16 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 109HS UT WOS:000316358000004 PM 23417505 ER PT J AU Dingerdissen, H Motwani, M Karagiannis, K Simonyan, V Mazumder, R AF Dingerdissen, Hayley Motwani, Mona Karagiannis, Konstantinos Simonyan, Vahan Mazumder, Raja TI Proteome-wide analysis of nonsynonymous single-nucleotide variations in active sites of human proteins SO FEBS JOURNAL LA English DT Article DE active site; genetic variance; nsSNP; nsSNV; proteome-wide analysis ID GLYCOGEN-STORAGE-DISEASE; 3-PHOSPHOGLYCERATE DEHYDROGENASE-DEFICIENCY; ABL TYROSINE KINASE; MOLECULAR CHARACTERIZATION; DIABETIC-NEPHROPATHY; INSULIN-RESISTANCE; GENE POLYMORPHISMS; ALPHA-GLUCOSIDASE; COMMON MUTATION; POINT MUTATION AB An enzyme's active site is essential to normal protein activity such that any disruptions at this site may lead to dysfunction and disease. Nonsynonymous single-nucleotide variations (nsSNVs), which alter the amino acid sequence, are one type of disruption that can alter the active site. When this occurs, it is assumed that enzyme activity will vary because of the criticality of the site to normal protein function. We integrate nsSNV data and active site annotations from curated resources to identify all active-site-impacting nsSNVs in the human genome and search for all pathways observed to be associated with this data set to assess the likely consequences. We find that there are 934 unique nsSNVs that occur at the active sites of 559 proteins. Analysis of the nsSNV data shows an over-representation of arginine and an under-representation of cysteine, phenylalanine and tyrosine when comparing the list of nsSNV-impacted active site residues with the list of all possible proteomic active site residues, implying a potential bias for or against variation of these residues at the active site. Clustering analysis shows an abundance of hydrolases and transferases. Pathway and functional analysis shows several pathways over- or under-represented in the data set, with the most significantly affected pathways involved in carbohydrate metabolism. We provide a table of 32 variationsubstrate/product pairs that can be used in targeted metabolomics experiments to assay the effects of specific variations. In addition, we report the significant prevalence of aspartic acid to histidine variation in eight proteins associated with nine diseases including glycogen storage diseases, lacrimo-auriculo-dento-digital syndrome, Parkinson's disease and several cancers. C1 [Dingerdissen, Hayley; Motwani, Mona; Karagiannis, Konstantinos; Mazumder, Raja] George Washington Univ, Dept Biochem & Mol Biol, Med Ctr, Washington, DC 20037 USA. [Simonyan, Vahan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Mazumder, R (reprint author), George Washington Univ, Dept Biochem & Mol Biol, Ross Hall,Room 540,2300 Eye St NW, Washington, DC 20037 USA. EM mazumder@gwu.edu FU George Washington University; Center for Biologics Evaluation and Research FX All computations were performed at HIVE located at The George Washington University and codeveloped by Drs Mazumder and Simonyan. Support for this work came from The George Washington University funds to RM. This project is also supported in part by an appointment to the Research Participation program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. NR 108 TC 7 Z9 7 U1 0 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1742-464X EI 1742-4658 J9 FEBS J JI FEBS J. PD MAR PY 2013 VL 280 IS 6 BP 1542 EP 1562 DI 10.1111/febs.12155 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 107YZ UT WOS:000316258400013 PM 23350563 ER PT J AU Liu, J Jadhav, PR Amur, S Fleischer, R Hammerstrom, T Lewis, L Naeger, L O'Rear, J Pacanowski, M Robertson, S Seo, S Soon, G Birnkrant, D AF Liu, Jiang Jadhav, Pravin R. Amur, Shashi Fleischer, Russell Hammerstrom, Thomas Lewis, Linda Naeger, Lisa O'Rear, Jule Pacanowski, Michael Robertson, Sarah Seo, Shirley Soon, Greg Birnkrant, Debra TI Response-guided telaprevir therapy in prior relapsers? The role of bridging data from treatment-naive and experienced subjects SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; LABELING DECISIONS; VIRUS-INFECTION; DRUG APPROVAL; PLUS RIBAVIRIN; HCV INFECTION; RETREATMENT; IMPACT AB The purpose of this report is to illustrate the US Food and Drug Administration's rationale for approving response-guided therapy (RGT) for telaprevir (TVR) in combination with pegylated interferon- and ribavirin (P/R) for the treatment of adults with genotype 1 chronic hepatitis C who were prior relapsers. RGT was prospectively evaluated in two registration trials of treatment-naive subjects. In these studies, RGT allowed subjects who achieved undetectable hepatitis C virus RNA from weeks 4 and 12, known as extended rapid virologic response (eRVR), to stop all treatments at 24 weeks. A patient without eRVR received an additional 36 weeks of P/R after 12 weeks of a TVR triple regimen (total of 48 weeks). However, RGT in prior P/R relapsers was not prospectively evaluated. Empirical cross-trial data indicated high sustained virologic response rates (>90%) in prior relapsers achieving eRVR, irrespective of P/R duration (24 or 48 weeks). Further analyses demonstrated that interferon responsiveness does not change in P/R-experienced subjects with a second round of P/R. The comparability in interferon responsiveness across treatment courses allowed us to bridge data between treatment-naive and P/R-experienced subjects to support the approval of RGT in prior relapse subjects. (HEPATOLOGY 2013) C1 [Liu, Jiang; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD 20993 USA. [Amur, Shashi; Pacanowski, Michael] US FDA, Genom Grp, Silver Spring, MD 20993 USA. [Fleischer, Russell; Lewis, Linda; Naeger, Lisa; O'Rear, Jule; Birnkrant, Debra] US FDA, Div Antiviral Prod, Silver Spring, MD 20993 USA. [Hammerstrom, Thomas; Soon, Greg] US FDA, Div Biometr 4, Silver Spring, MD 20993 USA. [Liu, Jiang; Robertson, Sarah; Seo, Shirley] US FDA, Silver Spring, MD 20993 USA. RP Liu, J (reprint author), US FDA, 10903 New Hampshire Ave,Room 1274,Bldg 51, Silver Spring, MD 20993 USA. EM jiang.liu@fda.hhs.gov NR 22 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2013 VL 57 IS 3 BP 897 EP 902 DI 10.1002/hep.25764 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TG UT WOS:000315644200009 PM 22487907 ER PT J AU Florian, J Jadhav, PR Amur, S Ayala, R Harrington, P Mishra, P O'Rear, J Pacanowski, M Robertson, S Singer, M Soon, G Zeng, W Murray, J AF Florian, Jeffry Jadhav, Pravin R. Amur, Shashi Ayala, Ruben Harrington, Patrick Mishra, Poonam O'Rear, Jules Pacanowski, Michael Robertson, Sarah Singer, Mary Soon, Greg Zeng, Wen Murray, Jeffrey TI Boceprevir dosing for late responders and null responders: The role of bridging data between treatment-naive and -experienced subjects SO HEPATOLOGY LA English DT Article ID GENOTYPE 1 INFECTION C1 [Florian, Jeffry; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Amur, Shashi; Pacanowski, Michael] US FDA, Genom Grp, Off Clin Pharmacol, Silver Spring, MD USA. [Ayala, Ruben; Robertson, Sarah] US FDA, Div Clin Pharmacol 4, Silver Spring, MD USA. [Harrington, Patrick; Mishra, Poonam; O'Rear, Jules; Singer, Mary; Murray, Jeffrey] US FDA, Div Antiviral Prod, Silver Spring, MD USA. [Soon, Greg; Zeng, Wen] US FDA, Div Biometr, Silver Spring, MD USA. RP Florian, J (reprint author), 10903 New Hampshire Ave,Bld 51 Rm 3158, Silver Spring, MD 20993 USA. EM Jeffry.Florian@fda.hhs.gov NR 9 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2013 VL 57 IS 3 BP 903 EP 907 DI 10.1002/hep.25843 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099TG UT WOS:000315644200010 PM 22610696 ER PT J AU Hsu, CS Hsu, SJ Chen, HC Liu, CH Jeng, J Liu, CJ Chen, PJ Chen, DS Kao, JH AF Hsu, Ching-Sheng Hsu, Shih-Jer Chen, Hung-Chia Liu, Chen-Hua Jeng, Jenher Liu, Chun-Jen Chen, Pei-Jer Chen, Ding-Shinn Kao, Jia-Horng TI Association of IL28B genotypes with metabolic profiles and viral clearance rate in chronic hepatitis C patients SO HEPATOLOGY INTERNATIONAL LA English DT Article DE HCV RNA; Hepatitis C virus; IL28B genotype; Mathematical model; Metabolic profiles; Pegylated interferon; Viral kinetics ID PEGYLATED INTERFERON-ALPHA; PLUS RIBAVIRIN THERAPY; INSULIN-RESISTANCE; GENETIC-VARIATION; VIRUS; LOAD; EXPRESSION; INFECTION; REPLICATION; CHOLESTEROL AB IL28B genotypes have a strong impact on treatment outcomes of chronic hepatitis C (CHC) and on-treatment viral kinetics. Since metabolic regulation and interferon response are highly integrated, metabolic profiles may play an important role in the link between IL28B genotypes and hepatitis C virus (HCV) infection. Thus, the association of IL28B rs8099917 genotypes with metabolic profiles and the impact of metabolic profiles on hepatitis C viral kinetic parameters were examined. A case-control analysis including 278 CHC patients and 280 subjects without chronic HCV infection was performed. The associations of IL28B rs8099917 genotype with pretreatment metabolic profiles and early viral kinetic parameters were evaluated. Compared to HCV genotype 1 patients, the differences in metabolic profiles were more significant in genotype 2 patients. HCV genotype 2 patients with TT genotype had higher serum total cholesterol and high density lipoprotein (HDL) levels than those with GT genotype, and the differences remained significant when adjusted for age, sex, and body mass index (p = 0.005 for total cholesterol; p = 0.006 for HDL). In addition, patients with higher serum TG, higher fasting blood glucose, and lower HDL had a lower viral clearance rate. IL28B genotypes may affect lipid profiles of CHC patients, especially in HCV-genotype 2 patients. Patients with higher serum fasting blood glucose, triglyceride, and lower HDL have a lower viral clearance rate during pegylated interferon plus ribavirin therapy. C1 [Hsu, Ching-Sheng] Buddhist Tzu Chi Gen Hosp, Dept Internal Med, Div Gastroenterol, Taipei, Taiwan. [Hsu, Ching-Sheng] Tzu Chi Univ, Sch Med, Hualien, Taiwan. [Hsu, Shih-Jer; Liu, Chen-Hua; Liu, Chun-Jen; Chen, Pei-Jer; Chen, Ding-Shinn; Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Grad Inst Clin Med, Taipei 10764, Taiwan. [Hsu, Shih-Jer] Natl Taiwan Univ Hosp, Yun Lin Branch, Dept Internal Med, Yunlin, Taiwan. [Chen, Hung-Chia] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Liu, Chen-Hua; Liu, Chun-Jen; Chen, Pei-Jer; Chen, Ding-Shinn; Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Dept Internal Med, Natl Taiwan Univ Hosp, Taipei 10764, Taiwan. [Jeng, Jenher] Natl Chiao Tung Univ, Ctr Math Modeling & Sci Comp, Hsinchu, Taiwan. [Chen, Pei-Jer; Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Hepatitis Res Ctr, Taipei 10764, Taiwan. [Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Med Res, Taipei 10764, Taiwan. RP Kao, JH (reprint author), Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Grad Inst Clin Med, Taipei 10764, Taiwan. EM kaojh@ntu.edu.tw OI LIU, CHUN-JEN/0000-0002-6202-0993; CHEN, DING-SHINN/0000-0001-7791-6154; KAO, JIA-HORNG/0000-0002-2442-7952; Chen, Pei-Jer/0000-0001-8316-3785 