FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Neupane, M Abu-Ali, GS Mitra, A Lacher, DW Manning, SD Riordan, JT AF Neupane, Mahesh Abu-Ali, Galeb S. Mitra, Avishek Lacher, David W. Manning, Shannon D. Riordan, James T. TI Shiga toxin 2 overexpression in Escherichia coli O157:H7 strains associated with severe human disease SO MICROBIAL PATHOGENESIS LA English DT Article DE Shiga toxin; E. coli O157:H7; Clade 8; Stx2; Hemolytic uremic syndrome ID COLI O157-H7; HEMORRHAGIC COLITIS; GENES; OUTBREAK; PHAGES; BACTERIOPHAGES; EXPRESSION; INDUCTION; PROPHAGES; SEQUENCES AB Variation in disease severity among Escherichia colt O157:H7 infections may result from differential expression of Shiga toxin 2 (Stx2). Eleven strains belonging to four prominent phylogenetic clades, including clade 8 strains representative of the 2006 U.S. spinach outbreak, were examined for stx2 expression by real-time PCR and western blot analysis. Clade 8 strains were shown to overexpress stx2 basally, and following induction with ciprofloxacin when compared to strains from clades 1-3. Differences in stx2 expression generally correlated with Stx2 protein levels. Single-nucleotide polymorphisms identified in regions upstream of stx2AB in clade 8 strains were largely absent in non-clade 8 strains. This study concludes that stx2 overexpression is common to strains from clade 8 associated with hemolytic uremic syndrome, and describes SNPs which may affect stx2 expression and which could be useful in the genetic differentiation of highly-virulent strains. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Mitra, Avishek; Riordan, James T.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33620 USA. [Neupane, Mahesh; Manning, Shannon D.] Michigan State Univ, Dept Microbiol & Mol Genet, Microbial Evolut & Epidemiol Lab, E Lansing, MI 48824 USA. [Abu-Ali, Galeb S.; Lacher, David W.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Riordan, JT (reprint author), Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, BSF218, Tampa, FL 33620 USA. EM jtriordan@usf.edu OI Manning, Shannon/0000-0001-9581-0660 FU NIAID under NIH [N01-AI-30058] FX We thank Cesar Taborta for assistance with DNA sequencing, and acknowledge that a significant portion of this research was supported by funds awarded to the late Thomas S. Whittam (Michigan State University) from NIAID under NIH research contract N01-AI-30058. This manuscript is dedicated to his memory. NR 44 TC 32 Z9 32 U1 1 U2 9 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD DEC PY 2011 VL 51 IS 6 BP 466 EP 470 DI 10.1016/j.micpath.2011.07.009 PG 5 WC Immunology; Microbiology SC Immunology; Microbiology GA 839LI UT WOS:000296366800011 PM 21864671 ER PT J AU Reaman, GH AF Reaman, Gregory H. TI Childhood Cancer Survivorship Educational Resources in North American Hematology/Oncology Fellowship Training Programs: A Survey Study SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material C1 [Reaman, Gregory H.] Childrens Natl Med Ctr, Div Oncol, Ctr Canc & Blood Disorders, Washington, DC 20010 USA. RP Reaman, GH (reprint author), US FDA, Off Oncol Drug Prod, OND, CDER, White Oak Bldg 22,Rm 2202,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM gregory.reaman@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2011 VL 57 IS 7 BP 1097 EP 1097 DI 10.1002/pbc.23243 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 837KN UT WOS:000296200800003 PM 21744484 ER PT J AU Billett, AL Reaman, GH AF Billett, Amy Louise Reaman, Gregory H. TI What Price Cure? SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA C1 [Billett, Amy Louise] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA. [Billett, Amy Louise] Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Billett, Amy Louise] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02215 USA. [Reaman, Gregory H.] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Billett, AL (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 450 Brookline Ave, Boston, MA 02215 USA. EM amy_billett@dfci.harvard.edu NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD DEC PY 2011 VL 57 IS 6 BP 908 EP 909 DI 10.1002/pbc.23302 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 825FX UT WOS:000295257700005 PM 22010290 ER PT J AU Anderson, M Jaykus, LA Beaulieu, S Dennis, S AF Anderson, Maren Jaykus, Lee-Ann Beaulieu, Steve Dennis, Sherri TI Pathogen-produce pair attribution risk ranking tool to prioritize fresh produce commodity and pathogen combinations for further evaluation (P(3)ARRT) SO FOOD CONTROL LA English DT Article DE Fresh produce; Pathogens; Risk ranking ID ESCHERICHIA-COLI; MICROBIOLOGICAL QUALITY; IMPORTED RASPBERRIES; UNITED-STATES; MULTISTATE OUTBREAK; FOODBORNE OUTBREAK; SALMONELLA; CYCLOSPORIASIS; FOOD; ILLNESS AB Foodborne disease outbreaks and cases associated with fresh produce have increased over the past decade. In developing approaches to prevent or reduce illnesses from consumption of contaminated produce, new tools are needed to identify and prioritize appropriate efforts. The purpose of this study was to develop a semi-quantitative risk ranking tool (Pathogen-Produce Pair Attribution Risk Ranking Tool, or P(3)ARRT) to rank the relative public health impact of pathogen-produce commodity combinations, based on explicit data-driven criteria. To identify candidate pathogen-commodity pairs, a database was created that included all published reports of fresh produce-associated outbreaks in the United States. A total risk score was calculated for each pathogen-commodity pair as the summation of nine criteria scores multiplied by the respective criteria weighting. A total of 53 pathogen-produce commodity pairs were included in the risk ranking, and based on scenario and sensitivity analyses, enterhemorrhagic E. coli in leafy greens consistently ranked first, followed by Salmonella spp. in tomatoes, and Salmonella spp. in leafy greens. The P(3)ARRT model provides a systematic, transparent, and customizable tool with which to prioritize produce pathogen-commodity pairs for further, more rigorous risk assessment modeling and evaluation efforts. The tool is available to the public at www.FoodRisk.org. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Anderson, Maren; Beaulieu, Steve] RTI Int, Dept Environm Hlth & Safety, Res Triangle Pk, NC 27709 USA. [Jaykus, Lee-Ann] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA. [Dennis, Sherri] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Anderson, M (reprint author), RTI Int, Dept Environm Hlth & Safety, 3040 Cornwallis Rd,POB 12194, Res Triangle Pk, NC 27709 USA. EM andersonm@rti.org NR 66 TC 27 Z9 27 U1 1 U2 21 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 DEC PY 2011 VL 22 IS 12 BP 1865 EP 1872 DI 10.1016/j.foodcont.2011.04.028 PG 8 WC Food Science & Technology SC Food Science & Technology GA 810AS UT WOS:000294098400011 ER PT J AU Iha, MH Barbosa, CB Okada, IA Trucksess, MW AF Iha, Maria Helena Barbosa, Cynara Baltazar Okada, Isaura Akemi Trucksess, Mary W. TI Occurrence of aflatoxin M-1 in dairy products in Brazil SO FOOD CONTROL LA English DT Article DE Aflatoxin M-1; Cheese; Yoghurt; Dairy drinks; Incidence ID YOGURT SAMPLES; MILK-PRODUCTS; CHEESE; TURKEY; ANKARA AB The objective of this study was to investigate the incidence and occurrence of aflatoxin M-1 (AFM(1)) in dairy products produced in Brazil. A total of 123 samples of three different groups of dairy products (cheese, yoghurt, and dairy drinks) consumed by Brazilians were collected during 2010. All samples including 58 cheese samples, 53 samples of yoghurt and 12 dairy drinks were purchased from grocery stores in the Ribeirao Preto-SP area. Cheese samples were classified into three categories depending on their moisture and fat contents: Minas Frescal cheese, Minas Frescal light cheese and Minas Padrao cheese. Samples were analyzed for AFM(1) by a published method. The method comprised aqueous methanol extraction, immunoaffinity column purification and isolation, reversed phase liquid chromatography separation and fluorescence detection. AFM(1) was detected in 84% of the analyzed cheese samples (>3 ng/kg) with levels ranging from 10 to 304 ng/kg in 67% of the samples. AFM(1) was detected in 95% of the yoghurt and dairy drink samples with levels ranging from 10 to 529 ng/kg in 72% of the samples. Despite the lack of a Brazilian regulatory limit for AFM(1) in yoghurt and dairy drinks the survey data of this study may offer information useful in the determination of whether the occurrence of AFM(1)) in Brazilian dairy products may be considered as a possible risk for consumer health and whether Brazilian regulatory guidelines for AFM(1) in dairy products are needed. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Iha, Maria Helena; Barbosa, Cynara Baltazar; Okada, Isaura Akemi] Adolfo Lutz Inst, CLR Ribeirao Preto, Nucleo Ciencias Quim & Bromatol, BR-14085410 Ribeirao Preto, SP, Brazil. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD USA. RP Iha, MH (reprint author), Adolfo Lutz Inst, CLR Ribeirao Preto, Nucleo Ciencias Quim & Bromatol, Rua Minas 877, BR-14085410 Ribeirao Preto, SP, Brazil. EM mhiha@ial.sp.gov.br FU FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) FX The authors are grateful to FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) for financial support. NR 25 TC 17 Z9 17 U1 1 U2 5 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 DEC PY 2011 VL 22 IS 12 BP 1971 EP 1974 DI 10.1016/j.foodcont.2011.05.013 PG 4 WC Food Science & Technology SC Food Science & Technology GA 810AS UT WOS:000294098400027 ER PT J AU Lemley, MA Shafir, Z AF Lemley, Mark A. Shafir, Ziv TI Who Chooses Open-Source Software? SO UNIVERSITY OF CHICAGO LAW REVIEW LA English DT Article AB Economists and legal scholars have debated the reasons people adopt open-source software, and accordingly whether and to what extent the open-source model can scale, replacing proprietary rights as a primary means of production. In this Article, we use the release by a biotechnology company of similar software under both proprietary and open-source licenses to investigate who uses open-source software and why. We find that academic users are somewhat more likely to adopt open-source software than private firms. We find only modest differences in the willingness of open-source users to modify or improve existing programs. And we find that users of open-source software often make business decisions that seem indifferent to the norms of open-source distribution. Our findings cast some doubt on the penetration of the open-source ethos beyond traditional software markets. C1 [Lemley, Mark A.; Shafir, Ziv] Stanford Law Sch, Palo Alto, CA USA. [Lemley, Mark A.] Durie Tangri LLP, San Francisco, CA USA. [Shafir, Ziv] US FDA, Rockville, MD 20857 USA. RP Lemley, MA (reprint author), Stanford Law Sch, Palo Alto, CA USA. NR 38 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO LAW SCH PI CHICAGO PA 1111 E 60TH ST, CHICAGO, IL 60637 USA SN 0041-9494 J9 U CHICAGO LAW REV JI Univ. Chic. Law Rev. PD WIN PY 2011 VL 78 IS 1 BP 139 EP 164 PG 26 WC Law SC Government & Law GA 768GD UT WOS:000290920900008 ER PT J AU Chen, G Yin, KP Shi, LM Fang, YZ Qi, Y Li, P Luo, J He, B Liu, MY Shi, TL AF Chen, Geng Yin, Kangping Shi, Leming Fang, Yuanzhang Qi, Ya Li, Peng Luo, Jian He, Bing Liu, Mingyao Shi, Tieliu TI Comparative Analysis of Human Protein-Coding and Noncoding RNAs between Brain and 10 Mixed Cell Lines by RNA-Seq SO PLOS ONE LA English DT Article ID HUMAN BREAST-CANCER; LEPTIN RECEPTOR; HUMAN GENOME; EXPRESSION; GENE; IDENTIFICATION; TRANSCRIPTS; REVEALS; ELEMENTS; BIOLOGY AB In their expression process, different genes can generate diverse functional products, including various protein-coding or noncoding RNAs. Here, we investigated the protein-coding capacities and the expression levels of their isoforms for human known genes, the conservation and disease association of long noncoding RNAs (ncRNAs) with two transcriptome sequencing datasets from human brain tissues and 10 mixed cell lines. Comparative analysis revealed that about two-thirds of the genes expressed between brain and cell lines are the same, but less than one-third of their isoforms are identical. Besides those genes specially expressed in brain and cell lines, about 66% of genes expressed in common encoded different isoforms. Moreover, most genes dominantly expressed one isoform and some genes only generated protein-coding (or noncoding) RNAs in one sample but not in another. We found 282 human genes could encode both protein-coding and noncoding RNAs through alternative splicing in the two samples. We also identified more than 1,000 long ncRNAs, and most of those long ncRNAs contain conserved elements across either 46 vertebrates or 33 placental mammals or 10 primates. Further analysis showed that some long ncRNAs differentially expressed in human breast cancer or lung cancer, several of those differentially expressed long ncRNAs were validated by RT-PCR. In addition, those validated differentially expressed long ncRNAs were found significantly correlated with certain breast cancer or lung cancer related genes, indicating the important biological relevance between long ncRNAs and human cancers. Our findings reveal that the differences of gene expression profile between samples mainly result from the expressed gene isoforms, and highlight the importance of studying genes at the isoform level for completely illustrating the intricate transcriptome. C1 [Chen, Geng; Yin, Kangping; Fang, Yuanzhang; Qi, Ya; Li, Peng; Luo, Jian; He, Bing; Liu, Mingyao; Shi, Tieliu] E China Normal Univ, Ctr Bioinformat & Comp Biol, Coll Life Sci, Shanghai 200062, Peoples R China. [Chen, Geng; Yin, Kangping; Fang, Yuanzhang; Qi, Ya; Li, Peng; Luo, Jian; He, Bing; Liu, Mingyao; Shi, Tieliu] E China Normal Univ, Inst Biomed Sci, Coll Life Sci, Shanghai 200062, Peoples R China. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Shi, Tieliu] Chinese Acad Sci, Shanghai Informat Ctr Life Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. RP Chen, G (reprint author), E China Normal Univ, Ctr Bioinformat & Comp Biol, Coll Life Sci, Shanghai 200062, Peoples R China. EM tlshi@sibs.ac.cn FU National 973 Key Basic Research Program [2010CB945401, 2008CB713807, 2007CB108800]; National Natural Science Foundation of China [30870575, 31071162, 31000590] FX This work was supported by the National 973 Key Basic Research Program (grant nos. 2010CB945401, 2008CB713807 and 2007CB108800), and the National Natural Science Foundation of China (grant no. 30870575, 31071162, 31000590). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 19 Z9 23 U1 1 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 NOV 30 PY 2011 VL 6 IS 11 AR e28318 DI 10.1371/journal.pone.0028318 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 863MI UT WOS:000298168100064 PM 22140575 ER PT J AU Sedrakyan, A Normand, SLT Dabic, S Jacobs, S Graves, S Marinac-Dabic, D AF Sedrakyan, Art Normand, Sharon-Lise T. Dabic, Stefan Jacobs, Samantha Graves, Stephen Marinac-Dabic, Danica TI Comparative assessment of implantable hip devices with different bearing surfaces: systematic appraisal of evidence SO BRITISH MEDICAL JOURNAL LA English DT Article ID METAL-ON-METAL; CERAMIC BEARING; FEMORAL HEADS; UNITED-STATES; FOLLOW-UP; ARTHROPLASTY; POLYETHYLENE; REPLACEMENT; ARTICULATION; REVISION AB Objective To determine comparative safety and effectiveness of combinations of bearing surfaces of hip implants. Design Systematic review of clinical trials, observational studies, and registries. Data sources Medline, Embase, Cochrane Controlled Trials Register, reference lists of articles, annual reports of major registries, summaries of safety and effectiveness for pre-market application and mandated post-market studies at the United States Food and Drug Administration. Study selection Criteria for inclusion were comparative studies in adults reporting information for various combinations of bearings (such as metal on metal and ceramic on ceramic). Data search, abstraction, and analyses were independently performed and confirmed by at least two authors. Qualitative data syntheses were performed. Results There were 3139 patients and 3404 hips enrolled in 18 comparative studies and over 830 000 operations in national registries. The mean age range in the trials was 42-71, and 26-88% were women. Disease specific functional outcomes and general quality of life scores were no different or they favoured patients receiving metal on polyethylene rather than metal on metal in the trials. While one clinical study reported fewer dislocations associated with metal on metal implants, in the three largest national registries there was evidence of higher rates of implant revision associated with metal on metal implants compared with metal on polyethylene. One trial reported fewer revisions with ceramic on ceramic compared with metal on polyethylene implants, but data from national registries did not support this finding. Conclusions There is limited evidence regarding comparative effectiveness of various hip implant bearings. Results do not indicate any advantage for metal on metal or ceramic on ceramic implants compared with traditional metal on polyethylene or ceramic on polyethylene bearings. C1 [Sedrakyan, Art] Weill Cornell Med Coll, New York, NY 10065 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Boston, MA USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Sedrakyan, Art; Dabic, Stefan; Jacobs, Samantha; Marinac-Dabic, Danica] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Graves, Stephen] Univ Melbourne, Melbourne, Vic 3010, Australia. RP Sedrakyan, A (reprint author), Weill Cornell Med Coll, 402 E 67th St,Suite 223, New York, NY 10065 USA. EM ars2013@med.cornell.edu FU US Food and Drug Administration Center for Devices and Radiological Health FX The study is funded by the US Food and Drug Administration Center for Devices and Radiological Health. The authors accept full responsibility for the conduct of the study, had access to the data, and controlled the decision to publish. The opinions expressed in this article are those of the authors and not necessarily those of the Food and Drug Administration. NR 39 TC 23 Z9 24 U1 2 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD NOV 29 PY 2011 VL 343 AR d7434 DI 10.1136/bmj.d7434 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 874EL UT WOS:000298938100007 PM 22127517 ER PT J AU Lee, JJ Liu, ST Nacif, MS Ugander, M Han, J Kawel, N Sibley, CT Kellman, P Arai, AE Bluemke, DA AF Lee, Jason J. Liu, Songtao Nacif, Marcelo S. Ugander, Martin Han, Jing Kawel, Nadine Sibley, Christopher T. Kellman, Peter Arai, Andrew E. Bluemke, David A. TI Myocardial T1 and Extracellular Volume Fraction Mapping at 3 Tesla SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE LA English DT Article ID CARDIOVASCULAR MAGNETIC-RESONANCE; INVERSION-RECOVERY; FIBROSIS; HUMANS; HEART; QUANTIFICATION; RELAXATION; VALIDATION; INFARCTION; FREQUENCY AB Background: To compare 11 heartbeat (HB) and 17 HB modified lock locker inversion recovery (MOLLI) pulse sequence at 3T and to establish preliminary reference values for myocardial T1 and the extracellular volume fraction (ECV). Methods: Both phantoms and normal volunteers were scanned at 3T using 11 HB and 17 HB MOLLI sequence with the following parameters: spatial resolution = 1.75 x 1.75 x 10 mm on a 256 x 180 matrix, TI initial = 110 ms, TI increment = 80 ms, flip angle = 35 degrees, TR/TE = 1.9/1.0 ms. All volunteers were administered Gadolinium-DTPA (Magnevist, 0.15 mmol/kg), and multiple post-contrast MOLLI scans were performed at the same pre-contrast position from 3.5-23.5 minutes after a bolus contrast injection. Late gadolinium enhancement (LGE) images were also acquired 12-30 minutes after the gadolinium bolus. Results: T1 values of 11 HB and 17 HB MOLLI displayed good agreement in both phantom and volunteers. The average pre-contrast myocardial and blood T1 was 1315 +/- 39 ms and 2020 +/- 129 ms, respectively. ECV was stable between 8.5 to 23.5 minutes post contrast with an average of 26.7 +/- 1.0%. Conclusion: The 11 HB MOLLI is a faster method for high-resolution myocardial T1 mapping at 3T. ECV fractions are stable over a wide time range after contrast administration. C1 [Lee, Jason J.; Liu, Songtao; Nacif, Marcelo S.; Kawel, Nadine; Sibley, Christopher T.; Bluemke, David A.] Natl Inst Hlth Clin Ctr, Bethesda, MD 20814 USA. [Liu, Songtao; Sibley, Christopher T.; Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Mol Biomed Imaging Lab, Bethesda, MD USA. [Ugander, Martin; Kellman, Peter; Arai, Andrew E.] NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. [Han, Jing] US FDA, Rockville, MD 20857 USA. RP Bluemke, DA (reprint author), Natl Inst Hlth Clin Ctr, Bethesda, MD 20814 USA. EM bluemked@nih.gov RI Sibley, Christopher/C-9900-2013; OI Bluemke, David/0000-0002-8323-8086; Ugander, Martin/0000-0003-3665-2038 FU NIH FX Research funding was provided by the NIH intramural research program. We thank Jacquin L. Jones, RN for recruiting the volunteers. NR 24 TC 50 Z9 56 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1097-6647 J9 J CARDIOVASC MAGN R JI J. Cardiov. Magn. Reson. PD NOV 28 PY 2011 VL 13 AR 75 DI 10.1186/1532-429X-13-75 PG 10 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 892XC UT WOS:000300317900001 PM 22123333 ER PT J AU Mitkus, RJ King, DB Hess, MA Forshee, RA Walderhaug, MO AF Mitkus, Robert J. King, David B. Hess, Maureen A. Forshee, Richard A. Walderhaug, Mark O. TI Updated aluminum pharmacokinetics following infant exposures through diet and vaccination SO VACCINE LA English DT Article DE Aluminum; Adjuvant; Safety; Pharmacokinetics; Modeling ID AL-26; TOXICOKINETICS; CHILDHOOD; ADJUVANTS; VACCINES; CHILDREN AB Aluminum is a ubiquitous element that is released naturally into the environment via volcanic activity and the breakdown of rocks on the earth's surface. Exposure of the general population to aluminum occurs primarily through the consumption of food, antacids, and buffered analgesics. Exposure to aluminum in the general population can also occur through vaccination, since vaccines often contain aluminum salts (frequently aluminum hydroxide or aluminum phosphate) as adjuvants. Because concerns have been expressed by the public that aluminum in vaccines may pose a risk to infants, we developed an up-to-date analysis of the safety of aluminum adjuvants. Keith et al. [1] previously analyzed the pharmacokinetics of aluminum for infant dietary and vaccine exposures and compared the resulting body burdens to those based on the minimal risk levels (MRLs) established by the Agency for Toxic Substances and Disease Registry. We updated the analysis of Keith et al. [1] with a current pediatric vaccination schedule [2]; baseline aluminum levels at birth; an aluminum retention function that reflects changing glomerular filtration rates in infants; an adjustment for the kinetics of aluminum efflux at the site of injection; contemporaneous MRLs; and the most recent infant body weight data for children 0-60 months of age [3]. Using these updated parameters we found that the body burden of aluminum from vaccines and diet throughout an infant's first year of life is significantly less than the corresponding safe body burden of aluminum modeled using the regulatory MRL We conclude that episodic exposures to vaccines that contain aluminum adjuvant continue to be extremely low risk to infants and that the benefits of using vaccines containing aluminum adjuvant outweigh any theoretical concerns. Published by Elsevier Ltd. C1 [Mitkus, Robert J.; King, David B.; Forshee, Richard A.; Walderhaug, Mark O.] 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. 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 30 TC 23 Z9 24 U1 1 U2 12 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 NOV 28 PY 2011 VL 29 IS 51 BP 9538 EP 9543 DI 10.1016/j.vaccine.2011.09.124 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 868NC UT WOS:000298529000019 PM 22001122 ER PT J AU Bushar, ND Snyder, JT Chakrabarty, S Shen, JJ Chen, Q Ragheb, JA AF Bushar, Nicholas D. Snyder, James T. Chakrabarty, Sagarika Shen, Jijia Chen, Qian Ragheb, Jack A. TI Peripheral blood monocytes, but not resting, activated, or transformed B cells, costimulate early CD40L expression Response SO BLOOD LA English DT Letter ID DIFFERENTIATION C1 [Ragheb, Jack A.] NIAID, Immunol Lab, Div Therapeut Prot, Off Biol Prod,Ctr Drug Evaluat & Res,US FDA,NIH, Bethesda, MD 20892 USA. [Chakrabarty, Sagarika] Scripps Res Inst, La Jolla, CA 92037 USA. [Shen, Jijia] Anhui Med Univ, Hefei, Anhui, Peoples R China. [Chen, Qian] Harvard Univ, Ragon Inst, Boston, MA 02115 USA. RP Ragheb, JA (reprint author), NIAID, Immunol Lab, Div Therapeut Prot, Off Biol Prod,Ctr Drug Evaluat & Res,US FDA,NIH, Bldg 10, Bethesda, MD 20892 USA. EM jr50b@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 24 PY 2011 VL 118 IS 22 BP 5980 EP 5981 DI 10.1182/blood-2011-09-372235 PG 4 WC Hematology SC Hematology GA 855PL UT WOS:000297576600041 ER PT J AU Strauss, DG Mewton, N Verrier, RL Nearing, B Killian, T Marchlinsky, FE Tereshchenko, LG Wu, KC Cox, C Spooner, PM Lima, JA AF Strauss, David G. Mewton, Nathan Verrier, Richard L. Nearing, Bruce Killian, Tony Marchlinsky, Francis E. Tereshchenko, Larisa G. Wu, Katherine C. Cox, Christopher Spooner, Peter M. Lima, Joao A. TI Screening Entire Health System ECG Databases to Identify Patients with Arrhythmogenic Myocardial Substrate at Increased Risk of Death SO CIRCULATION LA English DT Meeting Abstract DE Electrocardiography; Electrophysiology; Sudden cardiac death; Risk factors; Heart disease C1 [Strauss, David G.] US FDA, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Tereshchenko, Larisa G.; Wu, Katherine C.; Spooner, Peter M.; Lima, Joao A.] Johns Hopkins Med Insts, Div Cardiol, Baltimore, MD USA. [Verrier, Richard L.; Nearing, Bruce] Harvard Univ, Sch Med, Beth Israel Deaconess Med Cntr, Boston, MA USA. [Marchlinsky, Francis E.] Hosp Univ Penn, Div Cardiol, Philadelphia, PA 19104 USA. [Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 22 PY 2011 VL 124 IS 21 SU S MA A15548 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 884WE UT WOS:000299738707112 ER PT J AU Strauss, DG Selvester, RH Wagner, GH Loring, ZA Gerstenblith, G Weiss, RG Wu, KC AF Strauss, David G. Selvester, Ronald H. Wagner, Galen H. Loring, Zak A. Gerstenblith, Gary Weiss, Robert G. Wu, Katherine C. TI Right (Not Left) Bundle Branch Block is Associated with Large Anteroseptal Infarcts SO CIRCULATION LA English DT Meeting Abstract DE Electrocardiography; Magnetic resonance imaging; Infarct size; Bi-ventricular pacing; Heart conduction system C1 [Strauss, David G.] US FDA, Cntr Devices & Radiol Hlth, Silver Spring, MD USA. [Selvester, Ronald H.] Mem Hosp Rsch Cntr, Long Beach, CA USA. [Wagner, Galen H.; Loring, Zak A.] Duke Clin Rsch Insitute, Durham, NC USA. [Gerstenblith, Gary; Weiss, Robert G.; Wu, Katherine C.] Johns Hopkins Med Insts, Div Cardiol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 22 PY 2011 VL 124 IS 21 SU S MA A10375 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 884WE UT WOS:000299738702310 ER PT J AU Tavris, D Wang, YF Albrecht-Gallauresi, B Curtis, J Messenger, JC Resnic, FS Fitzgerald, S AF Tavris, Dale Wang, Yongfei Albrecht-Gallauresi, Beverly Curtis, Jeptha Messenger, John C. Resnic, Frederic S. Fitzgerald, Susan TI Bleeding and Vascular Complications at the Femoral Access Site Following Percutaneous Coronary Intervention (PCI): An Evaluation of Hemostasis Strategies SO CIRCULATION LA English DT Meeting Abstract DE Percutaneous coronary intervention; Hemostasis C1 [Tavris, Dale] US FDA, Div Epidemiol, Silver Spring, MD USA. [Wang, Yongfei] Yale Univ, Sch Med, Dept Med, New Haven, CT 06510 USA. [Albrecht-Gallauresi, Beverly] US FDA, Off Womens Hlth, Silver Spring, MD USA. [Curtis, Jeptha] Yale Univ, Sch Med, Cardiol Sect, New Haven, CT USA. Univ Colorado, NA, Aurora, CO USA. [Resnic, Frederic S.] Brigham & Womens Hosp, Div Cardiovasc, Silver Spring, MD USA. [Fitzgerald, Susan] Amer Coll Cardiol, NA, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 22 PY 2011 VL 124 IS 21 SU S MA A16084 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 884WE UT WOS:000299738707293 ER PT J AU Yoon, SS Dillon, C Illoh, K Carroll, M Wright, J AF Yoon, Sung Sug (Sarah) Dillon, Charles Illoh, Kachi Carroll, Margaret Wright, Jacqueline TI Trends In The Prevalence Of Coronary Heart Disease And Congestive Heart Failure Among Adult Population In The U.s.: National Health And Nutrition Examination Survey 2001-2008 SO CIRCULATION LA English DT Meeting Abstract DE Coronary heart disease; Population science; Epidemiology; Heart disease; Myocardial infarction C1 [Yoon, Sung Sug (Sarah); Dillon, Charles; Carroll, Margaret; Wright, Jacqueline] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Illoh, Kachi] US FDA, Div Neurol Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 22 PY 2011 VL 124 IS 21 SU S MA A9720 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 884WE UT WOS:000299738702107 ER PT J AU Klein, NP Gidudu, J Qiang, YD Pahud, B Rowhani-Rahbar, A Baxter, R Dekker, CL Edwards, KM Halsey, NA LaRussa, P Marchant, C Tokars, JI DeStefano, F AF Klein, Nicola P. Gidudu, Jane Qiang, Yandong Pahud, Barbara Rowhani-Rahbar, Ali Baxter, Roger Dekker, Cornelia L. Edwards, Kathryn M. Halsey, Neal A. LaRussa, Philip Marchant, Colin Tokars, Jerome I. DeStefano, Frank TI Developing the next generation of vaccinologists SO VACCINE LA English DT Letter ID IMMUNIZATION SAFETY; VARICELLA VACCINE; DISEASE C1 [Klein, Nicola P.; Rowhani-Rahbar, Ali; Baxter, Roger] Kaiser Permanente, Vaccine Study Ctr, Oakland, CA 94612 USA. [Qiang, Yandong] US FDA, Ctr Biol Evaluat & Review, Rockville, MD 20857 USA. [Pahud, Barbara] Univ Missouri, Childrens Mercy Hosp & Clin, Kansas City, MO 64110 USA. [Dekker, Cornelia L.] Stanford Univ, Sch Med, Stanford LPCH Vaccine Program, Stanford, CA 94305 USA. [Edwards, Kathryn M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Halsey, Neal A.] Johns Hopkins Bloomberg Sch Publ Hlth, Inst Vaccine Safety, Baltimore, MD USA. [LaRussa, Philip] Columbia Univ, Coll Phys & Surg, New York, NY USA. [Marchant, Colin] Boston Univ, Sch Med, Boston, MA 02118 USA. [Tokars, Jerome I.; DeStefano, Frank] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. RP Klein, NP (reprint author), Kaiser Permanente, Vaccine Study Ctr, Oakland, CA 94612 USA. EM Nicola.Kein@kp.org NR 14 TC 1 Z9 1 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 NOV 21 PY 2011 VL 29 IS 50 BP 9296 EP 9297 DI 10.1016/j.vaccine.2011.04.017 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 858ED UT WOS:000297777800005 PM 21510995 ER PT J AU Chen, ML Shah, VP Crommelin, DJ Shargel, L Bashaw, D Bhatti, M Blume, H Dressman, J Ducharme, M Fackler, P Hyslop, T Lutter, L Morais, J Ormsby, E Thomas, S Tsang, YC Velagapudi, R Yu, LX AF Chen, Mei-Ling Shah, Vinod P. Crommelin, Daan J. Shargel, Leon Bashaw, Dennis Bhatti, Masood Blume, Henning Dressman, Jennifer Ducharme, Murray Fackler, Paul Hyslop, Terry Lutter, Lorelei Morais, Jose Ormsby, Eric Thomas, Saji Tsang, Yu Chung Velagapudi, Raja Yu, Lawrence X. TI Harmonization of Regulatory Approaches for Evaluating Therapeutic Equivalence and Interchangeability of Multisource Drug Products: Workshop summary report SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Harmonization; Interchangeability; Regulatory standards; Bioequivalence; Therapeutic equivalence; Biopharmaceutics classification system ID HIGHLY VARIABLE DRUGS; BIOEQUIVALENCE AB Regulatory approaches for evaluating therapeutic equivalence of multisource (or generic) drug products vary among different countries and/or regions. Harmonization of these approaches may decrease the number of in vivo bioequivalence studies and avoid unnecessary drug exposure to humans. Global harmonization for regulatory requirements may be promoted by a better understanding of factors underlying product performance and expectations from different regulatory authorities. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on current regulatory issues and industry practices, facilitating harmonization of regulatory approaches for establishing therapeutic equivalence and interchangeability of multisource drug products. Published by Elsevier B.V. C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Shah, Vinod P.] Int Pharmaceut Federat FIP, The Hague, Netherlands. [Crommelin, Daan J.] Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. [Dressman, Jennifer] Goethe Univ Frankfurt, D-6000 Frankfurt, Germany. [Fackler, Paul] Merck Res Labs, Rahway, NJ 07055 USA. [Hyslop, Terry] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Morais, Jose] Univ Lisbon, P-1699 Lisbon, Portugal. [Tsang, Yu Chung] Apotex Inc, Toronto, ON, Canada. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 4108, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Fachbereich14, Dekanat/C-8553-2015; iMed.ULisboa, iMed.ULisboa/C-6292-2014; iMed.ULisboa, PharmRegSci /B-5723-2014; Morais, Jose/E-6322-2014 OI iMed.ULisboa, PharmRegSci /0000-0003-0910-7245; Morais, Jose/0000-0002-0007-3299 NR 24 TC 5 Z9 5 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD NOV 20 PY 2011 VL 44 IS 4 BP 506 EP 513 DI 10.1016/j.ejps.2011.09.010 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 864BY UT WOS:000298213200008 PM 21946259 ER PT J AU Gormley, NJ Wilder, J Khuu, H Pantin, J Donohue, T Kurlander, R Ito, S Battiwalla, M Barrett, AJ Grasmeder, S Cook, L Ramos, C Prince, P Stroncek, D Flegel, WA Berg, M Reger, R Bolan, CD Adams, S Childs, R AF Gormley, Nicole J. Wilder, Jennifer Khuu, Hahn Pantin, Jeremy Donohue, Theresa Kurlander, Roger Ito, Sawa Battiwalla, Minoo Barrett, A. John Grasmeder, Sophie Cook, Lisa Ramos, Catalina Prince, Patricia Stroncek, David Flegel, Willy A. Berg, Maria Reger, Robert Bolan, Charles D., Jr. Adams, Sharon Childs, Richard TI Co-Infusion of Allogeneic Cord Blood with Haploidentical CD34+Cells Improved Transplant Outcome for Patients with Severe Aplastic Anemia Undergoing Cord Blood Transplantation SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Gormley, Nicole J.] Fed Drug Adm, Off Oncol Drug Prod, Silver Spring, MD USA. [Wilder, Jennifer] SAIC, Clin Res Directorate CMRP, Frederick, MD USA. [Khuu, Hahn; Stroncek, David; Flegel, Willy A.; Adams, Sharon] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. [Pantin, Jeremy; Donohue, Theresa; Ito, Sawa; Battiwalla, Minoo; Barrett, A. John; Grasmeder, Sophie; Cook, Lisa; Ramos, Catalina; Berg, Maria; Reger, Robert; Bolan, Charles D., Jr.; Childs, Richard] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Kurlander, Roger] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 299 EP 299 PG 1 WC Hematology SC Hematology GA 882XL UT WOS:000299597100655 ER PT J AU Xu, F Gelderman-Fuhrmann, M Farrell, J Vostal, J AF Xu, Fei Gelderman-Fuhrmann, Monique Farrell, John Vostal, Jaroslav TI Temperature Cycling Improves In Vivo recovery of Cold Stored Human Platelets SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Xu, Fei; Gelderman-Fuhrmann, Monique; Farrell, John; Vostal, Jaroslav] FDA CBER OBRR, Lab Cellular Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 327 EP 327 PG 1 WC Hematology SC Hematology GA 882XL UT WOS:000299597100721 ER PT J AU Belcher, JD Nguyen, J Chen, CS Smith, A Alayash, AI Nair, SL Somani, A Hebbel, RP Vercellotti, GM AF Belcher, John D. Nguyen, Julia Chen, Chunsheng Smith, Ann Alayash, Abdu I. Nair, Sethu L. Somani, Arif Hebbel, Robert P. Vercellotti, Gregory M. TI Plasma Hemoglobin and Heme Trigger Weibel Palade Body Exocytosis and Vaso-Occlusion in Transgenic Sickle Mice SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Vercellotti, Gregory M.] Univ Minnesota, Hematol Oncol Transplantat Div, Minneapolis, MN USA. [Alayash, Abdu I.] FDA Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD USA. [Smith, Ann] Univ Missouri KC, Div Mol Biol & Biochem, Sch Biol Sci, Kansas City, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 409 EP 410 PG 2 WC Hematology SC Hematology GA 882XL UT WOS:000299597101167 ER PT J AU Pandey, GS Garfield, S Curran, JE Moses, EK Kimchi-Sarfaty, C Yanover, C Howard, TE Sauna, ZE AF Pandey, Gouri Shankar Garfield, Susan Curran, Joanne E. Moses, Eric K. Kimchi-Sarfaty, Chava Yanover, Chen Howard, Tom E. Sauna, Zuben E. TI The Entire Primary Sequence of Factor VIII Is Synthesized As Two Polypeptide Chains in Hemophilia A Patients with the Intron-22-Inversion SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Pandey, Gouri Shankar] US FDA, Lab Hemostasis, DH CBER, Bethesda, MD 20014 USA. [Garfield, Susan] NCI, NIH, Bethesda, MD 20892 USA. [Curran, Joanne E.] SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. [Kimchi-Sarfaty, Chava; Sauna, Zuben E.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 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, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 531 EP 532 PG 2 WC Hematology SC Hematology GA 882XL UT WOS:000299597101445 ER PT J AU Tseng, SC Katagiri, NH Simhadri, VL Jha, S Edwards, NC Kopelman, DB Sauna, ZE Stern, MZ Zichel, R Komar, AA Kimchi-Sarfaty, C AF Tseng, Sandra C. Katagiri, Nobuko H. Simhadri, Vijaya L. Jha, Sujata Edwards, Nathan C. Kopelman, David B. Sauna, Zuben E. Stern, Michael Z. Zichel, Ran Komar, Anton A. Kimchi-Sarfaty, Chava TI Single and Codon-Optimized Synonymous Mutations in Factor IX Alter Protein Properties SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Tseng, Sandra C.; Katagiri, Nobuko H.; Simhadri, Vijaya L.; Edwards, Nathan C.; Kopelman, David B.; Sauna, Zuben E.; Stern, Michael Z.; Zichel, Ran; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. [Jha, Sujata; Komar, Anton A.] Cleveland State Univ, Cleveland, OH 44115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 534 EP 535 PG 2 WC Hematology SC Hematology GA 882XL UT WOS:000299597101454 ER PT J AU Gourley, MJ Shestopal, SA Lee, TK Ovanesov, MV AF Gourley, Merek J. Shestopal, Svetlana A. Lee, Timothy K. Ovanesov, Mikhail V. TI Development of a Continuous Thrombin Generation-Based Test to Measure Potency in Factor VIII Concentrates SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Gourley, Merek J.; Shestopal, Svetlana A.; Lee, Timothy K.; Ovanesov, Mikhail V.] US FDA, CBER, Off Blood Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 542 EP 543 PG 2 WC Hematology SC Hematology GA 882XL UT WOS:000299597101475 ER PT J AU Shestopal, SA Kurasawa, JH Lee, TK Sarafanov, AG AF Shestopal, Svetlana A. Kurasawa, James H. Lee, Timothy K. Sarafanov, Andrey G. TI Expression of the Light Chain of Coagulation Factor VIII in Insect Cells SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Shestopal, Svetlana A.; Kurasawa, James H.; Lee, Timothy K.; Sarafanov, Andrey G.] US FDA, Off Blood Res & Review, CBER, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 985 EP 985 PG 1 WC Hematology SC Hematology GA 882XL UT WOS:000299597103136 ER PT J AU Shim, YK Rachel, J Ghia, P Boren, J Dagklis, A Venable, G Abbasi, F Plapp, F Vogt, R Menitove, JE Marti, G AF Shim, Youn K. Rachel, Jane Ghia, Paolo Boren, Jeff Dagklis, Antonis Venable, Geri Abbasi, Fatima Plapp, Fred Vogt, Robert Menitove, Jay E. Marti, Gerald TI Monoclonal B-Cell Lymphocytosis (MBL) in Blood Donors: Age- and Sex-Specific Prevalence, Clone Size, and IGHV-IGHD-IGHJ Rearrangements SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Shim, Youn K.] Agcy Tox Subst & Dis Registry, Div Hlth Sci, Atlanta, GA USA. [Rachel, Jane; Boren, Jeff; Plapp, Fred] St Lukes Hosp, Kansas City, MO USA. [Ghia, Paolo; Dagklis, Antonis] Univ Vita Salute San Raffaele, Div Mol Oncol, Milan, Italy. [Ghia, Paolo; Dagklis, Antonis] Univ Vita Salute San Raffaele, Dept Oncohematol, Milan, Italy. [Ghia, Paolo; Dagklis, Antonis] Ist Sci San Raffaele, Milan, Italy. [Venable, Geri; Menitove, Jay E.] Community Blood Ctr, Kansas City, MO USA. [Abbasi, Fatima] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Vogt, Robert] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA USA. [Marti, Gerald] US FDA, Off Vitro Diagnost Device Evaluat & Safety, Div Immunol & Hematol Devices, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 1224 EP 1225 PG 2 WC Hematology SC Hematology GA 882XL UT WOS:000299597104191 ER PT J AU Cokic, VP Mossuz, P Han, J Diklic, M Budec, M Sefer, D Lekovic, D Antic, D Brekovic, T Mojsilovic, S Puri, RK Noguchi, CT Schechter, AN AF Cokic, Vladan P. Mossuz, Pascal Han, Jing Diklic, Milos Budec, Mirela Sefer, Dijana Lekovic, Danijela Antic, Darko Brekovic, Tijana Mojsilovic, Sonja Puri, Raj K. Noguchi, Constance Tom Schechter, Alan N. TI Microarray and Proteomic Analysis of Myeloproliferative Neoplasms SO BLOOD LA English DT Meeting Abstract CT 53rd Annual Meeting and Exposition of the American-Society-of-Hematology (ASH)/Symposium on the Basic Science of Hemostasis and Thrombosis CY DEC 10-13, 2011 CL San Diego, CA SP Amer Soc Hematol (ASH) C1 [Cokic, Vladan P.; Diklic, Milos] Univ Belgrade, Inst Med Res, Lab Expt Hematol, Belgrade, Serbia. [Mossuz, Pascal] CHU Grenoble, Inst Biol & Pathol, Lab Hematol Cellulaire & Mol, F-38043 Grenoble, France. [Han, Jing; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Budec, Mirela; Brekovic, Tijana] Univ Belgrade, Inst Med Res, Lab Pathol & Cytol, Belgrade, Serbia. [Sefer, Dijana; Lekovic, Danijela; Antic, Darko] Univ Belgrade, Clin Ctr Serbia, Clin Hematol, Belgrade, Serbia. [Mojsilovic, Sonja] Univ Belgrade, Inst Med Res, Immunol Lab, Belgrade, Serbia. [Noguchi, Constance Tom; Schechter, Alan N.] NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 18 PY 2011 VL 118 IS 21 BP 1649 EP 1649 PG 1 WC Hematology SC Hematology GA 882XL UT WOS:000299597106026 ER PT J AU Yu, LR AF Yu, Li-Rong TI Pharmacoproteomics and toxicoproteomics: The field of dreams SO JOURNAL OF PROTEOMICS LA English DT Editorial Material DE Pharmacoproteomics; Toxicoproteomics; Drug development; Mechanism of action; Biomarker; Nanotechnology ID PERSONALIZED MEDICINE; KINASE INHIBITORS; DRUG DEVELOPMENT; PROTEOMICS; BIOMARKERS; TARGETS; TOXICOLOGY; TOXICITY; IDENTIFICATION; MECHANISMS C1 US FDA, Ctr Excellence Prote, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, LR (reprint author), US FDA, Ctr Excellence Prote, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 233, Jefferson, AR 72079 USA. EM Lirong.Yu@fda.hhs.gov NR 43 TC 9 Z9 10 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD NOV 18 PY 2011 VL 74 IS 12 BP 2549 EP 2553 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 865IZ UT WOS:000298305900001 PM 22015715 ER PT J AU Li, JN Kelm, KB Tezak, Z AF Li, Jinong Kelm, Kellie B. Tezak, Zivana TI Regulatory perspective on translating proteomic biomarkers to clinical diagnostics SO JOURNAL OF PROTEOMICS LA English DT Review DE Food and Drug Administration; In vitro diagnostics; Device regulation; Proteomics; Mass spectrometry; Complex tests ID MASS-SPECTROMETRIC QUANTITATION; C-REACTIVE PROTEIN; HUMAN PLASMA; AFFINITY-CHROMATOGRAPHY; TARGETED PROTEOMICS; ABUNDANCE PROTEINS; ISOTOPE-DILUTION; ION-TRAP; QUANTIFICATION; ASSAYS AB Issues associated with the translation of complex proteomic biomarkers from discovery to clinical diagnostics have been widely discussed among academic researchers, government agencies, as well as assay and instrumentation manufacturers. Here, we provide an overview of the regulatory framework and type of information that is typically required in order to evaluate in vitro diagnostic tests regulated by the Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD) at the US Food and Drug Administration (FDA), with the focus on some of the issues specific to protein-based complex tests. Technological points pertaining to mass spectrometry platforms and assessment of potential concerns important for assurance of safety and effectiveness of this type of assays when introduced into clinical diagnostic use, as well as general approaches for evaluating the performance of these devices, are discussed. Published by Elsevier B.V. C1 [Li, Jinong] US FDA, FDA CDRH OlVD DCTD, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Li, JN (reprint author), US FDA, FDA CDRH OlVD DCTD, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66,G454, Silver Spring, MD 20993 USA. EM Jinong.li@fda.hhs.gov NR 38 TC 17 Z9 17 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD NOV 18 PY 2011 VL 74 IS 12 BP 2682 EP 2690 DI 10.1016/j.jprot.2011.07.028 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 865IZ UT WOS:000298305900010 PM 21856459 ER PT J AU Gao, Y Gopee, NV Howard, PC Yu, LR AF Gao, Yuan Gopee, Neera V. Howard, Paul C. Yu, Li-Rong TI Proteomic analysis of early response lymph node proteins in mice treated with titanium dioxide nanoparticles SO JOURNAL OF PROTEOMICS LA English DT Article DE Proteomics; Mass spectrometry; TiO(2) nanoparticle; Mouse lymph node; (16)O/(18)O labeling; LC-MS/MS ID QUANTUM DOTS; GEL-ELECTROPHORESIS; TIO2 NANOPARTICLES; SURFACE-PROPERTIES; MASS-SPECTROMETRY; BACK-EXCHANGE; PPAR-GAMMA; IN-VIVO; TOXICITY; EXPOSURE AB Human exposure to nanoparticles is inevitable from natural and anthropogenic sources. Titanium dioxide (TiO(2)) nanoparticles are increasingly being used in pharmaceutical and cosmetic products. Previous studies revealed that TiO(2) levels were significantly increased in tissues (e.g., lymph nodes) after mice were injected with nanosized TiO(2). To identify early response lymph node proteins to TiO(2) nanoparticles, groups of mice were intradermally injected with a low dose of DeGussa P25 TiO(2) nanoparticles or vehicle alone. The proteomes of lymph nodes at 24 h were quantitatively analyzed using trypsin-catalyzed (16)O/(18)O labeling in conjunction with two-dimensional liquid chromatography separation and tandem mass spectrometry (2DLC-MS/MS). A total of 33 proteins were significantly changed (over 1.3-fold, p < 0.05) in the mice treated with TiO(2) nanoparticles, which accounted for approximately 1% of the total proteins identified. The differentially expressed proteins mainly involve the immune response (e.g., inflammation), lipid and fatty acid metabolism, mRNA processing, and nucleosome assembly. Regulation of functionally distinct classes of proteins could be mediated by estrogen receptor (ESR1), PPAR-gamma, and c-Myc signalings, etc. The differentially expressed proteins identified in this experiment could represent early response proteins to TiO(2) nanoparticle treatment in mouse lymph nodes. Published by Elsevier B.V. C1 [Gao, Yuan; Yu, Li-Rong] US FDA, Ctr Excellence Prote, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Gopee, Neera V.] US FDA, Div Vet Serv, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Howard, Paul C.] US FDA, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Howard, Paul C.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, LR (reprint author), US FDA, Ctr Excellence Prote, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd,HFT 233, Jefferson, AR 72079 USA. EM Paul.Howard@fda.hhs.gov; Lirong.Yu@fda.hhs.gov FU National Center for Toxicological Research, U.S. Food and Drug Administration (NCTR/FDA); FDA [FDA 224-07-0007]; NIEHS [NIH Y1ES1027] FX We are grateful to Dr. Donna Mendrick for critical reading and comments on this manuscript. This study was supported in part with funds from National Center for Toxicological Research, U.S. Food and Drug Administration (NCTR/FDA) and through an interagency agreement between the FDA and the National Toxicology Program at NIEHS (FDA 224-07-0007, NIH Y1ES1027). The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 64 TC 19 Z9 19 U1 2 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-3919 J9 J PROTEOMICS JI J. Proteomics PD NOV 18 PY 2011 VL 74 IS 12 BP 2745 EP 2759 DI 10.1016/j.jprot.2011.08.009 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 865IZ UT WOS:000298305900016 PM 21884834 ER PT J AU Xiao, YM Word, B Hammons, G Lyn-Cook, B AF Xiao, Yongmei Word, Beverly Hammons, George Lyn-Cook, Beverly TI Transcriptional activity of DNMT3B in pancreatic cancer cells: Effects of-149 (C -> T) promoter polymorphism SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE DNMT3B polymorphism; Transcriptional activity; Pancreatic cancer ID DNA METHYLATION; HEPATOCELLULAR-CARCINOMA; LUNG-CANCER; RISK; POPULATION; METHYLTRANSFERASES; EPIGENETICS; EXPRESSION; AGE AB Polymorphic C-to-T change in the promoter region of DNA-methyltransferase-3B (DNMT3B) gene is associated with risk of several cancers. The aim of this study was to investigate the effect of DNMT3B promoter genetic variant on its transcriptional activity and to compare activity in several pancreatic cell lines. DNMT3B promoter constructs carrying either -149C allele or -149T allele were transiently transfected into pancreatic cancer cells. In promoter assaying, carriage of -149T allele showed only a slight activity (1.1-fold) in Mia cells (p = 0.462). In contrast, significant increase (3.8-fold) in activity of -149T allele was shown in SU86.86 pancreatic cancer cells (p = 0.0001). These preliminary findings suggest that genetic variance may influence DNMT3B expression in pancreatic cancer. Further studies are needed. Published by Elsevier Inc. C1 [Xiao, Yongmei; Word, Beverly; Hammons, George; Lyn-Cook, Beverly] Natl Ctr Toxicol Res, Off Regulatory Act, Jefferson, AR 72079 USA. RP Lyn-Cook, B (reprint author), Natl Ctr Toxicol Res, Off Regulatory Act, Jefferson, AR 72079 USA. EM Beverly.lyn-cook@fda.hhs.gov NR 24 TC 3 Z9 3 U1 1 U2 4 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 NOV 18 PY 2011 VL 415 IS 2 BP 220 EP 223 DI 10.1016/j.bbrc.2011.07.115 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 855AB UT WOS:000297534800002 PM 21854760 ER PT J AU Zhang, XL Bull, RJ Fisher, J Cotruvo, JA Cummings, BS AF Zhang, Xiaoling Bull, Richard J. Fisher, Jeffery Cotruvo, Joseph A. Cummings, Brian S. TI The synergistic effect of sodium chlorite and bromochloroacetic acid on BrO3--induced renal cell death SO TOXICOLOGY LA English DT Article DE Bromate; Kidney; Cell death; Cell cycle arrest; Disinfection by-products; p21 ID DISINFECTION BY-PRODUCTS; POTASSIUM BROMATE; DNA-DAMAGE; DRINKING-WATER; OXIDATIVE STRESS; GENE-EXPRESSION; REACTIVE OXYGEN; HEK293 CELLS; RAT-KIDNEY; F344 RATS AB Bromate (BrO3-) is a drinking water disinfection by-product (DBP) that induces renal cell death via DNA damage-dependent and -independent mechanisms. Drinking water contains other DBPs in addition to BrO3-. We tested the effect of two of these, sodium chlorite (NaClO2) and bromochloroacetic acid (BCAA), on BrO3- cytotoxicity in normal rat kidney (NRK) cells. NaClO2 and BCAA alone induced cytotoxicity at concentrations of over 20 ppm, while BrO3- was only moderately cytotoxic at concentrations of 200 ppm. Combining BrO3- with NaClO2 or BCAA alone enhanced cytotoxicity 1.5-4 fold. Exposing cells to all three compounds induced synergistic-like increases in cytotoxicity. This effect did not correlate to increases in reactive oxygen species (ROS), even though all three compounds induced ROS formation alone. NaClO2, but not BCAA, increased BrO3--mediated DNA damage as measured by 8-hydroxydeoxyguanosine (8-OHdG) staining. In addition, NaClO2, but not BCAA, decreased BrO3--induced G2/M cell cycle arrest. Both compounds increased apoptosis in the presence of BrO3- as assessed by annexin V, PI, and DAPI staining. This is in contrast to BrO3- treatment alone, which induced necrosis. Immunoblot analysis showed that both NaClO2 and BCAA increased p38 activation; however, consistent with 8-OHdG staining, only NaClO2 increased BrO3--induced histone H2AX phosphorylation, a marker of DNA damage. In contrast, BCAA, but not NaClO2, increased BrO3--induced phosphorylation of p53. These data support the novel finding that mixtures of DBPs increase BrO3--induced renal cell death by DNA-dependent and -independent mechanisms, and could alter how the risk of these DBPs towards humans is assessed. (C) 2011 Elsevier Ireland Ltd. All rights reserved. C1 [Zhang, Xiaoling; Cummings, Brian S.] Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, Athens, GA 30602 USA. [Bull, Richard J.] Mo Bull Consulting, Richland, WA USA. [Fisher, Jeffery] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Cotruvo, Joseph A.] Joseph Cotruvo & Associates LLC, Washington, DC USA. RP Cummings, BS (reprint author), Univ Georgia, Coll Pharm, Dept Pharmaceut & Biomed Sci, 336 Pharm S, Athens, GA 30602 USA. EM bsc@rx.uga.edu FU Water Research Foundation [4042]; Georgia Cancer Coalition; Joseph Cotruvo Associates LLC; International Ozone Assoc.; Environment Agency of Abu Dhabi; Veolia Water; Metropolitan Water District of Southern Calif.; Los Angeles Department of Water and Power; National Water Research Institute; Walkerton Clean Water Centre; Calleguas Municipal Water District; Long Beach Water Department FX The authors thank Dr. Robert D. Arnold for use of his Nikon AZ100 fluorescence microscope. We also thank Mr. Narendrababu Kolisetty and Krelin Nadu for their help in preparing this manuscript. This work was supported by the Georgia Cancer Coalition and Joseph Cotruvo & Associates LLC with grants from the Water Research Foundation Project #4042 - International Ozone Assoc., Environment Agency of Abu Dhabi, Veolia Water, Metropolitan Water District of Southern Calif., Los Angeles Department of Water and Power, National Water Research Institute, Walkerton Clean Water Centre, Calleguas Municipal Water District, Long Beach Water Department, and in-kind contributions of the participants. We gratefully acknowledge and thank the Water Research Foundation and all of the sponsors for their financial, technical and administrative assistance in funding the project through which this information was discovered. NR 37 TC 10 Z9 11 U1 2 U2 10 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD NOV 18 PY 2011 VL 289 IS 2-3 BP 151 EP 159 DI 10.1016/j.tox.2011.08.008 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 833OS UT WOS:000295895400010 PM 21864635 ER PT J AU Fisher, JW Twaddle, NC Vanlandingham, M Doerge, DR AF Fisher, Jeffrey W. Twaddle, Nathan C. Vanlandingham, Michelle Doerge, Daniel R. TI Pharmacokinetic modeling: Prediction and evaluation of route dependent dosimetry of bisphenol A in monkeys with extrapolation to humans SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Bisphenol A; PBPK modeling; Kinetics; Monkey; Human ID SPRAGUE-DAWLEY RATS; RHESUS-MONKEY; IN-VITRO; CHILDREN YOUNGER; PROTEIN-BINDING; SMALL-INTESTINE; CARDIAC OUTPUT; GLUCURONIDATION; METABOLISM; ABSORPTION AB A physiologically based pharmacokinetic (PBPK) model was developed for bisphenol A (BPA) in adult rhesus monkeys using intravenous (iv) and oral bolus doses of 100 mu g d6-BPA/kg (Doerge et al., 2010). This calibrated PBPK adult monkey model for BPA was then evaluated against published monkey kinetic studies with BPA. Using two versions of the adult monkey model based on monkey BPA kinetic data from Doerge et al. (2010) and Taylor et al. (2011), the aglycone BPA pharmacokinetics were simulated for human oral ingestion of 5 mg d16-BPA per person (Volkel et al., 2002). Volkel et al. were unable to detect the aglycone BPA in plasma, but were able to detect BPA metabolites. These human model predictions of the aglycone BPA in plasma were then compared to previously published PBPK model predictions obtained by simulating the Volkel et al. kinetic study. Our BPA human model, using two parameter sets reflecting two adult monkey studies, both predicted lower aglycone levels in human serum than the previous human BPA PBPK model predictions. BPA was metabolized at all ages of monkey (PND 5 to adult) by the gut wall and liver. However, the hepatic metabolism of BPA and systemic clearance of its phase II metabolites appear to be slower in younger monkeys than adults. The use of the current non-human primate BPA model parameters provides more confidence in predicting the aglycone BPA in serum levels in humans after oral ingestion of BPA. Published by Elsevier Inc. C1 [Fisher, Jeffrey W.; Twaddle, Nathan C.; Vanlandingham, Michelle; Doerge, Daniel R.] Natl Ctr Toxicol Res, Food & Drug Adm, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fisher, JW (reprint author), Natl Ctr Toxicol Res, Food & Drug Adm, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jeffrey.fisher@fda.hhs.gov NR 60 TC 47 Z9 47 U1 0 U2 22 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 NOV 15 PY 2011 VL 257 IS 1 BP 122 EP 136 DI 10.1016/j.taap.2011.08.026 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 855YV UT WOS:000297603100014 PM 21920375 ER PT J AU Nakashima, H Terabe, M Berzofsky, JA Husain, SR Puri, RK AF Nakashima, Hideyuki Terabe, Masaki Berzofsky, Jay A. Husain, Syed R. Puri, Raj K. TI A Novel Combination Immunotherapy for Cancer by IL-13R alpha 2-Targeted DNA Vaccine and Immunotoxin in Murine Tumor Models SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELOID SUPPRESSOR-CELLS; RECEPTOR-ALPHA CHAIN; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; T-CELLS; CHEMOKINE; IMMUNITY; PROTEIN; EXPRESSION; CARCINOMA AB Optimum efficacy of therapeutic cancer vaccines may require combinations that generate effective antitumor immune responses, as well as overcome immune evasion and tolerance mechanisms mediated by progressing tumor. Previous studies showed that IL-13R alpha 2, a unique tumor-associated Ag, is a promising target for cancer immunotherapy. A targeted cytotoxin composed of IL-13 and mutated Pseudomonas exotoxin induced specific killing of IL-13Ra2(+) tumor cells. When combined with IL-13R alpha 2 DNA cancer vaccine, surprisingly, it mediated synergistic antitumor effects on tumor growth and metastasis in established murine breast carcinoma and sarcoma tumor models. The mechanism of synergistic activity involved direct killing of tumor cells and cell-mediated immune responses, as well as elimination of myeloid-derived suppressor cells and, consequently, regulatory T cells. These novel results provide a strong rationale for combining immunotoxins with cancer vaccines for the treatment of patients with advanced cancer. The Journal of Immunology, 2011, 187: 4935-4946. C1 [Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,US Food & Drug Adm, Bethesda, MD 20892 USA. [Terabe, Masaki; Berzofsky, Jay A.] NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,US Food & Drug Adm, Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov FU Intramural NIH HHS [Z99 OD999999] NR 46 TC 12 Z9 13 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 NOV 15 PY 2011 VL 187 IS 10 BP 4935 EP 4946 DI 10.4049/jimmunol.1102095 PG 12 WC Immunology SC Immunology GA 844SJ UT WOS:000296767300002 PM 22013118 ER PT J AU Chaimowitz, NS Martin, RK Cichy, J Gibb, DR Patil, P Kang, DJ Farnsworth, J Butcher, EC McCright, B Conrad, DH AF Chaimowitz, Natalia S. Martin, Rebecca K. Cichy, Joanna Gibb, David R. Patil, Pooja Kang, Dae-Joong Farnsworth, Julie Butcher, Eugene C. McCright, Brent Conrad, Daniel H. TI A Disintegrin and Metalloproteinase 10 Regulates Antibody Production and Maintenance of Lymphoid Architecture SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; CXC CHEMOKINE LIGAND-13; GERMINAL CENTER B; T-CELLS; AUTOIMMUNE-DISEASE; ACCESSORY CELLS; ADAM10; CD23; MICE AB A disintegrin and metalloproteinase 10 (ADAM10) is a zinc-dependent proteinase related to matrix metalloproteinases. ADAM10 has emerged as a key regulator of cellular processes by cleaving and shedding extracellular domains of multiple transmembrane receptors and ligands. We have developed B cell-specific ADAM10-deficient mice (ADAM10(B-/-)). In this study, we show that ADAM10 levels are significantly enhanced on germinal center B cells. Moreover, ADAM10(B-/-) mice had severely diminished primary and secondary responses after T-dependent immunization. ADAM10(B-/-) displayed impaired germinal center formation, had fewer follicular Th cells, decreased follicular dendritic cell networks, and altered chemokine expression in draining lymph nodes (LNs). Interestingly, when spleen and LN structures from immunized mice were analyzed for B and T cell localization, tissues structure was aberrant in ADAM10(B-/-) mice. Importantly, when ADAM10-deficient B cells were stimulated in vitro, they produced comparable Ab as wild type B cells. This result demonstrates that the defects in humoral responses in vivo result from inadequate B cell activation, likely because of the decrease in follicular Th cells and the changes in structure. Thus, ADAM10 is essential for the maintenance of lymphoid structure after Ag challenge. The Journal of Immunology, 2011, 187: 5114-5122. C1 [Chaimowitz, Natalia S.; Martin, Rebecca K.; Gibb, David R.; Patil, Pooja; Kang, Dae-Joong; Conrad, Daniel H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA. [Cichy, Joanna] Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, PL-30387 Krakow, Poland. [Farnsworth, Julie] Virginia Commonwealth Univ, Massey Canc Ctr Flow Cytometry Core, Sch Med, Richmond, VA 23298 USA. [Butcher, Eugene C.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA. [McCright, Brent] US FDA, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Conrad, DH (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, 1217 E Marshall St,MSB 419-430, Richmond, VA 23298 USA. EM dconrad@vcu.edu FU National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases [RO1AI19697, U19AI077435]; American Heart Association [11PRE7600119]; Fogarty International Research Collaborative Award [R03TW007174-01]; Ministry of Scientific Research, Poland [N N401 003635]; NIH/National Cancer Institute [P30 CA16059]; NIH/National Institute of Neurological Disorders and Stroke Center Core [5P30S047463] FX This work was supported by National Institutes of Health (NIH)/National Institute of Allergy and Infectious Diseases Grants RO1AI19697 and U19AI077435, Project 2 (to D.C.), American Heart Association Award 11PRE7600119 (to N.S.C.), Fogarty International Research Collaborative Award R03TW007174-01 (to E.C.B. and J.C.), and the Ministry of Scientific Research, Poland Grant N N401 003635 (to J.C.). Flow cytometry and imaging studies were supported by NIH/National Cancer Institute Grant P30 CA16059 to the Massey Cancer Center. Microscopy was supported, in part, with funding from NIH/National Institute of Neurological Disorders and Stroke Center Core Grant 5P30S047463. NR 48 TC 12 Z9 12 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 NOV 15 PY 2011 VL 187 IS 10 BP 5114 EP 5122 DI 10.4049/jimmunol.1102172 PG 9 WC Immunology SC Immunology GA 844SJ UT WOS:000296767300020 PM 21998451 ER PT J AU Abraham, B Hicks, W Jia, YP Baek, JH Miller, JL Alayash, AI AF Abraham, Bindu Hicks, Wayne Jia, Yiping Baek, Jin Hyen Miller, Jeffery L. Alayash, Abdu I. TI Isolated Hb Providence beta 82Asn and beta 82Asp Fractions Are More Stable than Native HbA(0) under Oxidative Stress Conditions SO BIOCHEMISTRY LA English DT Article ID HUMAN HEMOGLOBIN; HYDROGEN-PEROXIDE; BLOOD SUBSTITUTES; ESCHERICHIA-COLI; OXYGEN-TRANSPORT; NITRIC-OXIDE; MYOGLOBIN; HEME; BINDING; STABILITY AB We have previously shown that hydrogen peroxide (H2O2) triggers irreversible oxidation of amino acids exclusive to the beta-chains of purified human hemoglobin (HbAo). However, it is not clear, whether alpha- or beta-subunit Hb variants exhibit different oxidative resistance to H2O2 when compared to their native HbAo. Hb Providence contains two beta-subunit variants with single amino acid mutations at beta Lys82 -> Asp (beta K82D) and at beta Lys82 -> Asn (beta K82N) positions and binds oxygen at lower affinity than wild type HbA. We have separated Hb Providence into its 3 component fractions, and contrasted oxidative reactions of its beta-mutant fractions with HbAo. Relative to HbAo, both beta K82N and beta K82D fractions showed similar autoxidation kinetics and similar initial oxidation reaction rates with H2O2. However, a more profound pattern of changes was seen in HbAo than in the two Providence fractions. The structural changes in HbAo include a collapse of beta-subunits, and alpha-alpha dimer formation in the presence of excess H2O2. Mass spectrometric and amino acid analysis revealed that beta Cys93 and beta Cys112 were oxidized in the HbAo fraction, consistent with oxidative pathways driven by a ferrylHb and its protein radical. These amino acids were oxidized at a lesser extent in beta K82D fraction. While the 3 isolated components of Hb Providence exhibited similar ligand binding and oxidation reaction kinetics, the variant fractions were more effective in consuming H2O2 and safely internalizing radicals through the ferric/ferryl pseudoperoxidase cycle. C1 [Abraham, Bindu; Hicks, Wayne; Jia, Yiping; Baek, Jin Hyen; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20892 USA. [Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU CBER FX This work was supported in part by CBER Critical Path Research Program. NR 43 TC 7 Z9 7 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 15 PY 2011 VL 50 IS 45 BP 9752 EP 9766 DI 10.1021/bi200876e PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 842KK UT WOS:000296598100007 PM 21977904 ER PT J AU Kapogiannis, BG Soe, MM Nesheim, SR Abrams, EJ Carter, RJ Farley, J Palumbo, P Koenig, LJ Bulterys, M AF Kapogiannis, Bill G. Soe, Minn M. Nesheim, Steven R. Abrams, Elaine J. Carter, Rosalind J. Farley, John Palumbo, Paul Koenig, Linda J. Bulterys, Marc TI Mortality Trends in the US Perinatal AIDS Collaborative Transmission Study (1986-2004) SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED CHILDREN; IMMUNODEFICIENCY-VIRUS-INFECTION; DISEASE PROGRESSION; OPPORTUNISTIC INFECTIONS; HIV-1-INFECTED CHILDREN; PREDICT MORTALITY; VIRAL LOAD; UNINFECTED CHILDREN; CHANGING PATTERNS AB Background. Highly active antiretroviral therapy (HAART) has improved human immunodeficiency virus (HIV)-associated morbidity and mortality. The bimodal mortality distribution in HIV-infected children makes it important to evaluate temporal effects of HAART among a birth cohort with long-term, prospective follow-up. Methods. Perinatal AIDS Collaborative Transmission Study (PACTS)/PACTS-HIV Follow-up of Perinatally Exposed Children (HOPE) study was a Centers for Disease Control and Prevention-sponsored multicenter, prospective birth cohort study of HIV-exposed uninfected and infected infants from 1985 until 2004. Mortality was evaluated for the no/monotherapy, mono-/dual-therapy, and HAART eras, that is, 1 January 1986 through 31 December 1990, from 1 January 1991 through 31 December 1996, and 1 January 1997 through 31 December 2004. Results. Among 364 HIV-infected children, 56% were female and 69% black non-Hispanic. Of 98 deaths, 79 (81%) and 61 (62%) occurred in children < 3 and < 2 years old, respectively. The median age at death increased significantly across the eras (P < .0001). The average annual mortality rates were 18 (95% confidence interval [CI], 11.6-26.8), 6.9 (95% CI, 5.4-8.8), and 0.8 (95% CI, 0.4-1.5) events per 100 person-years for the no/monotherapy, mono-/dual-therapy and HAART eras, respectively. The corresponding 6-year survival rates for children born in these eras were 57%, 76%, and 91%, respectively (P < .0001). Among children who received HAART in the first 6 months of age, the probability of 6-year survival was 94%. Ten-year survival rates for HAART and non-HAART recipients were 94% and 45% (P < .05). HAART-associated reductions in mortality remained significant after adjustment for confounders (hazard ratio, 0.3; 95% CI, .08-.76). Opportunistic infections (OIs) caused 31.8%, 16.9%, and 9.1% of deaths across the respective eras (P = .051). Conclusions. A significant decrease in annual mortality and a prolongation in survival were seen in this US perinatal cohort of HIV-infected children. Temporal decreases in OI-associated mortality resulted in relative proportional increases of non-OI-associated deaths. C1 [Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. [Kapogiannis, Bill G.; Nesheim, Steven R.] Emory Univ, Sch Med, Dept Pediat, Div Infect Dis, Atlanta, GA USA. [Kapogiannis, Bill G.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. [Soe, Minn M.; Nesheim, Steven R.; Koenig, Linda J.; Bulterys, Marc] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV AIDS Viral Hepatitis STD & TB Preven, Atlanta, GA USA. [Abrams, Elaine J.] Columbia Univ, Dept Pediat, Harlem Hosp Ctr, New York, NY 10027 USA. [Abrams, Elaine J.; Carter, Rosalind J.] Columbia Univ, Mailman Sch Publ Hlth, ICAP, New York, NY USA. [Carter, Rosalind J.] Med & Hlth Res Assoc, New York, NY USA. [Farley, John] Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. [Farley, John] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Palumbo, Paul] Dartmouth Coll, Dept Pediat, Hanover, NH 03755 USA. [Palumbo, Paul] Univ Med & Dent New Jersey, Dept Pediat, Newark, NJ 07103 USA. RP Kapogiannis, BG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, NIH, 6100 Execut Blvd,Room 4B11J, Bethesda, MD 20892 USA. EM kapogiannisb@mail.nih.gov FU CDC (Medical and Health Research Association of New York City) [U64/CCU207228]; University of Medicine and Dentistry of New Jersey-New Jersey Medical School [U64/CCU202219]; University of Maryland School of Medicine [U64/CCU306825]; Emory University School of Medicine [U64/CCU404456] FX PACTS and PACTS-HOPE were funded between 1985 and 2004 by the CDC through cooperative agreements U64/CCU207228 (Medical and Health Research Association of New York City), U64/CCU202219 (University of Medicine and Dentistry of New Jersey-New Jersey Medical School), U64/CCU306825 (University of Maryland School of Medicine), and U64/CCU404456 (Emory University School of Medicine).; B. G. K. and S. R. N. were funded by a grant to Emory University School of Medicine, J. F. by a grant to the University of Maryland School of Medicine, and P. P. by a grant to the University of Medicine and Dentistry of New Jersey. All other authors report no potential conflicts. NR 66 TC 29 Z9 29 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2011 VL 53 IS 10 BP 1024 EP 1034 DI 10.1093/cid/cir641 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 834CV UT WOS:000295937100012 PM 22002982 ER PT J AU Tang, SX Zhao, JQ Setty, MKHG Devadas, K Gaddam, D Viswanath, R Wood, O Zhang, PH Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Setty, Mohan Kumar Haleyur Giri Devadas, Krishnakumar Gaddam, Durga Viswanath, Ragupathy Wood, Owen Zhang, Panhe Hewlett, Indira K. TI Absence of Detectable XMRV and Other MLV-Related Viruses in Healthy Blood Donors in the United States SO PLOS ONE LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; RETROVIRUS XMRV; MOUSE DNA; CELLS; CONTAMINATION; PREVALENCE; INFECTION; SEQUENCES; FAILURE AB Background: Preliminary studies in chronic fatigue syndrome (CFS) patients and XMRV infected animals demonstrated plasma viremia and infection of blood cells with XMRV, indicating the potential risk for transfusion transmission. XMRV and MLV-related virus gene sequences have also been detected in 4-6% of healthy individuals including blood donors in the U.S. These results imply that millions of persons in the U.S. may be carrying the nucleic acid sequences of XMRV and/or MLV-related viruses, which is a serious public health and blood safety concern. Methodology/Principal Findings: To gain evidence of XMRV or MLV-related virus infection in the U.S. blood donors, 110 plasma samples and 71 PBMC samples from blood donors at the NIH blood bank were screened for XMRV and MLV-related virus infection. We employed highly sensitive assays, including nested PCR and real-time PCR, as well as co-culture of plasma with highly sensitive indicator DERSE cells. Using these assays, none of the samples were positive for XMRV or MLV-related virus. Conclusions/Significance: Our results are consistent with those from several other studies, and demonstrate the absence of XMRV or MLV-related viruses in the U.S. blood donors that we studied. C1 [Tang, Shixing; Zhao, Jiangqin; Setty, Mohan Kumar Haleyur Giri; Devadas, Krishnakumar; Gaddam, Durga; Viswanath, Ragupathy; Wood, Owen; Zhang, Panhe; Hewlett, Indira K.] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM tangshixing@hotmail.com; Indira.hewlett@fda.hhs.gov RI Haleyur Giri Setty, Mohan Kumar/F-5841-2014 OI Haleyur Giri Setty, Mohan Kumar/0000-0001-6423-1420 FU Center for Biologics Evaluation and Research (CBER) FX This work was supported in part by a Critical Path grant from The Center for Biologics Evaluation and Research (CBER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 6 Z9 6 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2011 VL 6 IS 11 AR e27391 DI 10.1371/journal.pone.0027391 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 855HK UT WOS:000297554300025 PM 22110639 ER PT J AU Selzman, K Shein, M AF Selzman, Kimberly Shein, Mitchell TI QRS Morphology Rather Than QRS Duration for Predicting CRT Response SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID CARDIAC RESYNCHRONIZATION THERAPY C1 [Selzman, Kimberly; Shein, Mitchell] Ctr Devices & Radiol Hlth, Pacing Defibrillator & Leads Branch, Div Cardiovasc Devices, Off Device Evaluat,Food & Drug Adm, Silver Spring, MD 20993 USA. RP Shein, M (reprint author), Ctr Devices & Radiol Hlth, Pacing Defibrillator & Leads Branch, Div Cardiovasc Devices, Off Device Evaluat,Food & Drug Adm, 10903 New Hampshire Ave,WO66-1316, Silver Spring, MD 20993 USA. EM Mitchell.Shein@fda.hhs.gov NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 14 PY 2011 VL 171 IS 20 BP 1859 EP 1860 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 848MS UT WOS:000297056300020 PM 22083577 ER PT J AU Tang, YS Khan, RA Zhang, YH Xiao, SH Wang, M Hansen, DK Jayaram, HN Antony, AC AF Tang, Ying-Sheng Khan, Rehana A. Zhang, Yonghua Xiao, Suhong Wang, Mu Hansen, Deborah K. Jayaram, Hiremagalur N. Antony, Asok C. TI Incrimination of Heterogeneous Nuclear Ribonucleoprotein E1 (hnRNP-E1) as a Candidate Sensor of Physiological Folate Deficiency SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLOBIN MESSENGER-RNA; NEURAL-TUBE DEFECTS; POLY(C) BINDING-PROTEIN; 3' UNTRANSLATED REGION; KH-DOMAIN PROTEINS; 3'-UNTRANSLATED REGION; UP-REGULATION; IN-VITRO; POLY(C)-BINDING PROTEIN; STABILITY COMPLEX AB The mechanism underlying the sensing of varying degrees of physiological folate deficiency, prior to adaptive optimization of cellular folate uptake through the translational up-regulation of folate receptors (FR) is unclear. Because homocysteine, which accumulates intracellularly during folate deficiency, stimulated interactions between heterogeneous nuclear ribonucleoprotein E1 (hnRNP-E1) and an 18-base FR-alpha mRNA cis-element that led to increased FR biosynthesis and net up-regulation of FR at cell surfaces, hnRNP-E1 was a plausible candidate sensor of folate deficiency. Accordingly, using purified components, we evaluated the physiological basis whereby L-homocysteine triggered these RNA-protein interactions to stimulate FR biosynthesis. L-Homocysteine induced a concentration-dependent increase in RNA-protein binding affinity throughout the range of physiological folate deficiency, which correlated with a proportionate increase in translation of FR in vitro and in cultured human cells. Targeted reduction of newly synthesized hnRNP-E1 proteins by siRNA to hnRNP-E1 mRNA reduced both constitutive and L-homocysteine-induced rates of FR biosynthesis. Furthermore, L-homocysteine covalently bound hnRNP-E1 via multiple protein-cysteine-S-S-homocysteine mixed disulfide bonds within K-homology domains known to interact with mRNA. These data suggest that a concentration-dependent, sequential disruption of critical cysteine-S-S-cysteine bonds by covalently bound L-homocysteine progressively unmasks an underlying RNA-binding pocket in hnRNP-E1 to optimize interaction with FR-alpha mRNA cis-element preparatory to FR up-regulation. Collectively, such data incriminate hnRNP-E1 as a physiologically relevant, sensitive, cellular sensor of folate deficiency. Because diverse mammalian and viral mRNAs also interact with this RNA-binding domain with functional consequences to their protein expression, homocysteinylated hnRNP-E1 also appears well positioned to orchestrate a novel, nutrition-sensitive (homocysteine-responsive), posttranscriptional RNA operon in folate-deficient cells. C1 [Tang, Ying-Sheng; Khan, Rehana A.; Zhang, Yonghua; Xiao, Suhong; Antony, Asok C.] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA. [Wang, Mu; Jayaram, Hiremagalur N.] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. [Hansen, Deborah K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jayaram, Hiremagalur N.; Antony, Asok C.] Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. RP Antony, AC (reprint author), 980 W Walnut St,RIII C321B, Indianapolis, IN 46202 USA. EM aantony@iupui.edu FU National Institutes of Health [CA120843, HD39295]; Veterans Affairs Merit Review Award FX This work was supported, in whole or in part, by National Institutes of Health Grant CA120843 and HD39295 (to A. C. A.). This work was also supported by a Veterans Affairs Merit Review Award (to A. C. A. and H. N. J.). NR 76 TC 9 Z9 10 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 NOV 11 PY 2011 VL 286 IS 45 BP 39100 EP 39115 DI 10.1074/jbc.M111.230938 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 844PO UT WOS:000296759800029 PM 21930702 ER PT J AU Weisz, A Mazzola, EP Ito, Y AF Weisz, Adrian Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of 1,3,6-pyrenetrisulfonic acid trisodium salt from the color additive D&C Green No. 8 (pyranine) by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 242nd ACS National Meeting CY AUG 28-SEP 01, 2011 CL Denver, CO SP ACS DE Counter-current chromatography; pH-zone-refining CCC; Pyranine; D&C Green No. 8; Dyes; 8-Hydroxy-1,3,6-pyrenetrisulfonic acid; 1,3,6-Pyrenetrisulfonic acid ID QUINOLINE YELLOW; PURIFICATION AB In developing analytical methods for batch certification of the color additive D&C Green No.8 (G8), the U.S. Food and Drug Administration needed the trisodium salt of 1,3.6-pyrenetrisulfonic acid (P3S) for use as a reference material. Since P3S was not commercially available, preparative quantities of it were separated from portions of a sample of G8 that contained similar to 3.5% P3S. The separations were performed by pH-zone-refining counter-current chromatography using dodecylamine (DA) as the hydrophobic counterion. The added DA enabled partitioning of the polysulfonated components into the organic stationary phase of the two-phase solvent system used, 1-butanol-water (1:1). Thus, a typical separation that involved 20.3 g of G8, using sulfuric acid as the retainer acid and 20% DA in the stationary phase and 0.1 M sodium hydroxide as the mobile phase, resulted in similar to 0.58 g of P3S of greater than 99% purity. The identification and characterization of the separated P3S were performed by elemental analyses, proton nuclear magnetic resonance, high-resolution mass spectrometry, ultra-violet spectra, and high-performance liquid chromatography. Published by Elsevier B.V. C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, HFS 106,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [ZIA HL005107-04] NR 23 TC 13 Z9 14 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 11 PY 2011 VL 1218 IS 45 BP 8249 EP 8254 DI 10.1016/j.chroma.2011.09.049 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 846XV UT WOS:000296937400013 PM 21982993 ER PT J AU Simmons, G Glynn, SA Komaroff, AL Mikovits, JA Tobler, LH Hackett, J Tang, N Switzer, WM Heneine, W Hewlett, IK Zhao, JQ Lo, SC Alter, HJ Linnen, JM Gao, K Coffin, JM Kearney, MF Ruscetti, FW Pfost, MA Bethel, J Kleinman, S Holmberg, JA Busch, MP AF Simmons, Graham Glynn, Simone A. Komaroff, Anthony L. Mikovits, Judy A. Tobler, Leslie H. Hackett, John, Jr. Tang, Ning Switzer, William M. Heneine, Walid Hewlett, Indira K. Zhao, Jiangqin Lo, Shyh-Ching Alter, Harvey J. Linnen, Jeffrey M. Gao, Kui Coffin, John M. Kearney, Mary F. Ruscetti, Francis W. Pfost, Max A. Bethel, James Kleinman, Steven Holmberg, Jerry A. Busch, Michael P. CA Blood XMRV Sci Res Working Grp TI Failure to Confirm XMRV/MLVs in the Blood of Patients with Chronic Fatigue Syndrome: A Multi-Laboratory Study SO SCIENCE LA English DT Article ID VIRUS-RELATED VIRUS; RETROVIRUS XMRV; CELLS; CONTAMINATION; SEQUENCES; ABSENCE; DONORS; DETECT AB Murine leukemia viruses (MLVs), including xenotropic-MLV-related virus (XMRV), have been controversially linked to chronic fatigue syndrome (CFS). To explore this issue in greater depth, we compiled coded replicate samples of blood from 15 subjects previously reported to be XMRV/MLV-positive (14 with CFS) and from 15 healthy donors previously determined to be negative for the viruses. These samples were distributed in a blinded fashion to nine laboratories, which performed assays designed to detect XMRV/MLV nucleic acid, virus replication, and antibody. Only two laboratories reported evidence of XMRV/MLVs; however, replicate sample results showed disagreement, and reactivity was similar among CFS subjects and negative controls. These results indicate that current assays do not reproducibly detect XMRV/MLV in blood samples and that blood donor screening is not warranted. C1 [Simmons, Graham; Tobler, Leslie H.; Busch, Michael P.] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Simmons, Graham; Tobler, Leslie H.; Busch, Michael P.] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Glynn, Simone A.] NHLBI, Transfus Med & Cellular Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Komaroff, Anthony L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Komaroff, Anthony L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Mikovits, Judy A.; Pfost, Max A.] Univ Nevada, Whittemore Peterson Inst, Reno, NV 89557 USA. [Hackett, John, Jr.; Tang, Ning] Abbott Labs, Abbott Pk, IL 60064 USA. [Switzer, William M.; Heneine, Walid] Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. [Hewlett, Indira K.; Zhao, Jiangqin] US FDA, Off Blood Res, Rockville, MD 20852 USA. [Lo, Shyh-Ching] US FDA, Off Cellular Tissue & Gene Therapies Review, Bethesda, MD 20892 USA. [Alter, Harvey J.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Linnen, Jeffrey M.; Gao, Kui] Gen Probe, San Diego, CA 92121 USA. [Coffin, John M.] Tufts Univ, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. [Kearney, Mary F.; Ruscetti, Francis W.] NCI, Frederick, MD 21702 USA. [Bethel, James] WESTAT Corp, Rockville, MD 20850 USA. [Kleinman, Steven] Univ British Columbia, Dept Pathol, Victoria, BC V9A4W4, Canada. [Holmberg, Jerry A.] US Dept HHS, Rockville, MD 20852 USA. RP Busch, MP (reprint author), Blood Syst Res Inst, San Francisco, CA 94118 USA. EM mbusch@bloodsystems.org RI Simmons, Graham/G-3523-2012; Haleyur Giri Setty, Mohan Kumar/F-5841-2014 OI Simmons, Graham/0000-0002-9615-7023; Haleyur Giri Setty, Mohan Kumar/0000-0001-6423-1420 FU National Heart, Lung, and Blood Institute REDS-II Central Laboratory [N01 HB-57181]; F. M. Kirby Foundation FX The authors acknowledge the tremendous effort contributed by all Blood XMRV Scientific Research Working Group (SRWG) members; the roster of the SRWG is listed as supporting material on Science Online. The authors acknowledge the many laboratory members from all of the contributing laboratories, including I. Steffen, I. Wilson, L. Pitina, K. Murcia, P. Loanzon, S. Ng, and N. Gefter at the Blood Systems Research Institute; H. Zheng, H. Jia, S. Tang, and A. Shankar at CDC; C. Puccinelli, S. Rawat, A. McKenzie, K. Hagen, and D. T. Cramer at WPI; J. Carrick at Gen-Probe; D. Bertolette, Y. Huang, and C. Sadowski at NCI/Ruscetti; E. Anderson, J. Spindler, and A. Wiegand at DRP; K. Devadas, M. K. H. G. Setty, S. Tang, P. H. Zhang, and D. S. Gaddam in the Office of Blood Research and Review, FDA; B. Li, N. Pripuzova, and G.-C. Hung in the Office of Cellular, Tissue and Gene Therapies, FDA; R. Wang from the clinical center NIH; G. Leckie at Abbott Molecular; and X. Qiu at Abbott Diagnostics. The laboratory work was funded by the National Heart, Lung, and Blood Institute REDS-II Central Laboratory Contract to Blood Systems Research Institute (N01 HB-57181). J.M.C. was a research professor of the American Cancer Society with support from the F. M. Kirby Foundation. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the NIH, CDC, FDA, or the Department of Health and Human Services. M. P. B. is a member of the Scientific Advisory Board of Gen-Probe, which provides blood screening assays for pathogen nucleic acids. S. K. is a paid consultant to Novartis Diagnostics, a distributor of blood donor screening assays, and to Cerus Corporation, a manufacturer of pathogen inactivation systems for blood components. WPI has filed patent applications related to methods of testing XMRVs and variants in blood. Abbott Laboratories has filed patent applications relating to detection of XMRV by use of immunoassays and molecular-based assays. Gen-Probe has filed patent applications relating to the assays they performed in this paper. NR 21 TC 53 Z9 55 U1 1 U2 13 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 11 PY 2011 VL 334 IS 6057 BP 814 EP 817 DI 10.1126/science.1213841 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 845US UT WOS:000296849600049 PM 21940862 ER PT J AU Li, F Seillier-Moiseiwitsch, F AF Li, Feng Seillier-Moiseiwitsch, Francoise TI Analyzing 2D gel images using a two-component empirical bayes model SO BMC BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION; 2-GROUPS MODEL; MICROARRAY; ELECTROPHORESIS; NULL AB Background: Two-dimensional polyacrylomide gel electrophoresis (2D gel, 2D PAGE, 2-DE) is a powerful tool for analyzing the proteome of a organism. Differential analysis of 2D gel images aims at finding proteins that change under different conditions, which leads to large-scale hypothesis testing as in microarray data analysis. Two-component empirical Bayes (EB) models have been widely discussed for large-scale hypothesis testing and applied in the context of genomic data. They have not been implemented for the differential analysis of 2D gel data. In the literature, the mixture and null densities of the test statistics are estimated separately. The estimation of the mixture density does not take into account assumptions about the null density. Thus, there is no guarantee that the estimated null component will be no greater than the mixture density as it should be. Results: We present an implementation of a two-component EB model for the analysis of 2D gel images. In contrast to the published estimation method, we propose to estimate the mixture and null densities simultaneously using a constrained estimation approach, which relies on an iteratively re-weighted least-squares algorithm. The assumption about the null density is naturally taken into account in the estimation of the mixture density. This strategy is illustrated using a set of 2D gel images from a factorial experiment. The proposed approach is validated using a set of simulated gels. Conclusions: The two-component EB model is a very useful for large-scale hypothesis testing. In proteomic analysis, the theoretical null density is often not appropriate. We demonstrate how to implement a two-component EB model for analyzing a set of 2D gel images. We show that it is necessary to estimate the mixture density and empirical null component simultaneously. The proposed constrained estimation method always yields valid estimates and more stable results. The proposed estimation approach proposed can be applied to other contexts where large-scale hypothesis testing occurs. C1 [Li, Feng] Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21228 USA. [Li, Feng] US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Seillier-Moiseiwitsch, Francoise] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Li, F (reprint author), Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21228 USA. EM feng.li@fda.hhs.gov RI Li, Feng/E-1659-2011 FU NIH [5R01GM075298] FX Work for this paper was supported in part by NIH Grant 5R01GM075298. The authors thank Carol Whisnant for the use of her data. This article reflects the views of the author and should not be construed to represent FDA's view or policies. NR 36 TC 3 Z9 3 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 8 PY 2011 VL 12 AR 433 DI 10.1186/1471-2105-12-433 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 853YL UT WOS:000297461500001 PM 22067142 ER PT J AU Baylor, NW AF Baylor, Norman W. TI Perspective of the US Food and Drug Administration on concomitant administration of Zostavax and Pneumovax SO VACCINE LA English DT Letter ID ZOSTER VACCINE; HERPES-ZOSTER C1 US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Baylor, NW (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM norman.baylor@fda.hhs.gov NR 4 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 8 PY 2011 VL 29 IS 48 BP 8771 EP 8771 DI 10.1016/j.vaccine.2011.08.046 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 855YC UT WOS:000297601200001 PM 21864628 ER PT J AU Anez, G Morales-Betoulle, ME Rios, M AF Anez, German Morales-Betoulle, Maria E. Rios, Maria TI Circulation of Different Lineages of Dengue Virus Type 2 in Central America, Their Evolutionary Time-Scale and Selection Pressure Analysis SO PLOS ONE LA English DT Article ID MOLECULAR EVOLUTION; PHYLOGENETIC-RELATIONSHIPS; PUERTO-RICO; NICARAGUA; MICROEVOLUTION; GENOTYPE; BIOLOGY; MEXICO; PCR AB Dengue is caused by any of the four serotypes of dengue virus (DENV-1 to 4). Each serotype is genetically distant from the others, and each has been subdivided into different genotypes based on phylogenetic analysis. The study of dengue evolution in endemic regions is important since the diagnosis is often made by nucleic acid amplification tests, which depends upon recognition of the viral genome target, and natural occurring mutations can affect the performance of these assays. Here we report for the first time a detailed study of the phylogenetic relationships of DENV-2 from Central America, and report the first fully sequenced DENV-2 strain from Guatemala. Our analysis of the envelope (E) protein and of the open reading frame of strains from Central American countries, between 1999 and 2009, revealed that at least two lineages of the American/Asian genotype of DENV-2 have recently circulated in that region. In occasions the co-circulation of these lineages may have occurred and that has been suggested to play a role in the observed increased severity of clinical cases. Our time-scale analysis indicated that the most recent common ancestor for Central American DENV-2 of the American/Asian genotype existed about 19 years ago. Finally, we report positive selection in DENV-2 from Central America in codons of the genes encoding for C, E, NS2A, NS3, and NS5 proteins. Some of these identified codons are novel findings, described for the first time for any of the DENV-2 genotypes. C1 [Anez, German; Rios, Maria] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Morales-Betoulle, Maria E.] US Naval Med Res Unit 3 NAMRU 3, Cairo, Egypt. RP Anez, G (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM German.Anez@fda.hhs.gov; Maria.Rios@fda.hhs.gov OI Anez, German/0000-0001-5361-3001 FU Office of Blood Research and Review/Center for Biologics Evaluation and Research/Food and Drug Administration FX This study was funded by Office of Blood Research and Review/Center for Biologics Evaluation and Research/Food and Drug Administration Internal Operational Funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 26 Z9 26 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 4 PY 2011 VL 6 IS 11 AR e27459 DI 10.1371/journal.pone.0027459 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 850MH UT WOS:000297198200076 PM 22076162 ER PT J AU Zhou, WL Wang, PG Krynitsky, AJ Rader, JI AF Zhou, Wanlong Wang, Perry G. Krynitsky, Alexander J. Rader, Jeanne I. TI Rapid and simultaneous determination of hexapeptides (Ac-EEMQRR-amide and H2N-EEMQRR-amide) in anti-wrinkle cosmetics by hydrophilic interaction liquid chromatography-solid phase extraction preparation and hydrophilic interaction liquid chromatography with tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Acetyl hexapeptide; HILIC; ESI; MS/MS; SPE; Stable isotopically labeled peptides ID PEPTIDES; QUANTIFICATION; SUPPRESSION; PERFORMANCE; SEPARATION AB A rapid method for the simultaneous determination of Ac-EEMQRR-amide and H2N-EEMQRR-amide in cosmetic products was developed and evaluated. This analytical procedure involved extracting samples with 0.1:0.1:85:15 (v:v) trifluoroacetic acid (TFA):formic acid:acetonitrile (ACN):water and determination by hydrophilic interaction liquid chromatography with tandem mass spectrometry (HILIC-MS/MS). Samples showing serious ion suppression were further cleaned up using HILIC-SPE prior to HILIC-MS/MS analysis. Stable isotopically labeled peptides, corresponding to the above two peptides, were used as internal standards to correct for loss of recovery and matrix effects. Electrospray ionization (ESI) in the positive mode was used. The linear range was 2.0-1000 ng/mL for Ac-EEMQRR-amide and 25.0-2500 ng/mL for H2N-EEMQRR-amide. Thirteen commercial products were analyzed for the two peptides using this method. The amounts of Ac-EEMQRR-amide in the samples ranged from none detected to 42.3 mu g/g. H2N-EEMQRR-amide was not detected in any of the samples. The recoveries for Ac-EEMQRR-amide and H2N-EEMQRR-amide ranged from 85% to 110% and 84% to 119%, respectively, at the spiking level of 30 mu g/g. Published by Elsevier B.V. C1 [Zhou, Wanlong; Wang, Perry G.; Krynitsky, Alexander J.; Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wang, PG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-717, College Pk, MD 20740 USA. EM Perry.Wang@fda.hhs.gov FU ORISE FX Authors wish to thank ORISE program for partially finance support and Wayne Wamer, Hardy Chou, Robert Bronaugh, Margaret Kraeling, Oluwatosin Ogunsola, John Callahan, Jon Wong, and Peter Scholl (all from U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition) for helpful discussions. NR 29 TC 13 Z9 15 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD NOV 4 PY 2011 VL 1218 IS 44 BP 7956 EP 7963 DI 10.1016/j.chroma.2011.08.091 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 841XR UT WOS:000296549000007 PM 21959380 ER PT J AU Simhadri, VR Mariano, JL Zhou, Q DeBell, KE Borrego, F AF Simhadri, Venkateswara R. Mariano, John L. Zhou, Qing DeBell, Karen E. Borrego, Francisco TI Differential expression of CD300a/c on human T(H)1 and T(H)17 cells SO BMC IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; RECEPTOR IRP60 CD300A; HUMAN TH17 CELLS; INHIBITORY RECEPTOR; CHEMOKINE RECEPTOR; MYCOBACTERIUM-TUBERCULOSIS; IMMUNOGLOBULIN SUPERFAMILY; LINEAGE COMMITMENT; EFFECTOR FUNCTIONS; NK CELLS AB Background: Human memory CD4(+) T cells can be either CD300a/c(+) or CD300a/c(-) and subsequent analyses showed that CD4(+) effector memory T (T-EM) cells are mostly CD300a/c(+), whereas CD4(+) central memory T (T-CM) cells have similar frequencies of CD300a/c(+) and CD300a/c(-) cells. Results: Extensive phenotypical and functional characterization showed that in both T-CM and T-EM cells, the CD300a/c(+) subset contained a higher number of T(H)1 (IFN-gamma producing) cells. Alternatively, T(H)17 (IL-17a producing) cells tend to be CD300a/c(-), especially in the T-EM subset. Further characterization of the IL-17a(+) cells showed that cells that produce only this cytokine are mostly CD300a/c(-), while cells that produce IL-17a in combination with other cytokines, especially IFN-gamma, are mostly CD300a/c(+), indicating that the expression of this receptor is associated with cells that produce IFN-gamma. Co-ligation of the TCR and CD300a/c in CD4(+) T cells inhibited Ca2+ mobilization evoked by TCR ligation alone and modulated IFN-gamma production on T(H)1 polarized cells. Conclusion: We conclude that the CD300a/c receptors are differentially expressed on human T(H)1 and T(H)17 cells and that their ligation is capable of modulating TCR mediated signals. C1 [Simhadri, Venkateswara R.; Mariano, John L.; Zhou, Qing; DeBell, Karen E.; Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM Francisco.Borrego@fda.hhs.gov FU Food and Drug administration (FDA) FX This work was funded by the intramural program of the Food and Drug administration (FDA). We express thanks to the NIH Clinical Center Department of Transfusion Medicine for the blood samples. NR 53 TC 11 Z9 11 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD NOV 2 PY 2011 VL 12 AR 62 DI 10.1186/1471-2172-12-62 PG 11 WC Immunology SC Immunology GA 849GW UT WOS:000297114800001 PM 22046970 ER PT J AU Goldman, ER Anderson, GP Zabetakis, D Walper, S Liu, JL Bernstein, R Calm, A Carney, JP O'Brien, TW Walker, JL Garber, EAE AF Goldman, Ellen R. Anderson, George P. Zabetakis, Dan Walper, Scott Liu, Jinny L. Bernstein, Rachael Calm, Alena Carney, James P. O'Brien, Thomas W. Walker, Jennifer L. Garber, Eric A. E. TI Llama-Derived Single Domain Antibodies Specific for Abrus Agglutinin SO TOXINS LA English DT Article DE abrin; single domain antibody; reversible refolding ID RIBOSOME-INACTIVATING PROTEINS; HEAVY-CHAIN ANTIBODIES; BOTULINUM-A NEUROTOXIN; IN-VITRO SELECTION; PRECATORIUS AGGLUTININ; MONOCLONAL-ANTIBODIES; TOXINS ABRIN; RICIN; TOXICITY; VARIANTS AB Llama derived single domain antibodies (sdAb), the recombinantly expressed variable heavy domains from the unique heavy-chain only antibodies of camelids, were isolated from a library derived from llamas immunized with a commercial abrin toxoid preparation. Abrin is a potent toxin similar to ricin in structure, sequence and mechanism of action. The selected sdAb were evaluated for their ability to bind to commercial abrin as well as abrax (a recombinant abrin A-chain), purified abrin fractions, Abrus agglutinin protein related to abrin but with lower toxicity), ricin, and unrelated proteins. Isolated sdAb were also evaluated for their ability to refold after heat denaturation and ability to be used in sandwich assays as both capture and reporter elements. The best binders were specific for the Abrus agglutinin, showing minimal binding to purified abrin fractions or unrelated proteins. These binders had sub nM affinities and regained most of their secondary structure after heating to 95 degrees C. They functioned well in sandwich assays. Through gel analysis and the behavior of anti-abrin monoclonal antibodies, we determined that the commercial toxoid preparation used for the original immunizations contained a high percentage of Abrus agglutinin, explaining the selection of Abrus agglutinin binders. Used in conjunction with anti-abrin monoclonal and polyclonal antibodies, these reagents can fill a role to discriminate between the highly toxic abrin and the related, but much less toxic, Abrus agglutinin and distinguish between different crude preparations. C1 [Goldman, Ellen R.; Anderson, George P.; Zabetakis, Dan; Walper, Scott; Liu, Jinny L.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Bernstein, Rachael] Nova Res Inc, Alexandria, VA 22308 USA. [Calm, Alena; Carney, James P.] USA, Edgewood Chem Biol Ctr RDCB DRB C, Aberdeen Proving Ground, MD 21010 USA. [O'Brien, Thomas W.; Walker, Jennifer L.] Tetracore Inc, Rockville, MD 20850 USA. [Garber, Eric A. E.