FU National Taiwan University Hospital; Buddhist Tzu Chi General Hospital, Taipei Branch; Department of Health; National Science Council, Executive Yuan, Taiwan [TCRD-TPE-100-C1-2, NSC99-2314-B-303-004] FX The authors thank colleagues in the National Taiwan University Hospital and its Yun-Lin Branch, who helped enroll and follow-up the patients, and research assistants who assisted in laboratory analyses and collected clinical information. They also thank Dr Ming-Yieh Peng, Hsiang-Lin Wan, and colleagues in the Buddhist Tzu Chi General Hospital, Taipei Branch, Taiwan, for enrolling and following up the study subjects. This work was supported in part by grants from the National Taiwan University Hospital, the Buddhist Tzu Chi General Hospital, Taipei Branch, the Department of Health, and the National Science Council, Executive Yuan, Taiwan TCRD-TPE-100-C1-2, NSC99-2314-B-303-004]. NR 43 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-0533 J9 HEPATOL INT JI Hepatol. Int. PD MAR PY 2013 VL 7 IS 1 BP 171 EP 179 DI 10.1007/s12072-012-9390-3 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 109FC UT WOS:000316350600021 PM 26201631 ER PT J AU Sha, J Kirtley, ML van Lier, CJ Wang, SF Erova, TE Kozlova, EV Cao, A Cong, YZ Fitts, EC Rosenzweig, JA Chopra, AK AF Sha, Jian Kirtley, Michelle L. van Lier, Christina J. Wang, Shaofei Erova, Tatiana E. Kozlova, Elena V. Cao, Anthony Cong, Yingzi Fitts, Eric C. Rosenzweig, Jason A. Chopra, Ashok K. TI Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium SO INFECTION AND IMMUNITY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; YERSINIA-PESTIS KIM; PNEUMONIC PLAGUE; ESCHERICHIA-COLI; OUTER-MEMBRANE; RECEPTOR 4; LIPID-A; MUREIN LIPOPROTEIN; GENOME SEQUENCE; GUINEA-PIGS AB Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a Delta lpp Delta msbB double mutant of the highly virulent Y. pestis CO92 strain. Although the Delta msbB single mutant was minimally attenuated, the Delta lpp single mutant and the Delta lpp Delta msbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the Delta lpp Delta msbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines-chemokines in infected animal tissues. Importantly, mice that survived challenge with the Delta lpp Delta msbB double mutant, but not the Delta lpp or Delta msbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the Delta lpp Delta msbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the Delta lpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine-chemokine responses. Thus, the Delta lpp Delta msbB double mutant could provide a new live-attenuated background vaccine candidate strain, and this should be explored in the future. C1 [Sha, Jian; Kirtley, Michelle L.; van Lier, Christina J.; Wang, Shaofei; Erova, Tatiana E.; Kozlova, Elena V.; Cao, Anthony; Cong, Yingzi; Fitts, Eric C.; Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. [Sha, Jian; Cong, Yingzi; Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Cong, Yingzi; Chopra, Ashok K.] Univ Texas Med Branch, Sealy Ctr Vaccine Dev, Galveston, TX 77555 USA. [Cong, Yingzi] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Rosenzweig, Jason A.] Texas So Univ, CBER, Dept Biol, Houston, TX 77004 USA. RP Chopra, AK (reprint author), Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. EM achopra@utmb.edu FU NIH/NIAID [AI064389, NO1-AI-30065, AI060549]; UC7 [AI070083] FX This research was supported by NIH/NIAID grants AI064389 and NO1-AI-30065 awarded to A.K.C. We also acknowledge a UC7 grant (AI070083) which facilitated our research in the Galveston National Laboratory, Galveston, TX. C.J.V.L. was supported by an NIH/NIAID T32 predoctoral training grant on biodefense (AI060549). NR 64 TC 11 Z9 12 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2013 VL 81 IS 3 BP 815 EP 828 DI 10.1128/IAI.01067-12 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 108RH UT WOS:000316313200022 PM 23275092 ER PT J AU Thigpen, JE Setchell, KDR Kissling, GE Locklear, J Caviness, GF Whiteside, T Belcher, SM Brown, NM Collins, BJ Lih, FB Tomer, KB Padilla-Banks, E Camacho, L Adsit, FG Grant, M AF Thigpen, Julius E. Setchell, Kenneth D. R. Kissling, Grace E. Locklear, Jacqueline Caviness, Gordon F. Whiteside, Tanya Belcher, Scott M. Brown, Nadine M. Collins, Bradley J. Lih, Fred B. Tomer, Kenneth B. Padilla-Banks, Elizabeth Camacho, Luisa Adsit, Floyd G. Grant, Mary TI The Estrogenic Content of Rodent Diets, Bedding, Cages, and Water Bottles and Its Effect on Bisphenol A Studies SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID SPRAGUE-DAWLEY RATS; IMMATURE CD-1 MICE; ZEARALENONE SIGNIFICANTLY ADVANCES; ENDOCRINE-DISRUPTING CHEMICALS; REPRODUCTIVE ORGAN DEVELOPMENT; APPROPRIATE POSITIVE CONTROLS; EXPERIMENTAL-DESIGN REVEALS; GOOD LABORATORY PRACTICES; EXPOSED IN-UTERO; ETHINYL ESTRADIOL AB The lowest observed adverse effect level for bisphenol A (BPA) in mice and rats is currently poorly defined due to inconsistent study designs and results in published studies. The objectives of the current study were to (1) compare the estrogenic content of rodent diets, bedding, cages, and water bottles to evaluate their impact on the estrogenic activity of BPA and (2) review the literature on BPA to determine the most frequently reported diets, beddings, cages, and water bottles used in animal studies. Our literature review indicated that low-dose BPA animal studies have inconsistent results and that factors contributing to this inconsistency are the uses of high-phytoestrogen diets and the different routes of exposure. In 44% (76 of 172) of all reports, rodents were exposed to BPA via the subcutaneous route. Our literature review further indicated that the type of diet, bedding, caging, and water bottles used in BPA studies were not always reported. Only 37% (64 of 172) of the reports described the diet used. In light of these findings, we recommend the use of a diet containing low levels of phytoestrogen (less than 20 mu g/g diet) and metabolizable energy (approximately 3.1 kcal/g diet) and estrogen-free bedding, cages, and water bottles for studies evaluating the estrogenic activity of endocrine-disrupting compounds such as BPA. The oral route of BPA exposure should be used when results are to be extrapolated to humans. C1 [Thigpen, Julius E.; Locklear, Jacqueline; Caviness, Gordon F.; Whiteside, Tanya; Adsit, Floyd G.; Grant, Mary] NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. [Kissling, Grace E.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Collins, Bradley J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Lih, Fred B.; Tomer, Kenneth B.] NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. [Padilla-Banks, Elizabeth] NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. [Setchell, Kenneth D. R.; Brown, Nadine M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Belcher, Scott M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA. [Camacho, Luisa] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Thigpen, JE (reprint author), NIEHS, Comparat Med Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM thigpen@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 100 TC 19 Z9 19 U1 1 U2 36 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD MAR PY 2013 VL 52 IS 2 BP 130 EP 141 PG 12 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 106QL UT WOS:000316159700002 PM 23562095 ER PT J AU Abel, D Farb, A AF Abel, Dorothy Farb, Andrew TI Application of Investigational Device Exemptions regulations to endograft modification SO JOURNAL OF VASCULAR SURGERY LA English DT Article AB For patients with complex aortic aneurysms that cannot be treated effectively with currently approved endografts, physicians have made fenestrations in marketed devices and constructed branched grafts by creatively implanting available endograft components. For the most part, these procedures are being done outside of clinical studies by individual physicians. Although these novel approaches may be useful in the treatment of individual patients, the current ad hoc use of physician-created fenestrated and branched devices may not result in the unbiased capture and reporting of data regarding short- and longer-term outcomes. As a result, unsubstantiated conclusions regarding the safety and effectiveness of these procedures may be drawn. Well-designed and executed clinical studies are necessary to adequately assess the benefits and risks of these techniques. Because these interventions involve the use of significant risk devices, these studies need to be conducted under United States Food and Drug Administration-approved Investigational Device Exemptions (IDE) applications. Although this regulatory process adds complexity to the application of these creative techniques, the IDE regulations assure that patient protection measures are followed and data are captured to assess safety and effectiveness. This approach creates opportunities to advance the development of innovative, beneficial devices and procedures to treat complex aortic aneurysms. (J Vasc Surg 2013;57:823-5.) C1 [Abel, Dorothy; Farb, Andrew] US FDA, Silver Spring, MD 20993 USA. RP Abel, D (reprint author), US FDA, 10903 New Hampshire Ave,WO66-1204, Silver Spring, MD 20993 USA. EM dorothy.abel@fda.hhs.gov NR 2 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAR PY 2013 VL 57 IS 3 BP 823 EP 825 DI 10.1016/j.jvs.2012.12.025 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 103UH UT WOS:000315944400035 PM 23446122 ER PT J AU Eshera, N Marsh, A Chinn, L Zhang, L Fadiran, EO AF Eshera, Noha Marsh, Amber Chinn, Leslie Zhang, Lei Fadiran, Emmanuel O. TI Inclusion of Women and Sex Analyses in Pivotal Clinical Trials of New Molecular Entity (NME) Drugs and Biologics Approved by FDA from 2010 to 2011 SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Eshera, Noha; Marsh, Amber; Fadiran, Emmanuel O.] US FDA, Off Womens Hlth, Silver Spring, MD USA. [Chinn, Leslie; Zhang, Lei] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2013 VL 22 IS 3 MA P22 BP 10 EP 10 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 105IU UT WOS:000316061700023 ER PT J AU Sharma, D Badano, A AF Sharma, Diksha Badano, Aldo TI Validation of columnar CsI x-ray detector responses obtained with hybridMANTIS, a CPU-GPU Monte Carlo code for coupled x-ray, electron, and optical transport SO MEDICAL PHYSICS LA English DT Article DE Monte Carlo; MANTIS; hybridMANTIS; graphics processing units (GPU) ID IMAGING PERFORMANCE; SCINTILLATORS; MANTIS AB Purpose: hybridMANTIS is a Monte Carlo package for modeling indirect x-ray imagers using columnar geometry based on a hybrid concept that maximizes the utilization of available CPU and graphics processing unit processors in a workstation. Methods: The authors compare hybridMANTIS x-ray response simulations to previously published MANTIS and experimental data for four cesium iodide scintillator screens. These screens have a variety of reflective and absorptive surfaces with different thicknesses. The authors analyze hybridMANTIS results in terms of modulation transfer function and calculate the root mean square difference and Swank factors from simulated and experimental results. Results: The comparison suggests that hybridMANTIS better matches the experimental data as compared to MANTIS, especially at high spatial frequencies and for the thicker screens. hybridMANTIS simulations are much faster than MANTIS with speed-ups up to 5260. Conclusions: hybridMANTIS is a useful tool for improved description and optimization of image acquisition stages in medical imaging systems and for modeling the forward problem in iterative reconstruction algorithms. (C) 2013 American Association of Physicists in Medicine. [http://dx.doi.org/10.1118/1.4791642] C1 [Sharma, Diksha; Badano, Aldo] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 10 TC 4 Z9 4 U1 0 U2 8 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 MAR PY 2013 VL 40 IS 3 AR 031907 DI 10.1118/1.4791642 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 109LG UT WOS:000316369400030 PM 23464322 ER PT J AU Lee, S Raw, A Yu, L Lionberger, R Ya, N Verthelyi, D Rosenberg, A Kozlowski, S Webber, K Woodcock, J AF Lee, Sau Raw, Andre Yu, Lawrence Lionberger, Robert Ya, Naiqi Verthelyi, Daniela Rosenberg, Amy Kozlowski, Steve Webber, Keith Woodcock, Janet TI Scientific considerations in the review and approval of generic enoxaparin in the United States SO NATURE BIOTECHNOLOGY LA English DT Review ID MOLECULAR-WEIGHT HEPARINS; FACTOR 4/HEPARIN ANTIBODIES; INDUCED THROMBOCYTOPENIA; SEQUENCING APPROACH; SULFATE; OLIGOSACCHARIDES; ANTITHROMBIN; RECOMMENDATIONS; GUIDELINES; BINDING AB In 2010, the US Food and Drug Administration (FDA) approved a generic low-molecular-weight heparin without clinical safety or efficacy data under the Abbreviated New Drug Application (ANDA) pathway. To enable a determination of active ingredient sameness of generic and innovator enoxaparin products, the FDA developed a scientifically rigorous approach based on five criteria: first, equivalence of physicochemical properties; second, equivalence of heparin source material and mode of depolymerization; third, equivalence in disaccharide building blocks, fragment mapping and sequence of oligosaccharide species; fourth, equivalence in biological and biochemical assays; and finally, equivalence of in vivo pharmacodynamic profile. In addition to fulfillment of these criteria, FDA also used in vitro, ex vivo and model animal data to ensure there was no increased immunogenicity risk of the generic enoxaparin product relative to the brand name product. The approval of the highly complex enoxaparin product using this framework under the ANDA pathway represents a major development. It also suggests that analytical and scientific advancements may in certain cases allow the elimination of unnecessary in vivo testing in animals and humans. C1 [Lee, Sau; Raw, Andre; Yu, Lawrence; Lionberger, Robert; Ya, Naiqi; Webber, Keith] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA. [Verthelyi, Daniela; Rosenberg, Amy; Kozlowski, Steve] US FDA, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Bethesda, MD USA. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Raw, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20857 USA. EM andre.raw@fda.hhs.gov NR 67 TC 22 Z9 22 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAR PY 2013 VL 31 IS 3 BP 220 EP 226 DI 10.1038/nbt.2528 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 110JX UT WOS:000316439500015 PM 23471071 ER PT J AU Jeffrey, M Piccardo, P McGovern, G AF Jeffrey, M. Piccardo, P. McGovern, G. TI A previously unrecognised fatal bovine tauopathy is present in aged cattle throughout the UK SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Meeting Abstract CT 114th Meeting of the British-Neuropathological-Society / Symposium on Advances in Motor Neuron Diseases CY MAR 13-15, 2013 CL Inst Child Hlth, London, ENGLAND SP British Neuropathol Soc HO Inst Child Hlth C1 [Jeffrey, M.; McGovern, G.] AHVLA Lasswade, Penicuik EH26 0PZ, Midlothian, Scotland. [Piccardo, P.] US FDA, Lab Bacterial & TSE Agents, Rockville, MD 20852 USA. EM martin.jeffrey@ahvla.gsi.gov.uk RI Jeffrey, Martin/D-2251-2009; APHA, Staff publications/E-6082-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD MAR PY 2013 VL 39 SU 1 SI SI BP 37 EP 38 PG 2 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 109AV UT WOS:000316338400055 ER PT J AU Hess, CN Rao, SV Kong, DF Miller, JM Anstrom, KJ Bertrand, OF Collet, JP Effron, MB Eloff, BC Fadiran, EO Farb, A Gilchrist, IC Holmes, DR Jacobs, AK Kaul, P Newby, LK Rutledge, DR Tavris, DR Tsai, TT White, RM Peterson, ED Krucoff, MW AF Hess, Connie N. Rao, Sunil V. Kong, David F. Miller, Julie M. Anstrom, Kevin J. Bertrand, Olivier F. Collet, Jean-Philippe Effron, Mark B. Eloff, Benjamin C. Fadiran, Emmanuel O. Farb, Andrew Gilchrist, Ian C. Holmes, David R. Jacobs, Alice K. Kaul, Prashant Newby, L. Kristin Rutledge, David R. Tavris, Dale R. Tsai, Thomas T. White, Roseann M. Peterson, Eric D. Krucoff, Mitchell W. TI TransRadial Education And Therapeutics (TREAT): Shifting the balance of safety and efficacy of antithrombotic agents in percutaneous coronary intervention. A report from the Cardiac Safety Research Consortium SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-OUTCOMES; FEMORAL APPROACH; VASCULAR COMPLICATIONS; ANTIPLATELET THERAPY; GENDER-DIFFERENCES; RANDOMIZED-TRIALS; HEART-ASSOCIATION; BLOOD-TRANSFUSION; ADVERSE OUTCOMES AB Percutaneous coronary intervention (PCI) is an integral part of the treatment of coronary artery disease. The most common complication of PCI, bleeding, typically occurs at the vascular access site and is associated with short-term and long-term morbidity and mortality. Periprocedural bleeding also represents the primary safety concern of concomitant antithrombotic therapies essential for PCI success. Use of radial access for PCI reduces procedural bleeding and hence may change the risk profile and net clinical benefit of these drugs. This new drug-device safety interaction creates opportunities to advance the safe and effective use of antithrombotic agents during PCI. In June 2010 and March 2011, leaders from government, academia, professional societies, device manufacturing, and pharmaceutical industries convened for 2 think tank meetings. Titled TREAT I and II, these forums examined approaches to improve the overall safety of PCI by optimizing strategies for antithrombotic drug use and radial artery access. This article summarizes the content and proceedings of these sessions. (Am Heart J 2013;165:344-353.e1.) C1 [Hess, Connie N.; Rao, Sunil V.; Kong, David F.; Anstrom, Kevin J.; Newby, L. Kristin; Peterson, Eric D.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Miller, Julie M.] Johns Hopkins Univ, Baltimore, MD USA. [Bertrand, Olivier F.] Quebec Heart Lung Inst, Quebec City, PQ, Canada. [Collet, Jean-Philippe] Inst Cardiol, Paris, France. [Effron, Mark B.] Lilly USA LLC, Indianapolis, IN USA. [Eloff, Benjamin C.; Fadiran, Emmanuel O.; Farb, Andrew; Tavris, Dale R.] US FDA, Silver Spring, MD USA. [Gilchrist, Ian C.] Penn State Heart & Vasc Inst, Hershey, PA USA. [Holmes, David R.] Mayo Clin, Rochester, MN USA. [Jacobs, Alice K.] Boston Med Ctr, Boston, MA USA. [Kaul, Prashant] Univ N Carolina, Chapel Hill, NC USA. [Rutledge, David R.; White, Roseann M.] Abbott Vasc, San Francisco, CA USA. [Tsai, Thomas T.] Denver VA Med Ctr, Denver, CO USA. RP Krucoff, MW (reprint author), Duke Clin Res Inst, 508 Fulton, Durham, NC 27705 USA. EM kruco001@mc.duke.edu RI Effron, Mark/P-9300-2015; OI Gilchrist, Ian/0000-0001-8525-8454 FU NIH [5T32HL069749-09] FX We thank Drs Morton J. Kern, Venugopal Menon, Tejas Patel, Jon R. Resar, Tara A. Ryan, Jeffrey E. Shuren, Norman Stockbridge, and Jean-Francois Tanguay for their reviews of this manuscript. C.N.H. was funded by NIH grant 5T32HL069749-09. NR 47 TC 3 Z9 3 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2013 VL 165 IS 3 BP 344 EP + DI 10.1016/j.ahj.2012.09.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100OL UT WOS:000315710500018 PM 23453103 ER PT J AU Hulten, E Devine, P Welch, T Feuerstein, I Taylor, A Petrillo, S Luncheon, M Nguyen, B Villines, TC AF Hulten, Edward Devine, Patrick Welch, Timothy Feuerstein, Irwin Taylor, Allen Petrillo, Sara Luncheon, Minnetta Binh Nguyen Villines, Todd C. TI Comparison of Coronary CT Angiography Image Quality With and Without Breast Shields SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast shield; cardiac CT; coronary CT angiography; radiation ID CARDIAC COMPUTED-TOMOGRAPHY; MAGNETIC-RESONANCE; RADIATION-EXPOSURE; BISMUTH SHIELDS; DOSE-REDUCTION; METAANALYSIS; CANCER AB OBJECTIVE. The purpose of this study is to compare the image quality of coronary CT angiography performed with and without breast shields. MATERIALS AND METHODS. This study involved a retrospective cohort of 72 women with possible angina who underwent 64-MDCT retrospective ECG-gated coronary CT angiography at a single academic tertiary medical center. Images of 36 women scanned while wearing bismuth-coated latex breast shields and 36 control subjects scanned without shields, matched by heart rate and body mass index, were graded on a standardized Likert scale for image quality, stenosis, and plaque by two independent board-certified readers blinded to breast shields. RESULTS. Seventy-two patients (mean [+/- SD] age, 53 +/- 9 years) were included. The pre-scan heart rate, body mass index, and Agatston score did not differ between groups. The median estimated radiation dose was 13.4 versus 16.1 mSv for those with and without breast shields (p = 0.003). For shielded versus unshielded scans, 86% versus 83% of coronary segments were rated excellent or above average (p = 0.4), median image quality was 2.0 for both groups, mean signal was 474 +/- 75 and 452 +/- 91 HU (p = 0.27), mean noise was 33.9 +/- 8.5 and 29.8 +/- 8.3 HU (p = 0.04), and median signal-to-noise ratio was 14.4 and 14.7 (p = 0.56), respectively. CONCLUSION. Breast shields for women undergoing coronary CT angiography slightly increased noise but did not negatively affect signal, signal-to-noise ratio, quality, or interpretability. Breast shield use warrants further study. C1 [Hulten, Edward; Devine, Patrick; Welch, Timothy; Luncheon, Minnetta; Binh Nguyen; Villines, Todd C.] Walter Reed Natl Mil Med Ctr, Serv Cardiol, Bethesda, MD USA. [Feuerstein, Irwin] US FDA, Silver Spring, MD USA. [Taylor, Allen] Washington Hosp Ctr, Washington, DC 20010 USA. [Petrillo, Sara] Midatlantic Kaiser Permanente Grp, Rockville, MD USA. RP Hulten, E (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. EM ehulten@partners.org OI Villines, Todd/0000-0003-2674-3702; Hulten, Edward/0000-0001-9281-0032 NR 31 TC 2 Z9 2 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2013 VL 200 IS 3 BP 529 EP 536 DI 10.2214/AJR.11.8302 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 105GM UT WOS:000316054500024 PM 23436841 ER PT J AU Park, S Park, M Rafii, F AF Park, Sunny Park, Miseon Rafii, Fatemeh