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Goldman, ER (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, 4555 Overlook Ave SW, Washington, DC 20375 USA. EM ellen.goldman@nrl.navy.mil; george.anderson@nrl.navy.mil; daniel.zabetakis@nrl.navy.mil; scott.walper.ctr@nrl.navy.mil; jinny.liu@nrl.navy.mil; rachael267@gmail.com; alena.calm@us.army.mil; jpcarn@sandia.gov; tobrien@tetracore.com; jaldrich@tetracore.com; eric.garber@fda.hhs.gov RI Anderson, George/D-2461-2011 OI Anderson, George/0000-0001-7545-9893 FU JSTO-CBD/DTRA program [AA06SPO004-014]; Office of Naval Research NRL base funds FX This work was supported by JSTO-CBD/DTRA program AA06SPO004-014, and the Office of Naval Research NRL base funds. The opinions expressed here are those of the authors and do not represent those of the US Navy, the US Department of Defense, the Food and Drug Administration, or the US government. NR 49 TC 10 Z9 10 U1 1 U2 10 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD NOV PY 2011 VL 3 IS 11 BP 1405 EP 1419 DI 10.3390/toxins3111405 PG 15 WC Toxicology SC Toxicology GA 995BA UT WOS:000307980000003 PM 22174977 ER PT J AU Chakravarty, AG Rothmann, M Sridhara, R AF Chakravarty, Aloka G. Rothmann, Mark Sridhara, Rajeshwari TI Regulatory Issues in use of Biomarkers in Oncology Trials SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Personalized medicine; Predictive; Prognostic; Retrospective; Subgroup; Surrogate ID SURROGATE END-POINTS; CLINICAL-TRIALS; ENDPOINTS; CRITERIA; CANCER AB In the current era of personalized medicine, there has been an increased interest in biomarkers as a classifier for patient risk cohorts as well as a predictor of success for a therapeutic intervention. They hold promise to better screen patients who may or may not benefit from a particular treatment, but may experience toxicity inherent in oncology treatments. However, in general the classifier biomarkers are identified in post-hoc subgroup analyses. In this article we discuss the challenges in ascertaining true positive results from such post-hoc analyses. C1 [Chakravarty, Aloka G.] US FDA, Ctr Drug Evaluat & Res, Div Biometr 7, Silver Spring, MD 20993 USA. [Rothmann, Mark; Sridhara, Rajeshwari] US FDA, Ctr Drug Evaluat & Res, Div Biometr 5, Off Translat Sci, Silver Spring, MD 20993 USA. RP Chakravarty, AG (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 7, HFD 711,WO 21,Room 3514,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aloka.chakravarty@fda.hhs.gov NR 21 TC 2 Z9 2 U1 1 U2 3 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD NOV PY 2011 VL 3 IS 4 BP 569 EP 576 DI 10.1198/sbr.2011.09026 PG 8 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 893GP UT WOS:000300344600008 ER PT J AU Li, N Xia, QS Ruan, JQ Fu, PP Lin, G AF Li, Na Xia, Qingsu Ruan, Jianqing Fu, Peter P. Lin, Ge TI Hepatotoxicity and Tumorigenicity Induced by Metabolic Activation of Pyrrolizidine Alkaloids in Herbs SO CURRENT DRUG METABOLISM LA English DT Review DE Hepatotoxicity; herb-drug interactions; metabolic activation; pyrrolizidine alkaloids; tumorigenicity ID DNA ADDUCT FORMATION; FLAVIN-CONTAINING MONOOXYGENASE; GENE-EXPRESSION CHANGES; RAT-LIVER MICROSOMES; FORMATION IN-VIVO; BIG BLUE RATS; DIETARY-SUPPLEMENTS; GUINEA-PIG; MEDICINAL-PLANTS; ACUTE TOXICITY AB In the recent decades, the use of herbal products has been rapidly growing in the Western countries. While their use in many cases causes adverse effects, to date, safety issues of herbal products have not been adequately addressed. It is rarely determined whether the non-purported bioactive constituents in the herbs and the metabolites of the bioactive components can lead to adverse effects. In this review, we discuss, using pyrrolizidine alkaloids (PAs) as an example, the hepatotoxicity and tumorigenicity induced by metabolic activation of herbal components and by herb-herb and herb-drug interactions with other herbal ingredients and synthetic drugs. PAs are constitutively produced by plants as the secondary metabolites. There are more than 600 PAs and PA N-oxides identified in over 6000 plants, and more than half of them exhibit hepatotoxicity. Toxic PA-containing plants grow in many geographical regions worldwide, rendering it highly possible that PA-containing plants are the most common poisonous plants affecting livestock and humans. PAs require metabolic activation mediated by cytochrome P450 enzymes to generate reactive pyrrolic metabolites that react with cellular proteins and DNA leading to hepatotoxicity and genotoxicity. PAs can also modulate both phase I and phase II metabolizing enzymes, which may alter the metabolic fate of endogenous and exogenous chemicals. Alteration and/or competition of the metabolizing enzymes by PAs upon the co-administered herbal medicines or drugs can potentially result in serious clinical and toxicological consequences through decreased pharmacological activities or increased toxic effects. C1 [Li, Na; Ruan, Jianqing; Lin, Ge] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Lin, G (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. EM peter.fu@fda.hhs.gov; linge@cuhk.edu.hk FU Research Grant Council of Hong Kong [CUHK 2140485]; Hong Kong Jockey Club Charities Trust [JCICM-15-07] FX We thank Dr. Frederick A. Beland for critical review of this manuscript, and also the financial support from Research Grant Council of Hong Kong (Earmarked Research Grant CUHK 2140485) and Hong Kong Jockey Club Charities Trust Fund (JCICM-15-07). NR 144 TC 39 Z9 39 U1 3 U2 37 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 EI 1875-5453 J9 CURR DRUG METAB JI Curr. Drug Metab. PD NOV PY 2011 VL 12 IS 9 BP 823 EP 834 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 883YG UT WOS:000299670700004 PM 21619520 ER PT J AU Jankowska, E Cipollo, J AF Jankowska, Ewa Cipollo, John TI Platform for analysis of anthranilic acid N-glycan derivatives utilizing multipolarity mode LC-MS with hydrophilic interaction chromatography separation and ion trap MS/MS SO BIOANALYSIS LA English DT Article ID ASPARAGINE-LINKED OLIGOSACCHARIDES; INTERNAL RESIDUE LOSS; MASS-SPECTROMETRY; NEGATIVE-IONS; SIALYLATED OLIGOSACCHARIDES; STRUCTURAL CHARACTERIZATION; H-1-NMR SPECTROSCOPY; HUMAN-ERYTHROPOIETIN; REDUCING TERMINUS; BOVINE FETUIN AB Background: The structure of glycans is complex compared with linear polymers such as proteins and nucleic acids. Structural assignment of these compounds is particularly challenging to the bioanalyst. Here we present a multipolarity mode LC-MS platform for analysis of anthranilic acid-derivatized N-glycans. Results: Multipolarity mode LC-MS ana-lysis of N-glycan anthranilic aid (2AA) derivatives, collected under conditions that stabilize sialyloligosaccharides, provided more complete structural coverage than either mode when used alone. Structural assignment was simplified by the use of 2AA, which localizes charge to the reducing end in both modes facilitating the production of reducing end fragment dominant spectra. Conclusion: Multimode analysis of high-mannose, hybrid and complex N-glycans, under conditions used in this method, is superior to either mode when used alone. C1 [Jankowska, Ewa; Cipollo, John] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cipollo, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29,Rm 127,8800 Rockville Pike, Bethesda, MD 20892 USA. EM john.cipollo@fda.hhs.gov FU Center for Biologics Evaluation and Research; US FDA FX This work has been supported by funding provided by the Center for Biologics Evaluation and Research and 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. No writing assistance was utilized in the production of this manuscript. NR 41 TC 1 Z9 1 U1 0 U2 6 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD NOV PY 2011 VL 3 IS 21 BP 2401 EP 2417 DI 10.4155/BIO.11.247 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 860XJ UT WOS:000297981300012 PM 22074282 ER PT J AU Sarvazyan, A Hall, TJ Urban, MW Fatemi, M Aglyamov, SR Garra, BS AF Sarvazyan, Armen Hall, Timothy J. Urban, Matthew W. Fatemi, Mostafa Aglyamov, Salavat R. Garra, Brian S. TI An Overview of Elastography-An Emerging Branch of Medical Imaging SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE Elasticity; viscoelasticity; stiffness; modulus; ultrasound; MRI; elastography; MRE ID ACOUSTIC-RADIATION-FORCE; MAGNETIC-RESONANCE-ELASTOGRAPHY; ENDOSCOPIC ULTRASOUND ELASTOGRAPHY; REAL-TIME ELASTOGRAPHY; ASSESSMENT POSTCARDIAC CATHETERIZATION; NONINVASIVE MATERIAL CHARACTERIZATION; POISSONS RATIO ELASTOGRAPHY; PROSTATE-CANCER DETECTION; DYNAMIC MR ELASTOGRAPHY; DEEP VENOUS THROMBOSIS AB From times immemorial manual palpation served as a source of information on the state of soft tissues and allowed detection of various diseases accompanied by changes in tissue elasticity. During the last two decades, the ancient art of palpation gained new life due to numerous emerging elasticity imaging (EI) methods. Areas of applications of EI in medical diagnostics and treatment monitoring are steadily expanding. Elasticity imaging methods are emerging as commercial applications, a true testament to the progress and importance of the field. In this paper we present a brief history and theoretical basis of EI, describe various techniques of EI, analyze their advantages and limitations, and overview main clinical applications. We present a classification of elasticity measurement and imaging techniques based on the methods used for generating a stress in the tissue (external mechanical force, internal ultrasound radiation force, or an internal endogenous force), and measurement of the tissue response. The measurement method can be performed using differing physical principles including magnetic resonance imaging (MRI), ultrasound imaging, X-ray imaging, optical and acoustic signals. Until recently, EI was largely a research method used by a few select institutions having the special equipment needed to perform the studies. Since 2005 however, increasing numbers of mainstream manufacturers have added EI to their ultrasound systems so that today the majority of manufacturers offer some sort of Elastography or tissue stiffness imaging on their clinical systems. Now it is safe to say that some sort of elasticity imaging may be performed on virtually all types of focal and diffuse disease. Most of the new applications are still in the early stages of research, but a few are becoming common applications in clinical practice. C1 [Sarvazyan, Armen] Artann Labs, Trenton, NJ 08618 USA. [Hall, Timothy J.] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. [Urban, Matthew W.; Fatemi, Mostafa] Mayo Clin, Coll Med, Dept Physiol & Biomed Engn, Rochester, MN 55905 USA. [Aglyamov, Salavat R.] Univ Texas Austin, Dept Biomed Engn, Austin, TX 78751 USA. [Garra, Brian S.] Washington DC Vet Affairs Med Ctr, Dept Radiol, Washington, DC 20422 USA. [Garra, Brian S.] FDA, CDRH, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Sarvazyan, A (reprint author), Artann Labs, 1459 Lower Ferry Rd, Trenton, NJ 08618 USA. EM armen@artannlabs.com RI Urban, Matthew/A-8413-2009; Hall, Timothy/K-3632-2012; Aglyamov, Salavat/A-6412-2014; OI Urban, Matthew/0000-0003-1360-4287; Aglyamov, Salavat/0000-0001-9530-1225; Hall, Timothy/0000-0001-9850-6031 FU NIH [R01CA140271, R21CA133488, R44CA69175, R43CA94444, R44CA082620, R44 CA091392, R43AG034714, R21CA121579, R01CA127235, P50CA91956] FX TJH acknowledges the support of grants R01CA140271 and R21CA133488 from NIH. AS acknowledges the support of grants R44CA69175, R43CA94444, R44CA082620, R44 CA091392, and R43AG034714 from NIH. MWU and MF acknowledge the support of grants R21CA121579, R01CA127235, and P50CA91956 from the NIH. NR 348 TC 90 Z9 97 U1 7 U2 58 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 EI 1875-6603 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD NOV PY 2011 VL 7 IS 4 BP 255 EP 282 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 875DJ UT WOS:000299010300002 PM 22308105 ER PT J AU Hayward, DG Wong, JW Zhang, K Chang, J Shi, F Banerjee, K Yang, P AF Hayward, Douglas G. Wong, Jon W. Zhang, Kai Chang, James Shi, Feng Banerjee, Kaushik Yang, Paul TI Multiresidue Pesticide Analysis in Ginseng and Spinach by Nontargeted and Targeted Screening Procedures SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FLIGHT MASS-SPECTROMETRY; 2-DIMENSIONAL GAS-CHROMATOGRAPHY; FLAME PHOTOMETRIC DETECTION; SOLID-PHASE EXTRACTION; MULTI-RESIDUE METHOD; LIQUID-CHROMATOGRAPHY; POLYCHLORINATED-BIPHENYLS; RAPID METHOD; VEGETABLES; FRUITS AB Five different mass spectrometers interfaced to GC or LC were evaluated for their application to targeted and nontargeted screening of pesticides in two foods, spinach and ginseng. The five MS systems were capillary GC/MS/MS, GC-high resolution time-of-flight (GC/HR-TOF)-MS, TOF-MS interfaced with a comprehensive multidimensional GC (GCxGC/TOF-MS), an MS/MS ion trap hybrid mass (qTrap) system interfaced with an ultra-performance liquid chromatograph (UPLC-qTrap), and UPLC interfaced to an orbital trap high resolution mass spectrometer (UPLC/Orbitrap HR-MS). Each MS system was tested with spinach and ginseng extracts prepared through a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure. Each matrix was fortified at 10 and 50 ng/g for spinach or 25 and 100 ng/g for ginseng with subsets of 486 pesticides, isomers, and metabolites representing most pesticide classes. HR-TOF-MS was effective in a targeted search for characteristic accurate mass ions and identified 97% of 170 pesticides in ginseng at 25 ng/g. A targeted screen of either ginseng or spinach found 94-95% of pesticides fortified for analysis at 10 ng/g with GC/MS/MS or LC/MS/MS using multiple reaction monitoring (MRM) procedures. Orbitrap-MS successfully found 89% of 177 fortified pesticides in spinach at 25 ng/g using a targeted search of accurate mass pseudomolecular ions in the positive electrospray ionization mode. A comprehensive GCxGC/TOF-MS system provided separation and identification of 342 pesticides and metabolites in a single 32 min acquisition with standards. Only 67 or 81% of the pesticides were identified in ginseng and spinach matrixes at 25 ng/g or 10 ng/g, respectively. MS/MS or qTrap-MS operated in the MRM mode produced the lowest false-negative rates, at 10 ng/g. Improvements to instrumentation, methods, and software are needed for efficient use of nontargeted screens in parallel with triple quadrupole MS. C1 [Hayward, Douglas G.; Wong, Jon W.; Zhang, Kai] US FDA, College Pk, MD 20740 USA. [Chang, James] ThermoFisher Sci, San Jose, CA 95134 USA. [Shi, Feng] Givaudan Flavors Corp, Cincinnati, OH 45216 USA. [Banerjee, Kaushik] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India. [Yang, Paul] Ontario Minist Environm, Etobicoke, ON, Canada. RP Hayward, DG (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Douglas.Hayward@fda.hhs.gov FU National Institutes of Health (NIH), Office of Dietary Supplements (ODS) [Y1-0D-6412-01] FX This work was financially supported by an interagency agreement with the National Institutes of Health (NIH), Office of Dietary Supplements (ODS), Y1-0D-6412-01. We also acknowledge the unwavering support of Joseph M. Betz, ODS, NIH. NR 44 TC 18 Z9 18 U1 1 U2 44 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2011 VL 94 IS 6 BP 1741 EP 1751 DI 10.5740/jaoacint.SGEHayward PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 871EG UT WOS:000298720100007 PM 22320080 ER PT J AU Hoerner, R Feldpausch, J Gray, RL Curry, S Lewis, P Tolan, J Goldy, T Klein, F Neiditch, B Hosking, E Norton, P Rice, J Mozola, M Chen, Y Brodsky, M Ziemer, W AF Hoerner, Rebecca Feldpausch, Jill Gray, R. Lucas Curry, Stephanie Lewis, Paul Tolan, Jerry Goldy, Tim Klein, Frank Neiditch, Barry Hosking, Edan Norton, Paul Rice, Jennifer Mozola, Mark Chen, Yi Brodsky, Michael Ziemer, Wayne TI Reveal (R) E. coli 2.0 Method for Detection of Escherichia coli O157:H7 in Raw Beef SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ENVIRONMENTAL SWABS; MINOR MODIFICATION; METHOD VALIDATION; 20-HOUR METHOD; TEST SYSTEM; FOODS; O157/H7; SAMPLES AB Reveal (R) E. coli 2.0 is a new lateral-flow immunodiagnostic test for detection of E. coli O157:H7 and O157:NM in raw beef trim and ground beef. Compared with the original Reveal E. coli O157:H7 assay, the new test utilizes a unique antibody combination resulting in improved test specificity. The device architecture and test procedure have also been modified, and a single enrichment protocol was developed which allows the test to be performed at any point during an enrichment period of 12 to 20 h. Results of inclusivity and exclusivity testing showed that the test is specific for E. coli serotypes O157:H7 and O157:NM, with the exception of two strains of O157:H38 and one strain of O157:H43 which produced positive reactions. In internal and independent laboratory trials comparing the Reveal 2.0 method to the U.S. Department of Agriculture-Food Safety and Inspection Service reference culture procedure for detection of E. coli O157:H7 in 65 and 375 g raw beef trim and ground beef samples, there were no statistically significant differences in method performance with the exception of a single internal trial with 375 g ground beef samples in which the Reveal method produced significantly more positive results. There were no unconfirmed positive results by the Reveal assay, for specificity of 100%. Results of ruggedness testing showed that the Reveal test produces accurate results even with substantial deviation in sample volume or device incubation time or temperature. However, addition of the promoter reagent to the test sample prior to introducing the test device is essential to proper test performance. C1 [Hoerner, Rebecca; Feldpausch, Jill; Gray, R. Lucas; Curry, Stephanie; Lewis, Paul; Tolan, Jerry; Goldy, Tim; Klein, Frank; Neiditch, Barry; Hosking, Edan; Norton, Paul; Rice, Jennifer; Mozola, Mark] Neogen Corp, Lansing, MI 48912 USA. [Chen, Yi] Ctr Food Safety & Appl Nutr, US Food & Drug Adm, College Pk, MD 20740 USA. [Ziemer, Wayne] Food Safety & Inspect Serv, USDA, Athens, GA USA. [Ziemer, Wayne] Richter Int, Independent Lab, Columbus, OH 43228 USA. RP Mozola, M (reprint author), Neogen Corp, 620 Lesher Pl, Lansing, MI 48912 USA. EM mmozola@neogen.com NR 6 TC 0 Z9 0 U1 0 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2011 VL 94 IS 6 BP 1835 EP 1845 DI 10.5740/jaoacint.11067 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 871EG UT WOS:000298720100018 PM 22320091 ER PT J AU Junge, B Gronewald, C Berghof-Jager, K Hammack, T Chen, Y AF Junge, Benjamin Groenewald, Cordt Berghof-Jaeger, Kornelia Hammack, Thomas Chen, Yi TI BIOTECON Diagnostics foodproof (R) E. coli O157 Detection Kit, 5 ' Nuclease for E. coli O157 in Combination with foodproof ShortPrep II Kit SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ESCHERICHIA-COLI AB The method describes the detection of Escherichia coli O157 in food. The method is based on real-time PCR using hydrolysis probes (5' Nuclease). This advanced PCR method was designed to reduce the time necessary to achieve results from PCR reactions and enable the user to monitor the amplification of the PCR product simultaneously in real time. After DNA isolation using the BIOTECON foodproof (R) ShortPrep II Kit designed for the rapid preparation of E. coli O157 DNA for direct use in PCR, the real-time detection of E. coli O157 DNA is carried out using the foodproof E. coli O157 Detection Kit. The kit provides primers and hydrolysis probes for sequence-specific detection, convenient premixed reagents, and controls for reliable interpretation of results. For repeatability studies three different foods (egg salad, large bockwurst/frankfurter, and apple juice) were analyzed, chosen from the 15 food groups recommended by the AOAC Research Institute for E. coli O157 detection. From each food, 20 samples were inoculated with a low level (1-10 CFU/25 g) and 20 samples with a high level (10-50 CFU/25 g) of E. coli O157. Additionally, five nonspiked samples were prepared from each food. Depending on the matrix, the food samples were examined with the test kits and compared with the cultural methods according to the U.S. Food and Drug Administration Bacteriological Analytical Manual or the U.S. Department of Agriculture/Food Safety and Inspection Service Microbiology Laboratory Guidebook. C1 [Junge, Benjamin; Groenewald, Cordt; Berghof-Jaeger, Kornelia] BIOTECON Diagnost GmbH, D-14473 Potsdam, Germany. [Hammack, Thomas; Chen, Yi] US FDA, College Pk, MD 20740 USA. RP Junge, B (reprint author), BIOTECON Diagnost GmbH, Hermannswerder Haus 17, D-14473 Potsdam, Germany. EM bjunge@bc-diagnostics.com NR 7 TC 0 Z9 0 U1 1 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2011 VL 94 IS 6 BP 1846 EP 1852 DI 10.5740/jaoacint.11-097 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 871EG UT WOS:000298720100019 PM 22320092 ER PT J AU Kanungo, J Lantz, S Paule, MG AF Kanungo, Jyotshnabala Lantz, Susan Paule, Merle G. TI In vivo imaging and quantitative analysis of changes in axon length using transgenic zebrafish embryos SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Zebrafish; Transgenic embryo; Axon; High content imaging; Ethanol ID PRENATAL ALCOHOL EXPOSURE; CHRONIC ETHANOL EXPOSURE; TAGGED TRIAZINE LIBRARY; MODEL SYSTEM; DANIO-RERIO; FISH; IDENTIFICATION; MORPHOGENESIS; SENSITIVITY; PROTEINS AB We describe an imaging procedure to measure axon length in zebrafish embryos in vivo. Automated fluorescent image acquisition was performed with the ImageXpress Micro high content screening reader and further analysis of axon lengths was performed on archived images using AcuityXpress software. We utilized the Neurite Outgrowth Application module with a customized protocol (journal) to measure the axons. Since higher doses of ethanol (2-2.5%, v/v) have been shown to deform motor neurons and axons during development, here we used ethanol to treat transgenic [hb9:GFP (green fluorescent protein)] zebrafish embryos at 28 hpf (hours post-fertilization). These embryos express GFP in the motor neurons and their axons. Embryos after ethanol treatment were arrayed in 384-well plates for automated fluorescent image acquisition in vivo. Average axon lengths of high dose ethanol-treated embryos were significantly lower than the control. Another experiment showed that there was no significant difference in the axon lengths between the embryos grown for 24 h at 22 degrees C and 28.5 degrees C. These test experiments demonstrate that using axon development as an end-point, compound screening can be performed in a time-efficient manner. Published by Elsevier Inc. C1 [Kanungo, Jyotshnabala; Lantz, Susan; 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, Bldg 53D,Room 2030, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA). We thank Melanie Dumas for her help in zebrafish breeding. NR 46 TC 14 Z9 14 U1 0 U2 5 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 NOV-DEC PY 2011 VL 33 IS 6 SI SI BP 618 EP 623 DI 10.1016/j.ntt.2011.08.013 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 869SU UT WOS:000298619300003 PM 21903162 ER PT J AU Sapkota, AR Hulet, RM Zhang, GY McDermott, P Kinney, EL Schwab, KJ Joseph, SW AF Sapkota, Amy R. Hulet, R. Michael Zhang, Guangyu McDermott, Patrick Kinney, Erinna L. Schwab, Kellogg J. Joseph, Sam W. TI Lower Prevalence of Antibiotic-Resistant Enterococci on US Conventional Poultry Farms that Transitioned to Organic Practices SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antibiotic resistance; antibiotic-resistant bacteria; antimicrobial growth promoter; Enterococcus; organic poultry ID ANTIMICROBIAL RESISTANCE; HUMAN HEALTH; PRODUCTION ENVIRONMENT; GROWTH PROMOTION; UNITED-STATES; ANIMAL FEED; FAECIUM; AVOPARCIN; BROILERS; HUMANS AB BACKGROUND: In U.S. conventional poultry production, antimicrobials are used for therapeutic, prophylactic, and non-therapeutic purposes. Researchers have shown that this can select for antibiotic-resistant commensal and pathogenic bacteria on poultry farms and in poultry-derived products. However, no U.S. studies have investigated on-farm changes in resistance as conventional poultry farms transition to organic practices and cease using antibiotics. OBJECTIVE: We investigated the prevalence of antibiotic-resistant Enterococcus on U.S. conventional poultry farms that transitioned to organic practices. METHODS: Poultry litter, feed, and water samples were collected from 10 conventional and 10 newly organic poultry houses in 2008 and tested for Enterococcus. Enterococcus (n = 259) was identified using the Vitek (R) 2 Compact System and tested for susceptibility to 17 antimicrobials using the Sensititre (TM) micro-broth dilution system. Data were analyzed using SAS software (version 9.2), and statistical associations were derived based on generalized linear mixed models. RESULTS: Litter, feed, and water samples were Enterococcus positive. The percentages of resistant Enterococcus faecalis and resistant Enterococcus faecium were significantly lower (p < 0.05) among isolates from newly organic versus conventional poultry houses for two (erythromycin and tylosin) and five (ciprofloxacin, gentamicin, nitrofurantoin, penicillin, and tetracycline) antimicrobials, respectively. Forty-two percent of E. faecalis isolates from conventional poultry houses were multidrug resistant (MDR; resistant to three or more anti-microbial classes), compared with 10% of isolates from newly organic poultry houses (p = 0.02); 84% of E. faecium isolates from conventional poultry houses were MDR, compared with 17% of isolates from newly organic poultry houses (p < 0.001). CONCLUSIONS: Our findings suggest that the voluntary removal of antibiotics from large-scale U.S. poultry farms that transition to organic practices is associated with a lower prevalence of antibiotic-resistant and MDR Enterococcus. C1 [Sapkota, Amy R.; Kinney, Erinna L.; Joseph, Sam W.] Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, College Pk, MD 20742 USA. [Hulet, R. Michael] Penn State Univ, Dept Poultry Sci, University Pk, PA 16802 USA. [Zhang, Guangyu] Univ Maryland, Dept Epidemiol & Biostat, Sch Publ Hlth, College Pk, MD 20742 USA. [McDermott, Patrick] US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD USA. [Schwab, Kellogg J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Joseph, Sam W.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Sapkota, AR (reprint author), Univ Maryland, Sch Publ Hlth, Maryland Inst Appl Environm Hlth, 2234P SPH Bldg, College Pk, MD 20742 USA. EM ars@umd.edu RI Sapkota, Amy/A-6046-2011 FU Center for a Livable Future, Johns Hopkins Bloomberg School of Public Health FX This research was funded by the Center for a Livable Future, Johns Hopkins Bloomberg School of Public Health. NR 36 TC 20 Z9 20 U1 3 U2 31 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2011 VL 119 IS 11 BP 1622 EP 1628 DI 10.1289/ehp.1003350 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 844XL UT WOS:000296785900031 PM 21827979 ER PT J AU Williams, DK Galvin, TA Ma, HL Khan, AS AF Williams, Dhanya K. Galvin, Teresa A. Ma, Hailun Khan, Arifa S. TI Investigation of xenotropic murine leukemia virus-related virus (XMRV) in human and other cell lines SO BIOLOGICALS LA English DT Article DE Xenotropic murine leukemia virus-related virus (XMRV); Cell lines; Polymerase chain reaction (PCR) assay; Vaccines ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; UNITED-STATES; NO ASSOCIATION; HOST-RANGE; MOUSE DNA; CONTAMINATION; RETROVIRUS; SEQUENCES; PREVALENCE AB Xenotropic murine leukemia virus-related virus (XMRV) was discovered in human prostate tumors and later in some chronic fatigue syndrome (CFS) patients. However, subsequent studies have identified various sources of potential contamination with XMRV and other murine leukemia virus (MLV)-related sequences in test samples. Biological and nucleotide sequence analysis indicates that XMRV is distinct from known xenotropic MLVs and has a broad host range and cell tropism including human cells. Therefore, it is prudent to minimize the risk of human exposure to infection by evaluating XMRV contamination in cell lines handled in laboratory research and particularly those used in the manufacture of biological products. Nested DNA PCR assays were optimized for investigating XMRV gag and env sequences in various cell lines, which included MRC-5, Vero, HEK-293, MDCK, HeLa, and A549, that may be used in the development of some vaccines and other cell lines broadly used in research. The sensitivity of the DNA PCR assays was <10 copies in approximately 1.8 x 10(5) cells equivalent of human DNA. The results indicated the absence of XMRV in the cell lines tested; although in some cases DNA fragments identified as cellular sequences were seen following the first round of PCR amplification with the env primer pair. Published by Elsevier Ltd on behalf of The International Alliance for Biological Standardization. C1 [Williams, Dhanya K.; Galvin, Teresa A.; Ma, Hailun; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike,HFM-454, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov NR 48 TC 4 Z9 5 U1 0 U2 5 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 NOV PY 2011 VL 39 IS 6 BP 378 EP 383 DI 10.1016/j.biologicals.2011.08.011 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 853AT UT WOS:000297399300003 PM 21996050 ER PT J AU Ruiz, P Ray, M Fisher, J Mumtaz, M AF Ruiz, Patricia Ray, Meredith Fisher, Jeffrey Mumtaz, Moiz TI Development of a Human Physiologically Based Pharmacokinetic (PBPK) Toolkit for Environmental Pollutants SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Review DE volatile organic compounds; VOCs; metals; PBPK; toxicokinetic; National Health and Nutrition Examination Survey (NHANES) ID MERCURY FOLLOWING EXPOSURE; RISK-ASSESSMENT; CANCER-RISK; PERCUTANEOUS-ABSORPTION; CARBON-TETRACHLORIDE; TOXICOKINETIC MODEL; TISSUE DISTRIBUTION; METHYL MERCURY; RATS; PERCHLOROETHYLENE AB Physiologically Based Pharmacokinetic (PBPK) models can be used to determine the internal dose and strengthen exposure assessment. Many PBPK models are available, but they are not easily accessible for field use. The Agency for Toxic Substances and Disease Registry (ATSDR) has conducted translational research to develop a human PBPK model toolkit by recoding published PBPK models. This toolkit, when fully developed, will provide a platform that consists of a series of priority PBPK models of environmental pollutants. Presented here is work on recoded PBPK models for volatile organic compounds (VOCs) and metals. Good agreement was generally obtained between the original and the recoded models. This toolkit will be available for ATSDR scientists and public health assessors to perform simulations of exposures from contaminated environmental media at sites of concern and to help interpret biomonitoring data. It can be used as screening tools that can provide useful information for the protection of the public. C1 [Ruiz, Patricia; Mumtaz, Moiz] Agcy Tox Subst & Dis Registry, Div Toxicol & Environm Med, Computat Toxicol & Methods Dev Lab, Atlanta, GA 30333 USA. [Ray, Meredith] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. [Fisher, Jeffrey] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ruiz, P (reprint author), Agcy Tox Subst & Dis Registry, Div Toxicol & Environm Med, Computat Toxicol & Methods Dev Lab, Atlanta, GA 30333 USA. EM pruiz@cdc.gov; mere2110@yahoo.com; jeffrey.fisher@fda.hhs.gov; mgm4@cdc.gov NR 40 TC 5 Z9 5 U1 5 U2 23 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD NOV PY 2011 VL 12 IS 11 BP 7469 EP 7480 DI 10.3390/ijms12117469 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 857DS UT WOS:000297696100014 PM 22174611 ER PT J AU Courtney, B Hodge, JG AF Courtney, Brooke Hodge, James G., Jr. CA Task Force Pediat Emergency Mass C TI Legal considerations during pediatric emergency mass critical care events SO PEDIATRIC CRITICAL CARE MEDICINE LA English DT Article DE children; consent; critical care; disaster; emergency; emergency mass critical care; law; legal; liability; pediatric; security ID PUBLIC-HEALTH EMERGENCIES; DISASTER PREPAREDNESS; LIABILITY; ILL AB Introduction: Recent public health emergencies, such as the 2009 Influenza A/H1N1 Pandemic and Hurricane Katrina, underscore the importance of developing healthcare response plans and protocols for disasters impacting large populations. Significant research and scholarship, including the 2009 Institute of Medicine report on crisis standards of care and the 2008 Task Force for Mass Critical Care recommendations, provide guidance for healthcare responses to catastrophic emergencies. Most of these efforts recognize but do not focus on the unique needs of pediatric populations. In 2008, the Centers for Disease Control and Prevention supported the formation of a task force to address pediatric emergency mass critical care response issues, including legal issues. Liability is a significant concern for healthcare practitioners and facilities during pediatric emergency mass critical care that necessitates a shift to crisis standards of care. This article describes the legal considerations inherent in planning for and responding to catastrophic health emergencies and makes recommendations for pediatric emergency mass critical care legal preparedness. Methods: The Pediatric Emergency Mass Critical Care Task Force, composed of 36 experts from diverse public health, medical, and disaster response fields, convened in Atlanta, GA, on March 29-30, 2010, to review the pediatric emergency mass critical care recommendations developed by a 17-member steering committee. During the meeting, experts determined that the recommendations would be strengthened by a manuscript addressing legal issues. Authors drafted the manuscript through consensus-based study of peer-reviewed research, literature reviews, and expert opinion. The manuscript was reviewed by Pediatric Emergency Mass Critical Care Steering Committee members and additional legal counsel and revised. Task Force Recommendations: While the legal issues associated with providing pediatric emergency mass critical care are not unique within the overall context of disaster healthcare, the scope of the parens patriae power of states, informed consent principles, and security should be considered in pediatric emergency mass critical care planning and response efforts because parents and legal guardians may be unavailable to participate in healthcare decision making during disasters. In addition, practitioners who follow properly vetted and accepted pediatric emergency mass critical care disaster protocols in good faith should be protected from civil liability, and healthcare facilities that provide pediatric care should incorporate informed consent and security protocols into their disaster plans. (Pediatr Crit Care Med 2011; 12[Suppl.]: S152-S156) C1 [Courtney, Brooke] US FDA, Off Counterterrorism & Emerging Threats, Silver Spring, MD USA. [Hodge, James G., Jr.] Arizona State Univ, Publ Hlth Law & Policy Program, Sandra Day OConnor Coll Law, Tempe, AZ USA. RP Courtney, B (reprint author), US FDA, Off Counterterrorism & Emerging Threats, Silver Spring, MD USA. EM brooke.courtney@fda.hhs.gov FU Centers for Disease Control and Prevention FX The Pediatric Emergency Mass Critical Care Task Force was supported, in part, by the Centers for Disease Control and Prevention. NR 33 TC 5 Z9 5 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1529-7535 J9 PEDIATR CRIT CARE ME JI Pediatr. Crit. Care Med. PD NOV PY 2011 VL 12 IS 6 SU S BP S152 EP S156 DI 10.1097/PCC.0b013e318234a7e1 PG 5 WC Critical Care Medicine; Pediatrics SC General & Internal Medicine; Pediatrics GA 848LU UT WOS:000297053900007 PM 22067924 ER PT J AU Alger, HM Raben, N Pistilli, E Francia, DL Rawat, R Getnet, D Ghimbovschi, S Chen, YW Lundberg, IE Nagaraju, K AF Alger, Heather M. Raben, Nina Pistilli, Emidio Francia, Dwight L. Rawat, Rashmi Getnet, Derese Ghimbovschi, Svetlana Chen, Yi-Wen Lundberg, Ingrid E. Nagaraju, Kanneboyina TI The Role of TRAIL in Mediating Autophagy in Myositis Skeletal Muscle A Potential Nonimmune Mechanism of Muscle Damage SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; MHC CLASS-I; NF-KAPPA-B; CELL-DEATH; INFLAMMATORY MYOPATHIES; AUTOIMMUNE MYOSITIS; GOLGI-COMPLEX; UP-REGULATION; APOPTOSIS; DERMATOMYOSITIS AB Objective. Multinucleated cells are relatively resistant to classic apoptosis, and the factors initiating cell death and damage in myositis are not well defined. We hypothesized that nonimmune autophagic cell death may play a role in muscle fiber damage. Recent reports indicate that TRAIL may induce both NF-kappa B activation and autophagic cell death in other systems. We undertook this study to investigate the role of TRAIL in cell death and pathogenesis in vitro and in vivo, using myositis muscle tissues from humans and mice. Methods. Gene expression profiling was performed in myositis patient and control muscle specimens. Immunohistochemistry analysis was performed to confirm the gene array findings. We also analyzed TRAIL-induced cell death (apoptosis and autophagy) and NF-kappa B activation in vitro in cultured cells. Results. TRAIL was expressed predominantly in myositis muscle fibers, but not in biopsy specimens from normal or other dystrophic-diseased muscle. Autophagy markers were up-regulated in humans with myositis and in mouse models of myositis. TRAIL expression was restricted to regenerating/atrophic areas of muscle fascicles, blood vessels, and infiltrating lymphocytes. TRAIL induced NF-kappa B activation and I kappa B degradation in cultured cells that are resistant to TRAIL-induced apoptosis but that undergo autophagic cell death. Conclusion. Our data demonstrate that TRAIL is expressed in myositis muscle and may mediate both activation of NF-kappa B and autophagic cell death in myositis. Thus, this nonimmune pathway may be an attractive target for therapeutic intervention in myositis. C1 [Nagaraju, Kanneboyina] Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. [Alger, Heather M.; Francia, Dwight L.; Ghimbovschi, Svetlana; Chen, Yi-Wen; Nagaraju, Kanneboyina] George Washington Univ, Med Ctr, Washington, DC 20037 USA. [Raben, Nina] NIAMSD, NIH, Bethesda, MD 20892 USA. [Pistilli, Emidio] Univ Penn, Philadelphia, PA 19104 USA. [Rawat, Rashmi] FDA, Silver Spring, MD USA. [Getnet, Derese] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Lundberg, Ingrid E.] Karolinska Univ Hosp Solna, Stockholm, Sweden. [Lundberg, Ingrid E.] Karolinska Inst, Stockholm, Sweden. RP Nagaraju, K (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM knagaraju@cnmcresearch.org RI Getnet, Derese/C-5421-2012 FU NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases) [1-R01-AR-052027-01A2]; National Institute of Child Health and Human Development [1-U54-HD-053177-01A1, 1-R24-HD-050846-01]; Myositis Association; Association Francaise contre les Myopathies; NIH [R01-AR-050478, 5-U54-HD-053177] FX Dr. Chen's work was supported in part by the NIH (National Institute of Arthritis and Musculoskeletal and Skin Diseases grant 1-R01-AR-052027-01A2 and National Institute of Child Health and Human Development grants 1-U54-HD-053177-01A1 and 1-R24-HD-050846-01). Dr. Lundberg's work was supported by the Myositis Association and the Association Francaise contre les Myopathies. Dr. Nagaraju's work was supported by the NIH (grants R01-AR-050478 and 5-U54-HD-053177). NR 47 TC 11 Z9 12 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD NOV PY 2011 VL 63 IS 11 BP 3448 EP 3457 PG 10 WC Rheumatology SC Rheumatology GA 850TC UT WOS:000297221100029 PM 21769834 ER PT J AU Rao, VA Zhang, J Klein, SR Espandiari, P Knapton, A Dickey, JS Herman, E Shacter, EB AF Rao, V. Ashutosh Zhang, Jun Klein, Sarah R. Espandiari, Parvaneh Knapton, Alan Dickey, Jennifer S. Herman, Eugene Shacter, Emily B. TI The iron chelator Dp44mT inhibits the proliferation of cancer cells but fails to protect from doxorubicin-induced cardiotoxicity in spontaneously hypertensive rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Anthracyclines; Spontaneously hypertensive rats; Cardiotoxicity; Dexrazoxane; Dp44mT ID TOPOISOMERASE II-ALPHA; DOUBLE-STRAND BREAKS; ANTITUMOR-ACTIVITY; NITRIC-OXIDE; IN-VIVO; DEXRAZOXANE; GAMMA-H2AX; DAMAGE; CYTOTOXICITY; PREVENTION AB The iron chelator Dp44mT is a potent topoisomerase II alpha inhibitor with novel anticancer activity. Doxorubicin (Dox), the current front-line therapy for breast cancer, induces a dose-limiting cardiotoxicity, in part through an iron-mediated pathway. We tested the hypothesis that Dp44mT can improve clinical outcomes of treatment with Dox by alleviating cardiotoxicity. The general cardiac and renal toxicities induced by Dox were investigated in the presence and absence of Dp44mT. The iron chelating cardioprotectant Dexrazoxane (Drz), which is approved for this indication, was used as a positive control. In vitro studies were carried out with H9c2 rat cardiomyocytes and in vivo studies were performed using spontaneously hypertensive rats. Testing of the GI(50) profile of Dp44mT in the NCI-60 panel confirmed activity against breast cancer cells. An acute, toxic dose of Dox caused the predicted cellular and cardiac toxicities, such as cell death and DNA damage in vitro and elevated cardiac troponin T levels, tissue damage, and apoptosis in vivo. Dp44mT alone caused insignificant changes in hematological and biochemical indices in rats, indicating that Dp44mT is not significantly cardiotoxic as a single agent. In contrast to Drz, Dp44mT failed to mitigate Dox-induced cardiotoxicity in vivo. We conclude that although Dp44mT is a potent iron chelator, it is unlikely to be an appropriate cardioprotectant against Dox-induced toxicity. However, it should continue to be evaluated as a potential anticancer agent as it has a novel mechanism for inhibiting the growth of a broad range of malignant cell types while exhibiting very low intrinsic toxicity to healthy tissues. C1 [Rao, V. Ashutosh; Klein, Sarah R.; Dickey, Jennifer S.; Shacter, Emily B.] US FDA, Biochem Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Zhang, Jun; Espandiari, Parvaneh; Knapton, Alan; Herman, Eugene] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rao, VA (reprint author), US FDA, Biochem Lab, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 2A-11, Bethesda, MD 20892 USA. EM ashutosh.rao@fda.hhs.gov FU Food and Drug Administration; National Cancer Institute FX This study was funded by the intramural research program of the Food and Drug Administration and the National Cancer Institute. We thank Dr. Yves Pommier (NCI) for helpful discussions and Dr. Melanie Simpson (NCI) for critical reading of the manuscript. The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the U.S. Food and Drug Administration. NR 30 TC 13 Z9 16 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2011 VL 68 IS 5 BP 1125 EP 1134 DI 10.1007/s00280-011-1587-y PG 10 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 849KM UT WOS:000297124400004 PM 21373894 ER PT J AU Sonko, BJ Schmitt, TC Guo, L Shi, Q Boros, LG Leakey, JEA Beger, RD AF Sonko, Bakary J. Schmitt, Thomas C. Guo, Lei Shi, Qiang Boros, Laszlo G. Leakey, Julian E. A. Beger, Richard D. TI Assessment of usnic acid toxicity in rat primary hepatocytes using C-13 isotopomer distribution analysis of lactate, glutamate and glucose SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Usnic acid; Hepatotoxicity; U-C-13(6)-D-glucose; Mass isotopomer distribution analysis (MIDA) ID CHROMATOGRAPHY MASS-SPECTROMETRY; DRUG DEVELOPMENT; EMERGING APPLICATIONS; IN-VITRO; HEPATOTOXICITY; LIVER; VIVO AB The lichen metabolite usnic acid (UA) has been promoted as a dietary supplement for weight loss, although cases of hepatotoxicity have been reported. Here we evaluated UA-associated hepatotoxicity in vitro using isolated rat hepatocytes. We measured cell viability and ATP content to evaluate UA induced cytotoxicity and applied C-13 isotopomer distribution measuring techniques to gain a better understanding of glucose metabolism during cytotoxicity. The cells were exposed to 0, 1, 5 or 10 mu M UA concentrations for 2,6 or 24 h. Aliquots of media were collected at the end of these time periods and the C-13 mass isotopomer distribution determined for CO2, lactate, glucose and glutamate. The 1 mu M UA exposure did not appear to cause significant change in cell viability compared to controls. However, the 5 and 10 mu M UA concentrations significantly reduced cell viability as exposure time increased. Similar results were obtained for ATP depletion experiments. The 1 and 5 mu M UA doses suggest increased oxidative phosphorylation. Conversely, oxidative phosphorylation and gluconeogenesis were dramatically inhibited by 10 mu M UA. Augmented oxidative phosphorylation at the lower UA concentrations may be an adaptive response by the cells to compensate for diminished mitochondrial function. Published by Elsevier Ltd. C1 [Sonko, Bakary J.; Schmitt, Thomas C.; Shi, Qiang; Beger, Richard D.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Guo, Lei] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Boros, Laszlo G.] SIDMAP LLC, Los Angeles, CA 90064 USA. [Boros, Laszlo G.] Univ Calif Los Angeles, Sch Med, Dept Pediat Metab & Endocrinol, Los Angeles, CA USA. [Leakey, Julian E. A.] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov RI Qiang, Shi/E-6266-2012 FU FDA Commissioner's Office; National Center for Toxicological Research; NCTR/USFDA [IAG 224-07-007 NCTR/NTP]; National Toxicology Program [IAG 224-07-007 NCTR/NTP]; National Institute for Environmental Health Sciences, National Institutes of Health FX The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. This article is not an official guidance or policy statement of US Food and Drug Administration (FDA). Funding for this study was provided by the FDA Commissioner's Office as part of its "Commissioner's Fellowship Program" and by the National Center for Toxicological Research. This work was also supported in part by an Interagency Agreement (IAG 224-07-007 NCTR/NTP) between the NCTR/USFDA and National Toxicology Program and the National Institute for Environmental Health Sciences, National Institutes of Health. NR 26 TC 14 Z9 14 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2011 VL 49 IS 11 BP 2968 EP 2974 DI 10.1016/j.fct.2011.07.047 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 843OM UT WOS:000296681600032 PM 21802472 ER PT J AU Sulaiman, IM Anderson, M Khristova, M Tang, K Sulaiman, N Phifer, E Simpson, S Kerdahi, K AF Sulaiman, Irshad M. Anderson, Mickey Khristova, Marina Tang, Kevin Sulaiman, Nikhat Phifer, Edwin Simpson, Steven Kerdahi, Khalil TI Development of a PCR-Restriction Fragment Length Polymorphism Protocol for Rapid Detection and Differentiation of Four Cockroach Vectors (Group I "Dirty 22" Species) Responsible for Food Contamination and Spreading of Foodborne Pathogens: Public Health Importance SO JOURNAL OF FOOD PROTECTION LA English DT Article ID REGULATORY ACTION CRITERIA; RIBOSOMAL-RNA GENE; BLATTELLA-GERMANICA; FLIES DIPTERA; EVOLUTIONARY RELATIONSHIPS; CRYPTOSPORIDIUM PARASITES; PHYLOGENETIC ANALYSIS; MOLECULAR PHYLOGENY; SP APICOMPLEXA; FILTH AB Assessing the adulteration of food products and the presence of filth and extraneous materials is one of the measures that the U.S. Food and Drug Administration (FDA) utilizes in implementing regulatory actions of public health importance. To date, 22 common pest species (also known as the "Dirty 22" species) have been regarded by this agency as the spreaders of foodborne diseases. We have further categorized the Dirty 22 species into four groups: 1 has four cockroach species, 11 has two ant species, has 12 fly species, and TV has four rodent species. The presence of any Dirty 22 species is also considered an indicator of unsanitary conditions in food processing and storage facilities. In this study, we describe the development of a two-step nested PCR protocol to amplify the small subunit ribosomal gene of group I Dirty 22 species that include four cockroach species: Biotic Ila germanica, Blotto orientalis, Periplaneta americana, and Supella longipalpa, along with the development of a PCR restriction fragment length polymorphism method for rapid detection and differentiation of these violative species. This method will be utilized when the specimen cannot be identified with conventional microscopic taxonomic methods, especially when only small body parts are separated and recovered from food samples for analysis or when these body parts are in a decomposed state. This new PCR restriction fragment length polymorphism will provide correct identification of group I Dirty 22 species; this information can then be used in regulation and prevention of foodbome pathogens. C1 [Sulaiman, Irshad M.; Anderson, Mickey; Phifer, Edwin; Simpson, Steven; Kerdahi, Khalil] US FDA, S Reg Lab, Atlanta, GA 30309 USA. [Khristova, Marina; Tang, Kevin; Sulaiman, Nikhat] Ctr Dis Control & Prevent, Biotechnol Core Facil Branch, Atlanta, GA 30333 USA. RP Sulaiman, IM (reprint author), US FDA, S Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM irshad.sulaiman@fda.hhs.gov FU Biotechnology Core Facility Branch, CDC; Division of Field Sciences (DFS) of the FDA; DFS Challenge Initiative FX The authors thank Dr. Roberto M. Pereira, Urban Entomology Laboratory, Entomology and Nematology Department, University of Florida, for providing the specimens used in this study, and Dr. Jan Pohl, Biotechnology Core Facility Branch, CDC, for his support. The authors also thank Dr. Kathy Kellar, Division of Scientific Resources, CDC, for her comments on this manuscript. This study was supported in part by funding from the Division of Field Sciences (DFS) of the FDA; Dr. Irshad M. Sulaiman is Principal Investigator of the DFS Challenge Initiative Program grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 7 Z9 8 U1 0 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2011 VL 74 IS 11 BP 1883 EP 1890 DI 10.4315/0362-028X.JFP-11-242 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 844OL UT WOS:000296756800012 PM 22054189 ER PT J AU Anderson, NM Larkin, JW Cole, MB Skinner, GE Whiting, RC Gorris, LGM Rodriguez, A Buchanan, R Stewart, CM Hanlin, JH Keener, L Hall, PA AF Anderson, N. M. Larkin, J. W. Cole, M. B. Skinner, G. E. Whiting, R. C. Gorris, L. G. M. Rodriguez, A. Buchanan, R. Stewart, C. M. Hanlin, J. H. Keener, L. Hall, P. A. TI Food Safety Objective Approach for Controlling Clostridium botulinum Growth and Toxin Production in Commercially Sterile Foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID PROCESS CHEESE SPREADS; HEAT-RESISTANCE; IN-PROCESS; MODIFIED ATMOSPHERE; BACTERIAL-SPORES; MEAT-PRODUCTS; CANNED FOODS; B BOTULINUS; CURED MEAT; PH VALUES AB As existing technologies are refined and novel microbial inactivation technologies are developed, there is a growing need for a metric that can be used to judge equivalent levels of hazard control stringency to ensure food safety of commercially sterile foods. A food safety objective (FSO) is an output-oriented metric that designates the maximum level of a hazard (e.g., the pathogenic microorganism or toxin) tolerated in a food at the end of the food supply chain at the moment of consumption without specifying by which measures the hazard level is controlled. Using a risk-based approach, when the total outcome of controlling initial levels (H(0)), reducing levels (Sigma R), and preventing an increase in levels (Sigma I) is less than or equal to the target FSO, the product is considered safe. A cross-disciplinary international consortium of specialists from industry, academia, and government was organized with the objective of developing a document to illustrate the FSO approach for controlling Clostridium botulinum toxin in commercially sterile foods. This article outlines the general principles of an FSO risk management framework for controlling C. botulinum growth and toxin production in commercially sterile foods. Topics include historical approaches to establishing commercial sterility; a perspective on the establishment of an appropriate target FSO; a discussion of control of initial levels, reduction of levels, and prevention of an increase in levels of the hazard; and deterministic and stochastic examples that illustrate the impact that various control measure combinations have on the safety of well-established commercially sterile products and the ways in which variability all levels of control can heavily influence estimates in the FSO risk management framework. This risk-based framework should encourage development of innovative technologies that result in microbial safety levels equivalent to those achieved with traditional processing methods. C1 [Anderson, N. M.; Larkin, J. W.; Skinner, G. E.] US FDA, Inst Food Safety & Hlth, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Cole, M. B.; Rodriguez, A.; Stewart, C. M.] IIT, Inst Food Safety & Hlth, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Whiting, R. C.; Buchanan, R.] US FDA, College Pk, MD 20740 USA. [Gorris, L. G. M.] Unilever Safety & Environm Assurance Ctr, Sharnbrook MK44 1LQ, Beds, England. [Hanlin, J. H.] Gen Mills, Minneapolis, MN 55426 USA. [Keener, L.] Int Prod Safety Consultants, Seattle, WA 98199 USA. [Hall, P. A.] ConAgra Foods Inc, Omaha, NE 68102 USA. RP Anderson, NM (reprint author), US FDA, Inst Food Safety & Hlth, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM nathan.anderson@fda.hhs.gov NR 107 TC 17 Z9 