TI Comparative transcription analysis and toxin production of two fluoroquinolone-resistant mutants of Clostridium perfringens SO BMC MICROBIOLOGY LA English DT Article DE Clostridium perfringens; Fluoroquinolone; Resistance; Toxin; Virulence ID ANTIBIOTIC-ASSOCIATED DIARRHEA; ESCHERICHIA-COLI; ALPHA-TOXIN; STAPHYLOCOCCUS-AUREUS; VIRR/VIRS SYSTEM; VIRULENCE GENES; PHOSPHOLIPASE-C; DIFFICILE; CIPROFLOXACIN; EXPRESSION AB Background: Fluoroquinolone use has been listed as a risk factor for the emergence of virulent clinical strains of some bacteria. The aim of our study was to evaluate the effect of fluoroquinolone (gatifloxacin) resistance selection on differential gene expression, including the toxin genes involved in virulence, in two fluoroquinolone-resistant strains of Clostridium perfringens by comparison with their wild-type isogenic strains. Results: DNA microarray analyses were used to compare the gene transcription of two wild types, NCTR and ATCC 13124, with their gatifloxacin-resistant mutants, NCTRR and 13124(R). Transcription of a variety of genes involved in bacterial metabolism was either higher or lower in the mutants than in the wild types. Some genes, including genes for toxins and regulatory genes, were upregulated in NCTRR and downregulated in 13124(R). Transcription analysis by quantitative real-time PCR (qRT-PCR) confirmed the altered expression of many of the genes that were affected differently in the fluoroquinolone-resistant mutants and wild types. The levels of gene expression and enzyme production for the toxins phospholipase C, perfringolysin O, collagenase and clostripain had decreased in 13124(R) and increased in NCTRR in comparison with the wild types. After centrifugation, the cytotoxicity of the supernatants of NCTRR and 13224(R) cultures for mouse peritoneal macrophages confirmed the increased cytotoxicity of NCTRR and the decreased cytotoxicity of 13124(R) in comparison with the respective wild types. Fluoroquinolone resistance selection also affected cell shape and colony morphology in both strains. Conclusion: Our results indicate that gatifloxacin resistance selection was associated with altered gene expression in two C. perfringens strains and that the effect was strain-specific. This study clearly demonstrates that bacterial exposure to fluoroquinolones may affect virulence (toxin production) in addition to drug resistance. C1 [Park, Sunny; Park, Miseon; Rafii, Fatemeh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Fatemeh.Rafii@fda.hhs.gov FU FDA Commissioner's Fellowship Program FX We thank Drs. Mark Hart and John B. Sutherland for their helpful comments on the manuscript, Dr. Carl E. Cerniglia for support of research and Drs. Donald Schwartz and Jean-Marie Rouillard for DNA microarray experiments. S. P. was supported by the FDA Commissioner's Fellowship Program. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 53 TC 3 Z9 3 U1 1 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD MAR 1 PY 2013 VL 13 AR 50 DI 10.1186/1471-2180-13-50 PG 13 WC Microbiology SC Microbiology GA 104DP UT WOS:000315970600001 PM 23452396 ER PT J AU Azurmendi, HF Freedberg, DI AF Azurmendi, Hugo F. Freedberg, Daron I. TI Accurate determinations of one-bond C-13-C-13 couplings in C-13-labeled carbohydrates SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Carbon-carbon coupling; Carbon-carbon residual dipolar coupling; Constant time; Labeled carbohydrate; Carbohydrate structure ID RESIDUAL DIPOLAR COUPLINGS; SOLUTION NMR; BLOOD-GROUP; PROTEINS; SUCROSE; ANTIGENS; SPECTRA; PROTON; PULSES; ACID AB Carbon plays a central role in the molecular architecture of carbohydrates, yet the availability of accurate methods for D-1(CC) determination has not been sufficiently explored, despite the importance that such data could play in structural studies of oligo- and polysaccharides. Existing methods require fitting intensity ratios of cross- to diagonal-peaks as a function of the constant-time (CT) in CT-COSY experiments, while other methods utilize measurement of peak separation. The former strategies suffer from complications due to peak overlap, primarily in regions close to the diagonal, while the latter strategies are negatively impacted by the common occurrence of strong coupling in sugars, which requires a reliable assessment of their influence in the context of RDC determination. We detail a C-13-C-13 CT-COSY method that combines a variation in the CT processed with diagonal filtering to yield (1)J(CC) and RDCs. The strategy, which relies solely on cross-peak intensity modulation, is inspired in the cross-peak nulling method used for JHH determinations, but adapted and extended to applications where, like in sugars, large one-bond C-13-C-13 couplings coexist with relatively small long-range couplings. Because diagonal peaks are not utilized, overlap problems are greatly alleviated. Thus, one-bond couplings can be determined from different cross-peaks as either active or passive coupling. This results in increased accuracy when more than one determination is available, and in more opportunities to measure a specific coupling in the presence of severe overlap. In addition, we evaluate the influence of strong couplings on the determination of RDCs by computer simulations. We show that individual scalar couplings are notably affected by the presence of strong couplings but, at least for the simple cases studied, the obtained RDC values for use in structural calculations were not, because the errors introduced by strong couplings for the isotropic and oriented phases are very similar and therefore cancel when calculating the difference to determine D-1(CC) values. Published by Elsevier Inc. C1 [Azurmendi, Hugo F.; Freedberg, Daron I.] US FDA, Lab Bacterial Polysaccharides, Struct Biol Sect, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Freedberg, DI (reprint author), US FDA, Lab Bacterial Polysaccharides, Struct Biol Sect, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM hazur_99@yahoo.com; daron_freedberg@nih.gov NR 30 TC 4 Z9 4 U1 0 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 2013 VL 228 BP 130 EP 135 DI 10.1016/j.jmr.2013.01.001 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 103QT UT WOS:000315934700015 PM 23376482 ER PT J AU Yu, BW van Ingen, H Freedberg, DI AF Yu, Bingwu van Ingen, Hugo Freedberg, Daron I. TI Constant time INEPT CT-HSQC (CTi-CT-HSQC) - A new NMR method to measure accurate one-bond J and RDCs with strong H-1-H-1 couplings in natural abundance SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE Carbohydrates; Coupling constant; NMR spectroscopy; Residual dipolar coupling; Strong coupling ID RESIDUAL DIPOLAR COUPLINGS; LINKED OLIGOSACCHARIDES; RESOLUTION ENHANCEMENT; ANGULAR-DEPENDENCE; AQUEOUS-SOLUTION; SPECTRA; PROTEINS; SPECTROSCOPY; SUCROSE; PULSE AB Strong H-1-H-1 coupling can significantly reduce the accuracy of (1)J(CH) measured from frequency differences in coupled HSQC spectra. Although accurate (1)J(CH) values can be extracted from spectral simulation, it would be more convenient if the same accurate (1)J(CH) values can be obtained experimentally. Furthermore, simulations reach their limit for residual dipolar coupling (RDC) measurement, as many significant, but immeasurable RDCs are introduced into the spin system when a molecule is weakly aligned, thus it is impossible to have a model spin system that truly represents the real spin system. Here we report a new J modulated method, constant-time INEPT CT-HSQC (CTi-CT-HSQC), to accurately measure one-bond scalar coupling constant and RDCs without strong coupling interference. In this method, changing the spacing between the two 180 degrees pulses during a constant time INEPT period selectively modulates heteronuclear coupling in quantitative J fashion. Since the INEPT delays for measuring one-bond carbon-proton spectra are short compared to (3)J(HH), evolution due to (strong) H-1-H-1 coupling is marginal. The resulting curve shape is practically independent of H-1-H-1 coupling and only correlated to the heteronuclear coupling evolution. Consequently, an accurate (1)J(CH) can be measured even in the presence of strong coupling. We tested this method on N-acetyl-glucosamine and mannose whose apparent isotropic (1)J(CH) values are significantly affected by strong coupling with other methods. Agreement to within 0.5 Hz or better is found between (1)J(CH) measured by this method and previously published simulation data. We further examined the strong coupling effects on RDC measurements and observed an error up to 100% for one bond RDCs using coupled HSQC in carbohydrates. We demonstrate that RDCs can be obtained with higher accuracy by CTi-CT-HSQC, which compensates the limitation of simulation method. Published by Elsevier Inc. C1 [Yu, Bingwu; Freedberg, Daron I.] US FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD 20892 USA. [van Ingen, Hugo] Univ Utrecht, Bijvoet Ctr Biomol Res, NMR Spect Res Grp, NL-3584 CH Utrecht, Netherlands. RP Freedberg, DI (reprint author), US FDA, Lab Bacterial Polysaccharides, CBER, Bethesda, MD 20892 USA. EM daron_freedberg@nih.gov RI van Ingen, Hugo/Q-2883-2016 OI van Ingen, Hugo/0000-0002-0808-3811 NR 36 TC 12 Z9 12 U1 1 U2 30 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAR PY 2013 VL 228 BP 159 EP 165 DI 10.1016/j.jmr.2012.11.007 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 103QT UT WOS:000315934700018 PM 23294631 ER PT J AU Strader, MB Hervey, WJ Costantino, N Fujigaki, S Chen, CY Akal-Strader, A Ihunnah, CA Makusky, AJ Court, DL Markey, SP Kowalak, JA AF Strader, Michael Brad Hervey, William Judson Costantino, Nina Fujigaki, Suwako Chen, Cai Yun Akal-Strader, Ayca Ihunnah, Chibueze A. Makusky, Anthony J. Court, Donald L. Markey, Sanford P. Kowalak, Jeffrey A. TI A Coordinated Proteomic Approach for Identifying Proteins that Interact with the E. coli Ribosomal Protein S12 SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE affinity pull-down protein purification; peptide affinity pull-downs; PTM: post-translational modification; SPA: sequence peptide affinity; SPA-S12: SPA tagged ribosomal protein S12; 1D-LC-MS/MS: one-dimensional liquid chromatography tandem mass spectrometry; FDR: false positive discovery rate; metabolic labeling; relative quantification ID ESCHERICHIA-COLI; TRANSFER-RNA; POSTTRANSLATIONAL MODIFICATION; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; 70S RIBOSOME; MIAB PROTEIN; IDENTIFICATION; METHYLTRANSFERASE; ENZYME AB The bacterial ribosomal protein S12 contains a universally conserved D88 residue on a loop region thought to be critically involved in translation due to its proximal location to the A site of the 30S subunit. While D88 mutants are lethal this residue has been found to be post-translationally modified to beta-methylthioaspartic acid, a post-translational modification (PTM) identified in S12 orthologs from several phylogenetically distinct bacteria. In a previous report focused on characterizing this PTM, our results provided evidence that this conserved loop region might be involved in forming multiple proteins-protein interactions (Strader, M. B.; Costantino, N.; Elkins, C. A.; Chen, C. Y.; Patel, I.; Makusky, A. J.; Choy, J. S.; Court, D. L.; Markey, S. P.; Kowalak, J. A. A proteomic and transcriptomic approach reveals new insight into betamethylthiolation of Escherichia colt ribosomal protein S12. Mol. Cell. Proteomics 2011, 10, M110 005199). To follow-up on this study, the D88 containing loop was probed to identify candidate binders employing a two-step complementary affinity purification strategy. The first involved an endogenously expressed S12 protein containing a C-terminal tag for capturing S12 binding partners The second strategy utilized a synthetic biotinylated peptide representing the D88 conserved loop region for capturing S12 loop interaction partners. Captured proteins from both approaches were detected by utilizing SDS-PAGE and one-dimensional liquid chromatography-tandem mass spectrometry. The results presented in this report revealed proteins that form direct interactions with the 30S subunit and elucidated which are likely to interact with S12. In addition, we provide evidence that two proteins involved in regulating ribosome and/or mRNA transcript levels under stress conditions, RNase R and Hfq, form direct interactions with the S12 conserved loop, suggesting that it is likely part of a protein binding interface. C1 [Strader, Michael Brad; Fujigaki, Suwako; Chen, Cai Yun; Makusky, Anthony J.; Markey, Sanford P.; Kowalak, Jeffrey A.