17 U1 0 U2 43 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2011 VL 74 IS 11 BP 1956 EP 1989 DI 10.4315/0362-028X.JFP-11-082 PG 34 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 844OL UT WOS:000296756800023 PM 22054200 ER PT J AU Shelor, CP Campbell, CA Kroll, M Dasgupta, PK Smith, TL Abdalla, A Hamilton, M Muhammad, TW AF Shelor, C. Philip Campbell, Catrina A. Kroll, Martina Dasgupta, Purnendu K. Smith, Tammy L. Abdalla, Amir Hamilton, Mike Muhammad, Terri Wiley TI Fenton Digestion of Milk for Iodinalysis SO ANALYTICAL CHEMISTRY LA English DT Article ID PLASMA-MASS SPECTROMETRY; MEASURING URINARY IODINE; HYDROGEN-PEROXIDE; BREAST-MILK; SERUM THYROXINE; SEMIAUTOMATED METHOD; ADVANCED OXIDATION; HORMONE SYNTHESIS; WASTE-WATER; PERCHLORATE AB Iodine is an essential micronutrient especially important in the neurodevelopment of infants. Spot samples of urinary iodine (UI) are used as an epidemiologic index of adult iodine nutrition. Individual infant iodine nutrition is of vital importance, but infant urine is difficult to collect, much less a 24 h sample. Monitoring the intake provides a pragmatic solution for determining infant iodine nutrition. Because of the high solids content of milk and the possible existence of iodine in an organically bound form, sample digestion is obligatory. The U.S. Food and Drug Administration, for example, uses wet ashing by HClO4; special precautions and fume hoods are required. We present a method of Fenton digestion of human and bovine milk samples and infant formula. No specialized equipment or hazardous reagents are used; measurement is made by isotope dilution inductively coupled plasma mass spectrometry. In Fenton digestion, Fe (II) and H2O2 oxidizes the sample. In an interlaboratory study, excellent agreement (r(2) = 0.9934) was observed with results obtained by HClO4 digestion and Sandel-Kolthoff kinetic colorimetry. Average recoveries of iodide, triiodothyronine, and thyroxine ranged between 100% and 101%. Following digestion, iodine was found to exist entirely as iodide. Control of pH is imperative if loss cannot be corrected for by isotope dilution. Loss was below 20% for all samples when the pH was between 2.25 and 2.5 C1 [Shelor, C. Philip; Campbell, Catrina A.; Kroll, Martina; Dasgupta, Purnendu K.] Univ Texas Arlington, Dept Chem & Biochem, Arlington, TX 76019 USA. [Smith, Tammy L.; Abdalla, Amir; Hamilton, Mike; Muhammad, Terri Wiley] US FDA, Kansas City Dist Lab, Lenexa, KS 66214 USA. RP Dasgupta, PK (reprint author), Univ Texas Arlington, Dept Chem & Biochem, Arlington, TX 76019 USA. OI Shelor, Charles/0000-0002-2318-9411 FU Gerber Foundation; National Science Foundation [CHE-0821969] FX This work was primarily supported by a grant from the Gerber Foundation. Auxiliary support from the National Science Foundation through Grant CHE-0821969 is also acknowledged. NR 76 TC 8 Z9 8 U1 4 U2 30 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 NOV 1 PY 2011 VL 83 IS 21 BP 8300 EP 8307 DI 10.1021/ac202165e PG 8 WC Chemistry, Analytical SC Chemistry GA 837TE UT WOS:000296225300038 PM 21936491 ER PT J AU Pfefer, TJ Wang, QZ Drezek, RA AF Pfefer, T. Joshua Wang, Quanzeng Drezek, Rebekah A. TI Monte Carlo modeling of time-resolved fluorescence for depth-selective interrogation of layered tissue SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE Monte Carlo; Light-tissue interaction; Optical diagnostics; Cancer detection ID LASER-INDUCED FLUORESCENCE; FIBEROPTIC PROBE; TURBID MEDIA; SPECTROSCOPY; DISCRIMINATION; LESIONS; DESIGN AB Computational approaches for simulation of light-tissue interactions have provided extensive insight into biophotonic procedures for diagnosis and therapy. However, few studies have addressed simulation of time-resolved fluorescence (TRF) in tissue and none have combined Monte Carlo simulations with standard TRF processing algorithms to elucidate approaches for cancer detection in layered biological tissue. In this study, we investigate how illumination-collection parameters (e.g., collection angle and source-detector separation) influence the ability to measure fluorophore lifetime and tissue layer thickness. Decay curves are simulated with a Monte Carlo TRF light propagation model. Multi-exponential iterative deconvolution is used to determine lifetimes and fractional signal contributions. The ability to detect changes in mucosal thickness is optimized by probes that selectively interrogate regions superficial to the mucosal-submucosal boundary. Optimal accuracy in simultaneous determination of lifetimes in both layers is achieved when each layer contributes 40-60% of the signal. These results indicate that depth-selective approaches to TRF have the potential to enhance disease detection in layered biological tissue and that modeling can play an important role in probe design optimization. Published by Elsevier Ireland Ltd. C1 [Pfefer, T. Joshua; Wang, Quanzeng] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Drezek, Rebekah A.] Rice Univ, Dept Bioengn, Houston, TX 77005 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joshua.pfefer@fda.hhs.gov RI Drezek, Rebekah/A-5101-2012; Pfefer, Josh/I-9055-2012 NR 19 TC 3 Z9 3 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD NOV PY 2011 VL 104 IS 2 BP 161 EP 167 DI 10.1016/j.cmpb.2010.10.011 PG 7 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 847AU UT WOS:000296945100015 PM 21111507 ER PT J AU Zhang, J Stockbridge, N AF Zhang, Joanne Stockbridge, Norman TI SELECTION OF THE TIME POINTS FOR A THOROUGH QTC STUDY SO DRUG INFORMATION JOURNAL LA English DT Letter ID MOXIFLOXACIN C1 [Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Stockbridge, Norman] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhang, J (reprint author), US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD NOV PY 2011 VL 45 IS 6 BP 713 EP 715 PG 3 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 837TG UT WOS:000296225500006 ER PT J AU Norton, JD AF Norton, Jonathan D. TI A Longitudinal Model and Graphic for Benefit-risk Analysis, With Case Study SO DRUG INFORMATION JOURNAL LA English DT Article DE Benefit-risk; Graphics; Longitudinal; Safety; Missing data ID CLINICAL-TRIALS AB A novel method for simultaneously visualizing benefit and risk over time is presented. The underlying model represents a subject's benefit-risk state at a given time as one of five discrete clinical states, one being premature study withdrawal. The new graphic uses colors to represent each subject's changing state over the course of the clinical trial. The user can quickly grasp how a treatment affects subjects in aggregate, then further examine how individuals are affected. It is possible to tell whether the beneficial and harmful outcomes are correlated. The method is particularly appropriate for treatments that provide only symptomatic relief An approved drug for chronic pain is presented as a worked example. C1 [Norton, Jonathan D.] US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Norton, JD (reprint author), 10903 New Hampshire Ave,WO 22,Rm 3562, Silver Spring, MD 20904 USA. EM Jonathan.Norton@fda.hhs.gov NR 13 TC 5 Z9 5 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD NOV PY 2011 VL 45 IS 6 BP 741 EP 747 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 837TG UT WOS:000296225500010 ER PT J AU Beger, R AF Beger, Richard TI Metabolomics markers of drug induced liver and kidney injury SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 17th North American Regional ISSX Meeting CY OCT 16-20, 2011 CL Atlanta, GA C1 [Beger, Richard] US FDA, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD NOV PY 2011 VL 43 SU 2 SI SI BP 28 EP 28 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848MT UT WOS:000297056400059 ER PT J AU Einolf, H Chen, LF Fahmi, OA Gibson, CR Obach, RS Shebley, M Sinz, M Silva, J Unadkat, JD Zhang, L Zhao, P AF Einolf, Heidi Chen, Liangfu Fahmi, Odette A. Gibson, Christopher R. Obach, R. Scott Shebley, Mohamad Sinz, Michael Silva, Jose Unadkat, Jashvant D. Zhang, Lei Zhao, Ping TI assessing modeling and simulation tools and methods for predicting induction-based drug-drug interactions: A collaborative effort between academic, government regulatory, and pharmaceutical scientists from the IQ consortium (IQC) SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 17th North American Regional ISSX Meeting CY OCT 16-20, 2011 CL Atlanta, GA C1 [Einolf, Heidi] Novartis Inst BioMed Res Inc, Drug Metab & Pharmacokinet, E Hanover, NJ USA. [Chen, Liangfu] GlaxoSmithKline Inc, Drug Metab & Pharmacokinet, King Of Prussia, PA USA. [Fahmi, Odette A.] Pfizer Inc, Pharmacokinet & Drug Metab, Groton, CT 06340 USA. [Gibson, Christopher R.] Merck Res Labs, Drug Metab, West Point, PA USA. [Obach, R. Scott] Pfizer Global Res & Dev, Pdm, Groton, CT USA. [Shebley, Mohamad] Abbott Labs, Abbott Pk, IL USA. [Sinz, Michael] Bristol Myers Squibb Co, Metab & Pharmacokinet, Wallingford, CT 06492 USA. [Silva, Jose] Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Metab Pharmacokinet, Raritan, NJ USA. [Unadkat, Jashvant D.] Univ Washington, Seattle, WA 98195 USA. [Zhang, Lei] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Zhao, Ping] US FDA, CDER, Off Clin Pharmacol, Silver Spring, MD USA. RI Shebley, Mohamad/G-1368-2016 OI Shebley, Mohamad/0000-0002-0147-8933 NR 0 TC 0 Z9 0 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD NOV PY 2011 VL 43 SU 2 SI SI BP 100 EP 100 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848MT UT WOS:000297056400191 ER PT J AU Lee, CA Bentz, J O'Connor, M Palm, J Ellens, H Heredi-Szabo, K Bednarczyk, D Taub, M Perloff, ES Funk, C Balimane, P Salphati, L Guo, A Podila, L Hanna, I Xia, C Li, LB Xiao, GQ Wortelboer, HM Weitz, D Pak, YA Reyner, E Taur, J Chu, XY Gradhand, U Warren, M Rajaraman, G Zhang, L AF Lee, Caroline A. Bentz, Joseph O'Connor, Michael Palm, Johan Ellens, Harma Heredi-Szabo, Krisztina Bednarczyk, Dallas Taub, Mitchell Perloff, Elke S. Funk, Christoph Balimane, Praveen Salphati, Laurent Guo, Ailan Podila, Lalitha Hanna, Imad Xia, Cindy Li, Libin Xiao, Guangqing Wortelboer, Heleen M. Weitz, Dietmar Pak, Youngeen A. Reyner, Eric Taur, Jesse Chu, Xiaoyan Gradhand, Ulrike Warren, Mark Rajaraman, Ganesh Zhang, Lei TI Application of receiver operating characteristics to assess digoxin drug interaction potential SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 17th North American Regional ISSX Meeting CY OCT 16-20, 2011 CL Atlanta, GA C1 [Lee, Caroline A.] Pfizer Inc, Pharmacokinet Dynam & Metab, San Diego, CA USA. [Bentz, Joseph; O'Connor, Michael] Drexel Univ, Philadelphia, PA 19104 USA. [Palm, Johan] AstraZeneca, Molndal, Sweden. [Ellens, Harma] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Heredi-Szabo, Krisztina] SOLVO Biotechnol, Szeged, Hungary. [Bednarczyk, Dallas] Novartis, Cambridge, MA USA. [Taub, Mitchell] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Perloff, Elke S.] BD Biosci, Woburn, MA USA. [Funk, Christoph] Hoffmann La Roche Ltd, Dept Nonclin Drug Safety, Basel, Switzerland. [Balimane, Praveen] Bristol Myers Squibb, San Francisco, CA USA. [Salphati, Laurent] Genentech Inc, San Francisco, CA 94080 USA. [Guo, Ailan] Hoffmann La Roche Inc, Nonclin Drug Safety, Nutley, NJ 07110 USA. [Podila, Lalitha] Boehringer Ingelheim Pharmaceut Inc, Drug Metab & Pharmacokinet, Ridgefield, CT 06877 USA. [Hanna, Imad] Novartis Inst BioMed Res Inc, Drug Metab & Pharmacokinet, E Hanover, NJ USA. [Xia, Cindy] Millennium Pharmaceut Inc, Drug Metab & Pharmacokinet, Cambridge, MA USA. [Li, Libin] Absorpt Syst LP, Exton, PA USA. [Xiao, Guangqing] Biogen Inc, Cambridge, MA 02142 USA. [Wortelboer, Heleen M.] TNO Qual Life, Pharmacokinet, Zeist, Netherlands. [Weitz, Dietmar] Sanofi Aventis, Indianapolis, IN USA. [Pak, Youngeen A.] Eli Lilly & Co, Drug Disposit, Indianapolis, IN 46285 USA. [Reyner, Eric] Pfizer Global Res & Dev, San Diego, CA USA. [Taur, Jesse] Eisai & Co Ltd, Rahway, NJ USA. [Chu, Xiaoyan] Merck & Co Inc, Merck Rsch Lab, Drug Metab & Pharmacokinet, Rahway, NJ 07065 USA. [Gradhand, Ulrike] Merck KGaA, Austin, TX USA. [Warren, Mark] Optivia, Austin, TX USA. [Rajaraman, Ganesh] Life Technol CellzDirect, Austin, TX USA. [Zhang, Lei] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PD NOV PY 2011 VL 43 SU 2 SI SI BP 190 EP 191 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 848MT UT WOS:000297056400360 ER PT J AU Wear, KA Gammell, PM Maruvada, S Liu, YB Harris, GR AF Wear, Keith A. Gammell, Paul M. Maruvada, Subha Liu, Yunbo Harris, Gerald R. TI Time-Delay Spectrometry Measurement of Magnitude and Phase of Hydrophone Response SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID CALIBRATION; AMPLITUDE; MHZ AB A method based on time-delay spectrometry (TDS) was developed for measuring both magnitude and phase response of a hydrophone. The method was tested on several types of hydrophones used in medical ultrasound exposimetry over the range from 5 to 18 MHz. These included polyvinylidene fluoride (PVDF) spot-poled membrane, needle, and capsule designs. One needle hydrophone was designed for high-intensity focused ultrasound (HIFU) applications. The average reproducibility (after repositioning the hydrophone) of the phase measurement was 2.4 degrees. The minimum-phase model, which implies that the phase response is equal to the inverse Hilbert transform of the natural logarithm of the magnitude response, was tested with TDS hydrophone data. Direct TDS-based measurements of hydrophone phase responses agreed well with calculations based on the minimum-phase model, with rms differences of 1.76 degrees (PVDF spot-poled membrane hydrophone), 3.10 degrees (PVDF capsule hydrophone), 3.43 degrees (PVDF needle hydrophone), and 3.36 (ceramic needle hydrophone) over the range from 5 to 18 MHz. Therefore, phase responses for several types of hydrophones may be inferred from measurements of their magnitude responses. Calculation of phase response based on magnitude response using the minimum-phase model is a relatively simple and practical alternative to direct measurement of phase. C1 [Wear, Keith A.; Maruvada, Subha; Liu, Yunbo; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Gammell, Paul M.] Gammell Appl Technol LLC, Exmore, VA USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM keith.wear@fda.hhs.gov NR 23 TC 10 Z9 10 U1 0 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD NOV PY 2011 VL 58 IS 11 BP 2325 EP 2333 DI 10.1109/TUFFC.2011.2090 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 848PW UT WOS:000297065200008 PM 22083766 ER PT J AU Crane, NT Juan, WY Goldman, JD Ellwood, KC Schneeman, BO AF Crane, Nancy T. Juan, Wenyen Goldman, Joseph D. Ellwood, Kathleen C. Schneeman, Barbara O. TI National Nutrition Objectives and 10-Year Targets: Perspectives on Their Basis and Evolution SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article C1 [Schneeman, Barbara O.] US FDA, Off Nutr Labeling & Dietary Supplements HFS 800, College Pk, MD 20740 USA. [Goldman, Joseph D.] ARS, Food Surveys Res Grp, USDA, Beltsville, MD USA. RP Crane, NT (reprint author), US FDA, Off Nutr Labeling & Dietary Supplements HFS 830, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM nancy.crane@fda.hhs.gov NR 37 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD NOV PY 2011 VL 111 IS 11 BP 1660 EP 1669 DI 10.1016/j.jada.2011.08.010 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 847BK UT WOS:000296946700008 PM 22027047 ER PT J AU Kalasinsky, VF Tristan, JO Strausborger, SL Rumm, PD Luong, TT Pizzolato, KM Blubaugh, LM Mullick, FG MacIntosh, VH Gaydos, JC AF Kalasinsky, Victor F. Tristan, Jesse O. Strausborger, Stacy L. Rumm, Peter D. Luong, Thuy T. Pizzolato, Karen M. Blubaugh, Lynn M. Mullick, Florabel G. MacIntosh, Victor H. Gaydos, Joel C. TI The U.S. Department of Defense Internet-Accessible Directory of Public Health Laboratory Services SO MILITARY MEDICINE LA English DT Editorial Material ID EXPOSURE C1 [Kalasinsky, Victor F.; Tristan, Jesse O.; Strausborger, Stacy L.; Luong, Thuy T.; Pizzolato, Karen M.; Blubaugh, Lynn M.; Mullick, Florabel G.] Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. [Rumm, Peter D.] US FDA, Div Surg Orthoped & Restorat Devices, Silver Spring, MD 20993 USA. [MacIntosh, Victor H.; Gaydos, Joel C.] Armed Forces Hlth Surveillance Ctr, Div Global Emerging Infect Surveillance & Resp Sy, Silver Spring, MD 20904 USA. RP Kalasinsky, VF (reprint author), Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, 6825 16th St NW, Washington, DC 20306 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD NOV PY 2011 VL 176 IS 11 BP 1205 EP 1206 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 845NR UT WOS:000296830300001 PM 22165645 ER PT J AU Dunne, J Rodriguez, WJ Murphy, D Beasley, BN Burckart, GJ Filie, JD Lewis, LL Sachs, HC Sheridan, PH Starke, P Yao, LP AF Dunne, Julia Rodriguez, William J. Murphy, Dianne Beasley, B. Nhi Burckart, Gilbert J. Filie, Jane D. Lewis, Linda L. Sachs, Hari C. Sheridan, Philip H. Starke, Peter Yao, Lynne P. TI Extrapolation of Adult Data and Other Data in Pediatric Drug-Development Programs SO PEDIATRICS LA English DT Article DE extrapolation; efficacy; pediatric drug-development programs ID HEART-FAILURE; CARVEDILOL; CHILDREN; TRIAL AB OBJECTIVES: In 1994, the US Food and Drug Administration (FDA) proposed an approach, based on extrapolation of efficacy findings from adults to the pediatric population, to maximize the use of adult data and other data when designing pediatric drug-development programs. We examined the experience of the FDA in using extrapolation to evaluate how and when it was used and any changes in scientific assumptions over time. METHODS: We reviewed 370 pediatric studies submitted to the FDA between 1998 and 2008 in response to 159 written requests (166 products) issued under the Pediatric Exclusivity Provision. We identified cases in which efficacy was extrapolated from adult data or other data, we categorized the type of pediatric data required to support extrapolation, and we determined whether the data resulted in new pediatric labeling. RESULTS: Extrapolation of efficacy from adult data occurred for 82.5% of the drug products (137 of 166). Extrapolation was defined as complete for 14.5% of the products (24 of 166) and partial for 68% of them (113 of 166). Approaches to extrapolation changed over time for 19% of the therapeutic indications studied (13 of 67). When extrapolation was used, 61% of the drug products (84 of 137) obtained a new pediatric indication or extension into a new age group; this number decreased to 34% (10 of 29) when there was no extrapolation. CONCLUSIONS: Extrapolating efficacy from adult data or other data to the pediatric population can streamline pediatric drug development and help to increase the number of approvals for pediatric use. Pediatrics 2011; 128: e1242-e1249 C1 [Dunne, Julia; Rodriguez, William J.; Murphy, Dianne] US FDA, Ctr Drug Evaluat & Res, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD USA. [Beasley, B. Nhi] US FDA, Ctr Drug Evaluat & Res, Div Cardiorenal Prod, Silver Spring, MD USA. [Filie, Jane D.] US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Silver Spring, MD USA. [Lewis, Linda L.] US FDA, Ctr Drug Evaluat & Res, Div Antiviral Prod, Silver Spring, MD USA. [Sachs, Hari C.] US FDA, Ctr Drug Evaluat & Res, Div Pediat, Silver Spring, MD USA. [Sachs, Hari C.] US FDA, Ctr Drug Evaluat & Res, Maternal Hlth Staff, Silver Spring, MD USA. [Sheridan, Philip H.] US FDA, Ctr Drug Evaluat & Res, Div Neurol Prod, Silver Spring, MD USA. [Starke, Peter] US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Prod, Silver Spring, MD USA. [Yao, Lynne P.] US FDA, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Silver Spring, MD USA. [Burckart, Gilbert J.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. RP Dunne, J (reprint author), US FDA, Off Pediat, 13B-45,5600 Fishers Lane, Rockville, MD 20857 USA. EM julia.dunne@fda.hhs.gov NR 12 TC 60 Z9 61 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2011 VL 128 IS 5 BP E1242 EP E1249 DI 10.1542/peds.2010-3487 PG 8 WC Pediatrics SC Pediatrics GA 843YO UT WOS:000296714000025 PM 22025597 ER PT J AU Kemper, AR Mahle, WT Martin, GR Cooley, WC Kumar, P Morrow, WR Kelm, K Pearson, GD Glidewell, J Grosse, SD Howell, RR AF Kemper, Alex R. Mahle, William T. Martin, Gerard R. Cooley, W. Carl Kumar, Praveen Morrow, W. Robert Kelm, Kellie Pearson, Gail D. Glidewell, Jill Grosse, Scott D. Howell, R. Rodney TI Strategies for Implementing Screening for Critical Congenital Heart Disease SO PEDIATRICS LA English DT Article DE congenital heart defects; neonatal screening; oximetry ID PULSE OXIMETRY; FOLLOW-UP; HIGH-ALTITUDE; NEWBORNS; STATEMENT; DEFECTS; INFANTS; VALUES; IMPACT AB BACKGROUND: Although newborn screening for critical congenital heart disease (CCHD) was recommended by the US Health and Human Services Secretary's Advisory Committee on Heritable Disorders in Newborns and Children to promote early detection, it was deemed by the Secretary of the HHS as not ready for adoption pending an implementation plan from HHS agencies. OBJECTIVE: To develop strategies for the implementation of safe, effective, and efficient screening. METHODS: A work group was convened with members selected by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children, the American Academy of Pediatrics, the American College of Cardiology Foundation, and the American Heart Association. RESULTS: On the basis of published and unpublished data, the work group made recommendations for a standardized approach to screening and diagnostic follow-up. Key issues for future research and evaluation were identified. CONCLUSIONS: The work-group members found sufficient evidence to begin screening for low blood oxygen saturation through the use of pulse-oximetry monitoring to detect CCHD in well-infant and intermediate care nurseries. Research is needed regarding screening in special populations (eg, at high altitude) and to evaluate service infrastructure and delivery strategies (eg, telemedicine) for nurseries without on-site echocardiography. Public health agencies will have an important role in quality assurance and surveillance. Central to the effectiveness of screening will be the development of a national technical assistance center to coordinate implementation and evaluation of newborn screening for CCHD. Pediatrics 2011;128:e1259-e1267 C1 [Kemper, Alex R.] Duke Univ, Duke Clin Res Inst, Durham, NC 27705 USA. [Kemper, Alex R.] Duke Univ, Dept Pediat, Durham, NC 27705 USA. [Mahle, William T.] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. [Martin, Gerard R.] Childrens Natl Med Ctr, Div Cardiol, Washington, DC 20010 USA. [Cooley, W. Carl] Ctr Med Home Improvement, Concord, NH USA. [Kumar, Praveen] Northwestern Univ, Dept Pediat, Feinberg Sch Med, Chicago, IL 60611 USA. [Morrow, W. Robert] Univ Arkansas Med Sci, Sch Med, Dept Pediat, Little Rock, AR 72205 USA. [Kelm, Kellie] US Dept HHS, US FDA, Silver Spring, MD USA. [Pearson, Gail D.] NHLBI, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Glidewell, Jill; Grosse, Scott D.] Ctr Dis Control & Prevent, US Dept HHS, Atlanta, GA USA. [Howell, R. Rodney] Univ Miami, Miller Sch Med, Dept Pediat, Miami, FL 33136 USA. RP Kemper, AR (reprint author), Duke Univ, Duke Clin Res Inst, 2400 Pratt St,Room 0311 Terrace Level, Durham, NC 27705 USA. EM alex.kemper@duke.edu NR 21 TC 111 Z9 116 U1 1 U2 12 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 NOV PY 2011 VL 128 IS 5 BP E1259 EP E1267 DI 10.1542/peds.2011-1317 PG 9 WC Pediatrics SC Pediatrics GA 843YO UT WOS:000296714000027 PM 21987707 ER PT J AU McMahon, AW Levenson, MS McEvoy, BW Mosholder, AD Murphy, D AF McMahon, Ann W. Levenson, Mark S. McEvoy, Bradley W. Mosholder, Andrew D. Murphy, Dianne TI Age and Risks of FDA-Approved Long-Acting beta(2)-Adrenergic Receptor Agonists SO PEDIATRICS LA English DT Article DE asthma; meta-analysis; hospitalization; death ID ASTHMA MORTALITY; NEW-ZEALAND; SALMETEROL; METAANALYSIS; TRIALS; DEATHS; SAFETY AB OBJECTIVE: To determine the risk, by age group, of serious asthma-related events with long-acting beta(2)-adrenergic receptor agonists marketed in the United States for asthma. METHODS: The US Food and Drug Administration performed a meta-analysis of controlled clinical trials comparing the risk of LABA use with no LABA use for patients 4 to 11, 12 to 17, 18 to 64, and older than 64 years old. The effects of age on a composite of asthma-related deaths, intubations, and hospitalizations (asthma composite index) and the effects of concomitant inhaled corticosteroid (ICS) use were analyzed. RESULTS: One hundred ten trials with 60 954 patients were included in the meta-analysis. The composite event incidence difference for all ages was 6.3 events per 1000 patient-years (95% confidence interval [CI]: 2.2-10.3) for using LABAs compared with not using LABAs. The largest incidence difference was observed for the 4- to 11-year age group (30.4 events per 1000 patient-years [95% CI: 5.7-55.1]). Differences according to age were statistically significant (P = .020). Results for the subgroup of patients with concomitant ICS use (n = 36 210) were similar to the overall results; with assigned ICSs (n = 15 192), the incidence difference was 0.4 events per 1000 patient-years (95% CI: -3.8 to 4.6), and there was no statistically significant difference according to age group. CONCLUSIONS: The excess of serious asthma-related events attributable to LABAs was greatest among children. Additional data are needed to assess risks of LABA use for children with simultaneous ICS use. Pediatrics 2011; 128: e1147-e1154 C1 [McMahon, Ann W.; Murphy, Dianne] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. RP McMahon, AW (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 10903 New Hampshire Ave,W032-Room 5158, Silver Spring, MD 20993 USA. EM ann.mcmahon@fda.hhs.gov NR 18 TC 42 Z9 43 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2011 VL 128 IS 5 BP E1147 EP E1154 DI 10.1542/peds.2010-1720 PG 8 WC Pediatrics SC Pediatrics GA 843YO UT WOS:000296714000013 PM 22025595 ER PT J AU Jarman, DW Liang, JL Luce, RR Wright, JG Stennies, GM Bisgard, KM AF Jarman, Dwayne W. Liang, Jennifer L. Luce, Richard R. Wright, Jennifer G. Stennies, Gail M. Bisgard, Kristine M. TI Veterinary Public Health Capacity in the United States: Opportunities for Improvement SO PUBLIC HEALTH REPORTS LA English DT Article AB Objectives. In 2006, the Association of American Veterinary Medical Colleges reported that the shortage (>= 1,500) of public health veterinarians is expected to increase tenfold by 2020. In 2008, the Centers for Disease Control and Prevention (CDC) Preventive Medicine Fellows conducted a pilot project among CDC veterinarians to identify national veterinary public health workforce concerns and potential policy strategies. Methods. Fellows surveyed a convenience sample (19/91) of public health veterinarians at CDC to identify veterinary workforce recruitment and retention problems faced by federal agencies; responses were categorized into themes. A focus group (20/91) of staff veterinarians subsequently prioritized the categorized themes from least to most important. Participants identified activities to address the three recruitment concerns with the highest combined weight. Results. Participants identified the following three highest prioritized problems faced by federal agencies when recruiting veterinarians to public health: (1) lack of awareness of veterinarians' contributions to public health practice, (2) competitive salaries, and (3) employment and training opportunities. Similarly, key concerns identified regarding retention of public health practice veterinarians included: (1) lack of recognition of veterinary qualifications, (2) competitive salaries, and (3) seamless integration of veterinary and human public health. Conclusions. Findings identified multiple barriers that can affect recruitment and retention of veterinarians engaged in public health practice. Next steps should include replicating project efforts among a national sample of public health veterinarians. A committed and determined long-term effort might be required to sustain initiatives and policy proposals to increase U.S. veterinary public health capacity. C1 [Jarman, Dwayne W.] US FDA, Off Regulatory Affairs, Detroit Dist Off, Detroit, MI 48073 USA. [Jarman, Dwayne W.; Liang, Jennifer L.; Luce, Richard R.; Stennies, Gail M.; Bisgard, Kristine M.] Ctr Dis Control & Prevent, Sci Educ & Profess Dev Program Off, Atlanta, GA USA. [Jarman, Dwayne W.; Luce, Richard R.; Wright, Jennifer G.; Stennies, Gail M.; Bisgard, Kristine M.] US PHS, Rockville, MD USA. [Liang, Jennifer L.] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. [Luce, Richard R.] Ctr Dis Control & Prevent, Ethiopia Field Epidemiol & Lab Training Program, Addis Ababa, Ethiopia. [Wright, Jennifer G.] Ctr Dis Control & Prevent, Natl Ctr Emerging Zoonot & Infect Dis, Atlanta, GA USA. RP Jarman, DW (reprint author), US FDA, Off Regulatory Affairs, Detroit Dist Off, 300 River Pl Ave,Ste 5900, Detroit, MI 48073 USA. EM dwayne.jarman@fda.hhs.gov NR 18 TC 4 Z9 4 U1 1 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2011 VL 126 IS 6 BP 868 EP 874 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 848EN UT WOS:000297033200013 PM 22043103 ER PT J AU Wagner, RD Johnson, SJ Cerniglia, CE Erickson, BD AF Wagner, R. Doug Johnson, Shemedia J. Cerniglia, Carl E. Erickson, Bruce D. TI Bovine Intestinal Bacteria Inactivate and Degrade Ceftiofur and Ceftriaxone with Multiple beta-Lactamases SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; BACILLUS-CEREUS; GENETIC-ANALYSIS; DAIRY-CATTLE; IDENTIFICATION; CEPHALOSPORIN; RESISTANCE; CEFOXITIN; TISSUES; EXCRETA AB The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine intestinal tract. A cylinderplate assay was used to detect microbiologically active ceftiofur, and high-performance liquid chromatography-mass spectrometry analysis was used to quantify the amount of ceftiofur remaining after incubation with bovine intestinal anaerobic bacteria, which were isolated from colon contents or feces from 8 cattle. Ninety-six percent of the isolates were able to inactivate ceftiofur to some degree, and 54% actually degraded the drug. None of 9 fungal isolates inactivated or degraded ceftiofur. Facultative and obligate anaerobic bacterial species that inactivated or degraded ceftiofur were identified with Vitek and Biolog systems, respectively. A subset of ceftiofur degraders also degraded the chemically similar drug ceftriaxone. Most of the species of bacteria that degraded ceftiofur belonged to the genera Bacillus and Bacteroides. PCR analysis of bacterial DNA detected specific beta-lactamase genes. Bacillus cereus and B. mycoides isolates produced extended-spectrum beta-lactamases and metallo-beta-lactamases. Seven isolates of Bacteroides spp. produced multiple beta-lactamases, including possibly CepA, and metallo-beta-lactamases. Isolates of Eubacterium biforme, Bifidobacterium breve, and several Clostridium spp. also produced ceftiofur-degrading beta-lactamases. An agar gel overlay technique on isoelectric focusing separations of bacterial lysates showed that beta-lactamase enzymes were sufficient to degrade ceftiofur. These results suggest that ceftiofur is inactivated nonenzymatically and degraded enzymatically by multiple beta-lactamases from bacteria in the large intestines of cattle. C1 [Wagner, R. Doug; Johnson, Shemedia J.; Cerniglia, Carl E.; Erickson, Bruce D.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM doug.wagner@fda.hhs.gov FU Pfizer Animal Health, Kalamazoo, MI; U.S. Public Health Service FX This work was funded, in part, by a cooperative research agreement with Pfizer Animal Health, Kalamazoo, MI, and, in part, by U.S. Public Health Service funds. NR 46 TC 12 Z9 12 U1 1 U2 8 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 NOV PY 2011 VL 55 IS 11 BP 4990 EP 4998 DI 10.1128/AAC.00008-11 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 839NX UT WOS:000296375600006 PM 21876048 ER PT J AU Hill, VR Cohen, N Kahler, AM Jones, JL Bopp, CA Marano, N Tarr, CL Garrett, NM Boncy, J Henry, A Gomez, GA Wellman, M Curtis, M Freeman, MM Turnsek, M Benner, RA Dahourou, G Espey, D DePaola, A Tappero, JW Handzel, T Tauxe, RV AF Hill, Vincent R. Cohen, Nicole Kahler, Amy M. Jones, Jessica L. Bopp, Cheryl A. Marano, Nina Tarr, Cheryl L. Garrett, Nancy M. Boncy, Jacques Henry, Ariel Gomez, Gerardo A. Wellman, Michael Curtis, Maurice Freeman, Molly M. Turnsek, Maryann Benner, Ronald A., Jr. Dahourou, Georges Espey, David DePaola, Angelo Tappero, Jordan W. Handzel, Tom Tauxe, Robert V. TI Toxigenic Vibrio cholerae O1 in Water and Seafood, Haiti SO EMERGING INFECTIOUS DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; OUTBREAK; EPIDEMIC; STRAINS; DISEASE; AREA; GENE AB During the 2010 cholera outbreak in Haiti, water and seafood samples were collected to detect Vibrio cholerae. The outbreak strain of toxigenic V. cholerae 01 serotype Ogawa was isolated from freshwater and seafood samples. The cholera toxin gene was detected in harbor water samples. C1 [Hill, Vincent R.; Cohen, Nicole; Kahler, Amy M.; Bopp, Cheryl A.; Marano, Nina; Tarr, Cheryl L.; Garrett, Nancy M.; Gomez, Gerardo A.; Wellman, Michael; Curtis, Maurice; Freeman, Molly M.; Turnsek, Maryann; Espey, David; Tappero, Jordan W.; Handzel, Tom; Tauxe, Robert V.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Jones, Jessica L.; Benner, Ronald A., Jr.; DePaola, Angelo] US FDA, Dauphin Isl, AL USA. [Boncy, Jacques; Henry, Ariel] Haitian Minist Publ Hlth & Populat, Port Au Prince, Haiti. [Dahourou, Georges] Ctr Dis Control & Prevent, Port Au Prince, Haiti. RP Hill, VR (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop D66, Atlanta, GA 30333 USA. EM vhill@cdc.gov RI Hill, Vincent/G-1789-2012 OI Hill, Vincent/0000-0001-7069-7737 NR 15 TC 15 Z9 15 U1 0 U2 12 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD NOV PY 2011 VL 17 IS 11 BP 2147 EP 2150 DI 10.3201/eid1711.110748 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 843KI UT WOS:000296670300037 PM 22099121 ER PT J AU Malik, M Zhang, J Johannesen, L Hnatkova, K Garnett, C AF Malik, Marek Zhang, Joanne Johannesen, Lars Hnatkova, Katerina Garnett, Christine TI Assessing electrocardiographic data quality and possible replacement of pharmacologic positive control in thorough QT/QTc studies by investigations of drug-free QTc stability SO HEART RHYTHM LA English DT Article DE ECG measurement; Measurement reproducibility; Measurement stability; Positive control; QTc interval; Thorough QT study ID MOXIFLOXACIN; VARIABILITY; INTERVAL C1 [Malik, Marek] Univ London, London, England. [Zhang, Joanne] US FDA, Div Biometr 6, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Johannesen, Lars; Garnett, Christine] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Hnatkova, Katerina] St Pauls Cardiac Electrophysiol, London, England. RP Malik, M (reprint author), 16 Verulam Ave, Surrey CR8 3NQ, England. EM marek.malik@btinternet.com FU Center for Drug Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration 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. Dr. Malik is an Honorary ORISE Research Fellow of the U.S. Food and Drug Administration. The opinions presented here are those of the authors. No official support or endorsement by U.S. Food and Drug Administration is intended or should be inferred. NR 14 TC 12 Z9 12 U1 0 U2 1 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 NOV PY 2011 VL 8 IS 11 BP 1777 EP 1785 DI 10.1016/j.hrthm.2011.06.016 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 841ZY UT WOS:000296555800025 PM 21699874 ER PT J AU Reiter, CE Miller, JL Alayash, AI AF Reiter, Chad E. Miller, Jeffery L. Alayash, Abdu I. TI Effects of Carbon Monoxide on Vascular Endothelial Cells Under Hypoxia and in the Presence of Cell-Free Hemoglobin and Sickle Red Blood Cells SO HYPERTENSION LA English DT Meeting Abstract CT Scientific Sessions of High Blood Pressure Research CY SEP 20-24, 2011 CL Orlando, FL SP Council High Blood Pressure Res, Council Kidney Cardiovasc Dis & Inter-Amer Soc Hypertens (IASH) DE vascular mitochondria oxygen uptake C1 [Reiter, Chad E.; Alayash, Abdu I.] CBER, FDA, Bethesda, MD USA. [Miller, Jeffery L.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2011 VL 58 IS 5 BP E161 EP E161 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 842HQ UT WOS:000296588100532 ER PT J AU Balakumar, P Jagadeesh, G AF Balakumar, Pitchai Jagadeesh, Gowraganahalli TI Potential cross-talk between (pro)renin receptors and Wnt/frizzled receptors in cardiovascular and renal disorders SO HYPERTENSION RESEARCH LA English DT Review DE frizzled receptor; (pro)renin receptor; renin-angiotensin system; v-H(+)-ATPase; Wnt ID VACUOLAR H+-ATPASE; WNT SIGNALING PATHWAY; INDUCED CARDIAC-HYPERTROPHY; GLYCOGEN-SYNTHASE KINASE-3; PROTEIN-COUPLED RECEPTORS; CATENIN DOWN-REGULATION; HANDLE-REGION PEPTIDE; SMOOTH-MUSCLE-CELLS; BETA-CATENIN; ANGIOTENSIN-II AB The renin-angiotensin system and Wnt/frizzled receptor signaling pathways are important in the development of essential organs, and their aberrant activation results in cardiovascular and renal pathologies. The (pro) renin receptor ((P)RR)-bound (pro)renin is enzymatically active generating angiotensin-II and activating mitogen-activated protein kinases, leading to cell proliferation and to upregulation of profibrotic genes expression, resulting in end-organ damage. The (P)RR does more than bind to (pro) renin, because it is functionally linked to the vacuolar-H(+)-ATPase (v-H(+)-ATPase) that regulates pH of cellular and intracellular vesicles, and to Wnt signaling. This signaling pathway is essential for cell survival, embryonic development and has had a role in various disease states as evidenced by mutation or genetic ablation of the (P)RR gene. This suggests two types of functions of (P)RRs, first one as a receptor for (pro) renin and second one as an accessory subunit of the v-H+-ATPase and a cofactor of the Wnt/Fz receptor complex. This review will discuss both of these functions of (P)RRs thereby giving new perspectives as to the roles of (P) RRs in cardiovascular and renal pathologies. Hypertension Research (2011) 34, 1161-1170; doi:10.1038/hr.2011.113; published online 28 July 2011 C1 [Jagadeesh, Gowraganahalli] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Balakumar, Pitchai] Rajendra Inst Technol & Sci, Inst Pharm, Dept Pharmacol, Cardivasc Pharmacol Div, Sirsa, India. RP Jagadeesh, G (reprint author), US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4128, Silver Spring, MD 20993 USA. EM gowra.jagadeesh@fda.hhs.gov NR 140 TC 9 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0916-9636 J9 HYPERTENS RES JI Hypertens. Res. PD NOV PY 2011 VL 34 IS 11 BP 1161 EP 1170 DI 10.1038/hr.2011.113 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 844MX UT WOS:000296752400002 PM 21796133 ER PT J AU Gao, ZM AF Gao, Zongming TI Mathematical Modeling of Variables Involved in Dissolution Testing SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE variables; dissolution testing; dissolution rate; in vitro models; mathematical model ID VARIABILITY; RELEASE; APPARATUS; TABLETS; AGITATION; MECHANISM; CURVES AB Dissolution testing is an important technique used for development and quality control of solid oral dosage forms of pharmaceutical products. However, the variability associated with this technique, especially with USP apparatuses 1 and 2, is a concern for both the US Food and Drug Administration and pharmaceutical companies. Dissolution testing involves a number of variables, which can be divided into four main categories: (1) analyst, (2) dissolution apparatus, (3) testing environment, and (4) sample. Both linear and nonlinear models have been used to study dissolution profiles, and various mathematical functions have been used to model the observed data. In this study, several variables, including dissolved gases in the dissolution medium, off-center placement of the test tablet, environmental vibration, and various agitation speeds, were modeled. Mathematical models including Higuchi, Korsmeyer-Peppas, Weibull, and the Noyes-Whitney equation were employed to study the dissolution profile of 10mg prednisone tablets (NCDA # 2) using the USP paddle method. The results showed that the nonlinear models (Korsmeyer-Peppas and Weibull) accurately described the entire dissolution profile. The results also showed that dissolution variables affected dissolution rate constants differently, depending on whether the tablets disintegrated or dissolved. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 4934-4942, 2011 C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 28 TC 10 Z9 11 U1 3 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD NOV PY 2011 VL 100 IS 11 BP 4934 EP 4942 DI 10.1002/jps.22673 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 839MC UT WOS:000296369700036 PM 21702052 ER PT J AU Herrinton, LJ Curtis, JR Chen, L Liu, LY Delzell, E Lewis, JD Solomon, DH Griffin, MR Ouellet-Hellstom, R Beukelman, T Grijalva, CG Haynes, K Kuriya, B Lii, J Mitchel, E Patkar, N Rassen, J Winthrop, KL Nourjah, P Saag, KG AF Herrinton, Lisa J. Curtis, Jeffrey R. Chen, Lang Liu, Liyan Delzell, Elizabeth Lewis, James D. Solomon, Daniel H. Griffin, Marie R. Ouellet-Hellstom, Rita Beukelman, Timothy Grijalva, Carlos G. Haynes, Kevin Kuriya, Bindee Lii, Joyce Mitchel, Ed Patkar, Nivedita Rassen, Jeremy Winthrop, Kevin L. Nourjah, Parivash Saag, Kenneth G. TI Study design for a comprehensive assessment of biologic safety using multiple healthcare data systems SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE rheumatoid arthritis; juvenile idiopathic arthritis; psoriatic arthritis; psoriasis; Crohn's disease; ulcerative colitis; inflammatory bowel disease; ankylosing spondylitis; adverse events; pharmacoepidemiology; drug safety; drug toxicity; adverse events; cohort studies; propensity scores; computerized data; administrative data; Medicaid; Medicare ID PROPENSITY SCORES AB Background Although biologic treatments have excellent efficacy for many autoimmune diseases, safety concerns persist. Understanding the absolute and comparative risks of adverse events in patient and disease subpopulations is critical for optimal prescribing of biologics. Purpose The Safety Assessment of Biologic Therapy collaborative was federally funded to provide robust estimates of rates and relative risks of adverse events among biologics users using data from national Medicaid and Medicare plus Medicaid dual-eligible programs, Tennessee Medicaid, Kaiser Permanente, and state pharmaceutical assistance programs supplementing New Jersey and Pennsylvania Medicare programs. This report describes the organizational structure of the collaborative and the study population and methods. Methods This retrospective cohort study (1998-2007) examined risks of seven classes of adverse events in relation to biologic treatments prescribed for seven autoimmune diseases. Propensity scores were used to control for confounding and enabled pooling of individual-level data across data systems while concealing personal health information. Cox proportional hazard modeling was used to analyze study hypotheses. Results The cohort was composed of 159000 subjects with rheumatic diseases, 33000 with psoriasis, and 46000 with inflammatory bowel disease. This report summarizes demographic characteristics and drug exposures. Separate reports will provide outcome definitions and estimated hazard ratios for adverse events. Conclusion This comprehensive research will improve understanding of the safety of these treatments. The methods described may be useful to others planning similar evaluations. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Herrinton, Lisa J.; Liu, Liyan] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Curtis, Jeffrey R.; Chen, Lang; Delzell, Elizabeth; Beukelman, Timothy; Patkar, Nivedita; Saag, Kenneth G.] Univ Alabama, UAB Ctr Educ & Res & Therapeut Musculoskeletal Di, Birmingham, AL USA. [Lewis, James D.; Haynes, Kevin] Univ Penn, Dept Med, Dept Biostat & Epidemiol, Ctr Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Solomon, Daniel H.; Lii, Joyce] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Griffin, Marie R.; Grijalva, Carlos G.; Mitchel, Ed] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. [Griffin, Marie R.; Grijalva, Carlos G.; Mitchel, Ed] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. [Griffin, Marie R.; Grijalva, Carlos G.; Mitchel, Ed] Vet Adm Tennessee Valley Hlth Care Syst, Mids Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Ouellet-Hellstom, Rita] US FDA, Silver Spring, MD USA. [Kuriya, Bindee] Univ Toronto, Dept Rheumatol, Toronto, ON, Canada. [Rassen, Jeremy] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Nourjah, Parivash] US Agcy Healthcare Res & Qual, Ctr Outcomes & Evidence, Rockville, MD USA. RP Herrinton, LJ (reprint author), Kaiser Permanente No Calif, Div Res, 2000 Broadway Ave, Oakland, CA 94612 USA. EM lisa.herrinton@kp.org FU AHRQ; FDA; US Department of Health and Human Services (DHHS) [1U18HS17919] FX This work was supported by the AHRQ and the FDA, US Department of Health and Human Services (DHHS) as part of a grant (1U18HS17919) administered through the AHRQ Centers for Education & Research on Therapeutics program. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsements by AHRQ, FDA, or DHHS. NR 15 TC 17 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD NOV PY 2011 VL 20 IS 11 BP 1199 EP 1209 DI 10.1002/pds.2196 PG 11 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 847LL UT WOS:000296974300010 PM 21919113 ER PT J AU Lu, H Yang, XP Duggal, P Allen, CT Yan, B Cohen, J Nottingham, L Romano, RA Sinha, S King, KE Weinberg, WC Chen, Z Van Waes, C AF Lu, Hai Yang, Xinping Duggal, Praveen Allen, Clint T. Yan, Bin Cohen, Jonah Nottingham, Liesl Romano, Rose-Anne Sinha, Satrajit King, Kathryn E. Weinberg, Wendy C. Chen, Zhong Van Waes, Carter TI TNF-alpha Promotes c-REL/Delta Np63 alpha Interaction and TAp73 Dissociation from Key Genes That Mediate Growth Arrest and Apoptosis in Head and Neck Cancer SO CANCER RESEARCH LA English DT Article ID FACTOR-KAPPA-B; SQUAMOUS-CELL CARCINOMA; TUMOR-NECROSIS-FACTOR; TRANSCRIPTION FACTOR; BINDING MOTIFS; DELTA-NP63-ALPHA; P53; EXPRESSION; CISPLATIN; SURVIVAL AB Inflammation-induced activation of proto-oncogenic NF-kappa B/REL and dysfunction of tumor suppressor TP53/p63/p73 family transcription factors are key events in cancer progression. How inflammatory signaling coordinates dysregulation of these two transcription factor families during oncogenesis remains incompletely understood. Here, we observed that oncoprotein c-REL and tumor suppressor TAp73 are coexpressed and complex with Delta Np63 alpha in the nucleus of a subset of head and neck squamous cell carcinoma (HNSCC) cell lines with mutant (mt)TP53. TNF-alpha, a proinflammatory cytokine, promoted c-REL nuclear translocation, c-REL/Delta Np63 alpha interaction, and dissociation of TAp73 from Delta Np63 alpha and the nucleus to the cytoplasm, whereas c-REL siRNA knockdown attenuated this effect. Overexpression of c-REL or a c-REL kappa B-site DNA-binding mutant enhanced protein interaction with Delta Np63 alpha and TAp73 dissociation, implicating c-REL/Delta Np63 alpha-specific interactions in these effects. We discovered that TNF-alpha or genetic alteration of c-REL expression inversely modulates Delta Np63 alpha/TAp73 interactions on distinct p63 DNA-binding sites, including those for key growth arrest and apoptotic genes p21WAF1, NOXA, and PUMA. Functionally, c-REL repressed these genes and the antiproliferative effects of TNF-alpha or TAp73. Conversely, c-REL siRNA depletion enhanced TAp73 promoter interaction and expression of genes mediating growth arrest and apoptosis. Similar to TNF-alpha-treated HNSCC lines, human HNSCC tumors and hyperplastic squamous epithelia of transgenic mice overexpressing Delta Np63 alpha that exhibit inflammation also show increased nuclear c-REL/Delta Np63 alpha and cytoplasmic TAp73 localization. These findings unveil a novel and reversible dynamic mechanism whereby proinflammatory cytokine TNF-alpha-induced c-REL/Delta Np63 alpha interactions inactivate tumor suppressor TAp73 function, promoting TNF-alpha resistance and cell survival in cancers with mtTP53. Cancer Res; 71(21); 6867-77. (C) 2011 AACR. C1 [Lu, Hai; Yang, Xinping; Duggal, Praveen; Allen, Clint T.; Yan, Bin; Cohen, Jonah; Nottingham, Liesl; Chen, Zhong; Van Waes, Carter] Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. [King, Kathryn E.; Weinberg, Wendy C.] FDA Ctr Drug Evaluat & Res, Bethesda, MD USA. [Romano, Rose-Anne; Sinha, Satrajit] SUNY Buffalo, Dept Biochem, Ctr Excellence Bioinformat & Life Sci, Buffalo, NY 14214 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, CRC Rm 4-2732,10 Ctr Dr, Bethesda, MD 20892 USA. EM chenz@nidcd.nih.gov; vanwaesc@nidcd.nih.gov FU NIDCD [Z01-DC-000016, DC-000073]; NIH-Pfizer; HHMI-NIH FX The work received support from NIDCD Intramural Research Projects Z01-DC-000016 and DC-000073. C.T. Allen was supported by the NIH-Pfizer Clinical Research Training Program; J. Cohen was supported by the HHMI-NIH Scholars Program. NR 37 TC 37 Z9 37 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 2011 VL 71 IS 21 BP 6867 EP 6877 DI 10.1158/0008-5472.CAN-11-2460 PG 11 WC Oncology SC Oncology GA 842ML UT WOS:000296603500033 PM 21933882 ER PT J AU Miller, VA Luce, MF Nelson, RM AF Miller, Victoria A. Luce, Mary Frances Nelson, Robert M. TI Relationship of External Influence to Parental Distress in Decision Making Regarding Children with a Life-Threatening Illness SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE decision making; distress; emotion; ethical issues; external influence; informed consent ID BONE-MARROW-TRANSPLANTATION; INFORMED-CONSENT; HEALTH-CARE; PREFERENCES; INFORMATION; AUTONOMY; MOTHERS; STRESS; DESIRE; TRIALS AB Objective To examine the relationship of external influence to parental distress when making a decision about research or treatment for a child with a life-threatening illness and to test potential moderators of this relationship. Methods Parents (n = 219) who made a decision about research or treatment for a child completed measures of external influence, distress, decision-making preference, and coping. Results More external influence was associated with more hostility, uncertainty, and confusion. Decision-making preference and coping style moderated the relationship between external influence and distress: More external influence was associated with more distress when decision-making preference was low and task-focused coping was high. Conclusions External influence appears to be related to distress in parents making research and treatment decisions for children with life-threatening illnesses. However, it is important to consider parent characteristics, such as decision-making preference and coping style, when examining the effects of contextual factors on distress during decision making. C1 [Miller, Victoria A.] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA. [Miller, Victoria A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Luce, Mary Frances] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. RP Miller, VA (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 34th St & Civ Ctr Blvd,CHOP N Room 1425, Philadelphia, PA 19104 USA. EM millerv@email.chop.edu FU NCI NIH HHS [R21CA118377-01A1] NR 34 TC 9 Z9 9 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD NOV-DEC PY 2011 VL 36 IS 10 BP 1102 EP 1112 DI 10.1093/jpepsy/jsr033 PG 11 WC Psychology, Developmental SC Psychology GA 839AE UT WOS:000296335600005 PM 21693541 ER PT J AU Statler, JD Miller, DL Dixon, RG Kuo, MD Cohen, AM Duncan, JR Gordon, RL Gross, K Saad, WEA Silberzweig, JE Stecker, MS Suri, R Thornton, RH Bartel, G AF Statler, John D. Miller, Donald L. Dixon, Robert G. Kuo, Michael D. Cohen, Alan M. Duncan, James R. Gordon, Roy L. Gross, Kathleen Saad, Wael E. A. Silberzweig, James E. Stecker, Michael S. Suri, Rajeev Thornton, Raymond H. Bartel, Gabriel CA Soc Interventional Radiology Safet TI Society of Interventional Radiology Position Statement: Prevention of Unintentionally Retained Foreign Bodies during Interventional Radiology Procedures SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID OPERATING-ROOM; SPONGES; SAFETY C1 [Statler, John D.] Virginia Intervent & Vasc Associates, Fredericksburg, VA USA. [Saad, Wael E. A.] Univ Virginia Hlth Syst, Dept Radiol, Charlottesville, VA USA. [Statler, John D.] Uniformed Serv Univ Hlth Sci, Dept Radiol, Silver Spring, MD USA. [Miller, Donald L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Gross, Kathleen] Greater Baltimore Med Ctr, Dept Intervent Radiol, Baltimore, MD USA. [Dixon, Robert G.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. [Kuo, Michael D.] Univ Calif Los Angeles, Sch Med, Dept Radiol, Los Angeles, CA 90024 USA. [Gordon, Roy L.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA. [Cohen, Alan M.] Univ Texas Hlth Sci Ctr, Dept Vasc & Intervent Radiol, Houston, TX USA. [Suri, Rajeev] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiol, San Antonio, TX 78229 USA. [Duncan, James R.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. [Silberzweig, James E.] Beth Israel Deaconess Med Ctr, Dept Radiol, New York, NY 10003 USA. [Thornton, Raymond H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, Intervent Radiol Serv, New York, NY 10021 USA. [Stecker, Michael S.] Brigham & Womens Hosp, Div Angiog & Intervent Radiol, Boston, MA 02115 USA. [Bartel, Gabriel] Meir Med Ctr, Dept Diagnost & Intervent Radiol, Kefar Sava, Israel. RP Statler, JD (reprint author), Care of Katsarelis D, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA. EM jstatrad@aol.com OI Duncan, James/0000-0002-0337-8805 NR 10 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV PY 2011 VL 22 IS 11 BP 1561 EP 1562 DI 10.1016/j.jvir.2011.07.011 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 843HB UT WOS:000296661800012 PM 21937240 ER PT J AU Aikin, KJ O'Donoghue, AC Swasy, JL Sullivan, HW AF Aikin, Kathryn J. O'Donoghue, Amie C. Swasy, John L. Sullivan, Helen W. TI Randomized Trial of Risk Information Formats in Direct-to-Consumer Prescription Drug Advertisements SO MEDICAL DECISION MAKING LA English DT Article DE randomized trial methodology; risk factor evaluation; population based studies; scale development/validation ID HEALTH BEHAVIOR THEORIES; SELF-EFFICACY; FACTS BOX AB Background. Federal regulations specify that print advertisements for prescription drugs and biological products must provide a true statement of information "in brief summary" about each advertised product's 'side effects, contraindications, and effectiveness." Some of the current approaches to fulfilling the brief summary requirement, although adequate from a regulatory perspective, result in ads that may be difficult to read and understand when used in consumer-directed promotion. Objective. To explore ways in which the brief summary might be improved. Design. The authors conducted an experimental study that examined 300 consumers' (mall visitors ever told that they were overweight) understanding of and preference for 4 different brief summary formats: traditional (a plain-language version of the risk sections from professional labeling), question and answer (Q & A; with headings framed in the form of questions), highlights (a summary section from revised professional labeling), and prescription drug facts box (similar to the current over-the-counter drug facts label). Results. The format had several effects. For instance, participants who viewed the drug facts format were better able to recall risks (P < .01) and reported greater confidence to perform the tasks (P < .01) than those who saw the traditional format. Differences in preference were noted; for example, the drug facts format was ranked highest, followed by the Q&A format, the traditional format, and finally the highlights format, P < 0.001. Conclusions. Taken together, these data suggest that the traditional method of conveying information in the brief summary is neither the most comprehensible nor the most preferred by consumers. These data provide policy makers and researchers with important information regarding the role of format in consumers' understanding of the brief summary. C1 [Aikin, Kathryn J.; O'Donoghue, Amie C.; Sullivan, Helen W.] US FDA, Div Drug Mkt Advertising & Commun, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Swasy, John L.] American Univ, Kogod Sch Business, Washington, DC 20016 USA. RP Sullivan, HW (reprint author), US FDA, Div Drug Mkt Advertising & Commun, Off Med Policy, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Helen.Sullivan@fda.hhs.gov FU FDA FX Received 16 December 2010 from Division of Drug Marketing, Advertising and Communications, Office of Medical Policy, Center for Drug Evaluation and Research, Food and Drug Administration (FDA), Silver Spring, Maryland (KJA, ACO, HWS) and Kogod School of Business, American University, Washington, DC (JLS). Financial support for this study was provided entirely by the FDA. The funding agreement ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The following authors are employed by the sponsor: KA, AO, and HS. Supplementary material for this article is available on the Medical Decision Making Web site at http://mdm.sagepub.com/supplemental. Revision accepted for publication 6 May 2011. NR 20 TC 8 Z9 8 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2011 VL 31 IS 6 BP E23 EP E33 DI 10.1177/0272989X11413289 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 843UA UT WOS:000296697100002 PM 21690303 ER PT J AU Quinn, K Quirion, MR Lo, CY Misplon, JA Epstein, SL Chiorini, JA AF Quinn, Kathrina Quirion, Mary R. Lo, Chia-Yun Misplon, Julia A. Epstein, Suzanne L. Chiorini, John A. TI Intranasal Administration of Adeno-associated Virus Type 12 (AAV12) Leads to Transduction of the Nasal Epithelia and Can Initiate Transgene-specific Immune Response SO MOLECULAR THERAPY LA English DT Article ID CILIATED AIRWAY EPITHELIUM; T-CELL EPITOPES; INFLUENZA-VIRUS; NEUTRALIZING ANTIBODIES; EFFICIENT TRANSDUCTION; GERMLINE TRANSMISSION; GENE DELIVERY; IN-VIVO; VECTORS; VACCINATION AB A critical aspect in defining the utility of a vector for gene therapy applications is the cell tropism and biodistribution of the vector. Adeno-associated virus type 12 (AAV12) has several unique biological and immunological properties that could be exploited for gene therapy purposes, including a unique cell surface receptor, transduction of epithelial cells, and limited neutralization by pooled human antibodies. However, little is known about its cell tropism and biodistribution in vivo. In vivo biodistribution studies with AAV12 vectors encoding a cytomegalovirus promoted luciferase transgene indicated preferential transduction of the nasal epithelia which was not observed with AAV2-based vectors. Expression peaked 2 weeks postadministration, before decreasing to a persistent level. The level of neutralizing antibodies (Nab) induced was sevenfold lower for AAV12 than for AAV2, an advantage for use in repeat administration. Furthermore, vectors encoding influenza A nucleoprotein (NP), an antigen which has previously been shown to induce immune protection against challenge, resulted in generation of both anti-A/NP antibodies and lung anti-A/NP T cells. Our findings suggest further evaluation of AAV12 as a vector for gene therapy and as a potential nasal vaccine. C1 [Quinn, Kathrina; Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Quirion, Mary R.; Lo, Chia-Yun; Misplon, Julia A.; Epstein, Suzanne L.] US FDA, Gene Therapy & Immunogen Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bldg 10,Room 1A21, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov FU NIH FX We thank Sandra Wainer and Beverly Handelman (MPTB, NIDCR, NIH) for their expertise in AAV vector production, Giovanni DiPasquale (MPTB, NIDCR, NIH) for assistance with Xenogen Imaging, William Swaim (MPTB, NIDCR, NIH) for help with immunofluorescence and confocal microscopy, and Milton Papa (VRC, NIDCR, NIH) for assistance with retro-orbital bleeding. This work was funded by an NIH intramural grant, to J.A.C. NR 39 TC 5 Z9 5 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 NOV PY 2011 VL 19 IS 11 BP 1990 EP 1998 DI 10.1038/mt.2011.146 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 843VL UT WOS:000296703000010 PM 21829176 ER PT J AU Duncan, TV AF Duncan, Timothy V. TI The communication challenges presented by nanofoods SO NATURE NANOTECHNOLOGY LA English DT Article ID NANOTECHNOLOGY FOODS; RISK COMMUNICATION; PUBLIC ACCEPTANCE; UNITED-STATES; TECHNOLOGIES; CONSUMERS; BENEFITS; INFORMATION; PERCEPTIONS; ENGAGEMENT C1 US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. RP Duncan, TV (reprint author), US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. EM timothy.duncan@fda.hhs.gov NR 63 TC 23 Z9 26 U1 4 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1748-3387 J9 NAT NANOTECHNOL JI Nat. Nanotechnol. PD NOV PY 2011 VL 6 IS 11 BP 683 EP 688 DI 10.1038/nnano.2011.193 PG 6 WC Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Science & Technology - Other Topics; Materials Science GA 844HC UT WOS:000296737300001 PM 22036812 ER PT J AU Bashaw, ED Huang, SM Cote, TR Pariser, AR Garnett, CE Burckart, G Zhang, L Men, AY Le, CD Charlab, R Gobburu, JV Lesko, LJ AF Bashaw, Edward D. Huang, Shiew-Mei Cote, Timothy R. Pariser, Anne R. Garnett, Christine E. Burckart, Gilbert Zhang, Lei Men, Angela Y. Le, Christine D. Charlab, Rosane Gobburu, Jogaro V. Lesko, Lawrence J. TI Clinical pharmacology as a cornerstone of orphan drug development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 [Bashaw, Edward D.; Huang, Shiew-Mei; Garnett, Christine E.; Burckart, Gilbert; Zhang, Lei; Men, Angela Y.; Le, Christine D.; Charlab, Rosane; Gobburu, Jogaro V.] US FDA, Off Translat Sci, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Cote, Timothy R.] Natl Org Rare Disorders, Washington, DC 20008 USA. [Cote, Timothy R.] Keck Grad Inst, Claremont, CA 91711 USA. [Pariser, Anne R.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lesko, Lawrence J.] Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. RP Bashaw, ED (reprint author), US FDA, Off Translat Sci, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Edward.bashaw@fda.hhs.gov NR 5 TC 17 Z9 18 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD NOV PY 2011 VL 10 IS 11 BP 795 EP 796 DI 10.1038/nrd3595 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 842IR UT WOS:000296592100001 PM 22037026 ER PT J AU Trusheim, MR Burgess, B Hu, SX Long, T Averbuch, SD Flynn, AA Lieftucht, A Mazumder, A Milloy, J Shaw, PM Swank, D Wang, J Berndt, ER Goodsaid, F Palmer, MC AF Trusheim, Mark R. Burgess, Breon Hu, Sean Xinghua Long, Theresa Averbuch, Steven D. Flynn, Aiden A. Lieftucht, Alfons Mazumder, Abhijit Milloy, Judy Shaw, Peter M. Swank, David Wang, Jian Berndt, Ernst R. Goodsaid, Federico Palmer, Michael C. TI Quantifying factors for the success of stratified medicine SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID ANAPLASTIC LYMPHOMA KINASE; METASTATIC COLORECTAL-CANCER; HER2-POSITIVE BREAST-CANCER; MILD COGNITIVE IMPAIRMENT; GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; ALZHEIMERS-DISEASE; PERSONALIZED MEDICINE; PREDICTIVE BIOMARKERS; ADJUVANT CHEMOTHERAPY AB Co-developing a drug with a diagnostic to create a stratified medicine - a therapy that is targeted to a specific patient population on the basis of a clinical characteristic such as a biomarker that predicts treatment response - presents challenges for product developers, regulators, payers and physicians. With the aim of developing a shared framework and tools for addressing these challenges, here we present an analysis using data from case studies in oncology and Alzheimer's disease, coupled with integrated computational modelling of clinical outcomes and developer economic value, to quantify the effects of decisions related to key issues such as the design of clinical trials. This illustrates how such analyses can aid the coordination of diagnostic and drug development, and the selection of optimal development and commercialization strategies. It also illustrates the impact of the interplay of these factors on the economic feasibility of stratified medicine, which has important implications for public policy makers. C1 [Trusheim, Mark R.; Berndt, Ernst R.] MIT, Sloan Sch Management, Cambridge, MA 02139 USA. [Trusheim, Mark R.; Berndt, Ernst R.] MIT, Ctr Biomed Innovat, Cambridge, MA 02139 USA. [Burgess, Breon] Merck & Co Inc, N Wales, PA 19454 USA. [Hu, Sean Xinghua] IMS Hlth, New York, NY 10017 USA. [Long, Theresa] Chinese Acad Sci, Chinese Natl Human Genome Ctr Shanghai, Shanghai, Peoples R China. [Hu, Sean Xinghua] Beijing Genom Inst, Shenzhen, Peoples R China. [Hu, Sean Xinghua] Van Andel Inst, Grand Rapids, MI 49503 USA. [Averbuch, Steven D.; Swank, David] Bristol Myers Squibb Co, Princeton, NJ 08543 USA. [Flynn, Aiden A.; Lieftucht, Alfons] GlaxoSmithKline UK, Uxbridge UB11 1BT, Middx, England. [Milloy, Judy] Merck & Co Inc, Whitehouse Stn, NJ 08889 USA. [Shaw, Peter M.] Merck & Co Inc, West Point, PA 19486 USA. [Wang, Jian] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Goodsaid, Federico] US FDA, Silver Spring, MD 20903 USA. [Palmer, Michael C.] Adapt Pharmacogen, Morristown, NJ 07960 USA. RP Trusheim, MR (reprint author), MIT, Sloan Sch Management, 100 Main St, Cambridge, MA 02139 USA. EM Trusheim@mit.edu OI Trusheim, Mark/0000-0002-6318-9037 NR 53 TC 46 Z9 47 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD NOV PY 2011 VL 10 IS 11 BP 817 EP 833 DI 10.1038/nrd3557 PG 17 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 842IR UT WOS:000296592100021 PM 22037040 ER PT J AU Mockus, LN Paul, TW Pease, NA Harper, NJ Basu, PK Oslos, EA Sacha, GA Kuu, WY Hardwick, LM Karty, JJ Pikal, MJ Hee, E Khan, MA Nail, SL AF Mockus, Linas N. Paul, Timothy W. Pease, Nathan A. Harper, Nancy J. Basu, Prabir K. Oslos, Elizabeth A. Sacha, Gregory A. Kuu, Wei Y. Hardwick, Lisa M. Karty, Jacquelyn J. Pikal, Michael J. Hee, Eun Khan, Mansoor A. Nail, Steven L. TI Quality by design in formulation and process development for a freeze-dried, small molecule parenteral product: a case study SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE Sodium ethacrynate; lyophilization; design space; risk assessment; formulation development ID SODIUM ETHACRYNATE; STABILITY AB A case study has been developed to illustrate one way of incorporating a Quality by Design approach into formulation and process development for a small molecule, freeze-dried parenteral product. Sodium ethacrynate was chosen as the model compound. Principal degradation products of sodium ethacrynate result from hydrolysis of the unsaturated ketone in aqueous solution, and dimer formation from a Diels-Alder condensation in the freeze-dried solid state. When the drug crystallizes in a frozen solution, the eutectic melting temperature is above -5 degrees C. Crystallization in the frozen system is affected by pH in the range of pH 6-8 and buffer concentration in the range of 5-50 mM, where higher pH and lower buffer concentration favor crystallization. Physical state of the drug is critical to solid state stability, given the relative instability of amorphous drug. Stability was shown to vary considerably over the ranges of pH and buffer concentration examined, and vial-to-vial variability in degree of crystallinity is a potential concern. The formulation design space was constructed in terms of pH and drug concentration, and assuming a constant 5 mM concentration of buffer. The process design space is constructed to take into account limitations on the process imposed by the product and by equipment capability. C1 [Paul, Timothy W.; Pease, Nathan A.; Oslos, Elizabeth A.; Sacha, Gregory A.; Kuu, Wei Y.; Hardwick, Lisa M.; Karty, Jacquelyn J.; Nail, Steven L.] Baxter Pharmaceut Solut LLC, Pharmaceut Dev, Bloomington, IN 47403 USA. [Mockus, Linas N.; Basu, Prabir K.; Hee, Eun] Purdue Univ, W Lafayette, IN 47907 USA. [Harper, Nancy J.] Pfizer Inc, Pfizer Cent Res, Groton, CT 06340 USA. [Pikal, Michael J.] Univ Connecticut, Sch Pharm, Storrs, CT USA. [Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Nail, SL (reprint author), Baxter Pharmaceut Solut LLC, Pharmaceut Dev, 927 S Curry Pike, Bloomington, IN 47403 USA. EM steven_nail@baxter.com FU Food and Drug Administration FX This work was supported by a grant to Purdue University from the Food and Drug Administration. The authors report no declarations of interest. NR 15 TC 14 Z9 14 U1 1 U2 27 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD NOV PY 2011 VL 16 IS 6 BP 549 EP 576 DI 10.3109/10837450.2011.611138 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 843DJ UT WOS:000296652200001 PM 21932931 ER PT J AU Gelderman, MP Chi, X Zhi, L Vostal, JG AF Gelderman, Monique P. Chi, Xuan Zhi, Li Vostal, Jaroslav G. TI Ultraviolet B light-exposed human platelets mediate acute lung injury in a two-event mouse model of transfusion SO TRANSFUSION LA English DT Article ID STORED-BLOOD COMPONENTS; PATHOGEN INACTIVATION; AMOTOSALEN-HCL; PHOTOCHEMICAL INACTIVATION; CLINICAL-TRIAL; ANIMAL-MODELS; SPRINT TRIAL; A LIGHT; IRRADIATION; REDUCTION AB BACKGROUND: Ultraviolet B (UVB) light has been used alone on platelet (PLT) transfusion products to prevent alloimmunization or with chemical sensitizers to reduce pathogens. Such processing can damage PLTs and potentiate their storage lesion. Transfusion-related acute lung injury (ALI) has occurred in patients whose underlying condition led to an inflamed endothelium and who were transfused with products that contained either HLA or HNA antibodies or biologic modifiers such as lipids or antigens from stored cells. Clinical trials of UV-treated PLTs in patients with thrombocytopenia generated controversy regarding association of these cells with respiratory distress. We evaluated whether UVB PLTs could mediate ALI in an animal model of ALI. STUDY DESIGN AND METHODS: We used a two-event animal model where the sensitizing event was lipopolysaccharide (LPS) and the second event was infusion of human PLTs or UVB human PLTs (2.4 J/cm(2)). Infused human PLTs were followed with whole animal imaging, lung histology, confocal microscopy, lung water, and changes in bronchoalveolar lavage fluid (BALF) related to ALI. RESULTS: In LPS-treated mice UVB human PLTs accumulated in the lungs and were associated with ALI manifested by increased protein and white blood cells (WBCs) in BALF. Untreated human PLTs did not accumulate in the lungs or increase BALF protein or WBC counts. CONCLUSIONS: We provide a proof of principle that UVB human PLTs can accumulate in lungs of LPS-primed animals and mediate ALI. PLTs exposed to high doses of UVB could potentially mediate similar effects in patients predisposed with sepsis or other causes of endothelial cell inflammation. C1 [Gelderman, Monique P.; Chi, Xuan; Zhi, Li; Vostal, Jaroslav G.] US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol,OBRR, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol,OBRR, Bldg 29,Room 321,HFM 335,8800 Rockville Pike, Bethesda, MD 20892 USA. EM jaroslav.vostal@fda.hhs.gov NR 59 TC 17 Z9 17 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD NOV PY 2011 VL 51 IS 11 BP 2343 EP 2357 DI 10.1111/j.1537-2995.2011.03135.x PG 15 WC Hematology SC Hematology GA 839MQ UT WOS:000296371300013 PM 21492179 ER PT J AU Ramsay, JG Rappaport, BA AF Ramsay, James G. Rappaport, Bob A. TI SmartTots: A Multidisciplinary Effort to Determine Anesthetic Safety in Young Children SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material C1 [Ramsay, James G.] Emory Univ, Sch Med, Dept Anesthesiol, Emory Univ Hosp, Atlanta, GA 30322 USA. [Rappaport, Bob A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Ramsay, JG (reprint author), Emory Univ, Sch Med, Dept Anesthesiol, Emory Univ Hosp, Atlanta, GA 30322 USA. EM jramsay@emory.edu NR 4 TC 7 Z9 8 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2011 VL 113 IS 5 BP 963 EP 964 DI 10.1213/ANE.0b013e318232477f PG 2 WC Anesthesiology SC Anesthesiology GA 837VW UT WOS:000296236200001 PM 22021790 ER PT J AU Abernethy, DR Bai, JPF Burkhart, K Xie, HG Zhichkin, P AF Abernethy, D. R. Bai, J. P. F. Burkhart, K. Xie, H-G Zhichkin, P. TI Integration of Diverse Data Sources for Prediction of Adverse Drug Events SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PHARMACOLOGY AB The rapid evolution of large biological, pharmacological, and chemical databases has led to optimism that such data resources can be leveraged for prediction of drug action based on molecular descriptors of the drug. Challenges to realize this possibility include organization of each type of database in a manner that allows extraction of information across disparate data sources and the linkage of information across the biological, pharmacological, and chemical domains. C1 [Abernethy, D. R.; Bai, J. P. F.; Burkhart, K.; Xie, H-G; Zhichkin, P.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Abernethy, DR (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM darrell.abernethy@fda.hhs.gov NR 10 TC 5 Z9 5 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD NOV PY 2011 VL 90 IS 5 BP 645 EP 646 DI 10.1038/clpt.2011.171 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 840EI UT WOS:000296420700016 PM 22012310 ER PT J AU Coons, SJ Kothari, S Monz, BU Burke, LB AF Coons, S. J. Kothari, S. Monz, B. U. Burke, L. B. TI The Patient-Reported Outcome (PRO) Consortium: Filling Measurement Gaps for PRO End Points to Support Labeling Claims SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TASK-FORCE REPORT; QUALITY-OF-LIFE; CLINICAL-TRIALS; PRODUCT LABELS; PERSPECTIVE; SELECTION; VALIDITY; EXAMPLE; ISSUES AB The importance of appropriately and effectively incorporating the patient's voice into the evaluation of new medical products has been recognized and affirmed by regulators.(1-3) Patient-reported outcomes (PROs) are increasingly being assessed in clinical trials to quantify treatment benefits such as symptom relief and improved functioning. Translating PRO-based treatment benefits into labeling claims can provide information to physicians and patients and assist in prescribing decisions.(4,5) Hence, standardizing the valid and reliable measurement of PRO end points is critical. C1 [Coons, S. J.] Crit Path Inst, Patient Reported Outcome Consortium, Tucson, AZ USA. [Kothari, S.] Astellas Pharma US Inc, Hlth Econ & Outcomes Res, Deerfield, IL USA. [Monz, B. U.] Boehringer Ingelheim GmbH & Co KG, Global Hlth Econ & Outcomes Res, Ingelheim, Germany. [Burke, L. B.] US FDA, Off New Drugs, Ctr Drug Evaluat Res, Silver Spring, MD USA. RP Coons, SJ (reprint author), Crit Path Inst, Patient Reported Outcome Consortium, Tucson, AZ USA. EM sjcoons@c-path.org FU FDA [U01FD003865]; Science Foundation Arizona [SRG 0335-08] FX The authors gratefully acknowledge the substantial efforts of the other participants in the PRO Consortium who have helped create the structure and processes outlined in this article. The PRO Consortium is supported by grant U01FD003865 from the FDA and by Science Foundation Arizona under grant SRG 0335-08. NR 29 TC 24 Z9 24 U1 2 U2 4 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 NOV PY 2011 VL 90 IS 5 BP 743 EP 748 DI 10.1038/clpt.2011.203 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 840EI UT WOS:000296420700033 PM 21993428 ER PT J AU Patton, SM Ponnuru, P Snyder, AM Podskalny, GD Connor, JR AF Patton, S. M. Ponnuru, P. Snyder, A. M. Podskalny, G. D. Connor, J. R. TI Hypoxia-inducible factor pathway activation in restless legs syndrome patients SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE iron; hypoxia inducible factor; nitric oxide; restless legs syndrome; sleep disorders ID SUBSTANTIA-NIGRA; HUMAN-BRAIN; IRON; TRANSFERRIN; MACROPHAGES; CELLS; GENE; EXPRESSION; MECHANISM; FERRITIN AB Background and purpose: These studies tested the hypothesis that hypoxia inducible factor-1 alpha (HIF-1 alpha) pathway activation occurs in substantia nigra neurons and brain microvasculature in patients with restless legs syndrome. Methods: Immunohistochemical analyses of substantia nigra tissue from six RLS and six control subjects were analyzed for HIF-1 alpha, neuronal nitric oxide synthase (nNOS) and nitrotyrosine immunoreactivity. Microvessel lysates were obtained from cortex tissue from four RLS and four control subjects and the lysates were quantified for HIF-2 alpha and vascular endothelial growth factor (VEGF) expression using immunoblot analyses. HIF-1 alpha activation of peripheral blood monocyte cells (PBMCs) (14 RLS and 9 control) was determined through immunoblot analysis of PBMC lysates for EPO. Results: HIF-1 alpha immunoreactivity in substantia nigra neurons was significantly increased in five of six RLS patients as compared with controls. In addition, nNOS and nitrotyrosine expression are up-regulated in the substantia nigra of four of six RLS patients as compared with controls. HIF-2 alpha and VEGF expression are significantly up-regulated in the microvasculature lysates from four RLS cortical brain tissue as compared with controls. Erythropoietin levels are significantly increased in RLS PBMCs. Conclusions: These results demonstrate that the hypoxia pathway is activated in multiple cell types in individuals with RLS. Increased nNOS and nitrotyrosine suggests that nitric oxide is involved in the activation. Activation of the hypoxia pathway can result from or contribute to cellular iron deficiency. These observations suggest a novel direction to explore in RLS that is tied to the iron deficiency model but better explains the findings in postmortem studies. C1 [Patton, S. M.; Ponnuru, P.; Snyder, A. M.; Connor, J. R.] Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, Hershey, PA 17033 USA. [Podskalny, G. D.] US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Patton, SM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Dept Neurosurg, 500 Univ Dr,Mail Code H110, Hershey, PA 17033 USA. EM smp11@psu.edu FU Pennsylvania Department of Health; RLS Foundation; [R24 MH068855-06] FX This work was supported by grants from the Pennsylvania Department of Health (JRC) and the RLS Foundation (SMP). The Harvard Brain Tissue Resource Center is supported by a federal grant (R24 MH068855-06). Dr. Connor is a paid consultant for GlaxoSmithKline and the International Copper Association. NR 28 TC 18 Z9 19 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD NOV PY 2011 VL 18 IS 11 BP 1329 EP 1335 DI 10.1111/j.1468-1331.2011.03397.x PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 840DX UT WOS:000296419600011 PM 21985026 ER PT J AU Sempau, J Badal, A Brualla, L AF Sempau, Josep Badal, Andreu Brualla, Lorenzo TI A PENELOPE-based system for the automated Monte Carlo simulation of clinacs and voxelized geometries-application to far-from-axis fields SO MEDICAL PHYSICS LA English DT Article DE PENELOPE; PENEASY; PENEASYLINAC; voxelized geometry ID ELECTRON-BEAMS; DOSE DISTRIBUTIONS; PHOTON; TRANSPORT; REDUCTION; ALGORITHM; VARIANCE; CODE AB Purpose: Two new codes, PENEASY and PENEASYLINAC, which automate the Monte Carlo simulation of Varian Clinacs of the 600, 1800, 2100, and 2300 series, together with their electron applicators and multileaf collimators, are introduced. The challenging case of a relatively small and far-from-axis field has been studied with these tools. Methods: PENEASY is a modular, general-purpose main program for the PENELOPE Monte Carlo system that includes various source models, tallies and variance-reduction techniques (VRT). The code includes a new geometry model that allows the superposition of voxels and objects limited by quadric surfaces. A variant of the VRT known as particle splitting, called fan splitting, is also introduced. PENEASYLINAC, in turn, automatically generates detailed geometry and configuration files to simulate linacs with PENEASY. These tools are applied to the generation of phase-space files, and of the corresponding absorbed dose distributions in water, for two 6 MV photon beams from a Varian Clinac 2100 C/D: a 40 x 40 cm(2) centered field; and a 3 x 5 cm(2) field centered at (4.5, -11.5) cm from the beam central axis. This latter configuration implies the largest possible over-traveling values of two of the jaws. Simulation results for the depth dose and lateral profiles at various depths are compared, by using the gamma index, with experimental values obtained with a PTW 31002 ionization chamber. The contribution of several VRTs to the computing speed of the more demanding off-axis case is analyzed. Results: For the 40 x 40 cm(2) field, the percentages gamma(1) and gamma(1.2) of voxels with gamma indices (using 0.2 cm and 2% criteria) larger than unity and larger than 1.2 are 0.2% and 0%, respectively. For the 3 x 5 cm(2) field, gamma(1) = 0%. These figures indicate an excellent agreement between simulation and experiment. The dose distribution for the off-axis case with voxels of 2.5 x 2.5 x 2.5 mm(3) and an average standard statistical uncertainty of 2% (1 sigma) is computed in 3.1 h on a single core of a 2.8 GHz Intel Core 2 Duo processor. This result is obtained with the optimal combination of the tested VRTs. In particular, fan splitting for the off-axis case accelerates execution by a factor of 240 with respect to standard particle splitting. Conclusions: PENEASY and PENEASYLINAC can simulate the considered Varian Clinacs both in an accurate and efficient manner. Fan splitting is crucial to achieve simulation results for the off-axis field in an affordable amount of CPU time. Work to include Elekta linacs and to develop a graphical interface that will facilitate user input is underway. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3643029] C1 [Sempau, Josep] Univ Politecn Cataluna, Inst Tecn Energet, E-08028 Barcelona, Spain. [Badal, Andreu] CDRH US Food & Drug Adm, Div Imaging & Appl Math, OSEL, Silver Spring, MD 20993 USA. [Brualla, Lorenzo] Univ Klinikum Essen, Strahlenklin, NCTeam, D-45122 Essen, Germany. RP Sempau, J (reprint author), Univ Politecn Cataluna, Inst Tecn Energet, Diagonal 647, E-08028 Barcelona, Spain. EM josep.sempau@upc.es RI Brualla, Lorenzo/B-4672-2013; Sempau, Josep/J-7834-2013 OI Brualla, Lorenzo/0000-0003-3385-9623; Sempau, Josep/0000-0002-2754-7685 FU Spanish Ministerio de Ciencia e Innovacion [FPA2009-14091-C02-01]; Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain FX We thank Miguel L. Rodriguez, from the Centro Medico Paitilla (Panama), for providing the experimental measurements. We acknowledge partial financial support from the Spanish Ministerio de Ciencia e Innovacion, Project No. FPA2009-14091-C02-01, and from the Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain. NR 39 TC 66 Z9 66 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 NOV PY 2011 VL 38 IS 11 BP 5887 EP 5895 DI 10.1118/1.3643029 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 841SS UT WOS:000296534000009 PM 22047353 ER PT J AU Buchanan, RW Keefe, RSE Umbricht, D Green, MF Laughren, T Marder, SR AF Buchanan, Robert W. Keefe, Richard S. E. Umbricht, Daniel Green, Michael F. Laughren, Thomas Marder, Stephen R. TI The FDA-NIMH-MATRICS Guidelines for Clinical Trial Design of Cognitive-Enhancing Drugs: What Do We Know 5 Years Later? SO SCHIZOPHRENIA BULLETIN LA English DT Article DE study design; drug development; cognitive impairments; substance abuse; neuropsychological test battery ID 1ST-EPISODE SCHIZOPHRENIA; ANTIPSYCHOTIC-DRUGS; NEGATIVE SYMPTOMS; EARLY PSYCHOSIS; CATIE TRIAL; BATTERY; HALOPERIDOL; RELIABILITY; MEDICATIONS; RISPERIDONE AB The Food and Drug Administration (FDA)-National Institute of Mental Health (NIMH)-Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) clinical trial guidelines for cognitive-enhancing drugs in schizophrenia and the MATRICS Consensus Cognitive Battery (MCCB) were designed to facilitate novel compound development in the treatment of cognitive impairments. Several studies have recently utilized the FDA-NIMH-MATRICS guidelines and MCCB and allow an evaluation of the feasibility of guideline implementation and MCCB performance. In light of the study results, we would recommend the following inclusion criteria revisions-(1) clinical status and symptom inclusion criteria: maximum allowed score for hallucinations and delusions should be increased from moderate to moderately severe and the negative symptom criterion should be dropped in phase 2 studies; (2) antipsychotic medication inclusion criteria: first-generation antipsychotics should be allowed, but only in the context of no concomitant anticholinergic agents and minimal extrapyramidal symptoms, and antipsychotic polypharmacy should be allowed in the absence of pertinent pharmacokinetic or pharmacodynamic considerations; and (3) people who use illicit substances should not be allowed in phase 1B or 2A proof-of-concept studies but may be included in phase 2B and 3 studies in which proof of effectiveness and generalizability of results become more important goals. These revisions are recommended to enhance recruitment while maintaining sufficient methodological rigor to ensure the validity of study results. The MCCB has been shown to have excellent psychometric characteristics, including reliability for multisite clinical trials, clinical relevance for real-world functioning, and possible sensitivity to behavioral treatment, and should continue to serve as the standard outcome measure for cognitive enhancement studies in schizophrenia. C1 [Buchanan, Robert W.] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. [Keefe, Richard S. E.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. [Umbricht, Daniel] F Hoffmann La Roche Ltd, PDEN CRED Neurosci, CH-4070 Basel, Switzerland. [Green, Michael F.; Marder, Stephen R.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA. [Green, Michael F.; Marder, Stephen R.] Vet Adm Vet Integrated Serv Network, Mental Illness Res Educ & Clin Ctr 22, Los Angeles, CA 90073 USA. [Laughren, Thomas] Ctr Drug Evaluat & Res, Psychiat Prod Div, Food & Drug Adm, Silver Spring, MD 20993 USA. RP Buchanan, RW (reprint author), Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. EM rwbuchanan@mprc.umaryland.edu FU National Institute of Mental Health [MH22006, HHSN 278200441003C]; Measurement and Treatment Development Activities on Cognition in Schizophrenia (Marder, Green); Treatment Units for Research on Neurocognition and Schizophrenia (Marder); Janssen Pharmaceutica to Buchanan; Allon; Astra-Zeneca; GlaxoSmithKline; Novartis; Singapore National Medical Research Council FX National Institute of Mental Health (contract MH22006): Measurement and Treatment Development Activities on Cognition in Schizophrenia (Marder, Green); National Institute of Mental Health(HHSN 278200441003C): Treatment Units for Research on Neurocognition and Schizophrenia (Marder); Janssen Pharmaceutica to Buchanan; Allon, Astra-Zeneca, GlaxoSmithKline, Novartis, the Singapore National Medical Research Council to Dr Keefe; Novartis, GlaxoSmithKline to Marder. NR 41 TC 46 Z9 46 U1 3 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2011 VL 37 IS 6 BP 1209 EP 1217 DI 10.1093/schbul/sbq038 PG 9 WC Psychiatry SC Psychiatry GA 836ZD UT WOS:000296158100017 PM 20410237 ER PT J AU Fielden, MR Adai, A Dunn, RT Olaharski, A Searfoss, G Sina, J Aubrecht, J Boitier, E Nioi, P Auerbach, S Jacobson-Kram, D Raghavan, N Yang, Y Kincaid, A Sherlock, J Chen, SJ Car, B AF Fielden, Mark R. Adai, Alex Dunn, Robert T., II Olaharski, Andrew Searfoss, George Sina, Joe Aubrecht, Jiri Boitier, Eric Nioi, Paul Auerbach, Scott Jacobson-Kram, David Raghavan, Nandini Yang, Yi Kincaid, Andrew Sherlock, Jon Chen, Shen-Jue Car, Bruce CA Predictive Safety Testing Consorti Carcinogenicity Working Grp TI Development and Evaluation of a Genomic Signature for the Prediction and Mechanistic Assessment of Nongenotoxic Hepatocarcinogens in the Rat SO TOXICOLOGICAL SCIENCES LA English DT Article DE nongenotoxic; carcinogenesis; biomarkers; safety evaluation; liver; systems toxicology; toxicogenomics; methods; predictive toxicology; in vitro and alternatives ID CARCINOGENIC RISK-EVALUATION; ENHANCED CELL-PROLIFERATION; RODENT CARCINOGENICITY; IN-VIVO; TUMOR PROMOTION; CHEMICALS; TOXICOGENOMICS; LIVER; PHARMACEUTICALS; GENOTOXICITY AB Evaluating the risk of chemical carcinogenesis has long been a challenge owing to the protracted nature of the pathology and the limited translatability of animal models. Although numerous short-term in vitro and in vivo assays have been developed, they have failed to reliably predict the carcinogenicity of nongenotoxic compounds. Extending upon previous microarray work (Fielden, M. R., Nie, A., McMillian, M., Elangbam, C. S., Trela, B. A., Yang, Y., Dunn, R. T., II, Dragan, Y., Fransson-Stehen, R., Bogdanffy, M., et al. (2008). Interlaboratory evaluation of genomic signatures for predicting carcinogenicity in the rat. Toxicol. Sci. 103, 28-34), we have developed and extensively evaluated a quantitative PCR-based signature to predict the potential for nongenotoxic compounds to induce liver tumors in the rat as a first step in the safety assessment of potential nongenotoxic carcinogens. The training set was derived from liver RNA from rats treated with 72 compounds and used to develop a 22-gene signature on the TaqMan array platform, providing an economical and standardized assay protocol. Independent testing on over 900 diverse samples (66 compounds) confirmed the interlaboratory precision of the assay and its ability to predict known nongenotoxic hepatocarcinogens (NGHCs). When tested under different experimental designs, strains, time points, dose setting criteria, and other preanalytical processes, the signature sensitivity and specificity was estimated to be 67% (95% confidence interval [CI] = 38-88%) and 59% (95% CI = 44-72%), respectively, with an area under the receiver operating characteristic curve of 0.65 (95% CI = 0.46-0.83%). Compounds were best classified using expression data from short-term repeat dose studies; however, the prognostic expression changes appeared to be preserved after longer term treatment. Exploratory evaluations also revealed that different modes of action for nongenotoxic and genotoxic compounds can be discriminated based on the expression of specific genes. These results support a potential early preclinical testing paradigm to catalyze broader understanding of putative NGHCs. C1 [Fielden, Mark R.] Amgen Inc, Comparat Biol & Safety Sci, San Francisco, CA 94080 USA. [Adai, Alex; Kincaid, Andrew] Asuragen, Austin, TX 78744 USA. [Dunn, Robert T., II] Amgen Inc, Comparat Biol & Safety Sci, Thousand Oaks, CA 91320 USA. [Olaharski, Andrew] Roche, Non Clin Safety, Nutley, NJ 07110 USA. [Searfoss, George] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. [Sina, Joe] Merck Res Labs, West Point, PA 19486 USA. [Aubrecht, Jiri] Pfizer Inc, Groton, CT 06340 USA. [Boitier, Eric] Sanofi Aventis R&D, Vitry Sur Seine, France. [Nioi, Paul] Schering Plough Res Inst, Summit, NJ 08854 USA. [Auerbach, Scott] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27703 USA. [Jacobson-Kram, David] Food & Drug Adm, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. [Yang, Yi] Abbott Labs, Abbott Pk, IL 60064 USA. [Raghavan, Nandini] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ 08869 USA. [Sherlock, Jon] Life Technol, Foster City, CA 94404 USA. [Chen, Shen-Jue; Car, Bruce] Bristol Myers Squibb, Pharmaceut Candidate Optimizat, Princeton, NJ 08540 USA. RP Fielden, MR (reprint author), Amgen Inc, Comparat Biol & Safety Sci, 1120 Vet Blvd, San Francisco, CA 94080 USA. EM mfielden@amgen.com NR 45 TC 31 Z9 32 U1 3 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2011 VL 124 IS 1 BP 54 EP 74 DI 10.1093/toxsci/kfr202 PG 21 WC Toxicology SC Toxicology GA 836ZZ UT WOS:000296161100005 PM 21813463 ER PT J AU Ferguson, SA Law, CD Abshire, JS AF Ferguson, Sherry A. Law, Charles D., Jr. Abshire, Jordan S. TI Developmental Treatment with Bisphenol A or Ethinyl Estradiol Causes Few Alterations on Early Preweaning Measures SO TOXICOLOGICAL SCIENCES LA English DT Article DE bisphenol A; developmental; rat; behavior; anogenital distance; righting reflex ID SPRAGUE-DAWLEY RATS; SEXUAL-DIFFERENTIATION; LACTATIONAL EXPOSURE; IN-UTERO; REPRODUCTIVE TOXICITY; MATERNAL-BEHAVIOR; HORMONE-SECRETION; RESTRAINT STRESS; PREPUBERTAL MALE; NERVOUS-SYSTEM AB Because bisphenol A (BPA) exposure is nearly ubiquitous, increased knowledge of its potential effects on development will enable better risk assessment and regulatory guidance. Here, Sprague-Dawley rats were reared in low exogenous estrogen environments. After breeding at adulthood, dams were gavaged on gestational days (GDs) 6-21 with vehicle (VEH), 2.5 or 25.0 mu g/kg/day BPA, or 5.0 or 10.0 mu g/kg/day ethinyl estradiol (EE(2)). Offspring were orally treated on postnatal days (PNDs) 1-21 with the same dose the dam received. Relative to the VEH group, dams of both EE(2)-treated groups weighed less throughout gestation and lactation. PND 1 absolute anogenital distance and anogenital index were unaltered by any treatment. Ages at fur development and eye and ear opening were unaffected by any treatment. Despite a significant treatment effect, no group was significantly different from VEH in PNDs 3-6 righting latencies; although males had shorter latencies and all latencies decreased with age. PNDs 8-11 slant board behavior was unaffected by any treatment; however, males had shorter turning latencies and latencies decreased with age. Preweaning body weights of BPA- and EE(2)-treated groups as well as naive controls were less than VEH. No treatment affected PND 21 whole or regional brain weights or levels of estradiol, testosterone, corticosterone, T3, T4, luteinizing hormone, ghrelin, or leptin. These results add to the literature indicating that developmental BPA treatment at these doses has no effects on gestational or lactational body weight, offspring anogenital distance, preweaning behaviors or hormone levels, and whole and regional brain weights measured at weaning. C1 [Ferguson, Sherry A.; Law, Charles D., Jr.; Abshire, Jordan S.