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. [Costantino, Nina; Court, Donald L.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Akal-Strader, Ayca] Georgetown Univ, Dept Biol, Washington, DC 20057 USA. [Ihunnah, Chibueze A.] Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15206 USA. RP Strader, MB (reprint author), US FDA, Labs Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Michael.Strader@fda.hhs.gov FU National Institute of Mental Health [1ZIAMH000274] FX We would like to thank Jack Greenblatt (University of Toronto, Canada) for generously providing the SPA cassette used for generating SPA tagged genes. We would like to thank Mikhail Bunenko for his valuable comments and suggestions (National Cancer Institute/Frederick Cancer Research and Development Center, Frederick, MD). We would like to thank Chongle Pan for assistance in using ProRata software. We would like to thank Todd L. Mollan (CBER/FDA), Adele Bladder (NCI/NIMH) and Christopher Crutchfield (NICHD/NIH) for assistance with reading and/or editing this manuscript. This work was supported by the Intramural Research Program of the National Institute of Mental Health (1ZIAMH000274). NR 47 TC 5 Z9 5 U1 0 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 EI 1535-3907 J9 J PROTEOME RES JI J. Proteome Res. PD MAR PY 2013 VL 12 IS 3 BP 1289 EP 1299 DI 10.1021/pr3009435 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 100NN UT WOS:000315708000021 PM 23305560 ER PT J AU Pritchard-Jones, K Pieters, R Reaman, GH Hjorth, L Downie, P Calaminus, G Naafs-Wilstra, MC Steliarova-Foucher, E AF Pritchard-Jones, Kathy Pieters, Rob Reaman, Gregory H. Hjorth, Lars Downie, Peter Calaminus, Gabriele Naafs-Wilstra, Marianne C. Steliarova-Foucher, Eva TI Sustaining innovation and improvement in the treatment of childhood cancer: lessons from high-income countries SO LANCET ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; UNITED-STATES; BRAIN-TUMORS; ADOLESCENTS; CHILDREN; CARE; PATTERNS; OUTCOMES; VOLUME AB Cancer in children and adolescents is rare and biologically very different from cancer in adults. It accounts for 1.4% of all cancers worldwide, although this proportion ranges from 0.5% in Europe to 4.8% in Africa, largely because of differences in age composition and life expectancy. In high-income countries, survival from childhood cancer has reached 80% through a continuous focus on the integration of clinical research into front-line care for nearly all children affected by malignant disease. However, further improvement must entail new biology-driven approaches, since optimisation of conventional treatments has in many cases reached its limits. In many instances, such approaches can only be achieved through international collaborative research, since rare cancers are being subdivided into increasingly smaller subgroups on the basis of their molecular characteristics. The long-term effect of anticancer treatment on quality of life must also be taken into account because more than one in 1000 adults in high-income countries are thought to be survivors of cancer in childhood or adolescence. The introduction of drugs that are less toxic and more targeted than those currently used necessitates a partnership between clinical and translational researchers, the pharmaceutical industry, drug regulators, and patients and their families. This therapeutic alliance will ensure that efforts are focused on the unmet clinical needs of young people with cancer. Most children with cancer live in low-income and middle-income countries, and these countries account for 94% of all deaths from cancer in people aged 0-14 years. The immediate priority for these children is to improve access to an affordable, best standard of care in each country. Every country should have a national cancer plan that recognises the unique demographic characteristics and care needs of young people with cancer. Centralisation of the complex components of treatment of these rare diseases is essential to improve survival, accelerate research, and train the future specialist workforce. Referral routes and care pathways must take account of the large geographical distances between many patients' homes and treatment centres, and the economic, cultural, and linguistic diversity of the populations served. C1 [Pritchard-Jones, Kathy] UCL, Inst Child Hlth, London WC1N 1EH, England. [Pieters, Rob] Erasmus MC Sophia Childrens Hosp, Dept Oncol Haematol, Rotterdam, Netherlands. [Reaman, Gregory H.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hjorth, Lars] Clin Sci Lund Univ, Dept Paediat, Skane Univ Hosp, Lund, Sweden. [Downie, Peter] Monash Univ, Childrens Canc Ctr, Clayton, Vic, Australia. [Downie, Peter] Monash Univ, Dept Paediat, Clayton, Vic, Australia. [Calaminus, Gabriele] Univ Childrens Hosp Munster, Dept Paediat Haematol & Oncol, Munster, Germany. [Calaminus, Gabriele] Int Soc Paediat Oncol, Geneva, Switzerland. [Naafs-Wilstra, Marianne C.] Int Confederat Childhood Canc Parents Org, Nieuwegein, Netherlands. [Steliarova-Foucher, Eva] Int Agcy Res Canc, F-69372 Lyon, France. RP Pritchard-Jones, K (reprint author), UCL, Inst Child Hlth, 30 Guilford St, London WC1N 1EH, England. EM k.pritchard-jones@ucl.ac.uk RI Pritchard-Jones, Kathy/F-4286-2014 OI Pritchard-Jones, Kathy/0000-0002-2384-9475 FU European Union's Seventh Framework Programme under European Network for Cancer Research in Children and Adolescents project [261474] FX This work has received funding from the European Union's Seventh Framework Programme (FP7/2007-13) under the European Network for Cancer Research in Children and Adolescents project (grant number 261474). NR 51 TC 54 Z9 57 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD MAR PY 2013 VL 14 IS 3 BP E95 EP E103 DI 10.1016/S1470-2045(13)70010-X PG 9 WC Oncology SC Oncology GA 103OV UT WOS:000315928800016 PM 23434338 ER PT J AU Kouzine, F Gupta, A Baranello, L Wojtowicz, D Ben-Aissa, K Liu, JH Przytycka, TM Levens, D AF Kouzine, Fedor Gupta, Ashutosh Baranello, Laura Wojtowicz, Damian Ben-Aissa, Khadija Liu, Juhong Przytycka, Teresa M. Levens, David TI Transcription-dependent dynamic supercoiling is a short-range genomic force SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; TOPOLOGICAL DOMAIN SIZE; DNA TOPOISOMERASE-II; SHOCK GENE LOCUS; IN-VIVO; TORSIONAL TENSION; BETA-LAPACHONE; UPSTREAM DNA; HUMAN-CELLS; YEAST AB Transcription has the capacity to mechanically modify DNA topology, DNA structure and nucleosome arrangement. Resulting from ongoing transcription, these modifications in turn may provide instant feedback to the transcription machinery. To substantiate the connection between transcription and DNA dynamics, we charted an ENCODE map of transcription-dependent dynamic supercoiling in human Burkitt's lymphoma cells by using psoralen photobinding to probe DNA topology in vivo. Dynamic supercoils spread similar to 1.5 kilobases upstream of the start sites of active genes. Low- and high-output promoters handled this torsional stress differently, as shown by using inhibitors of transcription and topoisomerases and by chromatin immunoprecipation of RNA polymerase and topoisomerases I and II. Whereas lower outputs are managed adequately by topoisomerase I, high-output promoters additionally require topoisomerase II. The genome-wide coupling between transcription and DNA topology emphasizes the importance of dynamic supercoiling for gene regulation. C1 [Kouzine, Fedor; Gupta, Ashutosh; Baranello, Laura; Levens, David] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Gupta, Ashutosh] Univ Maryland, Dept Phys, College Pk, MD 20742 USA. [Wojtowicz, Damian; Przytycka, Teresa M.] Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. [Ben-Aissa, Khadija] NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. [Liu, Juhong] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Levens, D (reprint author), NCI, Pathol Lab, Bldg 10, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU Intramural Research Program of the US National Institutes of Health, National Cancer Institute and Center for Cancer Research; National Library of Medicine and Food and Drug Administration FX Our research is supported by the Intramural Research Program of the US National Institutes of Health, National Cancer Institute and Center for Cancer Research, National Library of Medicine and Food and Drug Administration. This study used the high-performance computational capabilities of the Helix Systems at the National Institutes of Health, Bethesda, Maryland (http://helix.nih.gov/). We thank R. Casellas and A. Yamane for Illumina sequencing, and D. Clark and E. Batchelor for critical comments. NR 60 TC 73 Z9 73 U1 3 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1545-9993 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAR PY 2013 VL 20 IS 3 BP 396 EP 403 DI 10.1038/nsmb.2517 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 105BQ UT WOS:000316041000023 PM 23416947 ER PT J AU Leder, HA Eydelman, M AF Leder, Henry A. Eydelman, Malvina TI Enzymatic Detergents and Toxic Anterior Segment Syndrome Reply SO OPHTHALMOLOGY LA English DT Letter C1 [Leder, Henry A.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Leder, Henry A.; Eydelman, Malvina] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD USA. RP Leder, HA (reprint author), Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2013 VL 120 IS 3 BP 652 EP 653 PG 3 WC Ophthalmology SC Ophthalmology GA 100XJ UT WOS:000315738200047 PM 23714616 ER PT J AU McMurry-Heath, M Eydelman, M AF McMurry-Heath, Michelle Eydelman, Malvina TI United States Food and Drug Administration TASS Program Reply SO OPHTHALMOLOGY LA English DT Letter C1 [McMurry-Heath, Michelle; Eydelman, Malvina] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP McMurry-Heath, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAR PY 2013 VL 120 IS 3 BP 654 EP 654 PG 1 WC Ophthalmology SC Ophthalmology GA 100XJ UT WOS:000315738200050 PM 23714618 ER PT J AU Lester, J Neyarapally, GA Lipowski, E Graham, CF Hall, M Dal Pan, G AF Lester, Jean Neyarapally, George A. Lipowski, Earlene Graham, Cheryl Fossum Hall, Marni Dal Pan, Gerald TI Evaluation of FDA safety-related drug label changes in 2010 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE drug labeling; postmarket drug safety; safety issue; pharmacoepidemiology ID SURVEILLANCE AB Purpose This study characterizes drug safety-related label changes by evidence source contribution, time from drug approval to label change, initiator (FDA or sponsor), and drug class. Methods A retrospective review of the FDA's internal files was used to obtain regulatory documentation on drugs undergoing a 2010 label change. Contribution of evidence sources were identified and label change initiator and drug class were determined for each drug. Results A total of 371 drugs were analyzed. Spontaneous reports contributed to 52% and 55% of label changes when analyzed by unique safety issue and drug, respectively. The median time from approval to 2010 safety-related label change was 11years. The sponsor was more likely than the FDA to initiate a label change (58% and 42%). Label changes were most common among nervous system drugs (23%), antiinfectives for systemic use (17%), and cardiovascular system drugs (14%). Conclusions Drug label changes involve contributions from multiple evidence sources. The findings from this comprehensive review are consistent with previous findings and demonstrate (i) the continued importance of the spontaneous reporting system and complementary evidence sources and (ii) safety-related label changes take place years after postmarket approval, emphasizing the importance of continued drug safety surveillance throughout a product's lifecycle. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Lester, Jean; Lipowski, Earlene] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32611 USA. [Lester, Jean; Neyarapally, George A.; Graham, Cheryl Fossum; Hall, Marni; Dal Pan, Gerald] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lester, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Mfg & Prod Qual,Drug Surveillance & Data Repo, Off Compliance, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jean.lester@fda.hhs.gov NR 10 TC 16 Z9 16 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2013 VL 22 IS 3 BP 302 EP 305 DI 10.1002/pds.3395 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 099VN UT WOS:000315651200011 PM 23280652 ER PT J AU Peters, SL Lind, JN Humphrey, JR Friedman, JM Honein, MA Tassinari, MS Moore, CA Mathis, LL Broussard, CS AF Peters, Stacey L. Lind, Jennifer N. Humphrey, Jasmine R. Friedman, Jan M. Honein, Margaret A. Tassinari, Melissa S. Moore, Cynthia A. Mathis, Lisa L. Broussard, Cheryl S. TI Safe lists for medications in pregnancy: inadequate evidence base and inconsistent guidance from Web-based information, 2011 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE medication; pregnancy; women; drug safety; Internet; TERIS; pharmacoepidemiology AB Purpose Medication use during pregnancy is common and increasing. Women are also increasingly getting healthcare information from sources other than their physicians. Methods This report summarizes an environmental scan that identified 25 active Internet sites that list medications reported to be safe for use in pregnancy and highlights the inadequate evidence base and inconsistent guidance provided by these sites. Results These lists included 245 different products, of which 103 unique components had been previously evaluated in terms of fetal risk by the Teratogen Information System (TERIS), a resource that assesses risk of birth defects after exposure under usual conditions by consensus of clinical teratology experts. For 43 (42%) of the 103 components that were listed as safe' on one or more of the Internet sites surveyed, the TERIS experts were unable to determine the fetal risk based on published scientific literature. For 40 (93%) of these 43, either no data were available to assess human fetal risk or the available data were limited. Conclusions Women who see a medication on one of these safe' lists would be led to believe that there is no increased risk of birth defects resulting from exposure. Thus, women are being reassured that fetal exposure to these medications is safe even though a sufficient evidence base to determine the relative safety or risk does not exist. Copyright (c) 2013 John Wiley & Sons, Ltd. C1 [Peters, Stacey L.; Humphrey, Jasmine R.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Peters, Stacey L.; Lind, Jennifer N.; Humphrey, Jasmine R.; Honein, Margaret A.; Moore, Cynthia A.; Broussard, Cheryl S.] Ctr Dis Control & Prevent, NCBDDD, Atlanta, GA 30333 USA. [Lind, Jennifer N.] Georgia State Univ, Inst Publ Hlth, Atlanta, GA 30303 USA. [Friedman, Jan M.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Tassinari, Melissa S.; Mathis, Lisa L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Broussard, CS (reprint author), Ctr Dis Control & Prevent, NCBDDD, 1600 Clifton Rd,MS E-86, Atlanta, GA 30333 USA. EM cbroussard@cdc.gov OI Friedman, Jan/0000-0002-7482-9570 FU Centers for Disease Control and Prevention FX This study was supported by the Centers for Disease Control and Prevention. NR 12 TC 14 Z9 14 U1 1 U2 9 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2013 VL 22 IS 3 BP 324 EP 328 DI 10.1002/pds.3410 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 099VN UT WOS:000315651200014 PM 23359404 ER PT J AU Orenstein, WA Gellin, BG Beigi, RH Buck, T Despres, S LaRussa, PS Lynfield, R Maldonado, Y Morita, J Mouton, C Pisani, A Rothholz, MC Stenvig, TE Tan, L Torres, C Hetherington, S Lewin, C Bailowitz, A Baker, C Daum, RS Douglas, C Hannan, C Jarris, P Rawlins, W Richardson, V Salisbury, D AF Orenstein, Walter A. Gellin, Bruce G. Beigi, Richard H. Buck, Tawny Despres, Sarah LaRussa, Philip S. Lynfield, Ruth Maldonado, Yvonne Morita, Julie Mouton, Charles Pisani, Amy Rothholz, Mitchel C. Stenvig, Thomas E. Tan, Litjen (LJ) Torres, Catherine Hetherington, Seth Lewin, Clement Bailowitz, Anne Baker, Carol Daum, Robert S. Douglas, Charlene Hannan, Claire Jarris, Paul Rawlins, Wayne Richardson, Vesta Salisbury, David CA Natl Vaccine Advisory Comm TI Protecting the Public's Health: Critical Functions of the Section 317 Immunization Program-A Report of the National Vaccine Advisory Committee SO PUBLIC HEALTH REPORTS LA English DT Article ID UNITED-STATES; COVERAGE; MEASLES C1 [Orenstein, Walter A.] Emory Univ, Atlanta, GA 30322 USA. [Gellin, Bruce G.] US Dept HHS, Natl Vaccine Program Off, Washington, DC 20201 USA. [Beigi, Richard H.] Magee Womens Hosp, Pittsburgh, PA USA. [LaRussa, Philip S.] Columbia Univ, Dept Pediat, New York, NY 10027 USA. [Lynfield, Ruth] Minnesota Dept Hlth, St Paul, MN USA. [Maldonado, Yvonne] Stanford Univ, Stanford, CA 94305 USA. [Morita, Julie] Chicago Dept Publ Hlth, Chicago, IL USA. [Mouton, Charles] Meharry Med Coll, Nashville, TN 37208 USA. [Pisani, Amy] Every Child Two, Mystic, CT USA. [Rothholz, Mitchel C.] Amer Pharmacists Assoc, Alexandria, VA USA. [Stenvig, Thomas E.] S Dakota State Univ, Coll Nursing, Brookings, SD 57007 USA. [Tan, Litjen (LJ)] Amer Med Assoc, Chicago, IL 60610 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Hetherington, Seth] Genocea Biosci, Cambridge, MA USA. [Lewin, Clement] Novartis Vaccines & Diagnost, Cambridge, MA USA. [Bailowitz, Anne] Natl Assoc Cty & City Hlth Officials, Baltimore, MD USA. [Baker, Carol] Ctr Dis Control & Prevent, Advisory Comm Immunizat Practices, Houston, TX USA. [Daum, Robert S.] US FDA, Vaccines & Related Biol Prod Advisory Comm, Chicago, IL USA. [Douglas, Charlene] Advisory Comm Childhood Vaccines, Fairfax, VA USA. [Hannan, Claire] Assoc Immunizat Management, Rockville, MD USA. [Jarris, Paul] Assoc State & Terr Hlth Officials, Arlington, VA USA. [Rawlins, Wayne] Amer Hlth Insurance Plans, Hartford, CT USA. [Richardson, Vesta] Hlth Minist Mexico, Mexico City, DF, Mexico. [Salisbury, David] Dept Hlth, London SE1 6TE, England. RP Orenstein, WA (reprint author), Emory Univ, Atlanta, GA 30322 USA. NR 35 TC 0 Z9 0 U1 1 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2013 VL 128 IS 2 BP 78 EP 95 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 098GT UT WOS:000315537600003 ER PT J AU Hing, ZA Schiller, T Wu, A Hamasaki-Katagiri, N Struble, EB Russek-Cohen, E Kimchi-Sarfaty, C AF Hing, Zachary A. Schiller, Tal Wu, Andrew Hamasaki-Katagiri, Nobuko Struble, Evi Budo Russek-Cohen, Estelle Kimchi-Sarfaty, Chava TI Multiple in silico tools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE thrombotic thrombocytopenic purpura; congenital; ADAMTS13; thrombocytopenia and microangiopathic haemolytic anaemia; genotype-phenotype correlations ID UPSHAW-SCHULMAN SYNDROME; VON-WILLEBRAND-FACTOR; RESIDUAL PLASMATIC ACTIVITY; FACTOR-CLEAVING PROTEASE; CODON USAGE; MUTATIONS; ADAMTS13; DISEASE; PREGNANCY; SEVERITY AB Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare, recessively inherited genetic disorder with varying clinical presentation that is caused by ADAMTS13 mutations. Several studies have found limited associations between ADAMTS13 mutations and cTTP phenotype. The use of in silico tools that examine multiple mutation characteristics may better predict phenotype. We analysed 118 ADAMTS13 mutations found in 144 cTTP patients reported in the literature and examined associations of several mutation characteristics, including N-terminal proximity, the evolutionary conservation of the affected amino acid position, as well as amino acid charge/phosphorylation and genetic codon usage to disease phenotype. Structure-altering mutations were examined for their impact on ADAMTS13 function based on existing ADAMTS13 crystallographic data (AA 77-685). Our in silico data indicate that: (i) The position of the mutation in the N- or C-terminus, (ii) evolutionary conservation and (iii) codon usage of the affected mutation position are associated with disease parameters, such as age of onset, organ damage and fresh frozen plasma prophylaxis. In conclusion, the usage of multiple in silico tools presents a promising strategy in refining predictions for the diverse presentation of cTTP. Enhancing our utilization of in silico tools to find genotype-phenotype associations will create better-tailored approaches for individual patient treatment. C1 [Hing, Zachary A.; Schiller, Tal; Wu, Andrew; Hamasaki-Katagiri, Nobuko; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20982 USA. [Struble, Evi Budo] US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20982 USA. [Russek-Cohen, Estelle] US FDA, Div Biostat, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Bethesda, MD 20982 USA. RP Kimchi-Sarfaty, C (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20982 USA. EM Chava.kimchi-sarfaty@fda.hhs.gov FU Laboratory of Hemostasis; Center for Biologics Evaluation and Research, Food and Drug Administration FX This work was supported by funds from the Laboratory of Hemostasis (C. K-S) and the Center for Biologics Evaluation and Research, Food and Drug Administration. 