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov FU National Center for Toxicological Research/Food and Drug Administration FX National Center for Toxicological Research/Food and Drug Administration. NR 83 TC 23 Z9 23 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2011 VL 124 IS 1 BP 149 EP 160 DI 10.1093/toxsci/kfr201 PG 12 WC Toxicology SC Toxicology GA 836ZZ UT WOS:000296161100012 PM 21813462 ER PT J AU Khurana, S Wu, J Verma, N Verma, S Raghunandan, R Manischewitz, J King, LR Kpamegan, E Pincus, S Smith, G Glenn, G Golding, H AF Khurana, Surender Wu, Jian Verma, Nitin Verma, Swati Raghunandan, Ramadevi Manischewitz, Jody King, Lisa R. Kpamegan, Eloi Pincus, Steven Smith, Gale Glenn, Gregory Golding, Hana TI H5N1 Virus-Like Particle Vaccine Elicits Cross-Reactive Neutralizing Antibodies That Preferentially Bind to the Oligomeric Form of Influenza Virus Hemagglutinin in Humans SO JOURNAL OF VIROLOGY LA English DT Article ID PROTECTIVE IMMUNE-RESPONSES; RECOMBINANT HEMAGGLUTININ; CRYSTAL-STRUCTURE; ELDERLY ADULTS; IMMUNOGENICITY; NEURAMINIDASE; SAFETY; ASSAY; INFECTION; PROTEINS AB Transmission of pathogenic avian influenza viruses (AIV) from wild birds to domestic poultry and humans is continuing in multiple countries around the world. In preparation for a potential AIV pandemic, multiple vaccine candidates are under development. In the case of H5N1 AIV, a clear shift in transmission from clade 1 to clade 2 viruses occurred in recent years. The virus-like particle (VLP) represents an economical approach to pandemic vaccine development. In the current study, we evaluated the humoral immune response in humans vaccinated with H5N1 A/Indonesia/05/2005 (clade 2.1) VLP vaccine manufactured in Sf9 insect cells. The VLPs were comprised of the influenza virus hemagglutinin (HA), neuraminidase (NA), and matrix 1 (M1) proteins. In an FDA-approved phase I/II human clinical study, two doses of H5N1 VLPs at 15, 45, or 90 mu g HA/dose resulted in seroconversion and production of functional antibodies. Moreover, cross-reactivity against other clade 2 subtypes was demonstrated using virus neutralization assays. H5N1 whole-genome fragment phage display libraries (GFPDL) were used to elucidate the antibody epitope repertoire in postvaccination human sera. Diverse epitopes in HA1/HA2 and NA were recognized by postvaccination sera from the two high-dose groups, including large segments spanning the HA1 receptor binding domain. Importantly, the vaccine elicited sera that preferentially bound to an oligomeric form of recombinant HA1 compared with monomeric HA1. The oligomeric/monomeric HA1 binding ratios of the sera correlated with the virus neutralizing titers. Additionally, the two high-dose VLP vaccine groups generated NA-inhibiting antibodies that were associated with binding to a C-terminal epitope close to the sialic acid binding site. These findings represent the first report describing the quality of the antibody responses in humans following AIV VLP immunization and support further development of such vaccines against emerging influenza virus strains. C1 [Khurana, Surender; Wu, Jian; Verma, Nitin; Verma, Swati; Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Raghunandan, Ramadevi; Kpamegan, Eloi; Pincus, Steven; Smith, Gale; Glenn, Gregory] Novavax Inc, Rockville, MD 20850 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov RI gurrapu, gopi/A-9801-2011; Wu, Jian/K-2038-2015 OI Wu, Jian/0000-0001-8011-9551 NR 52 TC 51 Z9 56 U1 0 U2 5 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 NOV PY 2011 VL 85 IS 21 BP 10945 EP 10954 DI 10.1128/JVI.05406-11 PG 10 WC Virology SC Virology GA 837ZL UT WOS:000296254400002 PM 21865396 ER PT J AU Nielsen, JA Chambers, MA Romm, E Lee, LYH Berndt, JA Hudson, LD AF Nielsen, Joseph A. Chambers, Meredith A. Romm, Elena Lee, Laurel Yong-Hwa Berndt, Jo Ann Hudson, Lynn D. TI Mouse transmembrane BAX inhibitor Motif 3 (Tmbim3) encodes a 38 kDa transmembrane protein expressed in the central nervous system SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE BAX-inhibitor; Grina; Transmembrane protein ID APOPTOSIS; PREDICTION; SITES; DEATH AB Cell survival proteins play an important role throughout nervous system development, normal physiological processes, and pathological conditions. Transmembrane BAX inhibitor motif 3 (TMBIM3, also known as GRINA), is a member of a family of proteins that contain a conserved BAX inhibitor-1 motif. This family of proteins includes several members that have been shown to protect cells from apoptosis. In this study, the authors show that TMBIM3 is expressed in the brain including high levels in the hippocampus. Biochemical and sequence analysis of TMBIM3 demonstrates that the rat, murine, and human genes encode an approximately 38 kDa protein with a predicted seven transmembrane domain topology. A Tmbim3 knockout mouse line did not have an obvious phenotype, but may prove useful in future studies of this family of proteins. C1 [Nielsen, Joseph A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Nielsen, Joseph A.; Chambers, Meredith A.; Romm, Elena; Lee, Laurel Yong-Hwa; Berndt, Jo Ann; Hudson, Lynn D.] NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Nielsen, JA (reprint author), US FDA, Ctr Devices & Radiol Hlth, WO66 Room G431,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM joseph.nielsen@fda.hhs.gov FU National Institute of Neurological Disorders and Stroke (NINDS) FX The authors thank Dr. Chang-Yu Wang for the whole brain membrane fraction. The authors thank Dr. Dragan Maric for his FACS expertise and analysis of the Tmbim3 cell survival experiments, and Dr. Jim Pickle for assistance with floxing. The authors thank Dr. Sara Szuchet for initiating this project. This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke (NINDS). NR 17 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2011 VL 357 IS 1-2 BP 73 EP 81 DI 10.1007/s11010-011-0877-3 PG 9 WC Cell Biology SC Cell Biology GA 834EF UT WOS:000295941500009 PM 21614515 ER PT J AU Dickey, JS Zemp, FJ Martin, OA Kovalchuk, O AF Dickey, Jennifer S. Zemp, Franz J. Martin, Olga A. Kovalchuk, Olga TI The role of miRNA in the direct and indirect effects of ionizing radiation SO RADIATION AND ENVIRONMENTAL BIOPHYSICS LA English DT Review ID MICRORNA EXPRESSION PATTERNS; IN-VIVO; INTERCELLULAR COMMUNICATION; EPIGENETIC EFFECTORS; DNA-DAMAGE; CANCER; CELLS; IDENTIFICATION; IRRADIATION; GAMMA-H2AX AB This review focuses on a number of recent studies that have examined changes in microRNA (miRNA) expression profiles in response to ionizing radiation and other forms of oxidative stress. In both murine and human cells and tissues, a number of miRNAs display significant alterations in expression levels in response to both direct and indirect radiation exposure. In terms of direct irradiation, or exposure to agents that induce oxidative stress, miRNA array analyses indicate that a number of miRNAs are up- and down-regulated and, in particular, the let-7 family of miRNAs may well be critical in the cellular response to oxidative stress. In bystander cells that are not directly irradiated, but close to, or share media with directly irradiated cells or tissues, the miRNA expression profiles are also altered, but are somewhat distinct from the directly irradiated cells. Based on the results of these numerous studies, as well as our own data presented here, we conclude that miRNA regulation is a critical step in the cellular response to radiation and oxidative stress and that future studies should elucidate the mechanisms through which this altered regulation affects cell metabolism. C1 [Dickey, Jennifer S.] US FDA, Biochem Lab, Div Therapeut Prot, CDER, Bethesda, MD 20892 USA. [Zemp, Franz J.; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Martin, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Dickey, JS (reprint author), US FDA, Biochem Lab, Div Therapeut Prot, CDER, 29 Lincoln Dr,Bldg 29A,Room 2B-24, Bethesda, MD 20892 USA. EM Jennifer.dickey@fda.hhs.gov; Olga.martin@petermac.org NR 34 TC 41 Z9 41 U1 5 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-634X J9 RADIAT ENVIRON BIOPH JI Radiat. Environ. Biophys. PD NOV PY 2011 VL 50 IS 4 BP 491 EP 499 DI 10.1007/s00411-011-0386-5 PG 9 WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging GA 836EV UT WOS:000296093600001 PM 21928045 ER PT J AU Moro, PL Broder, K Zheteyeva, Y Revzina, N Tepper, N Kissin, D Barash, F Arana, J Brantley, MD Ding, H Singleton, JA Walton, K Haber, P Lewis, P Yue, X DeStefano, F Vellozzi, C AF Moro, Pedro L. Broder, Karen Zheteyeva, Yenlik Revzina, Natalya Tepper, Naomi Kissin, Dmitry Barash, Faith Arana, Jorge Brantley, Mary D. Ding, Helen Singleton, James A. Walton, Kimp Haber, Penina Lewis, Paige Yue, Xin DeStefano, Frank Vellozzi, Claudia TI Adverse events following administration to pregnant women of influenza A (H1N1) 2009 monovalent vaccine reported to the Vaccine Adverse Event Reporting System SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE influenza A (H1N1); pregnancy; surveillance; vaccine safety ID IMMUNIZATION SAFETY DATA; UNITED-STATES; ROTAVIRUS VACCINE; CASE DEFINITIONS; BELLS-PALSY; INTUSSUSCEPTION; GUIDELINES; PREECLAMPSIA; COLLECTION; CHILDREN AB OBJECTIVE: The objective of the study was to evaluate and summarize reports to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system, in pregnant women who received influenza A (H1N1) 2009 monovalent vaccine to assess for potential vaccine safety problems. STUDY DESIGN: We reviewed reports of adverse events (AEs) in pregnant women who received 2009-H1N1 vaccines from Oct. 1, 2009, through Feb. 28, 2010. RESULTS: VAERS received 294 reports of AEs in pregnant women who received 2009-H1N1 vaccine: 288 after inactivated and 6 after the live attenuated vaccines. Two maternal deaths were reported. Fifty-nine women (20.1%) were hospitalized. We verified 131 pregnancy-specific outcomes: 95 spontaneous abortions (<20 weeks); 18 stillbirths (>= 20 weeks); 7 preterm deliveries (<37 weeks); 3 threatened abortions; 2 preterm labor; 2 preeclampsia; and 1 each of fetal hydronephrosis, fetal tachycardia, intrauterine growth retardation, and cleft lip. CONCLUSION: Review of reports to VAERS following H1N1 vaccination in pregnant women did not identify any concerning patterns of maternal or fetal outcomes. C1 [Moro, Pedro L.; Broder, Karen; Arana, Jorge; Walton, Kimp; Haber, Penina; Lewis, Paige; Yue, Xin; DeStefano, Frank; Vellozzi, Claudia] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Zheteyeva, Yenlik] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Workforce & Career Dev, Off Director, Atlanta, GA 30333 USA. [Revzina, Natalya; Tepper, Naomi; Kissin, Dmitry] Ctr Dis Control & Prevent, Womens Hlth & Fertil Branch, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Brantley, Mary D.] Ctr Dis Control & Prevent, Appl Sci Branch, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Ding, Helen; Singleton, James A.] Ctr Dis Control & Prevent, Assessment Branch, Immunizat Serv Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Barash, Faith] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Moro, PL (reprint author), Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd,MS D26, Atlanta, GA 30333 USA. EM pmoro@cdc.gov NR 43 TC 20 Z9 21 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2011 VL 205 IS 5 AR 473.e1 DI 10.1016/j.ajog.2011.06.047 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 842EB UT WOS:000296572300028 PM 21861964 ER PT J AU Mahmood, M Li, ZG Casciano, D Khodakovskaya, MV Chen, T Karmakar, A Dervishi, E Xu, Y Mustafa, T Watanabe, F Fejleh, A Whitlow, M Al-Adami, M Ghosh, A Biris, AS AF Mahmood, Meena Li, Zhiguang Casciano, Daniel Khodakovskaya, Mariya V. Chen, Tao Karmakar, Alokita Dervishi, Enkeleda Xu, Yang Mustafa, Thikra Watanabe, Fumiya Fejleh, Ashley Whitlow, Morgan Al-Adami, Mustafa Ghosh, Anindya Biris, Alexandru S. TI Nanostructural materials increase mineralization in bone cells and affect gene expression through miRNA regulation SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE LA English DT Article DE nanomaterials; bone cells; mineralization; miRNA regulation ID OSTEOBLAST-LIKE CELLS; CARBON NANOTUBES; INVITRO MINERALIZATION; EXTRACELLULAR-MATRIX; CHICKEN OSTEOBLASTS; MC3T3-E1 CELLS; GROWTH; NODULES; CULTURE; DIFFERENTIATION AB We report that several nanomaterials induced enhanced mineralization (increased numbers and larger areas of mineral nests) in MC3T3-E1 bone cells, with the highest response being induced by silver nanoparticles (AgNPs). We demonstrate that AgNPs altered microRNA expression resulting in specific gene expression associated with bone formation. We suggest that the identified essential transcriptional factors and bone morphogenetic proteins play an important role in activation of the process of mineralization in bone cells exposed to AgNPs. C1 [Mahmood, Meena; Casciano, Daniel; Khodakovskaya, Mariya V.; Karmakar, Alokita; Dervishi, Enkeleda; Xu, Yang; Mustafa, Thikra; Watanabe, Fumiya; Fejleh, Ashley; Whitlow, Morgan; Al-Adami, Mustafa; Biris, Alexandru S.] Univ Arkansas, Dept Appl Sci, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Li, Zhiguang; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Ghosh, Anindya] Univ Arkansas, Dept Chem, Nanotechnol Ctr, Little Rock, AR 72204 USA. RP Biris, AS (reprint author), Univ Arkansas, Dept Appl Sci, Nanotechnol Ctr, Little Rock, AR 72204 USA. EM asbiris@ualr.edu RI Biris, Alexandru/A-8507-2010 FU Arkansas Science and Technology Authority (ASTA) [08-CAT-03]; U.S. Army Telemedicine and Advanced Research Center FX Financial support from the Arkansas Science and Technology Authority (ASTA) grant # 08-CAT-03 and the U.S. Army Telemedicine and Advanced Research Center is highly appreciated. NR 43 TC 16 Z9 17 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1582-4934 J9 J CELL MOL MED JI J. Cell. Mol. Med. PD NOV PY 2011 VL 15 IS 11 BP 2297 EP 2306 DI 10.1111/j.1582-4934.2010.01234.x PG 10 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 859DQ UT WOS:000297855400003 PM 21143388 ER PT J AU Wamer, WG Yin, JJ AF Wamer, Wayne G. Yin, Jun-Jie TI Photocytotoxicity in human dermal fibroblasts elicited by permanent makeup inks containing titanium dioxide SO JOURNAL OF COSMETIC SCIENCE LA English DT Article AB Titanium dioxide (TiO2) is a pigment widely used in decorative tattoo and permanent makeup inks. However, little is known about the risks associated with its presence in these products. We have developed an in vitro assay to identify inks containing TiO2 that are cytotoxic and/or photocytotoxic. The presence of TiO2 in ten permanent makeup inks was established by X-ray fluorescence. Using X-ray diffraction, we found that seven inks contained predominately TiO2 (anatase), the more photocatalytically active crystalline form of TiO2. The remaining inks contained predominately TiO2(rutile). To identify cytotoxic and/or photocytotoxic inks, human dermal fibroblasts were incubated for 18 h in media containing inks or pigments isolated from inks. Fibroblasts were then irradiated with 10 J/cm(2) UVA radiation combined with 45 J/cm(2) visible light for determining photocytotoxicity, or kept in the dark for determining cytotoxicity. Toxicity was assessed as inhibition of colony formation. No inks were cytotoxic. However eight inks, and the pigments isolated from these inks, were photocytotoxic. Using ESR, we found that most pigments from photocytotoxic inks generated hydroxyl radicals when photoexcited with UV radiation. Therefore, the possibility of photocytotoxicity should be considered when evaluating the safety of permanent makeup inks containing TiO2. C1 [Wamer, Wayne G.; Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wamer, WG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM wayne.wamer@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 NR 47 TC 8 Z9 8 U1 0 U2 5 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD NOV-DEC PY 2011 VL 62 IS 6 BP 535 EP 547 PG 13 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA V34DM UT WOS:000209067100002 PM 22682398 ER PT J AU Cortese, MM Barskey, AE Tegtmeier, GE Zhang, C Ngo, L Kyaw, MH Baughman, AL Menitove, JE Hickman, CJ Bellini, WJ Dayan, GH Hansen, GR Rubin, S AF Cortese, Margaret M. Barskey, Albert E. Tegtmeier, Gary E. Zhang, Cheryl Ngo, Laurie Kyaw, Moe H. Baughman, Andrew L. Menitove, Jay E. Hickman, Carole J. Bellini, William J. Dayan, Gustavo H. Hansen, Gail R. Rubin, Steven TI Mumps Antibody Levels Among Students Before a Mumps Outbreak: In Search of a Correlate of Immunity SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; VIRUS; VACCINE; UNIVERSITY; EPIDEMIOLOGY; COVERAGE; PROTEIN; MEASLES AB Methods. Preoutbreak samples were available from 11 case patients, 22 nonpatients who reported mumps exposure but no mumps symptoms, and 103 nonpatients who reported no known exposure and no symptoms. Antibody titers were measured by plaque reduction neutralization assay using Jeryl Lynn vaccine virus and the outbreak virus Iowa-G/USA-06 and by enzyme immunoassay (EIA). Results. Preoutbreak Jeryl Lynn virus neutralization titers were significantly lower among case patients than unexposed nonpatients (P = .023), and EIA results were significantly lower among case patients than exposed nonpatients (P = .007) and unexposed nonpatients (P = .009). Proportionately more case patients than exposed nonpatients had a preoutbreak anti-Jeryl Lynn titer < 31 (64% vs 27%, respectively; P = .065), an anti-Iowa-G/USA-06 titer < 8 (55% vs 14%; P = .033), and EIA index standard ratio < 1.40 (64% vs 9%; P = .002) and < 1.71 (73% vs 14%, P = .001). Discussion. Case patients generally had lower preoutbreak mumps antibody levels than nonpatients. However, titers overlapped and no cutoff points separated all mumps case patients from all nonpatients. C1 [Cortese, Margaret M.; Barskey, Albert E.; Kyaw, Moe H.; Hickman, Carole J.; Bellini, William J.; Dayan, Gustavo H.] Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Baughman, Andrew L.] Ctr Dis Control & Prevent, Ctr Global Hlth, Atlanta, GA 30333 USA. [Tegtmeier, Gary E.; Menitove, Jay E.] Community Blood Ctr Greater Kansas City, Kansas City, MO USA. [Zhang, Cheryl; Ngo, Laurie; Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Hansen, Gail R.] Kansas Dept Hlth & Environm, Topeka, KS USA. RP Cortese, MM (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, 1600 Clifton Rd,MSA34, Atlanta, GA 30333 USA. EM mcortese@cdc.gov FU Centers for Disease Control and Prevention [200-2008-M-27695] FX This work was supported by the Centers for Disease Control and Prevention (contract 200-2008-M-27695). NR 20 TC 21 Z9 21 U1 0 U2 3 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 NOV 1 PY 2011 VL 204 IS 9 BP 1413 EP 1422 DI 10.1093/infdis/jir526 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 828NS UT WOS:000295509300015 PM 21933874 ER PT J AU Sommers, CD Ye, HP Kolinski, RE Nasr, M Buhse, LF Al-Hakim, A Keire, DA AF Sommers, Cynthia D. Ye, Hongping Kolinski, Richard E. Nasr, Moheb Buhse, Lucinda F. Al-Hakim, Ali Keire, David A. TI Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Heparin sodium; Low-molecular-weight heparin; Polyacrylamide gel electrophoresis; Size exclusion chromatography; Multi-angle laser light scattering ID POLYACRYLAMIDE-GEL ELECTROPHORESIS; SIZE-EXCLUSION CHROMATOGRAPHY; GLYCOSAMINOGLYCAN OLIGOSACCHARIDES; MASS; FRAGMENTS AB We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M (w)) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A (2)) for each sample prior to molecular weight assessment. For UFH, a mean +/- standard deviation value for M (w) of 16,773 +/- 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M (w) values for dalteparin, tinzaparin, and enoxaparin of 6,717 +/- 71 (n = 4), 6,670 +/- 417 (n = 3), and 3,959 +/- 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 +/- 643 (n = 20), 5,845 +/- 45 (n = 4), 6,049 +/- 95 (n = 3), and 4,772 +/- 69 (n = 3), respectively. These orthogonal measurements are the first M (w) results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity. C1 [Sommers, Cynthia D.; Ye, Hongping; Kolinski, Richard E.; Buhse, Lucinda F.; Keire, David A.] Food & Drug Adm, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. [Nasr, Moheb; Al-Hakim, Ali] Food & Drug Adm, Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA. RP Keire, DA (reprint author), Food & Drug Adm, Div Pharmaceut Anal, CDER, 1114 Market St,Rm 1002, St Louis, MO 63101 USA. EM David.Keire@fda.hhs.gov NR 27 TC 19 Z9 22 U1 0 U2 18 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD NOV PY 2011 VL 401 IS 8 BP 2445 EP 2454 DI 10.1007/s00216-011-5362-z PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 828NM UT WOS:000295508600013 PM 21901459 ER PT J AU Duncan, TV AF Duncan, Timothy V. TI Applications of nanotechnology in food packaging and food safety: Barrier materials, antimicrobials and sensors SO JOURNAL OF COLLOID AND INTERFACE SCIENCE LA English DT Article DE Nanotechnology; Food packaging; Antimicrobials; Sensors; Nanofoods; Nanocomposites ID LAYERED-SILICATE NANOCOMPOSITES; POLYMER-CLAY NANOCOMPOSITES; ZINC-OXIDE NANOPARTICLES; ENHANCED RAMAN-SPECTROSCOPY; VINYL-ALCOHOL COPOLYMER; IN-VITRO TOXICITY; RESISTANT STAPHYLOCOCCUS-AUREUS; FAIR ANTIBACTERIAL PROPERTIES; SPOILAGE-RELATED MICROFLORA; COATED ENDOTRACHEAL-TUBES AB In this article, several applications of nanomaterials in food packaging and food safety are reviewed, including: polymer/clay nanocomposites as high barrier packaging materials, silver nanoparticles as potent antimicrobial agents, and nanosensors and nanomaterial-based assays for the detection of food-relevant analytes (gasses, small organic molecules and food-borne pathogens). In addition to covering the technical aspects of these topics, the current commercial status and understanding of health implications of these technologies are also discussed. These applications were chosen because they do not involve direct addition of nanoparticles to consumed foods, and thus are more likely to be marketed to the public in the short term. Published by Elsevier Inc. C1 US FDA, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. RP Duncan, TV (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Bedford Pk, IL 60501 USA. EM timothy.duncan@fda.hhs.gov NR 429 TC 349 Z9 364 U1 44 U2 403 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0021-9797 EI 1095-7103 J9 J COLLOID INTERF SCI JI J. Colloid Interface Sci. PD NOV 1 PY 2011 VL 363 IS 1 BP 1 EP 24 DI 10.1016/j.jcis.2011.07.017 PG 24 WC Chemistry, Physical SC Chemistry GA 818GS UT WOS:000294740400001 PM 21824625 ER PT J AU Li, F Seillier-Moiseiwitsch, F Korostysheyskiy, VR AF Li, Feng Seillier-Moiseiwitsch, Francoise Korostysheyskiy, Valeriy R. TI Region-based statistical analysis of 2D PAGE images SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE Proteomics; 2D PAGE; Watershed region; Spot matching; Statistical image analysis; High dimension ID ELECTROPHORESIS; PROTEINS; GELS AB A new comprehensive procedure for statistical analysis of two-dimensional polyacrylamide gel electrophoresis (2D PAGE) images is proposed, including protein region quantification, normalization and statistical analysis. Protein regions are defined by the master watershed map that is obtained from the mean gel. By working with these protein regions, the approach bypasses the current bottleneck in the analysis of 2D PAGE images: it does not require spot matching. Background correction is implemented in each protein region by local segmentation. Two-dimensional locally weighted smoothing (LOESS) is proposed to remove any systematic bias after quantification of protein regions. Proteins are separated into mutually independent sets based on detected correlations, and a multivariate analysis is used on each set to detect the group effect. A strategy for multiple hypothesis testing based on this multivariate approach combined with the usual Benjamini-Hochberg FDR procedure is formulated and applied to the differential analysis of 2D PAGE images. Each step in the analytical protocol is demonstrated by using an actual dataset. The effectiveness of the proposed methodology is shown using simulated gels in comparison with the commercial software packages PDQuest and Dymension. We also introduce a new procedure for simulating gel images. Published by Elsevier B.V. C1 [Li, Feng] Univ Maryland Baltimore Cty, Dept Math & Stat, Baltimore, MD 21228 USA. [Seillier-Moiseiwitsch, Francoise] Uniformed Serv Univ Hlth Sci, Infect Dis Clin Res Program, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Korostysheyskiy, Valeriy R.] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Med Ctr, Washington, DC USA. RP Li, F (reprint author), US FDA, Div Biometr 2, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Room 3665,Bldg 21, Silver Spring, MD 20993 USA. EM feng.li@fda.hhs.gov; fseillier@idcrp.org; vrk@georgetown.edu RI Li, Feng/B-8021-2011 FU NIH [5R01GM075298] FX This research was supported in part by NIH grant 5R01GM075298. The authors thank Carol Whisnant for the use of her data. NR 21 TC 3 Z9 3 U1 0 U2 3 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 NOV 1 PY 2011 VL 55 IS 11 BP 3059 EP 3072 DI 10.1016/j.csda.2011.05.013 PG 14 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 799WS UT WOS:000293317500013 PM 21850152 ER PT J AU Furuno, JP Johnson, JK Schweizer, ML Uche, A Stine, OC Shurland, SM Forrest, GN AF Furuno, Jon P. Johnson, Jennifer K. Schweizer, Marin L. Uche, Anayochukwu Stine, Oscar C. Shurland, Simone M. Forrest, Graeme N. TI Community-associated Methicillin-resistant Staphylococcus aureus Bacteremia and Endocarditis among HIV Patients: A cohort study SO BMC INFECTIOUS DISEASES LA English DT Article ID INJECTION-DRUG USERS; INFECTIVE ENDOCARDITIS; RISK-FACTORS; ANTIRETROVIRAL THERAPY; ANTIBIOTIC-THERAPY; MRSA BACTEREMIA; UNITED-STATES; MORTALITY; USA300; STRAINS AB Background: HIV patients are at increased risk of development of infections and infection-associated poor health outcomes. We aimed to 1) assess the prevalence of USA300 community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) among HIV-infected patients with S. aureus bloodstream infections and. 2) determine risk factors for infective endocarditis and in-hospital mortality among patients in this population. Methods: All adult HIV-infected patients with documented S. aureus bacteremia admitted to the University of Maryland Medical Center between January 1, 2003 and December 31, 2005 were included. CA-MRSA was defined as a USA300 MRSA isolate with the MBQBLO spa-type motif and positive for both the arginine catabolic mobile element and Panton-Valentin Leukocidin. Risk factors for S. aureus-associated infective endocarditis and mortality were determined using logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). Potential risk factors included demographic variables, comorbid illnesses, and intravenous drug use. Results: Among 131 episodes of S. aureus bacteremia, 85 (66%) were MRSA of which 47 (54%) were CA-MRSA. Sixty-three patients (48%) developed endocarditis and 10 patients (8%) died in the hospital on the index admission Patients with CA-MRSA were significantly more likely to develop endocarditis (OR = 2.73, 95% CI = 1.30, 5.71). No other variables including comorbid conditions, current receipt of antiretroviral therapy, pre-culture severity of illness, or CD4 count were significantly associated with endocarditis and none were associated with in-hospital mortality. Conclusions: CA-MRSA was significantly associated with an increased incidence of endocarditis in this cohort of HIV patients with MRSA bacteremia. In populations such as these, in which the prevalence of intravenous drug use and probability of endocarditis are both high, efforts must be made for early detection, which may improve treatment outcomes. C1 [Forrest, Graeme N.] Portland VA Med Ctr, Div Infect Dis, Portland, OR USA. [Forrest, Graeme N.] Oregon Hlth & Sci Univ, Portland, OR USA. [Furuno, Jon P.] Oregon State Univ, Oregon Hlth & Sci Coll Pharm, Dept Pharm Practice, Portland, OR USA. [Johnson, Jennifer K.] Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. [Schweizer, Marin L.] Univ Iowa, Dept Internal Med, Carver Coll Med, Iowa City, IA 52242 USA. [Furuno, Jon P.; Stine, Oscar C.; Shurland, Simone M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Uche, Anayochukwu] Oro Valley Hosp, Oro Valley, AZ USA. [Shurland, Simone M.] US FDA, Silver Spring, MD USA. RP Forrest, GN (reprint author), Portland VA Med Ctr, Div Infect Dis, Portland, OR USA. EM forrestg@ohsu.edu FU National Institutes of Health [M01 RR16500]; University of Maryland General Clinical Research Center [1K01AI071015-03, 1K12RR023250-04]; Southern Medical Association; Cubist Pharmaceuticals, Inc.; Pfizer Inc. FX National Institutes of Health Grants M01 RR16500, University of Maryland General Clinical Research Center, 1K01AI071015-03 (J.P.F.) and 1K12RR023250-04 (J.K.J.) and a grant from the Southern Medical Association (A.U.).; In the past 5 years J.P.F. and M.L.S. have served as consults for Cubist Pharmaceuticals, Inc. Also, G.N.F. has received research funding and honoraria from Cubist Pharmaceuticals, Inc. and Pfizer Inc. M.L.S. has received research funding from Pfizer, Inc. NR 43 TC 20 Z9 21 U1 1 U2 1 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 OCT 31 PY 2011 VL 11 AR 298 DI 10.1186/1471-2334-11-298 PG 7 WC Infectious Diseases SC Infectious Diseases GA 846MX UT WOS:000296909000001 PM 22040268 ER PT J AU Xu, XM Khan, MA Burgess, DJ AF Xu, Xiaoming Khan, Mansoor A. Burgess, Diane J. TI A quality by design (QbD) case study on liposomes containing hydrophilic API: I. Formulation, processing design and risk assessment SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Liposome; QbD; Tenofovir; Encapsulation efficiency; Particle size; Risk analysis ID TENOFOVIR DISOPROXIL FUMARATE; PHARMACOKINETICS; CHOLESTEROL; INJECTION AB The purpose of this study was to extend QbD principles to liposomal drug products containing a hydrophilic active pharmaceutical ingredient (API) to demonstrate both the feasibility and the advantages of applying QbD concepts to liposome based complex parenteral controlled release systems. The anti-viral drug Tenofovir was selected as a model compound. Desired properties for two of the key liposome drug product qualities, namely the particle size and drug encapsulation efficiency, were defined and evaluated. It was observed that the liposome preparation process significantly affects liposome particle size, and this resulted in considerable variation in the drug encapsulation efficiency. Lipid chain length did not have a significant effect on drug encapsulation efficiency. However, lipid concentration did affect the drug encapsulation efficiency with higher lipid concentrations resulting in higher drug encapsulation. The use of risk assessment in this study assisted the identification of eight high risk factors that may impact liposome drug encapsulation efficiency and particle size. (C) 2011 Elsevier B.V. All rights reserved. C1 [Xu, Xiaoming; Burgess, Diane J.] Univ Connecticut, Dept Pharmaceut Sci, Storrs, CT 06269 USA. [Khan, Mansoor A.] FDA CDER DPQR, Silver Spring, MD 20993 USA. RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut Sci, 69 N Eagleville Rd U3092, Storrs, CT 06269 USA. EM xiaoming.xu@me.com; mansoor.khan@fda.hhs.gov; d.burgess@uconn.edu OI Xu, Xiaoming/0000-0003-1672-0830 FU FDA [REQ1044477] FX This research was supported by FDA critical path funding (Solicitation No.: REQ1044477). NR 21 TC 33 Z9 34 U1 2 U2 18 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 OCT 31 PY 2011 VL 419 IS 1-2 BP 52 EP 59 DI 10.1016/j.ijpharm.2011.07.012 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 838QJ UT WOS:000296307000007 PM 21787854 ER PT J AU Zhu, YM Luo, TM Jobin, C Young, HA AF Zhu, Yuanmin Luo, T. Michelle Jobin, Christian Young, Howard A. TI Gut microbiota and probiotics in colon tumorigenesis SO CANCER LETTERS LA English DT Review DE Microbiota; Inflammation; Probiotics; Colorectal cancer ID LACTOBACILLUS-RHAMNOSUS; COLORECTAL-CANCER; BIFIDOBACTERIUM-LACTIS; INTESTINAL MICROBIOTA; ULCERATIVE-COLITIS; ANTITUMOR-ACTIVITY; ESCHERICHIA-COLI; RESISTANT STARCH; FED INFANTS; IN-VIVO AB The human gastrointestinal tract harbors a complex and abundant microbial community reaching as high as 10(13)-10(14) microorganisms in the colon. This endogenous microbiota forms a symbiotic relationship with their eukaryotic host and this close partnership helps maintain homeostasis by performing essential and non-redundant tasks (e.g. nutrition/energy and, immune system balance, pathogen exclusion). Although this relationship is essential and beneficial to the host, various events (e.g. infection, diet, stress, inflammation) may impact microbial composition, leading to the formation of a dysbiotic microbiota, further impacting on health and disease states. For example, Crohn's disease and ulcerative colitis, collectively termed inflammatory bowel diseases (IBD), have been associated with the establishment of a dysbiotic microbiota. In addition, extra-intestinal disorders such as obesity and metabolic syndrome are also associated with the development of a dysbiotic microbiota. Consequently, there is an increasing interest in harnessing the power of the microbiome and modulating its composition as a means to alleviate intestinal pathologies/disorders and maintain health status. In this review, we will discuss the emerging relationship between the microbiota and development of colorectal cancer as well as present evidence that microbial manipulation (probiotic, prebiotic) impacts disease development. Published by Elsevier Ireland Ltd. C1 [Young, Howard A.] Natl Canc Inst, Ctr Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Frederick, MD 21702 USA. [Zhu, Yuanmin] Beijing Univ, Peoples Hosp, Dept Digest Dis, Beijing 100871, Peoples R China. [Jobin, Christian] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Luo, T. Michelle] US FDA, CDRH, OIVD, Silver Spring, MD USA. RP Young, HA (reprint author), Natl Canc Inst, Ctr Canc Res, Canc & Inflammat Program, Expt Immunol Lab, Bldg 560-31-23,Chandler St, Frederick, MD 21702 USA. EM YoungHow@mail.nih.gov FU NIH [HHSN261200800001E]; National Cancer Institute; Center for Cancer Research FX This work was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This project has been funded with federal funds from the National Cancer Institute, NIH, under contract HHSN261200800001E. NR 76 TC 62 Z9 72 U1 3 U2 65 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 OCT 28 PY 2011 VL 309 IS 2 BP 119 EP 127 DI 10.1016/j.canlet.2011.06.004 PG 9 WC Oncology SC Oncology GA 816CN UT WOS:000294576400001 PM 21741763 ER PT J AU LaPlante, SR Fader, LD Fandrick, KR Fandrick, DR Hucke, O Kemper, R Miller, SPF Edwards, PJ AF LaPlante, Steven R. Fader, Lee D. Fandrick, Keith R. Fandrick, Daniel R. Hucke, Oliver Kemper, Ray Miller, Stephen P. F. Edwards, Paul J. TI Assessing Atropisomer Axial Chirality in Drug Discovery and Development SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SYMMETRICAL HETEROARYL CARBOXAMIDES; BIOAVAILABLE CCR5 ANTAGONIST; NK1 RECEPTOR ANTAGONISTS; ENANTIOSELECTIVE SYNTHESIS; BIOLOGICAL EVALUATION; CAPILLARY-ELECTROPHORESIS; THERMODYNAMIC CONTROL; ASYMMETRIC-SYNTHESIS; DYNAMIC RESOLUTION; HIV-1 INHIBITORS C1 [LaPlante, Steven R.; Fader, Lee D.; Hucke, Oliver; Edwards, Paul J.] Boehringer Ingelheim Canada Ltd, Dept Chem, Laval, PQ H7S 2GS, Canada. [Fandrick, Keith R.; Fandrick, Daniel R.; Kemper, Ray] Boehringer Ingelheim Pharmaceut Inc, Chem Dev, Nonclin Drug Safety, Ridgefield, CT 06877 USA. [Miller, Stephen P. F.] US FDA, Off New Drug Qual Assessment, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP LaPlante, SR (reprint author), Boehringer Ingelheim Canada Ltd, Dept Chem, 2100 Cunard St, Laval, PQ H7S 2GS, Canada. EM steven.laplante@boehringer-ingelheim.com; paul.edwards@boehringer-ingelheim.com NR 98 TC 78 Z9 78 U1 5 U2 47 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 27 PY 2011 VL 54 IS 20 BP 7005 EP 7022 DI 10.1021/jm200584g PG 18 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 837LU UT WOS:000296205900001 PM 21848318 ER PT J AU Smith, JS Xu, ZL Tian, J Palmer, DJ Ng, P Byrnes, AP AF Smith, Jeffrey S. Xu, Zhili Tian, Jie Palmer, Donna J. Ng, Philip Byrnes, Andrew P. TI The Role of Endosomal Escape and Mitogen-Activated Protein Kinases in Adenoviral Activation of the Innate Immune Response SO PLOS ONE LA English DT Article ID IN-VIVO; GENE-THERAPY; MOUSE-LIVER; VECTORS; EXPRESSION; P38; VIRUS; TRIGGERS; PATHWAYS; CELLS AB Adenoviral vectors (AdV) activate multiple signaling pathways associated with innate immune responses, including mitogen-activated protein kinases (MAPKs). In this study, we investigated how systemically-injected AdVs activate two MAPK pathways (p38 and ERK) and the contribution of these kinases to AdV-induced cytokine and chemokine responses in mice. Mice were injected intravenously either with a helper-dependent Ad2 vector that does not express viral genes or transgenes, or with the Ad2 mutant ts1, which is defective in endosomal escape. We found that AdV induced rapid phosphorylation of p38 and ERK as well as a significant cytokine response, but ts1 failed to activate p38 or ERK and induced only a limited cytokine response. These results demonstrate that endosomal escape of virions is a critical step in the induction of these innate pathways and responses. We then examined the roles of p38 and ERK pathways in the innate cytokine response by administering specific kinase inhibitors to mice prior to AdV. The cytokine and chemokine response to AdV was only modestly suppressed by a p38 inhibitor, while an ERK inhibitor has mixed effects, lowering some cytokines and elevating others. Thus, even though p38 and ERK are rapidly activated after i.v. injection of AdV, cytokine and chemokine responses are mostly independent of these kinases. C1 [Smith, Jeffrey S.; Xu, Zhili; Tian, Jie; Byrnes, Andrew P.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Palmer, Donna J.; Ng, Philip] Baylor Coll Med, Houston, TX 77030 USA. RP Smith, JS (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM andrew.byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 FU Federal Drug Administration (FDA) FX This research was supported by the Federal Drug Administration (FDA), including the FDA's Critical Path program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 5 Z9 5 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 27 PY 2011 VL 6 IS 10 AR e26755 DI 10.1371/journal.pone.0026755 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 841OJ UT WOS:000296521400032 PM 22046344 ER PT J AU Davis, EM Benetatos, NM Regnault, WF Winey, KI Elabd, YA AF Davis, Eric M. Benetatos, Nicholas M. Regnault, William F. Winey, Karen I. Elabd, Yossef A. TI The influence of thermal history on structure and water transport in Parylene C coatings SO POLYMER LA English DT Article DE Glassy polymer; Crystallinity; Diffusion ID FLEXIBLE ELECTRONIC APPLICATIONS; TOTAL REFLECTANCE SPECTROSCOPY; CHEMICAL-VAPOR-DEPOSITION; MOLECULAR-DIFFUSION; BARRIER COATINGS; POLYMER; FILMS; TEMPERATURE; PERMEATION; MORPHOLOGY AB Poly(monochloro-p-xylylene) (Parylene C) coatings are commonly used in a number of applications due to their robust properties and unique ability to be deposited directly from the vapor phase. Recently, Parylene C has been used in new medical devices, where an accurate assessment and understanding of liquid transport and its relationship to the polymer structure is critical in design and evaluation. In this study, the diffusion of liquid water in Parylene C coatings was examined as a function of the thermal history with in situ time-resolved Fourier transform infrared-attenuated total reflectance (FTIR-ATR) spectroscopy, while the polymer structure was investigated with in situ X-ray scattering. Anomalous transport behavior was observed, where dynamic infrared spectra provide evidence of water diffusion and water-induced polymer relaxation occurring on similar time scales. Both of these phenomena were quantified and regressed to a diffusion relaxation model to determine the diffusion coefficient and polymer relaxation time constant. After thermal treatment of the Parylene C coating, the water diffusivity reduced by 2-fold, which can be attributed to the increase in crystallinity and the evolution of a new crystalline phase in Parylene C. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Davis, Eric M.; Elabd, Yossef A.] Drexel Univ, Dept Chem & Biol Engn, Philadelphia, PA 19104 USA. [Benetatos, Nicholas M.; Regnault, William F.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20903 USA. [Winey, Karen I.] Univ Penn, Dept Mat Sci & Engn, Philadelphia, PA 19104 USA. RP Elabd, YA (reprint author), Drexel Univ, Dept Chem & Biol Engn, Philadelphia, PA 19104 USA. EM nicholas.benetatos@fda.hhs.gov; elabd@drexel.edu RI Elabd, Yossef/G-9866-2014 OI Elabd, Yossef/0000-0002-7790-9445 FU National Science Foundation [CBET-0644593]; U.S. Food and Drug Administration through Oak Ridge Institute for Science and Education; NSF-MRSEC [05-20020] FX The authors acknowledge the financial support of the National Science Foundation (CBET-0644593) and the U.S. Food and Drug Administration Biomedical Devices Fellowship through Oak Ridge Institute for Science and Education. The authors also acknowledge Prof. Paul Heiney in the Department of Physics at the University of Pennsylvania for helpful discussions and assistance with the X-ray scattering. The X-ray scattering facility is supported by NSF-MRSEC 05-20020. NR 35 TC 18 Z9 18 U1 2 U2 29 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD OCT 27 PY 2011 VL 52 IS 23 BP 5378 EP 5386 DI 10.1016/j.polymer.2011.08.010 PG 9 WC Polymer Science SC Polymer Science GA 838QK UT WOS:000296307100019 ER PT J AU Ma, HL Shaheduzzaman, S Willliams, DK Gao, YM Khan, AS AF Ma, Hailun Shaheduzzaman, Syed Willliams, Dhanya K. Gao, Yamei Khan, Arifa S. TI Investigations of porcine circovirus type 1 (PCV1) in vaccine-related and other cell lines SO VACCINE LA English DT Article DE Porcine circovirus; PCR assay; Infectivity assays; Vaccine-related cell lines; Animal-derived raw materials ID ANTIBODIES; VIRUS; REPLICATION; INFECTION; DNA; AMPLIFICATION; PAPOVAVIRUS; PIGS; METAGENOMICS; CULTURES AB Porcine circovirus type 1 (PCV1) is highly prevalent in swine and was recently reported in some rotavirus vaccines. Since animal-derived raw materials, such as cells, trypsin, and serum, can be a major source of introducing virus contamination in biological products, we have investigated PCV1 in several cell lines obtained from ATCC that have broad use in research, diagnostics, or vaccine development. It is expected that these cell lines have been exposed to bovine and porcine viruses during their establishment and passage history due to the use of serum and trypsin that was not qualified according to current testing guidances or processed using new virus-inactivation methods. This study showed that Vero, MRC-5, and CEFs, which represent cell substrates used in some U.S. licensed vaccines, and other cell lines used in investigational vaccines, such as MDCK, HEK-293, HeLa, and A549, were negative for PCV1 using a nested PCR assay: some were also confirmed negative by infectivity analysis. However, MDBK cells, which are used for some animal vaccines, contained PCV1 sequences, although no virus was isolated. Although the results showed that PCV infection may not have occurred under previous culture conditions, the recent cases of vaccine contamination emphasizes the need for continued efforts to reduce the likelihood of introducing viruses from animal-derived materials used in product manufacture. Published by Elsevier Ltd. C1 [Ma, Hailun; Shaheduzzaman, Syed; Willliams, Dhanya K.; Gao, Yamei; Khan, Arifa S.] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), 8800 Rockville Pike,HFM-454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov FU U.S. Food and Drug Administration FX We thank Hana Golding, Keith Peden, Jerry Weir, and Theresa Finn for review of the manuscript. This work was supported by the U.S. Food and Drug Administration. NR 48 TC 14 Z9 16 U1 0 U2 6 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 OCT 26 PY 2011 VL 29 IS 46 BP 8429 EP 8437 DI 10.1016/j.vaccine.2011.07.123 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 847QV UT WOS:000296988500035 PM 21835219 ER PT J AU Handy, SM Parks, MB Deeds, JR Liston, A de Jager, LS Luccioli, S Kwegyir-Afful, E Fardin-Kia, AR Begley, TH Rader, JI Diachenko, GW AF Handy, Sara M. Parks, Matthew B. Deeds, Jonathan R. Liston, Aaron de Jager, Lowri S. Luccioli, Stefano Kwegyir-Afful, Ernest Fardin-Kia, Ali R. Begley, Timothy H. Rader, Jeanne I. Diachenko, Gregory W. TI Use of the Chloroplast Gene ycf1 for the Genetic Differentiation of Pine Nuts Obtained from Consumers Experiencing Dysgeusia SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE pine nut; dysgeusia; pine mouth; Pinus armandii; ycf1; DNA ID CHAIN-REACTION METHOD; DNA BARCODES; IDENTIFICATION; PCR; PRODUCTS; PINACEAE; PRIMERS; UTILITY; PLANTS; MATK AB Pine nuts are a part of traditional cooking in many parts of the world and have seen a significant increase in availability/use in the United States over the past 10 years. The U.S. Food and Drug Administration (US FDA) field offices received 411 complaints from U.S. consumers over the past three years regarding taste disturbances following the consumption of pine nuts. Using analysis of fatty acids by gas chromatography with flame ionization detection, previous reports have implicated nuts from Pinus armandii (Armand Pine) as the causative species for similar taste disturbances. This method was found to provide insufficient species resolution to link FDA consumer complaint samples to a single species of pine, particularly when samples contained species mixtures of pine nuts. Here we describe a DNA based method for differentiating pine nut samples using the ycf1 chloroplast gene. Although the exact cause of pine nut associated dysgeusia is still not known, we found that 15 of 15 samples from consumer complaints contained at least some Pinus armandii, confirming the apparent association of this species with taste disturbances. C1 [Handy, Sara M.; Deeds, Jonathan R.; de Jager, Lowri S.; Fardin-Kia, Ali R.; Begley, Timothy H.; Rader, Jeanne I.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. [Parks, Matthew B.; Liston, Aaron] Oregon State Univ, Dept Bot & Plant Pathol, Corvallis, OR 97331 USA. [Luccioli, Stefano; Kwegyir-Afful, Ernest] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. RP Handy, SM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. EM Sara.Handy@fda.hhs.gov RI Handy, Sara/C-6195-2008 NR 33 TC 12 Z9 12 U1 2 U2 13 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 OCT 26 PY 2011 VL 59 IS 20 BP 10995 EP 11002 DI 10.1021/jf203215v PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 833WD UT WOS:000295915000029 PM 21932798 ER PT J AU Harigaya, Y Ngo, D Lesse, AJ Huang, V Tsuji, BT AF Harigaya, Yoriko Ngo, Dung Lesse, Alan J. Huang, Vanthida Tsuji, Brian T. TI Characterization of heterogeneous vancomycin-intermediate resistance, MIC and accessory gene regulator (agr) dysfunction among clinical bloodstream isolates of staphyloccocus aureus SO BMC INFECTIOUS DISEASES LA English DT Article ID STAPHYLOCOCCUS-AUREUS; REDUCED SUSCEPTIBILITY; BACTEREMIA; GLYCOPEPTIDES; PREVALENCE; STRAINS AB Background: The development of hVISA has been associated with vancomycin clinical failures and is commonly misidentified in clinical microbiology laboratories. Therefore, the objectives of this present study was to improve the reliability of methodologies and criteria for identifying hVISA, evaluate the prevalence of hVISA among clinical bloodstream isolates of S. aureus and determine if there exists a relationship between accessory gene regulator (agr) dysfunction and the hVISA phenotype. Methods: The presence of hVISA in 220 clinical S. aureus isolates (121 MSSA, 99 MRSA) from bloodstream infections was examined by CLSI broth microdilution, Macro & Standard Etest. Isolates which were classified as hVISA by Macro Etest, were additionally evaluated using a modified PAP-AUC method using a modified starting inoculum of 10(10) CFU/mL, and growth on brain heart infusion agar with 4 mg/L vancomycin (BHIV4) at 10(8) and 10(10) CFU/mL, and agr function was assessed by delta-hemolysin production. Results: Broth microdilution MIC(50/90) of S. aureus and hVISA was 1.0/2.0 and 1.5/2.0 mg/L (p= 0.02), respectively. Macro Etest identified 12 (5.5%) hVISA isolates; higher among MRSA (9.1%) versus MSSA (2.5%) (p = 0.03). The mean modified PAP-AUC ratios (> 0.8) of 7 MRSA strains and 3 MSSA strains were significantly different (p = 0.001). 58% of hVISA strains were found to be agr dysfunctional when 21% of MRSA strains were agr dysfunctional. hVISA was detected among S. aureus bloodstream isolates, which were classified as susceptible among clinical microbiology laboratories. Conclusions: Evaluating the correlation between Etest MICs and modified PAP-AUC ratio values will add further improvement of discriminating hVISA, and agr dysfunction may be predictive of strains which display a greater predilection to display the hVISA phenotype. C1 [Harigaya, Yoriko; Ngo, Dung; Tsuji, Brian T.] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Lab Antimicrobial Pharmacodynam, New York, NY USA. [Harigaya, Yoriko; Ngo, Dung; Tsuji, Brian T.] SUNY Buffalo, New York State Ctr Excellence Bioinformat & Life, New York, NY USA. [Lesse, Alan J.] SUNY Buffalo, Sch Med & Biomed Sci, New York, NY USA. [Huang, Vanthida] Mercer Univ, Coll Pharm, Atlanta, GA USA. [Tsuji, Brian T.] Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. [Harigaya, Yoriko] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Tsuji, BT (reprint author), SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Lab Antimicrobial Pharmacodynam, New York, NY USA. EM btsuji@buffalo.edu FU University at Buffalo, State University of New York FX We would like to thank Michael Ma for excellent technical assistance. This study was funded by the University at Buffalo, State University of New York, Interdisciplinary Research Fund. NR 17 TC 13 Z9 15 U1 0 U2 4 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 OCT 25 PY 2011 VL 11 AR 287 DI 10.1186/1471-2334-11-287 PG 7 WC Infectious Diseases SC Infectious Diseases GA 848LL UT WOS:000297053000001 PM 22026752 ER PT J AU Pantchenko, OS Seidman, SJ Guag, JW AF Pantchenko, Oxana S. Seidman, Seth J. Guag, Joshua W. TI Analysis of induced electrical currents from magnetic field coupling inside implantable neurostimulator leads SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article ID SPINAL-CORD STIMULATION; ELECTROMAGNETIC COMPATIBILITY AB Background: Over the last decade, the number of neurostimulator systems implanted in patients has been rapidly growing. Nearly 50, 000 neurostimulators are implanted worldwide annually. The most common type of implantable neurostimulators is indicated for pain relief. At the same time, commercial use of other electromagnetic technologies is expanding, making electromagnetic interference (EMI) of neurostimulator function an issue of concern. Typically reported sources of neurostimulator EMI include security systems, metal detectors and wireless equipment. When near such sources, patients with implanted neurostimulators have reported adverse events such as shock, pain, and increased stimulation. In recent in vitro studies, radio frequency identification (RFID) technology has been shown to inhibit the stimulation pulse of an implantable neurostimulator system during low frequency exposure at close distances. This could potentially be due to induced electrical currents inside the implantable neurostimulator leads that are caused by magnetic field coupling from the low frequency identification system. Methods: To systematically address the concerns posed by EMI, we developed a test platform to assess the interference from coupled magnetic fields on implantable neurostimulator systems. To measure interference, we recorded the output of one implantable neurostimulator, programmed for best therapy threshold settings, when in close proximity to an operating low frequency RFID emitter. The output contained electrical potentials from the neurostimulator system and those induced by EMI from the RFID emitter. We also recorded the output of the same neurostimulator system programmed for best therapy threshold settings without RFID interference. Using the Spatially Extended Nonlinear Node (SENN) model, we compared threshold factors of spinal cord fiber excitation for both recorded outputs. Results: The electric current induced by low frequency RFID emitter was not significant to have a noticeable effect on electrical stimulation. Conclusions: We demonstrated a method for analyzing effects of coupled magnetic field interference on implantable neurostimulator system and its electrodes which could be used by device manufacturers during the design and testing phases of the development process. C1 [Pantchenko, Oxana S.; Seidman, Seth J.; Guag, Joshua W.] US FDA, Silver Spring, MD 20993 USA. [Pantchenko, Oxana S.] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA. RP Pantchenko, OS (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Oxana.S.Pantchenko@gmail.com NR 18 TC 4 Z9 4 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-925X J9 BIOMED ENG ONLINE JI Biomed. Eng. Online PD OCT 21 PY 2011 VL 10 AR 94 DI 10.1186/1475-925X-10-94 PG 11 WC Engineering, Biomedical SC Engineering GA 844PM UT WOS:000296759600001 PM 22014169 ER PT J AU Bhattacharjee, A Pal, S Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Pal, Srabani Feldman, Gerald M. Cathcart, Martha K. TI Hck Is a Key Regulator of Gene Expression in Alternatively Activated Human Monocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; KINASE-C-DELTA; HUMAN ATHEROSCLEROTIC PLAQUES; CENTRIFUGAL ELUTRIATION CCE; SIGNAL-TRANSDUCTION PATHWAY; PERIPHERAL-BLOOD MONOCYTES; POLAR STEROL ESTERS; SRC-FAMILY KINASES; NF-KAPPA-B; PROTEIN-KINASE AB IL-13 is a Th2 cytokine that promotes alternative activation (M2 polarization) in primary human monocytes. Our studies have characterized the functional IL-13 receptor complex and the downstream signaling events in response to IL-13 stimulation in alternatively activated monocytes/macrophages. In this report, we present evidence that IL-13 induces the activation of a Src family tyrosine kinase, which is required for IL-13 induction of M2 gene expression, including 15-lipoxygenase (15-LO). Our data show that Src kinase activity regulates IL-13-induced p38 MAPK tyrosine phosphorylation via the upstream kinases MKK3or MKK6. Our findings also reveal that the IL-13 receptor-associated tyrosine kinase Jak2 is required for the activation of both Src kinase as well as p38 MAPK. Further, we found that Src tyrosine kinase-mediated activation of p38 MAPK is required for Stat1 and Stat3 serine 727 phosphorylation in alternatively activated monocytes/macrophages. Additional studies identify Hck as the specific Src family member, stimulated by IL-13 and involved in regulating both p38 MAPK activation and p38 MAPK-mediated 15-LO expression. Finally we show that the Hck regulates the expression of other alternative state (M2)-specific genes (Mannose receptor, MAO-A, and CD36) and therefore conclude that Hck acts as a key regulator controlling gene expression in alternatively activated monocytes/macrophages. C1 [Bhattacharjee, Ashish; Pal, Srabani; Cathcart, Martha K.