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. NR 35 TC 4 Z9 4 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2013 VL 160 IS 6 BP 825 EP 837 DI 10.1111/bjh.12214 PG 13 WC Hematology SC Hematology GA 100ZF UT WOS:000315743700012 PM 23346910 ER PT J AU Nekhai, S Kumari, N Dhawan, S AF Nekhai, Sergei Kumari, Namita Dhawan, Subhash TI Role of cellular iron and oxygen in the regulation of HIV-1 infection SO FUTURE VIROLOGY LA English DT Review DE CDK2; CDK9; HIV-1; hypoxia; iron chelators; protein phosphatase-1; Tat ID HUMAN-IMMUNODEFICIENCY-VIRUS; DEPENDENT KINASE INHIBITORS; P-TEFB; GENE-EXPRESSION; 7SK SNRNP; TRANSCRIPTION-ELONGATION; INTRACELLULAR IRON; IN-VITRO; CYCLE PROGRESSION; BLOOD-CELLS AB Despite efficient antiretroviral therapy, eradication of HIV-1 infection is challenging and requires novel biological insights and therapeutic strategies. Among other physiological and environmental factors, intracellular iron greatly affects HIV-1 replication. Higher iron stores were shown to be associated with faster progression of HIV-1 infection and to inversely correlate with the survival of HIV-1 infected patients. Iron is required for several steps in the HIV-1 life cycle, including reverse transcription, HIV-1 gene expression and capsid assembly. Here, the authors present a comprehensive review of the molecular mechanisms involved in iron- and oxygen-mediated regulation of HIV-1 replication. We also propose key intracellular pathways that may be involved in regulating HIV-1 replication via protein kinase complexes, CDK9/cyclin T1 and CDK2/cyclin E, protein phosphatase-1 and other host factors. C1 [Nekhai, Sergei; Kumari, Namita] Howard Univ, Dept Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. [Dhawan, Subhash] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Nekhai, S (reprint author), Howard Univ, Dept Med, Ctr Sickle Cell Dis, 520 W St NW, Washington, DC 20059 USA. FU NIH [1SC1GM082325, 1P3.0HL107253-01, 5UH1 HL03679, AI043894]; District of Columbia Developmental Center for AIDS Research [P30AI087714, 8G12MD007597]; GW [31440-16-CCLS90469F]; Howard University FX Work in S Nekhai's laboratory is supported by extramural NIH grants 1SC1GM082325, 1P3.0HL107253-01, 5UH1 HL03679, AI043894, District of Columbia Developmental Center for AIDS Research (P30AI087714), 8G12MD007597, GW Project No.: 31440-16-CCLS90469F and intramural funding from Howard University. Work in S Dhawan's laboratory is supported by intramural funding from the US FDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 119 TC 11 Z9 11 U1 0 U2 7 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0794 J9 FUTURE VIROL JI Future Virol. PD MAR PY 2013 VL 8 IS 3 BP 301 EP 311 DI 10.2217/FVL.13.6 PG 11 WC Virology SC Virology GA 100LR UT WOS:000315703200013 PM 23678366 ER PT J AU Dickensheets, H Sheikh, F Park, O Gao, B Donnelly, RP AF Dickensheets, Harold Sheikh, Faruk Park, Ogyi Gao, Bin Donnelly, Raymond P. TI Interferon-lambda (IFN-lambda) induces signal transduction and gene expression in human hepatocytes, but not in lymphocytes or monocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE IFN-alpha; tyrosine-phosphorylated; hepatitis C virus; ISG; STAT ID C VIRUS-REPLICATION; CHRONIC HEPATITIS-C; JAK-STAT PATHWAY; TARGETED DISRUPTION; RECEPTOR; ALPHA; CELLS; IDENTIFICATION; TRANSCRIPTION; ACTIVATION AB This study compared the ability of IFN-alpha and IFN-lambda to induce signal transduction and gene expression in primary human hepatocytes, PBLs, and monocytes. IFN-alpha drug products are widely used to treat chronic HCV infection; however, IFN-alpha therapy often induces hematologic toxicities as a result of the broad expression of IFNARs on many cell types, including most leukocytes. rIFN-lambda 1 is currently being tested as a potential alternative to IFN-alpha for treating chronic HCV. Although IFN-lambda has been shown to be active on hepatoma cell lines, such as HepG2 and Huh-7, its ability to induce responses in primary human hepatocytes or leukocytes has not been examined. We found that IFN-lambda induces activation of Jak/STAT signaling in mouse and human hepatocytes, and the ability of IFN-lambda to induce STAT activation correlates with induction of numerous ISGs. Although the magnitude of ISG expression induced by IFN-alpha in hepatocytes was generally lower than that induced by IFN-lambda, the repertoire of regulated genes was quite similar. Our findings demonstrate that although IFN-alpha and IFN-lambda signal through distinct receptors, they induce expression of a common set of ISGs in hepatocytes. However, unlike IFN-alpha, IFN-lambda did not induce STAT activation or ISG expression by purified lymphocytes or monocytes. This important functional difference may provide a clinical advantage for IFN-lambda as a treatment for chronic HCV infection, as it is less likely to induce the leukopenias that are often associated with IFN-alpha therapy. J. Leukoc. Biol. 93: 377-385; 2013. C1 [Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20892 USA. [Park, Ogyi; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, CDER, Bldg 29A,Room 3B15,HFD-122,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raymond.donnelly@fda.hhs.gov FU U.S. Food and Drug Administration, Center for Drug Evaluation and Research; U.S. National Institutes of Health FX This study was supported by intramural research funds from the U.S. Food and Drug Administration, Center for Drug Evaluation and Research, and the U.S. National Institutes of Health. NR 42 TC 34 Z9 34 U1 0 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2013 VL 93 IS 3 BP 377 EP 385 DI 10.1189/jlb.0812395 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 098WL UT WOS:000315579700007 PM 23258595 ER PT J AU Angel, M Kimble, JB Pena, L Wan, HQ Perez, DR AF Angel, Matthew Kimble, J. Brian Pena, Lindomar Wan, Hongquan Perez, Daniel R. TI In Vivo Selection of H1N2 Influenza Virus Reassortants in the Ferret Model SO JOURNAL OF VIROLOGY LA English DT Article ID SWINE-ORIGIN H1N1; AVIAN H5N1; A-VIRUS; UNITED-STATES; TRANSMISSION; H3N2; PATHOGENICITY; PIGS; NEURAMINIDASE; COMPATIBILITY AB Although the ferret model has been extensively used to study pathogenesis and transmission of influenza viruses, little has been done to determine whether ferrets are a good surrogate animal model to study influenza virus reassortment. It has been previously shown that the pandemic 2009 H1N1 (H1N1pdm) virus was able to transmit efficiently in ferrets. In coinfection studies with either seasonal H1N1 or H3N2 strains (H1N1s or H3N2s, respectively), the H1N1pdm virus was able to outcompete these strains and become the dominant transmissible virus. However, lack of reassortment could have been the result of differences in the cell or tissue tropism of these viruses in the ferret. To address this issue, we performed coinfection studies with recombinant influenza viruses carrying the surface genes of a seasonal H3N2 strain in the background of an H1N1pdm strain and vice versa. After serial passages in ferrets, a dominant H1N2 virus population was obtained with a constellation of gene segments, most of which, except for the neuraminidase (NA) and PB1 segments, were from the H1N1pdm strain. Our studies suggest that ferrets recapitulate influenza virus reassortment events. The H1N2 virus generated through this process resembles similar viruses that are emerging in nature, particularly in pigs. C1 [Angel, Matthew; Kimble, J. Brian; Pena, Lindomar; Perez, Daniel R.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, Dept Vet Med, College Pk, MD 20742 USA. [Wan, Hongquan] US FDA, Div Virol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Perez, DR (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, Dept Vet Med, College Pk, MD 20742 USA. EM dperez1@umd.edu OI Perez, Daniel/0000-0002-6569-5689 FU CDC-HHS grant [1U01CI000355]; NIAID-NIH contract [HHSN266200700010C] FX This research was made possible through funding by a CDC-HHS grant (1U01CI000355) and an NIAID-NIH contract (HHSN266200700010C). NR 32 TC 8 Z9 8 U1 3 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2013 VL 87 IS 6 BP 3277 EP 3283 DI 10.1128/JVI.02591-12 PG 7 WC Virology SC Virology GA 095QD UT WOS:000315348500028 PM 23302886 ER PT J AU Uehara, T Ainslie, GR Kutanzi, K Pogribny, IP Muskhelishvili, L Izawa, T Yamate, J Kosyk, O Shymonyak, S Bradford, BU Boorman, GA Bataller, R Rusyn, I AF Uehara, Takeki Ainslie, Garrett R. Kutanzi, Kristi Pogribny, Igor P. Muskhelishvili, Levan Izawa, Takeshi Yamate, Jyoji Kosyk, Oksana Shymonyak, Svitlana Bradford, Blair U. Boorman, Gary A. Bataller, Ramon Rusyn, Ivan TI Molecular Mechanisms of Fibrosis-Associated Promotion of Liver Carcinogenesis SO TOXICOLOGICAL SCIENCES LA English DT Article DE liver; fibrosis; cancer; mechanisms; genotoxic ID TUMOR-INITIATING CELLS; CANCER STEM-CELLS; HEPATOCELLULAR-CARCINOMA; CARBON-TETRACHLORIDE; MOUSE MODELS; OXIDATIVE STRESS; INCIDENCE RATES; GROWTH-FACTOR; HEPATOCARCINOGENESIS; EXPRESSION AB Hepatocellular carcinoma (HCC) mostly develops in patients with advanced fibrosis; however, the mechanisms of interaction between a genotoxic insult and fibrogenesis are not well understood. This study tested a hypothesis that fibrosis promotes HCC via a mechanism that involves activation of liver stem cells. First, B6C3F1 mice were administered diethylnitrosamine (DEN; single ip injection of 1mg/kg at 14 days of age). Second, carbon tetrachloride (CCl4; 0.2ml/kg, 2/week ip starting at 8 weeks of age) was administered for 9 or 14 weeks to develop advanced liver fibrosis. In animals treated with DEN as neonates, presence of liver fibrosis led to more than doubling (to 100%) of the liver tumor incidence as early as 5 months of age. This effect was associated with activation of cells with progenitor features in noncancerous liver tissue, including markers of replicative senescence (p16), oncofetal transformation (Afp, H19, and Bex1), and increased stemness (Prom1 and Epcam). In contrast, the dose of DEN used did not modify the extent of liver inflammation, fibrogenesis, oxidative stress, proliferation, or apoptosis induced by subchronic CCl4 administration. This study demonstrates the potential role of liver stem-like cells in the mechanisms of chemical-induced, fibrosis-promoted HCC. We posit that the combination of genotoxic and fibrogenic insults is a sensible approach to model liver carcinogenesis in experimental animals. These results may contribute to identification of cirrhotic patients predisposed to HCC by analyzing the expression of hepatic progenitor cell markers in the noncancerous liver tissue. C1 [Uehara, Takeki; Ainslie, Garrett R.; Kosyk, Oksana; Shymonyak, Svitlana; Bradford, Blair U.; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27515 USA. [Kutanzi, Kristi; Pogribny, Igor P.; Muskhelishvili, Levan] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Izawa, Takeshi; Yamate, Jyoji] Osaka Prefecture Univ, Dept Vet Pathol, Osaka, Japan. [Boorman, Gary A.] Covance, Chantilly, VA USA. [Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27515 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [P42 ES005948, R01 ES015241, P30 ES010126] FX National Institutes of Health (P42 ES005948, R01 ES015241, P30 ES010126). NR 53 TC 18 Z9 18 U1 1 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2013 VL 132 IS 1 BP 53 EP 63 DI 10.1093/toxsci/kfs342 PG 11 WC Toxicology SC Toxicology GA 096WB UT WOS:000315434300006 PM 23288052 ER PT J AU Fisher, JW Li, S Crofton, K Zoeller, RT McLanahan, ED Lumen, A Gilbert, ME AF Fisher, Jeffrey W. Li, Shuang Crofton, Kevin Zoeller, R. Thomas McLanahan, Eva D. Lumen, Annie Gilbert, Mary E. TI Evaluation of Iodide Deficiency in the Lactating Rat and Pup Using a Biologically Based Dose-Response Model SO TOXICOLOGICAL SCIENCES LA English DT Article DE BBDR; HPT axis; lactation; rat; iodide deficiency; thyroid hormones ID PITUITARY-THYROID AXIS; HORMONE ECONOMY; NEONATAL RAT; PERCHLORATE; IODOTHYRONINE; THYROXINE; EXPOSURE; VOLUME; FETAL; MILK AB A biologically based dose-response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model parameters, were used as a technique to evaluate HPT axis adaptations to dietary iodide intake in euthyroid (4.139 g iodide/day) and iodide-deficient (0.31 and 1.2 g iodide/day) conditions. Iodide-deficient conditions in both the dam and the pup were described with increased blood flow to the thyroid gland, TSH-mediated increase in thyroidal uptake of iodide and binding of iodide in the thyroid gland (organification), and, in general, reduced thyroid hormone production and metabolism. Alterations in thyroxine (T4) homeostasis were more apparent than for triiodothyronine (T3). Model-predicted average daily area-under-the-serum-concentration-curve (nM-day) values for T4 at steady state in the dam and pup decreased by 1415% for the 1.2 g iodide/day iodide-deficient diet and 4252% for the 0.31 g iodide/day iodide-deficient diet. In rat pups that were iodide deficient during gestation and lactation, these decreases in serum T4 levels were associated with declines in thyroid hormone in the fetal brain and a suppression of synaptic responses in the hippocampal region of the brain of the adult offspring (Gilbert et al., 2013). C1 [Fisher, Jeffrey W.; Lumen, Annie] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Li, Shuang] Georgia Hlth Sci Univ, Dept Biostat & Epidemiol, Augusta, GA USA. [Crofton, Kevin] US EPA, Integrated Syst Biol Div, Res Triangle Pk, NC 27711 USA. [Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. [McLanahan, Eva D.] US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. [Gilbert, Mary E.] US EPA, Toxic Assessment Div, Res Triangle Pk, NC 27711 USA. RP Fisher, JW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jeffrey.fisher@fda.hhs.gov RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 FU STAR USEPA [R832134, R8321380]; FDA National Center for Toxicological Research FX STAR USEPA Cooperative grants (R832134, R8321380); the FDA National Center for Toxicological Research internal funding. NR 30 TC 4 Z9 4 U1 5 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2013 VL 132 IS 1 BP 75 EP 86 DI 10.1093/toxsci/kfs336 PG 12 WC Toxicology SC Toxicology GA 096WB UT WOS:000315434300008 PM 23288054 ER PT J AU Gilbert, ME Hedge, JM Valentin-Blasini, L Blount, BC Kannan, K Tietge, J Zoeller, RT Crofton, KM Jarrett, JM Fisher, JW AF Gilbert, Mary E. Hedge, Joan M. Valentin-Blasini, Liza Blount, Benjamin C. Kannan, Kurunthachalam Tietge, Joseph Zoeller, R. Thomas Crofton, Kevin M. Jarrett, Jeffrey M. Fisher, Jeffrey W. TI An Animal Model of Marginal Iodine Deficiency During Development: The Thyroid Axis and Neurodevelopmental Outcome SO TOXICOLOGICAL SCIENCES LA English DT Article DE thyroid; iodine; hypothyroidism; hippocampus; neurodevelopment; learning; synaptic function; biologically based dose-response models; BBDR ID TANDEM MASS-SPECTROMETRY; IMPAIR NEURAL DEVELOPMENT; NEONATAL-RAT HIPPOCAMPUS; HORMONE DISRUPTION; POLYCHLORINATED-BIPHENYLS; SODIUM/IODIDE SYMPORTER; BRAIN-DEVELOPMENT; SYNAPTIC-TRANSMISSION; ION CHROMATOGRAPHY; REPRODUCTIVE AGE AB Thyroid hormones (THs) are essential for brain development, and iodine is required for TH synthesis. Environmental chemicals that perturb the thyroid axis result in modest reductions in TH, yet there is a paucity of data on the extent of neurological impairments associated with low-level TH disruption. This study examined the dose-response characteristics of marginal iodine deficiency (ID) on parameters of thyroid function and neurodevelopment. Diets deficient in iodine were prepared by adding 975, 200, 125, 25, or 0 g/kg potassium iodate to the base casein diet to produce five nominal iodine levels ranging from ample (Diet 1: 1000 g iodine/kg chow, D1) to deficient (Diet 5: 25 g iodine/kg chow, D5). Female Long Evans rats were maintained on these diets beginning 7 weeks prior to breeding until the end of lactation. Dams were sacrificed on gestational days 16 and 20, or when pups were weaned on postnatal day (PN) 21. Fetal tissue was harvested from the dams, and pups were sacrificed on PN14 and PN21. Blood, thyroid gland, and brain were collected for analysis of iodine, TH, and TH precursors and metabolites. Serum and thyroid gland iodine and TH were reduced in animals receiving two diets that were most deficient in iodine. T4 was reduced in the fetal brain but was not altered in the neonatal brain. Neurobehavior, assessed by acoustic startle, water maze learning, and fear conditioning, was unchanged in adult offspring, but excitatory synaptic transmission was impaired in the dentate gyrus in animals receiving two diets that were most deficient in iodine. A 15% reduction in cortical T4 in the fetal brain was sufficient to induce permanent reductions in synaptic function in adults. These findings have implications for regulation of TH-disrupting chemicals and suggest that standard behavioral assays do not readily detect neurotoxicity induced by modest developmental TH disruption. C1 [Gilbert, Mary E.] US EPA, Tox Assessment Div, Res Triangle Pk, NC 27711 USA. [Hedge, Joan M.; Crofton, Kevin M.] US EPA, Integrated Syst Biol Div, Res Triangle Pk, NC 27711 USA. [Valentin-Blasini, Liza; Blount, Benjamin C.; Jarrett, Jeffrey M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kannan, Kurunthachalam] SUNY Albany, New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12222 USA. [Kannan, Kurunthachalam] SUNY Albany, Dept Environm Hlth Sci, Sch Publ Hlth, Albany, NY USA. [Tietge, Joseph] US EPA, MidAtlantic Ecol Div, Duluth, MN USA. [Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA. [Fisher, Jeffrey W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gilbert, ME (reprint author), US EPA, Tox Assessment Div MD B105 05, Natl Hlth & Environm Effects Res Lab, 109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM gilbert.mary@epa.gov RI Crofton, Kevin/J-4798-2015; OI Crofton, Kevin/0000-0003-1749-9971; Jarrett, Jeffery/0000-0001-5755-3552 FU U.S. Environmental Protection Agency [R832138, R832134] FX This work was partially supported by U.S. Environmental Protection Agency (R832138 to J.F.) and (R832134 to R.T.Z.). NR 71 TC 9 Z9 9 U1 1 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2013 VL 132 IS 1 BP 177 EP 195 DI 10.1093/toxsci/kfs335 PG 19 WC Toxicology SC Toxicology GA 096WB UT WOS:000315434300017 PM 23288053 ER PT J AU Tallent, SM DeGrasse, JA Wang, NY Mattis, DM Kranz, DM AF Tallent, Sandra M. DeGrasse, Jeffrey A. Wang, Ningyan Mattis, Daiva M. Kranz, David M. TI Novel Platform for the Detection of Staphylococcus aureus Enterotoxin B in Foods SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TOXIC-SHOCK-SYNDROME; T-CELL-RECEPTORS; HIGH-AFFINITY; SUPERANTIGENS; MILK AB Staphylococcal contamination of food products and staphylococcal food-borne illnesses continue to be a problem worldwide. Screening of food for the presence of Staphylococcus aureus and/or enterotoxins using traditional methods is laborious. Reliable and rapid multiplex detection methods from a single food extract or culture supernatant would simplify testing. A fluorescence-based cytometric bead array was developed for the detection of staphylococcal enterotoxin B (SEB), using magnetic microspheres coupled with either an engineered, enterotoxin-specific V beta domain of the T-cell receptor (V beta-TCR) or polyclonal antibodies. The binding affinity of the V beta-TCR for SEB has been shown to be in the picomolar range, comparable to the best monoclonal antibodies. The coupled beads were validated with purified enterotoxins and tested in a variety of food matrices spiked with enterotoxins. The V beta-TCR or antibody was shown to specifically bind SEB in four different food matrices, including milk, mashed potatoes, vanilla pudding, and cooked chicken. The use of traditional polyclonal antibodies and V beta-TCR provides a redundant system that ensures accurate identification of the enterotoxin, and the use of labeled microspheres permits simultaneous testing of multiple enterotoxins from a single sample. C1 [Tallent, Sandra M.; DeGrasse, Jeffrey A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Wang, Ningyan; Mattis, Daiva M.; Kranz, David M.] Univ Illinois, Dept Biochem, Champaign, IL 61820 USA. RP Tallent, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM Sandra.Tallent@fda.hhs.gov RI DeGrasse, Jeffrey/J-1151-2014 OI DeGrasse, Jeffrey/0000-0003-3178-6301 FU NIAID/NIH [HHSN272200700055C: NRS100, HHSN272200700055C: NRS109, HHSN272200700055C: NRS111, HHSN272200700055C: NRS113, HHSN272200700055C: NRS114, HHSN272200700055C: NRS120, HHSN272200700055C: NRS121]; National Institutes of Health [U54 AI57153]; NIAID/NIH. [HHSN272200700055C: NRS166, HHSN272200700055C: NRS185, HHSN272200700055C: NRS193, HHSN272200700055C: NRS194, HHSN272200700055C: NRS387, HHSN272200700055C: NRS483] FX The following isolates were obtained through the Network on Antimicrobial Resistance in Staphylococcus aureus (NARSA) Program, supported under NIAID/NIH contract no. HHSN272200700055C: NRS100, NRS109, NRS111, NRS113, NRS114, NRS120, NRS121, NRS166, NRS185, NRS193, NRS194, NRS387, and NRS483. This work was partially supported by a grant from the National Institutes of Health-supported Great Lakes Regional Center for Excellence in Biodefense and Emerging Diseases (grant U54 AI57153 to D.M.K.). NR 17 TC 9 Z9 9 U1 0 U2 29 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2013 VL 79 IS 5 BP 1422 EP 1427 DI 10.1128/AEM.02743-12 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 089ES UT WOS:000314893300001 PM 23241982 ER EF