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44195 USA. [Bhattacharjee, Ashish; Pal, Srabani; Cathcart, Martha K.] Case Western Reserve Univ, Lerner Coll Med, Dept Mol Med, Cleveland Clin, Cleveland, OH 44195 USA. [Feldman, Gerald M.] US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bhattacharjee, A (reprint author), Cleveland Clin, Lerner Res Inst, Dept Cell Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM bhattaa@ccf.org; cathcam@ccf.org FU National Institutes of Health [HL051068, HL087018]; National Center for Research Resources [1UL1RR024989] FX This work was supported, in whole or in part, by National Institutes of Health Grants HL051068 and HL087018 (to M. K. C.). This work was also supported by the National Center for Research Resources (Grant Center for Translational Science Activities 1UL1RR024989). NR 71 TC 15 Z9 15 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2011 VL 286 IS 42 BP 36709 EP 36723 DI 10.1074/jbc.M111.291492 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 841UC UT WOS:000296538300054 PM 21878628 ER PT J AU Parveen, S Kaur, S David, SAW Kenney, JL McCormick, WM Gupta, RK AF Parveen, Seema Kaur, Simleen David, Selwyn A. Wilson Kenney, James L. McCormick, William M. Gupta, Rajesh K. TI Evaluation of growth based rapid microbiological methods for sterility testing of vaccines and other biological products SO VACCINE LA English DT Article DE Rapid microbiological methods; Sterility method; ATP bioluminescence technology; Detection of growth by CO(2) monitoring ID MICROBIAL DETECTION SYSTEM; BLOOD CULTURE BOTTLES; BODY-FLUIDS; BACT/ALERT BLOOD; BACTERIA; MEDIA; BIOLUMINESCENCE; CONTAMINATION; BACTEC-9240 AB Most biological products, including vaccines, administered by the parenteral route are required to be tested for sterility at the final container and also at various stages during manufacture. The sterility testing method described in the Code of Federal Regulations (21 CFR 610.12) and the United States Pharmacopoeia (USP, Chapter < 71 >) is based on the observation of turbidity in liquid culture media due to growth of potential contaminants. We evaluated rapid microbiological methods (RMM) based on detection of growth 1) by adenosine triphosphate (ATP) bioluminescence technology (Rapid Milliflex (R) Detection System [RMDS], and 2) by CO(2) monitoring technologies (BacT/Alert and the BACTEC systems), as alternate sterility methods. Microorganisms representing Gram negative, Gram positive, aerobic, anaerobic, spore forming, slow growing bacteria, yeast, and fungi were prepared in aliquots of Fluid A or a biological matrix (including inactivated influenza vaccines) to contain approximately 0.1, 1, 10 and 100 colony forming units (CFU) in an inoculum of 10 ml. These preparations were inoculated to the specific media required for the various methods: 1) fluid thioglycollate medium (FTM) and tryptic soy broth (TSB) of the compendial sterility method (both membrane filtration and direct inoculation): 2) tryptic soy agar (TSA), Sabouraud dextrose agar (SDA) and Schaedler blood agar (SBA) of the RMDS; 3) iAST and iNST media of the BacT/Alert system and 4) Standard 10 Aerobic/F and Standard Anaerobic/F media of the BACTEC system. RMDS was significantly more sensitive in detecting various microorganisms at 0.1 CFU than the compendia] methods (p < 0.05), whereas the compendial membrane filtration method was significantly more sensitive than the BACTEC and BacT/Alert methods (p < 0.05). RMDS detected all microorganisms significantly faster than the compendial method (p < 0.05). BacT/Alert and BACTEC methods detected most microorganisms significantly faster than the compendial method (p < 0.05), but took almost the same time to detect the slow growing microorganism P. acnes, compared to the compendial method. RMDS using SBA detected all test microorganisms in the presence of a matrix containing preservative 0.01% thimerosal, whereas the BacT/Alert and BACTEC systems did not consistently detect all the test microorganisms in the presence of 0.01% thimerosal. RMDS was compatible with inactivated influenza vaccines and aluminum phosphate or aluminum hydroxide adjuvants at up to 8 mg/ml without any interference in bioluminescence. RMDS was shown to be acceptable as an alternate sterility method taking 5 days as compared to the 14 days required of the compendial method. Isolation of microorganisms from the RMDS was accomplished by reincubation of membranes with fresh SBA medium and microbial identification was confirmed using the MicroSEQ Identification System. BacT/Alert and BACTEC systems may be applicable as alternate methods to the compendial direct inoculation sterility method for products that do not contain preservatives or anti-microbial agents. Published by Elsevier Ltd. C1 [Parveen, Seema; Kaur, Simleen; David, Selwyn A. Wilson; Kenney, James L.; McCormick, William M.; Gupta, Rajesh K.] US FDA, Div Biol Stand & Qual Control, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Gupta, RK (reprint author), 1401 Rockville Pike,HFM 680, Rockville, MD 20852 USA. EM Rajesh.Gupta@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration FX This project was supported in part by an appointment of Dr. Seema Parveen, Dr. Selwyn Wilson David and Ms. Simleen Kaur 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 authors thank Martha C. Anderson, Dr. Bryan Riley, Dr. Randa Melhem and Dr. John Bishop for reviewing the manuscript and for their valuable comments. NR 36 TC 10 Z9 12 U1 1 U2 22 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 OCT 19 PY 2011 VL 29 IS 45 BP 8012 EP 8023 DI 10.1016/j.vaccine.2011.08.055 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 843PF UT WOS:000296683700019 PM 21871516 ER PT J AU Moody, MA Zhang, RJ Walter, EB Woods, CW Ginsburg, GS McClain, MT Denny, TN Chen, X Munshaw, S Marshall, DJ Whitesides, JF Drinker, MS Amos, JD Gurley, TC Eudailey, JA Foulger, A DeRosa, KR Parks, R Meyerhoff, RR Yu, JS Kozink, DM Barefoot, BE Ramsburg, EA Khurana, S Golding, H Vandergrift, NA Alam, SM Tomaras, GD Kepler, TB Kelsoe, G Liao, HX Haynes, BF AF Moody, M. Anthony Zhang, Ruijun Walter, Emmanuel B. Woods, Christopher W. Ginsburg, Geoffrey S. McClain, Micah T. Denny, Thomas N. Chen, Xi Munshaw, Supriya Marshall, Dawn J. Whitesides, John F. Drinker, Mark S. Amos, Joshua D. Gurley, Thaddeus C. Eudailey, Joshua A. Foulger, Andrew DeRosa, Katherine R. Parks, Robert Meyerhoff, R. Ryan Yu, Jae-Sung Kozink, Daniel M. Barefoot, Brice E. Ramsburg, Elizabeth A. Khurana, Surender Golding, Hana Vandergrift, Nathan A. Alam, S. Munir Tomaras, Georgia D. Kepler, Thomas B. Kelsoe, Garnett Liao, Hua-Xin Haynes, Barton F. TI H3N2 Influenza Infection Elicits More Cross-Reactive and Less Clonally Expanded Anti-Hemagglutinin Antibodies Than Influenza Vaccination SO PLOS ONE LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; MEMORY B-CELLS; VIRUS HEMAGGLUTININ; UNITED-STATES; NEUTRALIZING ANTIBODIES; SEASONAL INFLUENZA; IMMUNE-RESPONSE; A VIRUS; AFFINITY; BINDING AB Background: During the recent H1N1 influenza pandemic, excess morbidity and mortality was seen in young but not older adults suggesting that prior infection with influenza strains may have protected older subjects. In contrast, a history of recent seasonal trivalent vaccine in younger adults was not associated with protection. Methods and Findings: To study hemagglutinin (HA) antibody responses in influenza immunization and infection, we have studied the day 7 plasma cell repertoires of subjects immunized with seasonal trivalent inactivated influenza vaccine (TIV) and compared them to the plasma cell repertoires of subjects experimentally infected (EI) with influenza H3N2 A/Wisconsin/67/2005. The majority of circulating plasma cells after TIV produced influenza-specific antibodies, while most plasma cells after EI produced antibodies that did not react with influenza HA. While anti-HA antibodies from TIV subjects were primarily reactive with single or few HA strains, anti-HA antibodies from EI subjects were isolated that reacted with multiple HA strains. Plasma cell-derived anti-HA antibodies from TIV subjects showed more evidence of clonal expansion compared with antibodies from EI subjects. From an H3N2-infected subject, we isolated a 4-member clonal lineage of broadly cross-reactive antibodies that bound to multiple HA subtypes and neutralized both H1N1 and H3N2 viruses. This broad reactivity was not detected in post-infection plasma suggesting this broadly reactive clonal lineage was not immunodominant in this subject. Conclusion: The presence of broadly reactive subdominant antibody responses in some EI subjects suggests that improved vaccine designs that make broadly reactive antibody responses immunodominant could protect against novel influenza strains. C1 [Moody, M. Anthony; Zhang, Ruijun; Denny, Thomas N.; Chen, Xi; Marshall, Dawn J.; Whitesides, John F.; Drinker, Mark S.; Amos, Joshua D.; Gurley, Thaddeus C.; Eudailey, Joshua A.; Foulger, Andrew; DeRosa, Katherine R.; Parks, Robert; Meyerhoff, R. Ryan; Yu, Jae-Sung; Kozink, Daniel M.; Barefoot, Brice E.; Ramsburg, Elizabeth A.; Vandergrift, Nathan A.; Alam, S. Munir; Tomaras, Georgia D.; Kepler, Thomas B.; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27706 USA. [Moody, M. Anthony; Walter, Emmanuel B.] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Woods, Christopher W.; Ginsburg, Geoffrey S.; McClain, Micah T.; Denny, Thomas N.; Whitesides, John F.; Yu, Jae-Sung; Vandergrift, Nathan A.; Alam, S. Munir; Liao, Hua-Xin; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Woods, Christopher W.; Ginsburg, Geoffrey S.; Ramsburg, Elizabeth A.; Alam, S. Munir] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Tomaras, Georgia D.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Tomaras, Georgia D.; Kelsoe, Garnett; Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. [Munshaw, Supriya; Kepler, Thomas B.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USA. [Ramsburg, Elizabeth A.] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC USA. [Woods, Christopher W.; Ginsburg, Geoffrey S.] Duke Univ, Med Ctr, Inst Genome Sci & Policy, Durham, NC USA. [Woods, Christopher W.; McClain, Micah T.] Durham Vet Affairs Med Ctr, Div Infect Dis, Durham, NC USA. [Khurana, Surender; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Moody, MA (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27706 USA. EM moody007@mc.duke.edu RI Tomaras, Georgia/J-5041-2016; OI Kepler, Thomas/0000-0002-1383-6865; Moody, Tony/0000-0002-3890-5855; Denny, Thomas/0000-0002-7364-8276; Meyerhoff, Ryan/0000-0003-1253-2250 FU Bill and Melinda Gates Foundation; Center For HIV/AIDS Vaccine Immunology (CHAVI) [U19 AI067854]; United States Defense Advanced Research Projects Agency [N66001-07-C-2024]; Duke Translational Medicine Institute [NCRR/NIH 5UL1-RR024128-03] FX Support for this work was provided by a Collaboration for AIDS Vaccine Discovery grant to BH from the Bill and Melinda Gates Foundation and by the Center For HIV/AIDS Vaccine Immunology (CHAVI; grant U19 AI067854). Support was also provided by a contract to GG from the United States Defense Advanced Research Projects Agency (contract N66001-07-C-2024) and to EW from the Duke Translational Medicine Institute (Robert Califf PI, NCRR/NIH 5UL1-RR024128-03). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 67 Z9 67 U1 0 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 19 PY 2011 VL 6 IS 10 AR e25797 DI 10.1371/journal.pone.0025797 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 841JB UT WOS:000296507500022 PM 22039424 ER PT J AU Bisgin, H Liu, ZC Fang, H Xu, XW Tong, WD AF Bisgin, Halil Liu, Zhichao Fang, Hong Xu, Xiaowei Tong, Weida TI Mining FDA drug labels using an unsupervised learning technique - topic modeling SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 8th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society (MCBIOS) CY APR 01-02, 2011 CL Coll Stn, TX SP MidSouth Computat Biol & Bioinformat Soc (MCBIOS) ID ONLINE MENDELIAN INHERITANCE; LITERATURE-BASED DISCOVERY; GENETIC-DISORDERS; FISH-OIL; MAN OMIM; KNOWLEDGEBASE; RAYNAUDS AB Background: The Food and Drug Administration (FDA) approved drug labels contain a broad array of information, ranging from adverse drug reactions (ADRs) to drug efficacy, risk-benefit consideration, and more. However, the labeling language used to describe these information is free text often containing ambiguous semantic descriptions, which poses a great challenge in retrieving useful information from the labeling text in a consistent and accurate fashion for comparative analysis across drugs. Consequently, this task has largely relied on the manual reading of the full text by experts, which is time consuming and labor intensive. Method: In this study, a novel text mining method with unsupervised learning in nature, called topic modeling, was applied to the drug labeling with a goal of discovering "topics" that group drugs with similar safety concerns and/or therapeutic uses together. A total of 794 FDA-approved drug labels were used in this study. First, the three labeling sections (i.e., Boxed Warning, Warnings and Precautions, Adverse Reactions) of each drug label were processed by the Medical Dictionary for Regulatory Activities (MedDRA) to convert the free text of each label to the standard ADR terms. Next, the topic modeling approach with latent Dirichlet allocation (LDA) was applied to generate 100 topics, each associated with a set of drugs grouped together based on the probability analysis. Lastly, the efficacy of the topic modeling was evaluated based on known information about the therapeutic uses and safety data of drugs. Results: The results demonstrate that drugs grouped by topics are associated with the same safety concerns and/or therapeutic uses with statistical significance (P<0.05). The identified topics have distinct context that can be directly linked to specific adverse events (e. g., liver injury or kidney injury) or therapeutic application (e. g., antiinfectives for systemic use). We were also able to identify potential adverse events that might arise from specific medications via topics. Conclusions: The successful application of topic modeling on the FDA drug labeling demonstrates its potential utility as a hypothesis generation means to infer hidden relationships of concepts such as, in this study, drug safety and therapeutic use in the study of biomedical documents. C1 [Bisgin, Halil; Xu, Xiaowei] Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA. [Liu, Zhichao; Xu, Xiaowei; Tong, Weida] US FDA, Ctr Bioinformat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fang, Hong] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Xu, XW (reprint author), Univ Arkansas, Dept Informat Sci, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM xwxu@ualr.edu; weida.tong@fda.hhs.gov RI Liu, Zhichao/C-4035-2011 NR 28 TC 27 Z9 28 U1 1 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 18 PY 2011 VL 12 SU 10 AR S11 DI 10.1186/1471-2105-12-S10-S11 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 941AG UT WOS:000303933600011 PM 22166012 ER PT J AU Chen, MJ Shi, LM Kelly, R Perkins, R Fang, H Tong, WD AF Chen, Minjun Shi, Leming Kelly, Reagan Perkins, Roger Fang, Hong Tong, Weida TI Selecting a single model or combining multiple models for microarray-based classifier development? - A comparative analysis based on large and diverse datasets generated from the MAQC-II project SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 8th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society (MCBIOS) CY APR 01-02, 2011 CL Coll Stn, TX SP MidSouth Computat Biol & Bioinformat Soc (MCBIOS) ID GENE-EXPRESSION SIGNATURE; BREAST-CANCER; MOLECULAR CLASSIFICATION; CROSS-VALIDATION; PREDICTION; SENSITIVITY; PROFILES; SURVIVAL; MYELOMA; SETS AB Background: Genomic biomarkers play an increasing role in both preclinical and clinical application. Development of genomic biomarkers with microarrays is an area of intensive investigation. However, despite sustained and continuing effort, developing microarray-based predictive models (i.e., genomics biomarkers) capable of reliable prediction for an observed or measured outcome (i.e., endpoint) of unknown samples in preclinical and clinical practice remains a considerable challenge. No straightforward guidelines exist for selecting a single model that will perform best when presented with unknown samples. In the second phase of the MicroArray Quality Control (MAQC-II) project, 36 analysis teams produced a large number of models for 13 preclinical and clinical endpoints. Before external validation was performed, each team nominated one model per endpoint (referred to here as 'nominated models') from which MAQC-II experts selected 13 'candidate models' to represent the best model for each endpoint. Both the nominated and candidate models from MAQC-II provide benchmarks to assess other methodologies for developing microarray-based predictive models. Methods: We developed a simple ensemble method by taking a number of the top performing models from cross-validation and developing an ensemble model for each of the MAQC-II endpoints. We compared the ensemble models with both nominated and candidate models from MAQC-II using blinded external validation. Results: For 10 of the 13 MAQC-II endpoints originally analyzed by the MAQC-II data analysis team from the National Center for Toxicological Research (NCTR), the ensemble models achieved equal or better predictive performance than the NCTR nominated models. Additionally, the ensemble models had performance comparable to the MAQC-II candidate models. Most ensemble models also had better performance than the nominated models generated by five other MAQC-II data analysis teams that analyzed all 13 endpoints. Conclusions: Our findings suggest that an ensemble method can often attain a higher average predictive performance in an external validation set than a corresponding "optimized" model method. Using an ensemble method to determine a final model is a potentially important supplement to the good modeling practices recommended by the MAQC-II project for developing microarray-based genomic biomarkers. C1 [Chen, Minjun; Shi, Leming; Perkins, Roger; Tong, Weida] US FDA, Ctr Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kelly, Reagan; Fang, Hong] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Ctr Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov NR 36 TC 10 Z9 10 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 18 PY 2011 VL 12 SU 10 AR S3 DI 10.1186/1471-2105-12-S10-S3 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 941AG UT WOS:000303933600003 PM 22166133 ER PT J AU Martha, VS Liu, ZC Guo, L Su, ZQ Ye, YB Fang, H Ding, D Tong, WD Xu, XW AF Martha, Venkata-Swamy Liu, Zhichao Guo, Li Su, Zhenqiang Ye, Yanbin Fang, Hong Ding, Don Tong, Weida Xu, Xiaowei TI Constructing a robust protein-protein interaction network by integrating multiple public databases SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 8th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society (MCBIOS) CY APR 01-02, 2011 CL Coll Stn, TX SP MidSouth Computat Biol & Bioinformat Soc (MCBIOS) AB Background: Protein-protein interactions (PPIs) are a critical component for many underlying biological processes. A PPI network can provide insight into the mechanisms of these processes, as well as the relationships among different proteins and toxicants that are potentially involved in the processes. There are many PPI databases publicly available, each with a specific focus. The challenge is how to effectively combine their contents to generate a robust and biologically relevant PPI network. Methods: In this study, seven public PPI databases, BioGRID, DIP, HPRD, IntAct, MINT, REACTOME, and SPIKE, were used to explore a powerful approach to combine multiple PPI databases for an integrated PPI network. We developed a novel method called k-votes to create seven different integrated networks by using values of k ranging from 1-7. Functional modules were mined by using SCAN, a Structural Clustering Algorithm for Networks. Overall module qualities were evaluated for each integrated network using the following statistical and biological measures: (1) modularity, (2) similarity-based modularity, (3) clustering score, and (4) enrichment. Results: Each integrated human PPI network was constructed based on the number of votes (k) for a particular interaction from the committee of the original seven PPI databases. The performance of functional modules obtained by SCAN from each integrated network was evaluated. The optimal value for k was determined by the functional module analysis. Our results demonstrate that the k-votes method outperforms the traditional union approach in terms of both statistical significance and biological meaning. The best network is achieved at k=2, which is composed of interactions that are confirmed in at least two PPI databases. In contrast, the traditional union approach yields an integrated network that consists of all interactions of seven PPI databases, which might be subject to high false positives. Conclusions: We determined that the k-votes method for constructing a robust PPI network by integrating multiple public databases outperforms previously reported approaches and that a value of k=2 provides the best results. The developed strategies for combining databases show promise in the advancement of network construction and modeling. C1 [Martha, Venkata-Swamy; Xu, Xiaowei] Univ Arkansas, Dept Informat Sci, Little Rock, AR 72204 USA. [Liu, Zhichao; Tong, Weida; Xu, Xiaowei] US FDA, Ctr Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Guo, Li] Chinese Acad Sci, Inst Proc Engn, State Key Lab Multiphase Complex Syst, Beijing 100190, Peoples R China. [Su, Zhenqiang; Ye, Yanbin; Fang, Hong; Ding, Don] US FDA, ICF Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Ctr Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov; xwxu@ualr.edu RI Su, Zhenqiang/H-3914-2012; Su, Zhiguo/G-2422-2011; Liu, Zhichao/C-4035-2011 NR 21 TC 12 Z9 12 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 18 PY 2011 VL 12 SU 10 AR S7 DI 10.1186/1471-2105-12-S10-S7 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 941AG UT WOS:000303933600007 PM 22165958 ER PT J AU Hayden, JE AF Hayden, James E. TI REVISION OF CLINIODES GUENEE (LEPIDOPTERA: CRAMBIDAE: ODONTIINAE) SO ANNALS OF CARNEGIE MUSEUM LA English DT Article DE Afrotropics; biogeography; Heortia; Mabilleodes; Neotropics; Thymelaeaceae ID PHYLOGENETIC ANALYSIS; PYRALIDAE; MOTHS; GENUS; THYMELAEACEAE; PARSIMONY; GENERA; AREAS AB Cliniodes Guenee, 1854, is revised to include 28 species of predominantly Neotropical distribution. The genus is found to be monophyletic in a phylogenetic analysis of all Odontiinae known to feed as larvae on Thymelaeaceae, and diagnoses of taxa are derived from the cladistic results. Heortia Lederer, 1863, and Mabilleodes Marion and Viette, 1956, are reviewed, and the following species are transferred to Heortia, Mabilleodes, Viettessa Minet, 1980, and Hemiscopis Warren, 1890: Heortia flavispila (Hampson, 1913a), new combination (from Epipagis Hubner); Heortia ocellata (Hampson, 1916), new combination (from Epipagis); Heortia plumbatalis (Zeller, 1852), new combination (from Laxostege Hubner); Heortia iospora (Meyrick, 1936), new combination (from Hapalia), and its synonym, Heortia pyrographa (Meyrick, 1937), new combination (from Hapalia Hubner); Mabilleodes kenrickalis (Marion and Viette, 1956), new combination (from Tegostoma Zeller); Mabilleodes catalalis (Viette, 1953a: I36), new combination (from Mecyna Doubleday); Mabilleodes lithosialis (Hampson, 1899b), new combination (from Pyrausta Schrank); Viettessa villiersi (Marion, 1957), new combination (from Noorda Walker); and Hemiscopis purpurea (Inoue, 1982), new combination (from Clupeosoma Snellen). Mabilleodes alacralis, new name, is proposed as a replacement name for Mabilleodes catalalis Marion and Viette, 1956. Within Cliniodes, three subgenera and certain subordinate species-groups are diagnosed based on a phylogenetic analysis of maculation, genitalia, and external morphology of imagines. Procliniodes, new subgenus, is proposed, and Metrea Grote, 1882, new rank, is revised as a subgenus of Cliniodes. Three described species are synonymized with Cliniodes euphrosinalis Moschler, 1886: Cliniodes cyllarusalis Druce, 1895, new synonym; C. nomadalis Dyar, 1912, new synonym; and C. paucilinealis Snellen, 1895, new synonym. Cliniodes mossalis Dyar, 1914, new synonym, is synonymized with Cliniodes underwoodi Druce, 1899. Ten species are newly described: Cliniodes additalis, new species; C. beckeralis, new species; C. festivalis, new species; C. inferalis, new species; C. insignialis, new species; C. iopolia, new species; C. mellalis, new species; C. muralis, new species; C. opertalis, new species; and C. subflavescens, new species. Lectotypes, paralectotypes, and a neotype for C.. saburralis Guenee, 1854, are designated. Reconciled tree analysis supports the hypothesis that the type localities of C. semilunalis Moschler, 1890, and C. latipennis Munroe, 1964, are erroneous and that the species are restricted to southern and central Brazil. The same analysis predicts that new distribution records will be most abundant in southern Brazil, the northern Andes, and tropical Mexico. C1 [Hayden, James E.] Cornell Univ, Field Entomol, Carnegie Museum Nat Hist, Sect Invertebrate Zool, Ithaca, NY 14853 USA. RP Hayden, JE (reprint author), FDACS DPI, Gainesville, FL 32614 USA. EM james.hayden@freshfromflorida.com FU National Science Foundation [DEB-0808415]; Cornell University; Carnegie Museum of Natural History FX The majority of the research was accomplished during a Ph.D. candidacy at Cornell University. National Science Foundation Doctoral Dissertation Improvement Grant DEB-0808415 (J.K. Liebherr, PI) generously enabled the extended tour of European institutions, the visit to the Becker Collection, and the SEM images. The Grace Griswold and Art Rawlins Endowments (Cornell University) provided several small grants for travel and publication. Substantial improvements to the study, including maps, biogeographic analysis, and description of immature stages, were made with support from the James and Julia Rea Postdoctoral Fellowship at the Carnegie Museum of Natural History. NR 166 TC 4 Z9 4 U1 0 U2 8 PU CARNEGIE MUSEUM NATURAL HISTORY PI PITTSBURGH PA 4400 FORBES AVE, PITTSBURGH, PA 15213 USA SN 0097-4463 EI 1943-6300 J9 ANN CARNEGIE MUS JI Ann. Carnegie Mus. PD OCT 15 PY 2011 VL 79 IS 4 BP 231 EP 347 PG 117 WC Paleontology; Zoology SC Paleontology; Zoology GA 841AK UT WOS:000296484100001 ER PT J AU Wang, X Ragupathy, V Zhao, JQ Hewlett, I AF Wang, Xue Ragupathy, Viswanath Zhao, Jiangqin Hewlett, Indira TI Molecules from apoptotic pathways modulate HIV-1 replication in Jurkat cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Apoptosis; Bax; Fos; HIV-1; Replication AB The replication of viruses involves control of some aspects of host cell homeostasis by modification of target cell metabolism and regulation of the apoptotic machinery. It is not well known whether molecules involved in apoptotic pathways affect human immunodeficiency virus type 1 (HIV-1) replication and regulate viral yields. Using the susceptible Jurkat cell line, we studied the relationship of apoptosis-associated molecules with HIV-1 virus production using a sensitive real-time RT-PCR assay. Here, we found that expression of proapoptotic proteins, including Fas ligand (FasL), FADD, or p53 significantly increased HIV-1 virus production. In contrast, the expression of antiapoptotic molecules, such as FLIP, Bcl-X(L), and XIAP, decreased HIV-1 virus production. Knockdown of Bax with siRNA and FADD with expression of its antisense mRNA also inhibited viral replication and the caspase-3 inhibitor, Z-DEVD, and decreased virus production. These data indicate that HIV-1 infection regulates the apoptosis process to facilitate viral replication and inhibition of apoptosis may inhibit HIV-1 replication and cytopathogenesis. We also discuss the effects of MAPK signaling pathways and apoptosis on HIV-1 replication. (C) 2011 Elsevier Inc. All rights reserved. C1 [Wang, Xue; Ragupathy, Viswanath; Zhao, Jiangqin; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. RP Wang, X (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bldg 29B,Rm 4NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM xue.wang@fda.hhs.gov NR 15 TC 10 Z9 10 U1 0 U2 3 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 OCT 14 PY 2011 VL 414 IS 1 BP 20 EP 24 DI 10.1016/j.bbrc.2011.09.007 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 837PH UT WOS:000296215200005 PM 21945613 ER PT J AU Jiang, WL Kim, S Zhang, XY Lionberger, RA Davit, BM Conner, DP Yu, LX AF Jiang, Wenlei Kim, Stephanie Zhang, Xinyuan Lionberger, Robert A. Davit, Barbara M. Conner, Dale P. Yu, Lawrence X. TI The role of predictive biopharmaceutical modeling and simulation in drug development and regulatory evaluation SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Biopharmaceutics; Physiologically based modeling; Quality-by-design; Bioequivalence; In vitro-in vivo correlation; Drug development and review ID CLASSIFICATION-SYSTEM BCS; HIGHLY VARIABLE DRUGS; WATER-SOLUBLE DRUG; ORAL DOSAGE FORMS; CLASS-III DRUGS; GASTROINTESTINAL SIMULATION; PHARMACOKINETIC SIMULATION; FORMULATION DEVELOPMENT; BIOWAIVER EXTENSION; TISSUE DISTRIBUTION AB Advances in predicting in vivo performance of drug products has the potential to change how drug products are developed and reviewed. Modeling and simulation methods are now more commonly used in drug product development and regulatory drug review. These applications include, but are not limited to: the development of biorelevant specifications, the determination of bioequivalence metrics for modified release products with rapid therapeutic onset, the design of in vitro-in vivo correlations in a mechanistic framework, and prediction of food effect. As new regulatory concepts such as quality by design require better application of biopharmaceutical modeling in drug product development, regulatory challenges in bioequivalence demonstration of complex drug products also present exciting opportunities for creative modeling and simulation approaches. A collaborative effort among academia, government and industry in modeling and simulation will result in improved safe and effective new/generic drugs to the American public. Published by Elsevier B.V. C1 [Jiang, Wenlei; Kim, Stephanie; Zhang, Xinyuan; Lionberger, Robert A.; Davit, Barbara M.; Conner, Dale P.; Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. RP Lionberger, RA (reprint author), 7519 Standish Pl, Rockville, MD 20855 USA. EM Robert.Lionberger@fda.hhs.gov NR 79 TC 32 Z9 35 U1 3 U2 24 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 OCT 14 PY 2011 VL 418 IS 2 SI SI BP 151 EP 160 DI 10.1016/j.ijpharm.2011.07.024 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 834YJ UT WOS:000296000100002 PM 21803144 ER PT J AU Lau, CY Swann, EM Singh, S Kafaar, Z Meissner, HI Stansbury, JP AF Lau, Chuen-Yen Swann, Edith M. Singh, Sagri Kafaar, Zuhayr Meissner, Helen I. Stansbury, James P. TI Conceptual framework for behavioral and social science in HIV vaccine clinical research SO VACCINE LA English DT Article DE HIV vaccine; Behavioral social science; Conceptual framework; Clinical trial ID RANDOMIZED-CONTROLLED-TRIAL; DZIVE SHIRI PROJECT; SOUTH-AFRICA; STRUCTURAL INTERVENTIONS; PREVENTION INTERVENTION; EDUCATIONAL-ATTAINMENT; ECONOMIC COOPERATION; HEALTH INTERVENTION; REPRODUCTIVE HEALTH; TREATMENT ADHERENCE AB HIV vaccine clinical research occurs within a context where biomedical science and social issues are inter-linked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd. C1 [Lau, Chuen-Yen] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA. [Swann, Edith M.] VRP DAIDS NIAID NIH DHHS, Vaccine Clin Res Branch, Bethesda, MD 20892 USA. [Singh, Sagri] Int AIDS Vaccine Initiat, Country Programme, New York, NY 10038 USA. [Singh, Sagri] Int AIDS Vaccine Initiat, Reg Programme, New York, NY 10038 USA. [Kafaar, Zuhayr] Univ Stellenbosch, Dept Psychol, ZA-7602 Matieland, South Africa. [Meissner, Helen I.] NIH, Off Behav & Social Sci Res, Off Director, Bethesda, MD 20892 USA. [Stansbury, James P.] FDA CDER OND SEALD, Silver Spring, MD 20993 USA. RP Lau, CY (reprint author), NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, 6700B Rockledge Dr,Rm 1112, Bethesda, MD 20892 USA. EM lauc@mail.nih.gov; swanne@niaid.nih.gov; ssingh@iavi.org; zkafaar@sun.ac.za; meissneh@od.nih.gov; james.p.stansbury@fda.hhs.gov FU Intramural NIH HHS [Z99 AI999999] NR 82 TC 6 Z9 6 U1 1 U2 2 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 OCT 13 PY 2011 VL 29 IS 44 BP 7794 EP 7800 DI 10.1016/j.vaccine.2011.07.108 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 841WW UT WOS:000296546900036 PM 21821083 ER PT J AU Crawford, MA Lowe, DE Fisher, DJ Stibitz, S Plaut, RD Beaber, JW Zemansky, J Mehrad, B Glomski, IJ Strieter, RM Hughes, MA AF Crawford, Matthew A. Lowe, David E. Fisher, Debra J. Stibitz, Scott Plaut, Roger D. Beaber, John W. Zemansky, Jason Mehrad, Borna Glomski, Ian J. Strieter, Robert M. Hughes, Molly A. TI Identification of the bacterial protein FtsX as a unique target of chemokine-mediated antimicrobial activity against Bacillus anthracis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CXC chemokine; CXCR3; innate immune system; transposon mutant library; ABC transporter ID ESCHERICHIA-COLI; ABC TRANSPORTER; CXC CHEMOKINES; SUBTILIS; IMMUNITY; GENE AB Chemokines are a family of chemotactic cytokines that function in host defense by orchestrating cellular movement during infection. In addition to this function, many chemokines have also been found to mediate the direct killing of a range of pathogenic microorganisms through an as-yet-undefined mechanism. As an understanding of the molecular mechanism and microbial targets of chemokine-mediated antimicrobial activity is likely to lead to the identification of unique, broad-spectrum therapeutic targets for effectively treating infection, we sought to investigate the mechanism by which the chemokine CXCL10 mediates bactericidal activity against the Gram-positive bacterium Bacillus anthracis, the causative agent of anthrax. Here, we report that disruption of the gene ftsX, which encodes the transmembrane domain of a putative ATP-binding cassette transporter, affords resistance to CXCL10-mediated antimicrobial effects against vegetative B. anthracis bacilli. Furthermore, we demonstrate that in the absence of FtsX, CXCL10 is unable to localize to its presumed site of action at the bacterial cell membrane, suggesting that chemokines interact with specific, identifiable bacterial components to mediate direct microbial killing. These findings provide unique insight into the mechanism of CXCL10-mediated bactericidal activity and establish, to our knowledge, the first description of a bacterial component critically involved in the ability of host chemokines to target and kill a bacterial pathogen. These observations also support the notion of chemokine-mediated antimicrobial activity as an important foundation for the development of innovative therapeutic strategies for treating infections caused by pathogenic, potentially multidrug-resistant microorganisms. C1 [Crawford, Matthew A.; Fisher, Debra J.; Hughes, Molly A.] Univ Virginia, Dept Med, Div Infect Dis, Charlottesville, VA 22908 USA. [Lowe, David E.; Glomski, Ian J.] Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. [Mehrad, Borna; Strieter, Robert M.] Univ Virginia, Dept Med, Div Pulm & Crit Care Med, Charlottesville, VA 22908 USA. [Stibitz, Scott; Plaut, Roger D.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Beaber, John W.; Zemansky, Jason] Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA. RP Hughes, MA (reprint author), Univ Virginia, Dept Med, Div Infect Dis, Charlottesville, VA 22908 USA. EM mah3x@virginia.edu RI Mehrad, Borna/D-9363-2015; Plaut, Roger/B-2340-2013 OI Mehrad, Borna/0000-0001-5198-065X; Plaut, Roger/0000-0002-0883-972X FU Virginia Commonwealth Health Research Board; National Institutes of Health/National Institute of Allergy and Infectious Diseases [R21 AI072469]; National Institutes of Health [T32 AI055432-08] FX We thank Theresa M. Koehler for kindly providing plasmid pUTE973, David S. Weiss and Marie D. Burdick for helpful discussions, and Stephanie M. Zilora for assistance with preliminary studies. This work was supported by the Virginia Commonwealth Health Research Board (M. A. H.), National Institutes of Health/National Institute of Allergy and Infectious Diseases Grant R21 AI072469 (M. A. H.), and National Institutes of Health Grant T32 AI055432-08 (M.A.C.). NR 30 TC 16 Z9 17 U1 0 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2011 VL 108 IS 41 BP 17159 EP 17164 DI 10.1073/pnas.1108495108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 834PD UT WOS:000295973800057 PM 21949405 ER PT J AU Camacho, L Kelly, KP Beland, FA da Costa, GG AF Camacho, Luisa Kelly, Kevin P. Beland, Frederick A. da Costa, Goncalo Gamboa TI Gene expression of biomarkers of nephrotoxicity in F344 rats co-exposed to melamine and cyanuric acid for seven days SO TOXICOLOGY LETTERS LA English DT Article DE Melamine; Cyanuric acid; Kidney; Gene expression; Biomarkers ID KIDNEY INJURY MOLECULE-1; RENAL INJURY; QUALIFICATION; GENTAMICIN; TOXICITY; CATS AB A number of studies have demonstrated that co-exposure to low levels of melamine and cyanuric acid elicits renal toxicity due to the formation of melamine cyanurate crystals in the kidney nephrons. In this work, we investigated if co-exposure of rats to these compounds leads to alterations in the expression of the genes encoding kidney injury molecule 1 (KIM-1), metallopeptidase inhibitor 1 (TIMP1), clusterin, osteopontin, and neutrophil gelatinase-associated lipocalin/lipocalin 2 (NGAL), which have been proposed as urinary biomarkers for nephrotoxicity. Six-week-old male and female F344 rats were fed ad libitum a diet fortified with 0 (control), 7, 23, 69, 229, or 694 ppm melamine and cyanuric acid (co-exposure groups), 1388 ppm melamine, or 1388 ppm cyanuric acid for seven days. Histopathology and clinical chemistry examination indicated marked toxicity only in the animals exposed to the two highest combined doses of melamine and cyanuric acid. Consistent with these observations, quantitative real-time polymerase chain reaction analysis of kidney tissue indicated increased expression of all genes analyzed relative to the control in both male and female rats fed daily with 229 or 694 ppm melamine and cyanuric acid. Exposure to lower levels of both compounds or to the individual compounds did not induce gene expression changes. These data indicate that quantifying the expression levels of the selected biomarker genes constitutes a useful endpoint to assess the combined toxicity of melamine and cyanuric acid in both male and female rats. Published by Elsevier Ireland Ltd. C1 [Camacho, Luisa; Kelly, Kevin P.; Beland, Frederick A.; da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Camacho, L (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM luisa.camacho@fda.hhs.gov RI Camacho, Luisa/D-1088-2012 FU National Center for Toxicological Research/Food and Drug Administration [224-07-0007/Y1ES1027]; National Institute of Environmental Health Sciences [224-07-0007/Y1ES1027]; National Center for Toxicological Research; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was partly supported by Interagency Agreement No. 224-07-0007/Y1ES1027 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. K.P.K. was supported by an appointment to the Research Participation Program at the National Center for Toxicological 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 opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. NR 18 TC 11 Z9 13 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 10 PY 2011 VL 206 IS 2 BP 166 EP 171 DI 10.1016/j.toxlet.2011.07.009 PG 6 WC Toxicology SC Toxicology GA 825RC UT WOS:000295298800008 PM 21784140 ER PT J AU Zeng, RP Petrick, N Gavrielides, MA Myers, KJ AF Zeng, Rongping Petrick, Nicholas Gavrielides, Marios A. Myers, Kyle J. TI Approximations of noise covariance in multi-slice helical CT scans: impact on lung nodule size estimation SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RAY COMPUTED-TOMOGRAPHY; MODERN DIAGNOSTIC MDCT; MULTIDETECTOR ROW CT; POWER SPECTRUM; THORACIC CT; SPIRAL CT; SINOGRAM DATA; TRUTH DATA; PART II; PARAMETERS AB Multi-slice computed tomography (MSCT) scanners have become popular volumetric imaging tools. Deterministic and random properties of the resulting CT scans have been studied in the literature. Due to the large number of voxels in the three-dimensional (3D) volumetric dataset, full characterization of the noise covariance in MSCT scans is difficult to tackle. However, as usage of such datasets for quantitative disease diagnosis grows, so does the importance of understanding the noise properties because of their effect on the accuracy of the clinical outcome. The goal of this work is to study noise covariance in the helical MSCT volumetric dataset. We explore possible approximations to the noise covariance matrix with reduced degrees of freedom, including voxel-based variance, one-dimensional (1D) correlation, two-dimensional (2D) in-plane correlation and the noise power spectrum (NPS). We further examine the effect of various noise covariance models on the accuracy of a prewhitening matched filter nodule size estimation strategy. Our simulation results suggest that the 1D longitudinal, 2D in-plane and NPS prewhitening approaches can improve the performance of nodule size estimation algorithms. When taking into account computational costs in determining noise characterizations, the NPS model may be the most efficient approximation to the MSCT noise covariance matrix. C1 [Zeng, Rongping; Petrick, Nicholas; Gavrielides, Marios A.; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Zeng, RP (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM rongping.zeng@fda.hhs.gov FU FDA Critical Path Initiative FX The authors would like to thank Dr Berkman Sahiner for his helpful discussion. The authors also thank the referees for their constructive comments. This work is supported in part by funding from the FDA Critical Path Initiative. 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 48 TC 6 Z9 6 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2011 VL 56 IS 19 BP 6223 EP 6242 DI 10.1088/0031-9155/56/19/005 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 823WE UT WOS:000295156900006 PM 21896963 ER PT J AU Biris, AR Mahmood, M Lazar, MD Dervishi, E Watanabe, F Mustafa, T Baciut, G Baciut, M Bran, S Ali, S Biris, AS AF Biris, Alexandru R. Mahmood, Meena Lazar, Mihaela D. Dervishi, Enkeleda Watanabe, Fumiya Mustafa, Thikra Baciut, Grigore Baciut, Mihaela Bran, Simion Ali, Syed Biris, Alexandru S. TI Novel Multicomponent and Biocompatible Nanocomposite Materials Based on Few-Layer Graphenes Synthesized on a Gold/Hydroxyapatite Catalytic System with Applications in Bone Regeneration SO JOURNAL OF PHYSICAL CHEMISTRY C LA English DT Article ID CHEMICAL-VAPOR-DEPOSITION; WALLED CARBON NANOTUBES; MECHANICAL-PROPERTIES; RAMAN-SPECTROSCOPY; RADIO-FREQUENCY; HYDROXYAPATITE; PURIFICATION; COMPOSITES; ALUMINA AB We present the synthesis of few-layer graphenes over a novel Au/hydroxyapatite catalytic system by radio-frequency chemical vapor deposition, with acetylene and methane as the carbon sources. The synthesis time was found to influence linearly the dimensions of the graphitic layers and asymptotically their corresponding thermal decomposition temperature. The resulting multicomponent nanocomposite material formed out of graphene layers, Au nanoparticles (AuNPs) supported on the surface of hydroxyapatite nanoparticles, was found to have good biocompatibility and induce excellent bone cellular proliferation. Such multicomponent composites could find numerous applications in the area of bone regeneration given the excellent biocompatibility, 3D structure, and unique composition. C1 [Biris, Alexandru R.; Lazar, Mihaela D.] Natl Inst Res & Dev Isotop & Mol Technol, Cluj Napoca, Romania. [Mahmood, Meena; Dervishi, Enkeleda; Watanabe, Fumiya; Mustafa, Thikra; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Dept Appl Sci, Dept Syst Engn, Little Rock, AR 72204 USA. [Baciut, Grigore; Baciut, Mihaela; Bran, Simion] Iuliu Hatieganu Univ Med & Pharm, Dept Craniomaxillofacial Surg & Implantol, Cluj Napoca, Romania. [Ali, Syed] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Biris, AR (reprint author), Natl Inst Res & Dev Isotop & Mol Technol, Cluj Napoca, Romania. EM biris@itim-cj.ro; asbiris@ualr.edu RI Lazar, Mihaela/B-7578-2011; Biris, Alexandru/A-8507-2010; Baciut, Grigore/C-4966-2012 OI Lazar, Mihaela/0000-0002-1679-1324; FU U.S. Army Telemedicine and Advanced Technology Research Center (TATRC); Arkansas Science and Technolgy Authority (ASTA) FX Financial support from the U.S. Army Telemedicine and Advanced Technology Research Center (TATRC) and the Arkansas Science and Technolgy Authority (ASTA) is highly appreciated. NR 39 TC 36 Z9 39 U1 1 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1932-7447 J9 J PHYS CHEM C JI J. Phys. Chem. C PD OCT 6 PY 2011 VL 115 IS 39 BP 18967 EP 18976 DI 10.1021/jp203474y PG 10 WC Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 825BI UT WOS:000295245500006 ER PT J AU Weagant, SD Jinneman, KC Yoshitomi, KJ Zapata, R Fedio, WM AF Weagant, Stephen D. Jinneman, Karen C. Yoshitomi, Ken J. Zapata, Ruben Fedio, Willis M. TI Optimization and evaluation of a modified enrichment procedure combined with immunomagnetic separation for detection of E. coli O157:H7 from artificially contaminated alfalfa sprouts SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Detection; Real time PCR; Immunomagnetic separation ID HEMOLYTIC-UREMIC SYNDROME; REAL-TIME PCR; ESCHERICHIA-COLI; RADISH SPROUTS; O157-H7 INFECTIONS; MULTISTATE OUTBREAK; WATERBORNE OUTBREAK; BLOODY DIARRHEA; RAW-MILK; CONSUMPTION AB Escherichia coli O157:H7 has been linked to foodborne disease outbreaks with alfalfa sprouts. Detection of the organism in sprouts by standard cultural methods can be difficult due to the high background microflora. The objective of this study was to develop and optimize an enrichment protocol with and without post-enrichment immunomagnetic separation (IMS) for the rapid detection by real-time PCR (RTiPCR) and cultural recovery of E. coli O157:H7 from artificially contaminated alfalfa sprouts. Initially we found that the FDA BAM procedure, enriching samples in modified buffered peptone water with pyruvate and at 37 degrees C for 5 h, followed by the addition of acriflavin, cefsulodin and vancomycin (mBPWp + ACV) and static incubation at 42 degrees C gave poor results for both PCR detection and isolation for alfalfa sprouts artificially contaminated at 0.2 cfu/g. The addition of post-enrichment IMS improved detection but not isolation. This procedure was modified and optimized by changing to mBPWp with cefsulodin and vancomycin at 42 degrees C and shaking for 24 h with and without IMS prior to PCR detection and cultural isolation. Using the resulting protocol we were able to detect E. coli O157:H7 in 100% of samples of alfalfa sprouts contaminated at 0.2 cfu/g. This was validated for five strains of E. coli O157:H7. Isolation was 84% without added post-enrichment IMS and 100% with IMS. The optimized procedure was effective for detection and isolation of E. coli O157:H7 from this difficult food matrix. (C) 2011 Elsevier B.V. All rights reserved. C1 [Zapata, Ruben; Fedio, Willis M.] New Mexico State Univ, Food Safety Lab, Ctr Anim Hlth Food Safety & Biosecur, Las Cruces, NM 88003 USA. [Weagant, Stephen D.] US FDA, Poulsbo, WA USA. [Jinneman, Karen C.; Yoshitomi, Ken J.] US FDA, Pacific Reg Lab, Bothell, WA USA. RP Fedio, WM (reprint author), New Mexico State Univ, Food Safety Lab, Ctr Anim Hlth Food Safety & Biosecur, 2990 Knox St, Las Cruces, NM 88003 USA. EM wfedio@nmsu.edu FU US FDA [WL5QKN-05-D-0022] FX We would like to thank Paul Browning and ChitraWendakoon for technical support. This study was supported in part by US FDA contract no. WL5QKN-05-D-0022. NR 40 TC 17 Z9 19 U1 2 U2 15 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 OCT 3 PY 2011 VL 149 IS 3 BP 209 EP 217 DI 10.1016/j.ijfoodmicro.2011.06.008 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 826JR UT WOS:000295350900003 PM 21784545 ER PT J AU Warfel, JM D'Agnillo, F AF Warfel, Jason M. D'Agnillo, Felice TI Anthrax Lethal Toxin-Mediated Disruption of Endothelial VE-Cadherin Is Attenuated by Inhibition of the Rho-Associated Kinase Pathway SO TOXINS LA English DT Article DE anthrax lethal toxin; vascular endothelium; adherens junction; barrier function; cadherin; actin stress fibers ID INHALATIONAL ANTHRAX; PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; TYROSINE PHOSPHORYLATION; VASCULAR-PERMEABILITY; BARRIER FUNCTION; BETA-CATENIN; IN-VIVO; PATHOGENESIS; PATHOLOGY AB Systemic anthrax disease is characterized by vascular leakage pathologies. We previously reported that anthrax lethal toxin (LT) induces human endothelial barrier dysfunction in a cell death-independent manner with actin stress fiber formation and disruption of adherens junctions (AJs). In the present study, we further characterize the molecular changes in the AJ complex and investigate whether AJ structure and barrier function can be preserved by modulating key cytoskeletal signaling pathways. Here, we show that LT reduces total VE-cadherin protein and gene expression but the expression of the key linker protein beta-catenin remained unchanged. The changes in VE-cadherin expression correlated temporally with the appearance of actin stress fibers and a two-fold increase in phosphorylation of the stress fiber-associated protein myosin light chain (p-MLC) and cleavage of Rho-associated kinase-1 (ROCK-1). Co-treatment with ROCK inhibitors (H-1152 and Y27632), but not an inhibitor of MLC kinase (ML-7), blocked LT-induced p-MLC enhancement and stress fiber formation. This was accompanied by the restoration of VE-cadherin expression and membrane localization, and attenuation of the LT-induced increase in monolayer permeability to albumin. Together, these findings suggest the ROCK pathway may be a relevant target for countering LT-mediated endothelial barrier dysfunction. C1 [Warfel, Jason M.; D'Agnillo, Felice] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Warfel, Jason M.] Georgetown Univ, Dept Microbiol & Immunol, Med Ctr, Washington, DC 20057 USA. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM jason.warfel@fda.hhs.gov; felice.dagnillo@fda.hhs.gov FU Research Fellowship Program for the Center for Biologics Evaluation and Research; National Institutes of Health-Georgetown University Graduate Partnership Program FX We thank S. H. Leppla for kindly providing the anthrax toxin proteins. This project was supported in part by an appointment of J. M. Warfel to the National Institutes of Health-Georgetown University Graduate Partnership Program and the Research Fellowship Program for the Center for Biologics Evaluation and Research 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. NR 46 TC 12 Z9 13 U1 1 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD OCT PY 2011 VL 3 IS 10 BP 1278 EP 1293 DI 10.3390/toxins3101278 PG 16 WC Toxicology SC Toxicology GA 995AY UT WOS:000307979600004 PM 22069696 ER PT J AU Bhalli, JA Vohr, HW Heflich, RH AF Bhalli, J. A. Vohr, H. W. Heflich, R. H. TI Pig-a Mutation Analysis of Benzo[a]Pyrene Treated Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Bhalli, J. A.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Vohr, H. W.] Bayer HealthCare, Toxicol, Wuppertal, Germany. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S60 EP S60 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800195 ER PT J AU Chen, DH Heflich, RH Mittelstaedt, RA AF Chen, D. H. Heflich, R. H. Mittelstaedt, R. A. TI Cytotoxic and Genotoxic Effects of Silver Nanoparticles in TK6 Lymphoblastoid Cells. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Chen, D. H.] Little Rock Cent High Sch, Little Rock, AR USA. [Heflich, R. H.; Mittelstaedt, R. A.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S82 EP S82 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800281 ER PT J AU Elespuru, RK Rajani, A AF Elespuru, R. K. Rajani, A. TI Miniaturization of a Salmonella Typhimurium Genotoxicity Assay SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Elespuru, R. K.; Rajani, A.] US FDA, Silver Spring, MD USA. [Rajani, A.] Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S75 EP S75 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800253 ER PT J AU Elespuru, RK Rajani, A AF Elespuru, R. K. Rajani, A. TI Evolution of Colon Cancer Is Reflected in DNA Mutational Sequence Profiles. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Elespuru, R. K.; Rajani, A.] US FDA, Silver Spring, MD USA. [Rajani, A.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S68 EP S68 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800225 ER PT J AU Euling, SY White, L Ovacik, AM Makris, SL Sen, B Androulakis, IP Hester, S Gaido, KW Kim, AS Benson, R Wilson, VS Keshava, C Keshava, N Foster, PM Gray, LE Chiu, WA Thompson, C AF Euling, S. Y. White, L. Ovacik, A. M. Makris, S. L. Sen, B. Androulakis, I. P. Hester, S. Gaido, K. W. Kim, A. S. Benson, R. Wilson, V. S. Keshava, C. Keshava, N. Foster, P. M. Gray, Jr. L. E. Chiu, W. A. Thompson, C. TI An Approach to Using Toxicogenomic Data in Risk Assessment: Dibutyl Phthalate Case Study. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Euling, S. Y.; Makris, S. L.; Chiu, W. A.] US EPA, NCEA, Washington, DC 20460 USA. [Hester, S.; Wilson, V. S.; Keshava, C.; Keshava, N.; Gray, Jr. L. E.] US EPA, Res Triangle Pk, NC 27711 USA. [White, L.; Sen, B.; Foster, P. M.] NIEHS, Res Triangle Pk, NC 27709 USA. [Ovacik, A. M.; Androulakis, I. P.] Rutgers State Univ, UMDNJ, ebCTC, Piscataway, NJ USA. [Gaido, K. W.] US FDA, Rockville, MD 20857 USA. [Kim, A. S.] Allergan Pharmaceut Inc, Irvine, CA USA. [Benson, R.] US EPA, Denver, CO USA. [Thompson, C.] ToxStrategies Inc, Katy, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S16 EP S16 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800016 ER PT J AU Gudi, R AF Gudi, R. TI Evaluation and Interpretation of Chromosome Aberration Data on Chromium Picolinate: A Dietary Supplement Ingredient. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Gudi, R.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S33 EP S33 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800084 ER PT J AU Kimoto, T Chikura, S Suzuki, K Kobayashi, XM Itano, Y Horibata, K Honma, M Dobrovolsky, VN Heflich, RH Miura, D Kasahara, Y AF Kimoto, T. Chikura, S. Suzuki, K. Kobayashi, X. M. Itano, Y. Horibata, K. Honma, M. Dobrovolsky, V. N. Heflich, R. H. Miura, D. Kasahara, Y. TI New Assays for Measuring Pig-a Mutant Frequency in Rat Peripheral Blood Reticulocytes (the PIGRET assay) and Bone Marrow Erythroids SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Kimoto, T.; Chikura, S.; Suzuki, K.; Kobayashi, X. M.; Itano, Y.; Miura, D.; Kasahara, Y.] Teijin Pharma Ltd, Tokyo, Japan. [Horibata, K.; Honma, M.] Natl Inst Hlth Sci, Tokyo, Japan. [Dobrovolsky, V. N.; Heflich, R. H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S61 EP S61 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800196 ER PT J AU Manjanatha, MG Bishop, ME Lyn-Cook, LE Ding, W AF Manjanatha, M. G. Bishop, M. E. Lyn-Cook, L. E. Ding, W. TI Genotoxicity of Doxorubicin in F344 Rats by Combining the Comet Assay, Flow Cytometric Peripheral Blood Micronucleus Test and Pathway-focused Gene Expression Profiling SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Manjanatha, M. G.; Bishop, M. E.; Lyn-Cook, L. E.; Ding, W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Ding, Wei/L-1503-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S57 EP S57 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800181 ER PT J AU Petibone, DM Kulkarni, R Chang, CW Chen, JJ Churchwell, MI Beland, FA Morris, SM AF Petibone, D. M. Kulkarni, R. Chang, C-W Chen, J. J. Churchwell, M., I Beland, F. A. Morris, S. M. TI Evaluation of p53 Genotype on Gene Expression and O-6-Ethylguanine Levels in Kidney Tissue from Male C57BL/6 Mice Exposed to ENU. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Petibone, D. M.; Kulkarni, R.; Morris, S. M.] NCTR, Div Genet & Mol Toxicol, Jefferson, AR USA. [Chang, C-W; Chen, J. J.] NCTR, Div Personalized Nutr & Med, Jefferson, AR USA. [Churchwell, M., I; Beland, F. A.] NCTR, Div Biochem Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S51 EP S51 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800157 ER PT J AU Wang, Y McKim, KL Myers, MB Arlt, VM Parsons, BL AF Wang, Y. McKim, K. L. Myers, M. B. Arlt, V. M. Parsons, B. L. TI Tissue Specificity of Aristolochic Acid-Induced Carcinogenesis Examined by ACB-PCR Quantification of H-Ras Codon 61 CTA Mutant Fraction SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 42nd Annual Meeting of the Environmental-Mutagen-Society on Environmental Impacts on the Genome and Epigenome - Mechanisms and Risks CY OCT 15-19, 2011 CL Montreal, CANADA SP Environm Mutagen Soc C1 [Wang, Y.; McKim, K. L.; Myers, M. B.; Parsons, B. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Arlt, V. M.] Inst Canc Res, Sutton, Surrey, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2011 VL 52 SU 1 BP S40 EP S40 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 860DU UT WOS:000297929800112 ER PT J AU Monach, PA Warner, RL Tomasson, G Specks, U Stone, JH Ding, L Fervenza, F Fessler, BJ Hoffman, GS Ikle, D Kallenberg, CGM Krischer, J Langford, CA Mueller, M Seo, P St Clair, EW Spiera, R Tchao, N Ytterberg, SR Johnson, KJ Merkel, PA AF Monach, Paul A. Warner, Roscoe L. Tomasson, Gunnar Specks, Ulrich Stone, John H. Ding, Linna Fervenza, Fernando Fessler, Barri J. Hoffman, Gary S. Ikle, David Kallenberg, Cees G. M. Krischer, Jeffrey Langford, Carol A. Mueller, Mark Seo, Philip St Clair, E. William Spiera, Robert Tchao, Nadia Ytterberg, Steven R. Johnson, Kent J. Merkel, Peter A. TI Serum Proteins Reflecting Inflammation, Injury, and Repair As Biomarkers of Disease Activity in ANCA-Associated Vasculitis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Tomasson, Gunnar; Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02215 USA. [Warner, Roscoe L.; Johnson, Kent J.] Univ Michigan, Ann Arbor, MI 48109 USA. [Specks, Ulrich; Fervenza, Fernando; Ytterberg, Steven R.] Mayo Clin, Rochester, MN USA. [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Hoffman, Gary S.] Cleveland Clin Found A50, Cleveland, OH USA. [Ikle, David] Rho, Chapel Hill, NC USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Krischer, Jeffrey] Univ S Florida, Tampa, FL USA. [Langford, Carol A.] Cleveland Clin, Cleveland, OH 44106 USA. [Mueller, Mark] US FDA, Bethesda, MD 20014 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [St Clair, E. William] Duke Univ, Med Ctr, Durham, NC USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Tchao, Nadia] Immune Tolerance Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 792 BP S312 EP S312 PG 1 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500788 ER PT J AU Specks, U Merkel, PA Seo, P Spiera, RF Langford, CA Hoffman, GS Kallenberg, CGM Clair, EWS Tole, S Brunetta, P Shen, SY Tchao, N Fessler, BJ Webber, L Ding, L Sejismundo, LP Mieras, K Phippard, DJ Asare, A Lim, N Ikle, D Jepson, B Lail, A Mueller, M AF Specks, Ulrich Merkel, Peter A. Seo, Philip Spiera, Robert F. Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. Clair, E. William St. Tole, Swati Brunetta, Paul Shen, Shuyi Tchao, Nadia Fessler, Barri J. Webber, Lisa Ding, Linna Sejismundo, Lourdes P. Mieras, Kathleen Phippard, Deborah J. Asare, Adam Lim, Noha Ikle, David Jepson, Brett Lail, Alice Mueller, Mark TI Immunoglobulin Concentrations and Infection Risk Among Patients with ANCA-Associated Vasculitis Treated with Rituximab or Cyclophosphamide. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Specks, Ulrich; Mieras, Kathleen] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert F.] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, Cees G. M.] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [Clair, E. William St.] Duke Univ, Med Ctr, Durham, NC 27706 USA. [Tole, Swati; Shen, Shuyi] Genentech Inc, San Francisco, CA USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. [Tchao, Nadia; Phippard, Deborah J.; Asare, Adam; Lim, Noha] Immune Tolerance Network, Bethesda, MD USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Webber, Lisa; Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Sejismundo, Lourdes P.] Johns Hopkins Univ, Baltimore, MD USA. [Ikle, David; Jepson, Brett; Lail, Alice] Rho, Chapel Hill, NC USA. [Mueller, Mark] US FDA, Bethesda, MD 20014 USA. NR 0 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 789 BP S310 EP S311 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621500785 ER PT J AU Stone, JH Merkel, PA Seo, P Spiera, R Langford, CA Hoffman, GS Kallenberg, CGM St Clair, EW Fessler, BJ Tchao, N Webber, L Ding, LN Sejismundo, LP Mieras, K Ikle, D Phippard, DJ Jepson, B Lail, A Asare, A Lim, N Mueller, M Brunetta, P Allen, NB Fervenza, F Geetha, D Keogh, K Kissin, EY Monach, PA Peikert, T Stegeman, C Ytterberg, SR Specks, U AF Stone, John H. Merkel, Peter A. Seo, Philip Spiera, Robert Langford, Carol A. Hoffman, Gary S. Kallenberg, Cees G. M. St Clair, E. William Fessler, Barri J. Tchao, Nadia Webber, Lisa Ding, Linna Sejismundo, Lourdes P. Mieras, Kathleen Ikle, David Phippard, Deborah J. Jepson, Brett Lail, Alice Asare, Adam Lim, Noha Mueller, Mark Brunetta, Paul Allen, Nancy B. Fervenza, Fernando Geetha, Duvuru Keogh, Karina Kissin, Eugene Y. Monach, Paul A. Peikert, Tobias Stegeman, Coen Ytterberg, Steven R. Specks, Ulrich CA RAVE-ITN Res Grp TI Extended Follow-up of Treatment with Rituximab Versus Cyclophosphamide for Remission-Induction of ANCA-Associated Vasculitis: Which Subsets Are At Greatest Risk for Flare? SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Rheumatology/46th Annual Scientific Meeting of the Association-of-Rheumatology-Health-Professionals (ARHP) CY NOV 04-09, 2011 CL Chicago, IL SP Amer Coll Rheumatol (ACR), Assoc Rheumatol Hlth Profess (ARHP) C1 [Stone, John H.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Seo, Philip] Johns Hopkins Vasculitis Ctr, Baltimore, MD USA. [Spiera, Robert] Hosp Special Surg, New York, NY 10021 USA. [Langford, Carol A.; Hoffman, Gary S.] Cleveland Clin, Cleveland, OH 44106 USA. [Kallenberg, Cees G. M.; Stegeman, Coen] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands. [St Clair, E. William; Allen, Nancy B.] Duke Univ, Med Ctr, Durham, NC USA. [Fessler, Barri J.] Univ Alabama Birmingham, Birmingham, AL USA. [Tchao, Nadia; Phippard, Deborah J.; Asare, Adam; Lim, Noha] Immune Tolerance Network, Bethesda, MD USA. [Webber, Lisa; Ding, Linna] NIAID, Bethesda, MD 20892 USA. [Sejismundo, Lourdes P.] Johns Hopkins Univ, Baltimore, MD USA. [Mieras, Kathleen; Fervenza, Fernando; Keogh, Karina; Peikert, Tobias; Ytterberg, Steven R.; Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Ikle, David; Jepson, Brett; Lail, Alice] Rho, Chapel Hill, NC USA. [Mueller, Mark] US FDA, Bethesda, MD 20014 USA. [Brunetta, Paul] Genentech Inc, So San Francisco, CA USA. [Geetha, Duvuru] Johns Hopkins Univ, York, PA USA. NR 0 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0004-3591 J9 ARTHRITIS RHEUM-US JI Arthritis Rheum. PD OCT PY 2011 VL 63 IS 10 SU S MA 2432 BP S946 EP S947 PG 2 WC Rheumatology SC Rheumatology GA 856EV UT WOS:000297621503003 ER PT J AU Choi, SC Simhadri, VR Tian, LJ Gil-Krzewska, A Krzewski, K Borrego, F Coligan, JE AF Choi, Seung-Chul Simhadri, Venkateswara R. Tian, Linjie Gil-Krzewska, Aleksandra Krzewski, Konrad Borrego, Francisco Coligan, John E. TI Cutting Edge: Mouse CD300f (CMRF-35-Like Molecule-1) Recognizes Outer Membrane-Exposed Phosphatidylserine and Can Promote Phagocytosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NEGATIVE REGULATION; RECEPTOR; CELLS; CLEARANCE; FAMILY; LMIR3 AB Reportedly, CD300f negatively regulates interactions between dendritic and T cells and acts as an anti-inflammatory molecule in a multiple sclerosis mouse model. We found that a CD300f/Fc chimeric protein specifically binds to apoptotic/dead splenocytes and to apoptotic cells from starved or irradiated lymphocytic cell lines, an observation extended to insect cells. CD300f also binds PMA/ionomycin-activated splenocytes and Ag-stimulated T cells, an interaction inhibited by Annexin V. By ELISA, cosedimentation, and surface plasmon resonance using phospholipid-containing liposomes, we show that CD300f preferentially binds phosphatidylserine and requires a metal ion. Exogenous expression of CD300f in cell lines results in enhanced phagocytosis of apoptotic cells. We conclude that expression of CD300f conveys additional capacity to recognize phosphatidylserine to myeloid cells. The result of this recognition may vary with the overall qualitative and quantitative receptor content, as well as signaling capacity of the expressing effector cell, but enhanced phagocytosis is one measurable outcome. The Journal of Immunology, 2011, 187: 3483-3487. C1 [Choi, Seung-Chul; Tian, Linjie; Gil-Krzewska, Aleksandra; Krzewski, Konrad; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. [Simhadri, Venkateswara R.; Borrego, Francisco] US FDA, Div Monoclonal Antibodies, Lab Mol & Dev Immunol, Off Biotechnol Prod,Ctr Drug Evaluat & Review, Bethesda, MD 20892 USA. RP Coligan, JE (reprint author), NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr,Twinbrook 2,Room 205, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov RI Tian, Linjie/E-6878-2014 FU Food and Drug Administration; National Institute of Allergy and Infectious Diseases FX This work was supported by the intramural programs of the Food and Drug Administration and the National Institute of Allergy and Infectious Diseases. NR 15 TC 29 Z9 29 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 OCT 1 PY 2011 VL 187 IS 7 BP 3483 EP 3487 DI 10.4049/jimmunol.1101549 PG 5 WC Immunology SC Immunology GA 822IB UT WOS:000295036400005 PM 21865548 ER PT J AU Rani, A Afzali, B Kelly, A Tewolde-Berhan, L Hackett, M Kanhere, AS Pedroza-Pacheco, I Bowen, H Jurcevic, S Jenner, RG Cousins, DJ Ragheb, JA Lavender, P John, S AF Rani, Aradhana Afzali, Behdad Kelly, Audrey Tewolde-Berhan, Lemlem Hackett, Mark Kanhere, Aditi S. Pedroza-Pacheco, Isabela Bowen, Holly Jurcevic, Stipo Jenner, Richard G. Cousins, David J. Ragheb, Jack A. Lavender, Paul John, Susan TI IL-2 Regulates Expression of C-MAF in Human CD4 T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TH2 DIFFERENTIATION; STAT5 ACTIVATION; HUMAN GENOME; IFN-GAMMA; CYTOKINES; PLAYS; ROLES; IDENTIFICATION; INTERLEUKIN-4; TRANSCRIPTION AB Blockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2 responses in human T cells. Recent murine studies have shown that IL-2 also plays a significant role in regulating Th2 cell differentiation by activated STAT5. To explore the role of activated STAT5 in the Th2 differentiation of primary human T cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression. Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to specific sites in the C-MAF promoter. These sites corresponded to regions enriched for markers of chromatin architectural features in both resting CD4 and differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T cells with or without prior TCR stimulation. TCR-induced C-MAF expression was significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333. Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR-activated T cells, suggesting functional cooperation between these cytokines. Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus, our findings demonstrate the importance of IL-2 in Th2 differentiation in human T cells and support the notion that IL-2R-directed therapies may have utility in the treatment of allergic disorders. The Journal of Immunology, 2011, 187: 3721-3729. C1 [Rani, Aradhana; Tewolde-Berhan, Lemlem; Hackett, Mark; John, Susan] Kings Coll London, Dept Immunobiol, London SE1 9RT, England. [Rani, Aradhana; Afzali, Behdad; Jurcevic, Stipo] Kings Coll London, MRC, Ctr Transplantat, London SE1 9RT, England. [Kelly, Audrey; Bowen, Holly; Cousins, David J.; Lavender, Paul] Kings Coll London, Dept Resp Med & Allergy, MRC, London SE1 9RT, England. [Kelly, Audrey; Bowen, Holly; Cousins, David J.; Lavender, Paul] Kings Coll London, Asthma UK Ctr Allerg Mech Asthma, London SE1 9RT, England. [Kanhere, Aditi S.; Jenner, Richard G.] UCL, Div Infect & Immun, MRC, Ctr Med Mol Virol, London W1T 4JF, England. [Pedroza-Pacheco, Isabela] UCL, Anthony Nolan Res Inst, London W1T 4JF, England. [Ragheb, Jack A.] US FDA, Immunol Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. RP John, S (reprint author), Kings Coll London, Dept Immunobiol, 2nd Floor,Guys Campus, London SE1 9RT, England. EM susan.john@kcl.ac.uk RI Jenner, Richard/J-8683-2012; Afzali, Behdad/H-8565-2013; OI Afzali, Behdad/0000-0003-2968-1156; John, Susan/0000-0002-5620-1982; Cousins, David/0000-0003-3821-9596; Rani, Aradhana/0000-0003-4273-9826 FU Wellcome Trust UK [074656/Z/04/Z]; Medical Research Council UK [G0400197, G9536930, G0500429]; Dorothy Hodgkin postgraduate award; Medical Research Council Centre for Transplantation; Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Centre; King's College London; King's College Hospital National Health Service Foundation Trust FX This work was supported by Wellcome Trust UK Grant 074656/Z/04/Z (to S.J.) and by Medical Research Council UK Grant G0400197 (to S.J.). P.L. was supported by Medical Research Council UK Grant G9536930, B.A. was supported by Medical Research Council UK Grant G0500429, and A.R. was supported by a Dorothy Hodgkin postgraduate award. We acknowledge the support of the Medical Research Council Centre for Transplantation and financial support from the Department of Health via the National Institute for Health Research Comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service Foundation Trust in partnership with King's College London and King's College Hospital National Health Service Foundation Trust. NR 44 TC 16 Z9 17 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 OCT 1 PY 2011 VL 187 IS 7 BP 3721 EP 3729 DI 10.4049/jimmunol.1002354 PG 9 WC Immunology SC Immunology GA 822IB UT WOS:000295036400031 PM 21876034 ER PT J AU He, GX Thorpe, C Walsh, D Crow, R Chen, HZ Kumar, S Varela, MF AF He, Gui-Xin Thorpe, Conner Walsh, Dennis Crow, Robert Chen, Huizhong Kumar, Sanath Varela, Manuel F. TI EmmdR, a new member of the MATE family of multidrug transporters, extrudes quinolones from Enterobacter cloacae SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE Multidrug transporter; Enterobacter cloacae; Resistance; MATE Family ID EFFLUX PUMP; PSEUDOMONAS-AERUGINOSA; ANTIMICROBIAL RESISTANCE; VIBRIO-PARAHAEMOLYTICUS; ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; CLONING; NORM; H+; SUSCEPTIBILITY AB We cloned a gene, ECL_03329, from the chromosome of Enterobacter cloacae ATCC13047, using a drug-hypersensitive Escherichia coli KAM32 cell as the host. We show here that this gene, designated as emmdR, is responsible for multidrug resistance in E. cloacae. E. coli KAM32 host cells containing the cloned emmdR gene (KAM32/pEMMDR28) showed decreased susceptibilities to benzalkonium chloride, norfloxacin, ciprofloxacin, levofloxacin, ethidium bromide, acriflavine, rhodamine6G, and trimethoprim. emmdR-deficient E. cloacae cells (Ec Delta emmdR) showed increased susceptibilities to several of the antimicrobial agents tested. EmmdR has twelve predicted transmembrane segments and some shared identity with members of the multidrug and toxic compound extrusion (MATE) family of transporters. Study of the antimicrobial agent efflux activities revealed that EmmdR is an H+-drug antiporter but not a Na+ driven efflux pump. These results indicate that EmmdR is responsible for multidrug resistance and pumps out quinolones from E. cloacae. C1 [He, Gui-Xin; Thorpe, Conner; Walsh, Dennis] Univ Massachusetts, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. [Crow, Robert; Kumar, Sanath; Varela, Manuel F.] Eastern New Mexico Univ, Dept Biol, Portales, NM 88130 USA. [Chen, Huizhong] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP He, GX (reprint author), Univ Massachusetts, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. EM Guixin_He@uml.edu RI Varela, Manuel/A-7782-2009 OI Varela, Manuel/0000-0001-8667-7853 FU University of Massachusetts Lowell; NIH, National Center for Research Resources [P20 RR016480] FX This work was supported by an Internal Research Grant from the University of Massachusetts Lowell (G. HE), and an NIH Grant P20 RR016480 (M.F.V.) which is from the NM-INBRE program of the National Center for Research Resources. We truly appreciate Dr. Tomofusa Tsuchiya for providing KAM32 and plasmids. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 35 TC 10 Z9 13 U1 1 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-8933 EI 1432-072X J9 ARCH MICROBIOL JI Arch. Microbiol. PD OCT PY 2011 VL 193 IS 10 BP 759 EP 765 DI 10.1007/s00203-011-0738-1 PG 7 WC Microbiology SC Microbiology GA 850UC UT WOS:000297224000008 PM 21822795 ER PT J AU Hayford, AE Mammel, MK Lacher, DW Brown, EW AF Hayford, Alice E. Mammel, Mark K. Lacher, David W. Brown, Eric W. TI Single nucleotide polymorphism (SNP)-based differentiation of Shigella isolates by pyrosequencing SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Shigella; Single nucleotide polymorphisms; Phylogenetics; Pyrosequencing ID ENTEROINVASIVE ESCHERICHIA-COLI; TANDEM-REPEAT ANALYSIS; PHYLOGENETIC NETWORKS; SEQUENCE ALIGNMENT; GENOME SEQUENCE; GENUS SHIGELLA; FLEXNERI; STRAINS; EVOLUTIONARY; IDENTIFICATION AB Analysis of single nucleotide polymorphisms (SNPs) is an important genetic tool that provides molecular markers for rapid differentiation of closely related strains. We have applied SNP discovery and analysis for distinguishing each of the four Shigella serogroups (Boydii, Dysenteriae, Flexneri, and Sonnei) and for discriminating individual strains within the same serogroup by using 24 SNPs selected from nine genes. Five SNPs were identified from sequence analysis of two housekeeping genes (gapA and thrB) used previously in our lab to differentiate Shigella isolates into distinct lineages. The remaining 19 SNPs were identified by in silico analyses of eight Shigella genomes and are within the genes lpxC, sanA, yaaH, ybaP, ygaZ, yhbO, and ynhA. A total of 118 Shigella strains comprising 20 Boydii, 29 Dysenteriae, 42 Flexneri, and 27 Sonnei isolates were analyzed using the SNP typing scheme reported here. The combination of the 24 SNPs resulted in the identification of 26 SNP genotypes among the four Shigella serogroups and also provided some discriminatory resolution among individual strains within the same serogroup. The SNPs presented here should prove useful in identifying Shigella using PCR amplification and rapid sequence typing strategies. Published by Elsevier B.V. C1 [Hayford, Alice E.; Mammel, Mark K.; Lacher, David W.] US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Hayford, AE (reprint author), 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM alice.hayford@fda.hhs.gov FU Department of Homeland Security [IAG 224-04-2806] FX We thank the National Bioforensics Analysis Center of the Department of Homeland Security, the Centers for Disease Control and Prevention, and the Navy Environmental and Preventive Medicine Unit for providing some of the Shigella isolates used in this study. We acknowledge the Department of Homeland Security (IAG 224-04-2806) for supporting this work. NR 43 TC 7 Z9 7 U1 0 U2 3 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 OCT PY 2011 VL 11 IS 7 BP 1761 EP 1768 DI 10.1016/j.meegid.2011.07.015 PG 8 WC Infectious Diseases SC Infectious Diseases GA 849LK UT WOS:000297126800030 PM 21839856 ER PT J AU Goff, A Mucker, E Raymond, J Fisher, R Bray, M Hensley, L Paragas, J AF Goff, Arthur Mucker, Eric Raymond, Jolynne Fisher, Robert Bray, Mike Hensley, Lisa Paragas, Jason TI Infection of cynomolgus macaques with a recombinant monkeypox virus encoding green fluorescent protein SO ARCHIVES OF VIROLOGY LA English DT Article ID VACCINIA VIRUS; SMALLPOX; EFFICACY; ASSAY AB Monkeypox virus (MPXV) causes a vesiculopustular rash illness resembling smallpox in humans and produces a similar disease in nonhuman primates. To enhance the ability of researchers to study experimental MPXV infections, we inserted a gene encoding green fluorescent protein (GFP) into Monkeypox virus Zaire-79. Wild-type and MPXV-GFP replicated with similar kinetics in cell culture and caused a similar disease when injected intravenously into cynomolgus macaques. In MPXV-GFP-infected animals, examination under fluorescent light facilitated the identification of skin lesions during disease development and internal sites of replication at necropsy. MPXV-GFP could improve the quantitative assessment of antiviral therapy and vaccine efficacy. C1 [Goff, Arthur; Mucker, Eric; Hensley, Lisa] USA, Div Virol, Viral Therapeut Branch, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Raymond, Jolynne] Armed Forces Inst Pathol, Silver Spring, MD USA. [Fisher, Robert] US FDA, Lab Plasma Derivat, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Bray, Mike; Paragas, Jason] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD 21702 USA. RP Goff, A (reprint author), USA, Div Virol, Viral Therapeut Branch, Med Res Inst Infect Dis, 1425 Porter St, Ft Detrick, MD 21702 USA. EM arthur.goff@amedd.army.mil FU Defense Threat Reduction Agency; Department of Homeland Security's National Biodefense Analysis and Countermeasures Center (NBACC) FX The research described in this paper was funded by the Defense Threat Reduction Agency and The Department of Homeland Security's National Biodefense Analysis and Countermeasures Center (NBACC). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the U.S. Army. NR 12 TC 6 Z9 6 U1 0 U2 4 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD OCT PY 2011 VL 156 IS 10 BP 1877 EP 1881 DI 10.1007/s00705-011-1065-1 PG 5 WC Virology SC Virology GA 841KC UT WOS:000296510200022 PM 21814864 ER PT J AU Makris, SL Kim, JH Ellis, A Faber, W Harrouk, W Lewis, JM Paule, MG Seed, J Tassinari, M Tyl, R AF Makris, Susan L. Kim, James H. Ellis, Amy Faber, Willem Harrouk, Wafa Lewis, Joseph M. Paule, Merle G. Seed, Jennifer Tassinari, Melissa Tyl, Rochelle TI Current and Future Needs for Developmental Toxicity Testing SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE developmental toxicology testing; pharmaceuticals; environmental chemicals; food additives; cosmetics; consumer products; risk assessment ID ABNORMALITIES; TERMINOLOGY; FDA AB A review is presented of the use of developmental toxicity testing in the United States and international regulatory assessment of human health risks associated with exposures to pharmaceuticals (human and veterinary), chemicals (agricultural, industrial, and environmental), food additives, cosmetics, and consumer products. Developmental toxicology data are used for prioritization and screening of pharmaceuticals and chemicals, for evaluating and labeling of pharmaceuticals, and for characterizing hazards and risk of exposures to industrial and environmental chemicals. The in vivo study designs utilized in hazard characterization and dose-response assessment for developmental outcomes have not changed substantially over the past 30 years and have served the process well. Now there are opportunities to incorporate new technologies and approaches to testing into the existing assessment paradigm, or to apply innovative approaches to various aspects of risk assessment. Developmental toxicology testing can be enhanced by the refinement or replacement of traditional in vivo protocols, including through the use of in vitro assays, studies conducted in alternative nonmammalian species, the application of new technologies, and the use of in silico models. Potential benefits to the current regulatory process include the ability to screen large numbers of chemicals quickly, with the commitment of fewer resources than traditional toxicology studies, and to refine the risk assessment process through an enhanced understanding of the mechanisms of developmental toxicity and their relevance to potential human risk. As the testing paradigm evolves, the ability to use developmental toxicology data to meet diverse critical regulatory needs must be retained. Birth Defects Res (Part B) 92:384-394, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Makris, Susan L.] US EPA, ORD, NCEA W, Natl Ctr Environm Assessment, Washington, DC 20460 USA. [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Ellis, Amy; Harrouk, Wafa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Faber, Willem] Willem Faber Toxicol Consulting, Victor, NY USA. [Lewis, Joseph M.] EI du Pont de Nemours & Co, Wilmington, DE USA. [Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Seed, Jennifer] US EPA, Off Pollut Prevent & Tox, Washington, DC 20460 USA. [Tassinari, Melissa] Pfizer Inc, Groton, CT 06340 USA. [Tyl, Rochelle] RTI Int, Res Triangle Pk, NC USA. RP Makris, SL (reprint author), US EPA, ORD, NCEA W, Natl Ctr Environm Assessment, Mailcode 8623P,1200 Penn Ave NW, Washington, DC 20460 USA. EM makris.susan@epa.gov NR 57 TC 8 Z9 9 U1 0 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD OCT PY 2011 VL 92 IS 5 SI SI BP 384 EP 394 DI 10.1002/bdrb.20335 PG 11 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 842PT UT WOS:000296612100002 PM 21922641 ER PT J AU Carney, EW Ellis, AL Tyl, RW Foster, PMD Scialli, AR Thompson, K Kim, J AF Carney, Edward W. Ellis, Amy L. Tyl, Rochelle W. Foster, Paul M. D. Scialli, Anthony R. Thompson, Kary Kim, James TI Critical Evaluation of Current Developmental Toxicity Testing Strategies: A Case of Babies and Their Bathwater SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE safety testing; maternal toxicity; pharmacokinetics; alternatives to animal testing ID HUMAN RISK-ASSESSMENT; MATERNAL TOXICITY; FETAL MALFORMATIONS; ETHYLENE-GLYCOL; SCORING SYSTEM; WAVY RIBS; RABBIT; EMBRYO; REACH; RAT AB This review is the second in a series of four papers emanating from a workshop entitled "Developmental Toxicology-New Directions," which was sponsored by the ILSI Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee. The present review analyzes the strengths and weaknesses of current developmental safety testing approaches in an effort to identify those strengths that should be retained in the future versus the weaknesses that should be eliminated. Workshop participants considered the following to be key strengths of current testing approaches: the integrated biology of pregnant animal models including pharmacokinetic and pharmacodynamic processes, the ability to detect low incidence malformations as well as maternally mediated toxicity, and the long history of use coupled with extensive historical data. A number of weaknesses were related to the resource-intensive nature of developmental toxicity testing (e. g., large number of animals, high costs, low throughput, the inability to keep pace with the demand for more toxicity data). Other weaknesses included the use of very high dose levels that often far exceed human exposure levels, the confounding influence of maternal toxicity, sparse understanding of basic developmental mechanisms and genetics of standard animal models relative to mouse or lower organisms, difficulties interpreting low incidence findings, and issues surrounding the interpretation of minor skeletal variations. An appreciation of these strengths and weaknesses is critical for the design of new approaches to developmental toxicity testing in the 21st century. Birth Defects Res (Part B) 92:395-403, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Carney, Edward W.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Ellis, Amy L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Tyl, Rochelle W.] RTI Int, Discovery & Analyt Sci, Res Triangle Pk, NC USA. [Foster, Paul M. D.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. [Scialli, Anthony R.] Tetra Tech Sci, Arlington, VA USA. [Thompson, Kary] Bristol Myers Squibb Co, Reprod Toxicol, New Brunswick, NJ USA. [Kim, James] ILSI Hlth & Environm Sci Inst HESI, Washington, DC USA. RP Carney, EW (reprint author), Dow Chem Co USA, Toxicol & Environm Res & Consulting, 1803 Bldg, Midland, MI 48674 USA. EM ecarney@dow.com NR 55 TC 7 Z9 7 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD OCT PY 2011 VL 92 IS 5 SI SI BP 395 EP 403 DI 10.1002/bdrb.20318 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 842PT UT WOS:000296612100003 PM 21770028 ER PT J AU Brannen, KC Fenton, SE Hansen, DK Harrouk, W Kim, JH Shuey, D AF Brannen, Kimberly C. Fenton, Suzanne E. Hansen, Deborah K. Harrouk, Wafa Kim, James H. Shuey, Dana TI Developmental Toxicology-New Directions Workshop: Refining Testing Strategies and Study Designs SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE refined study designs; testing strategies; developmental toxicology; safety assessment AB In April 2009, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute's (HESI) Developmental and Reproductive Toxicology Technical Committee held a two-day workshop entitled "Developmental Toxicology-New Directions." The third session of the workshop focused on ways to refine animal studies to improve relevance and predictivity for human risk. The session included five presentations on: (1) considerations for refining developmental toxicology testing and data interpretation; (2) comparative embryology and considerations in study design and interpretation; (3) pharmacokinetic considerations in study design; (4) utility of genetically modified models for understanding mode-of-action; and (5) special considerations in reproductive testing for biologics. The presentations were followed by discussion by the presenters and attendees. Much of the discussion focused on aspects of refining current animal testing strategies, including use of toxicokinetic data, dose selection, tiered/triggered testing strategies, species selection, and use of alternative animal models. Another major area of discussion was use of non-animal-based testing paradigms, including how to define a "signal" or adverse effect, translating in vitro exposures to whole animal and human exposures, validation strategies, the need to bridge the existing gap between classical toxicology testing and risk assessment, and development of new technologies. Although there was general agreement among participants that the current testing strategy is effective, there was also consensus that traditional methods are resource-intensive and improved effectiveness of developmental toxicity testing to assess risks to human health is possible. This article provides a summary of the session's presentations and discussion and describes some key areas that warrant further consideration. Birth Defects Res (Part B) 92:404-412, 2011. (C) 2011 Wiley Periodicals, Inc. C1 [Brannen, Kimberly C.] Charles River Labs, Preclin Serv, Horsham, PA USA. [Fenton, Suzanne E.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. [Hansen, Deborah K.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Harrouk, Wafa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Shuey, Dana] Endo Pharmaceut Inc, Chadds Ford, PA USA. RP Brannen, KC (reprint author), Charles River Labs, Preclin Serv, Horsham, PA USA. EM kimberly.brannen@crl.com FU Intramural NIH HHS [ZIA ES102785-02, ZIA ES102785-01] NR 13 TC 3 Z9 3 U1 0 U2 5 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 OCT PY 2011 VL 92 IS 5 SI SI BP 404 EP 412 DI 10.1002/bdrb.20326 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 842PT UT WOS:000296612100004 PM 22006510 ER PT J AU Lin, A Nguyen, L Lee, T Clotilde, LM Kase, JA Son, I Carter, JM Lauzon, CR AF Lin, Andrew Lam Nguyen Lee, Teresa Clotilde, Laurie M. Kase, Julie A. Son, Insook Carter, J. Mark Lauzon, Carol R. TI Rapid O serogroup identification of the ten most clinically relevant STECs by Luminex microbead-based suspension array SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE STEC; O serogroup identification; Multi-plex PCR; Luminex ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; ANTIGEN GENE-CLUSTER; HEMOLYTIC UREMIC SYNDROME; HEALTHY DOMESTIC-ANIMALS; NON-O157 SHIGA TOXIN; VIRULENCE MARKERS; UNITED-STATES; INFECTIONS; PREVALENCE; CATTLE AB Identification and serotyping of Shiga toxin-producing Escherichia calf during foodborne outbreaks can aid in matching clinical, food, and environmental isolates when trying to identify the source of illness and ultimately food contamination. Herein we describe a Luminex microbead-based suspension array to identify the O serogroup of the ten most clinically relevant STECs: O26, O45, O91, O103, O111, O113, O121, O128, O145, and O157. The use of PCR followed by Luminex xMAP (R) technology enables the detection of multiple analytes in a single multiplex reaction with high throughput capabilities. One hundred and fourteen STEC isolates were correctly identified with no false positives among forty-six other organisms using this assay. Assay performance was tested in multiple laboratories using a panel of eleven different STEC serogroups on the BioPlex 200 and MAGPIX instruments. The STEC microbead-based suspension array can be performed in a 96-well plate format for high throughput screening in less than 4 h. Furthermore, it is expandable, allowing for the addition of O serogroups should the need arise. Published by Elsevier B.V. C1 [Lin, Andrew; Lee, Teresa] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. [Lam Nguyen; Lauzon, Carol R.] Calif State Univ Hayward, Dept Biol Sci, Hayward, CA 94542 USA. [Clotilde, Laurie M.; Carter, J. Mark] Agr Res Serv, USDA, Albany, CA 94710 USA. [Kase, Julie A.; Son, Insook] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Lin, A (reprint author), 1431 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM andrew.lin@fda.hhs.gov RI Carter, John Mark/K-2485-2015 OI Carter, John Mark/0000-0001-8251-4168 FU FDA San Francisco District Laboratory; ORA Division of Field Science; California State University FX The authors would like to thank the STEC Center at Michigan State University's National Food Safety and Toxicology Center, East Lansing, MI, Robert Mandrell, United States Department of Agriculture-Agricultural Research Services, Albany, CA, the Ohio Department of Agriculture, Reynoldsburg, OH, Atin Datta, U. S. Food and Drug Administration, Center for Food Safety and Nutrition, Laurel, MD, and the Orange County Public Health Laboratory, Santa Ana, CA for generously sharing their bacterial cultures. The authors would like to thank Sherry Dunbar, Luminex Corporation, Austin, TX for technical support. The authors would also like to thank the FDA San Francisco District Laboratory and the ORA Division of Field Science for their support of this research. This work was primarily supported by the California State University Program for Education and Research in Biotechnology. NR 32 TC 33 Z9 34 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD OCT PY 2011 VL 87 IS 1 BP 105 EP 110 DI 10.1016/j.mimet.2011.07.019 PG 6 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 847BH UT WOS:000296946400016 PM 21835211 ER PT J AU Zook, JM Rastogi, V MacCuspie, RI Keene, AM Fagan, J AF Zook, Justin M. Rastogi, Vinayak MacCuspie, Robert I. Keene, Athena M. Fagan, Jeffrey TI Measuring Agglomerate Size Distribution and Dependence of Localized Surface Plasmon Resonance Absorbance on Gold Nanoparticle Agglomerate Size Using Analytical Ultracentrifugation SO ACS NANO LA English DT Article DE gold colloid; aggregate; analytical ultracentrifugation; nanoparticle toxicity; biosensors ID OPTICAL-PROPERTIES; EQUATION; DNA AB Agglomeration of nanopartides daring measurements In relevant biological and environmental media is a frequent problem in nanomaterial property characterization. The primary problem is typically that any changes to the size distribution on dramatically affect the potential nanotoxicity or other size-determined properties, such as the absorbance signal in a biosensor measurement Herein we demonstrate analytical ultracentrifugation (AUC) as a powerful method for measuring two critical characteristics of nanoparticle (NP) agglomerates In situ in biological media: the NP agglomerate size distribution, and the localized surface plasmon resonance (LSPR) absorbance spectrum of precise sizes of gold NP agglomerates. To characterize the size distribution, we present a theoretical framework for calculating the hydrodynamic diameter distribution of NP agglomerates from their sedimentation coefficient distribution. We measure sedimentation rates for monomers, rimers, and trimers, as well as for larger agglomerates with up to 600 NPs. The AUC size distributions were found generally to be broader than the size distributions estimated from dynamic light scattering and diffusion-limited colloidal aggregation theory, an alternative bulk measurement method that relies on seven! assumptions. In addition, the measured sedimentation coefficients can be used in nanotoxicity studies to predict how quickly the agglomerates sediment out of solution under normal gravitational forces, such as In the environment We also calculate the absorbance spectra for monomer, dimer, timer, and larger gold NP agglomerates up to 600 NPs, to enable a better understanding of LSPR biosensors. Finally, we validate a new method that uses these spectra to deconvolute the net absorbance spectrum of an unknown bulk sample and approximate the proportions of monomers, dimers, and trimers In a polydisperse sample of small agglomerates, so that every sample does not need to be measured by AUC. These results demonstrate the potential utility of AUC to characterize NP agglomeration and sedimentation for nanotoxicity and biosensor studies, as well as to characterize NP agglomerate size and absorbance to improve LSPR and surface-enhanced Raman spectroscopy based biosensors. C1 [Zook, Justin M.; Rastogi, Vinayak; MacCuspie, Robert I.; Fagan, Jeffrey] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena M.] US FDA, Silver Spring, MD USA. RP Zook, JM (reprint author), Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM jzook@nist.gov RI Zook, Justin/B-7000-2008; OI Zook, Justin/0000-0003-2309-8402; MacCuspie, Robert/0000-0002-6618-6499; Fagan, Jeffrey/0000-0003-1483-5554 FU National Research Council at NIST; Center for Drug Evaluation and Research FX J.Z. acknowledges support from a National Research Council postdoctoral fellowship at NIST. Also, 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. 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. 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 27 TC 49 Z9 49 U1 9 U2 74 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD OCT PY 2011 VL 5 IS 10 BP 8070 EP 8079 DI 10.1021/nn202645b PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 837MU UT WOS:000296208700059 PM 21888410 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI Literature Review and Global Consensus on Management of Acute Radiation Syndrome Affecting Nonhematopoietic Organ Systems SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; acute radiation syndrome management; treatment of ARS; narrative review of countermeasures for ARS ID MESENCHYMAL STEM-CELLS; RESPIRATORY-DISTRESS-SYNDROME; MEDICAL-MANAGEMENT; CRITICALLY-ILL; GLUCOSE CONTROL; PUBLIC-HEALTH; CRITICAL-CARE; SEPTIC SHOCK; DOUBLE-BLIND; LUNG INJURY AB Objectives: The World Health Organization convened a panel of experts to rank the evidence for medical countermeasures for management of acute radiation syndrome (ARS) in a hypothetical scenario involving the hospitalization of 100 to 200 victims. The goal of this panel was to achieve consensus on optimal management of ARS affecting nonhematopoietic organ systems based upon evidence in the published literature. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to conferees in advance of and updated during the meeting. Published case series and case reports of ARS, publications of randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation system. In cases in which data were limited or incomplete, a narrative review of the observations was made. Results: No randomized controlled trials of medical countermeasures have been completed for individuals with ARS. Reports of countermeasures were often incompletely described, making it necessary to rely on data generated in nonirradiated humans and in experimental animals. A strong recommendation is made for the administration of a serotonin-receptor antagonist prophylactically when the suspected exposure is >2 Gy and topical steroids, antibiotics, and antihistamines for radiation burns, ulcers, or blisters; excision and grafting of radiation ulcers or necrosis with intractable pain; provision of supportive care to individuals with neurovascular syndrome; and administration of electrolyte replacement therapy and sedatives to individuals with significant burns, hypovolemia, and/orshock. A strong recommendation is made against the use of systemic steroids in the absence of a specific indication. A weak recommendation is made for the use of fluoroquinolones, bowel decontamination, loperamide, and enteral nutrition, and for selective oropharyngeal/digestive decontamination, blood glucose maintenance, and stress ulcer prophylaxis in critically ill patients. Conclusions: High-quality studies of therapeutic interventions in humans exposed to nontherapeutic radiation are not available, and because of ethical concerns regarding the conduct of controlled studies in humans, such studies are unlikely to emerge in the near future. C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to Richard Hatchett and the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 181 TC 28 Z9 28 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 183 EP 201 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300007 PM 21986999 ER PT J AU Dainiak, N Gent, RN Carr, Z Schneider, R Bader, J Buglova, E Chao, N Coleman, CN Ganser, A Gorin, C Hauer-Jensen, M Huff, LA Lillis-Hearne, P Maekawa, K Nemhauser, J Powles, R Schunemann, H Shapiro, A Stenke, L Valverde, N Weinstock, D White, D Albanese, J Meineke, V AF Dainiak, Nicholas Gent, Robert Nicolas Carr, Zhanat Schneider, Rita Bader, Judith Buglova, Elena Chao, Nelson Coleman, C. Norman Ganser, Arnold Gorin, Claude Hauer-Jensen, Martin Huff, L. Andrew Lillis-Hearne, Patricia Maekawa, Kazuhiko Nemhauser, Jeffrey Powles, Ray Schuenemann, Holger Shapiro, Alla Stenke, Leif Valverde, Nelson Weinstock, David White, Douglas Albanese, Joseph Meineke, Viktor TI First Global Consensus for Evidence-Based Management of the Hematopoietic Syndrome Resulting From Exposure to Ionizing Radiation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE countermeasures for ARS; cytokines and radiation injury; transplantation for ARS; acute radiation syndrome management; hematopoietic syndrome management ID COLONY-STIMULATING FACTOR; MEDICAL-MANAGEMENT; PROGENITOR CELLS; RHESUS-MONKEYS; RECOMMENDATIONS; ACCIDENT; MYELOSUPPRESSION; RADIOSENSITIVITY; TRANSPLANTATION; GROWTH AB Objective: Hematopoietic syndrome (HS) is a clinical diagnosis assigned to people who present with >1 new-onset cytopenias in the setting of acute radiation exposure. The World Health Organization convened a panel of experts to evaluate the evidence and develop recommendations for medical countermeasures for the management of HS in a hypothetical scenario involving the hospitalization of 100 to 200 individuals exposed to radiation. The objective of this consultancy was to develop recommendations for treatment of the HS based upon the quality of evidence. Methods: English-language articles were identified in MEDLINE and PubMed. Reference lists of retrieved articles were distributed to panel members before the meeting and updated during the meeting. Published case series and case reports of individuals with HS, published randomized controlled trials of relevant interventions used to treat nonirradiated individuals, reports of studies in irradiated animals, and prior recommendations of subject matter experts were selected. Studies were extracted using the Grading of Recommendations Assessment Development and Evaluation (GRADE) system. In cases in which data were limited or incomplete, a narrative review of the observations was made. No randomized controlled trials of medical countermeasures have been completed for individuals with radiation-associated HS. The use of GRADE analysis of countermeasures for injury to hematopoietic tissue was restricted by the lack of comparator groups in humans. Reliance on data generated in nonirradiated humans and experimental animals was necessary. Results: Based upon GRADE analysis and narrative review, a strong recommendation was made for the administration of granulocyte colony-stimulating factor or granulocyte macrophage colony-stimulating factor and a weak recommendation was made for the use of erythropoiesis-stimulating agents or hematopoietic stem cell transplantation. Conclusions: Assessment of therapeutic interventions for HS in humans exposed to nontherapeutic radiation is difficult because of the limits of the evidence. (Disaster Med Public Health Preparedness. 2011;5:202-212) C1 [Meineke, Viktor] Bundeswehr Inst Radiobiol, D-80937 Munich, Germany. [Dainiak, Nicholas] Yale Univ, Sch Med, New Haven, CT 06520 USA. [Dainiak, Nicholas] Yale New Haven Hlth Bridgeport Hosp, New Haven, CT USA. [Carr, Zhanat] World Hlth Org, Geneva, Switzerland. [Schneider, Rita] Univ Wurzburg, Dept Nucl Med, D-97070 Wurzburg, Germany. [Bader, Judith; Coleman, C. Norman] Natl Canc Inst, Bethesda, MD 20892 USA. [Chao, Nelson] Duke Univ, Durham, NC 27706 USA. [Ganser, Arnold] Hannover Med Sch, Dept Hematol Hemostasis Oncol & Stem Cell Transpl, Hannover, Germany. [Gorin, Claude] Hosp St Antoine, St Antoine, France. [Hauer-Jensen, Martin] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [Huff, L. Andrew; Lillis-Hearne, Patricia] Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. [Maekawa, Kazuhiko] Kanto Cent Hosp, Tokyo, Japan. [Nemhauser, Jeffrey] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Schuenemann, Holger] McMaster Univ, Hamilton, ON L8S 4L8, Canada. [Shapiro, Alla] US FDA, Rockville, MD 20857 USA. [Stenke, Leif] Karolinska Inst, S-10401 Stockholm, Sweden. [Weinstock, David] Dana Farber Canc Inst, Boston, MA 02115 USA. [White, Douglas] Univ Pittsburgh, Program Eth & Crit Care Med, Pittsburgh, PA 15260 USA. [Albanese, Joseph] Yale New Haven Hlth Ctr Emergency Preparedness &, New Haven, CT USA. RP Meineke, V (reprint author), Bundeswehr Inst Radiobiol, Neuherbergstr 11, D-80937 Munich, Germany. EM ViktorMeineke@bundeswehr.org FU National Institute of Allergy and Infectious Diseases FX Owing to their seminal contributions in the field of radiation biology and their pioneering approaches to treatment of victims of radiation injury, this consultancy report is dedicated to Theodor M. Fliedner and Angelina Guskova. The authors thank Makoto Akashi, Axel Bottger, Thierry de Revel, Patrick Gourmelon, Richard Hatchett, Mikhail Konchalovski, Ying Liu, Maria Julia Marinissen, Hilary Walker, Helmut Walerius, and Wei Zhang for participating in the consultancy and contributing to consensus building. The authors are grateful to the National Institute of Allergy and Infectious Diseases for providing financial support for this consultancy. NR 44 TC 32 Z9 34 U1 2 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD OCT PY 2011 VL 5 IS 3 BP 202 EP 212 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 839JU UT WOS:000296362300008 PM 21987000 ER PT J AU Junod, S AF Junod, Suzanne TI The Fertility Doctor: John Rock and the Reproductive Revolution SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 [Junod, Suzanne] US FDA, Hist Off, Silver Spring, MD 20993 USA. RP Junod, S (reprint author), US FDA, Hist Off, Bldg 32,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suzanne.junod@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD OCT PY 2011 VL 66 IS 4 BP 594 EP 597 DI 10.1093/jhmas/jrr045 PG 4 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 835US UT WOS:000296062100015 ER PT J AU Yanover, C Jain, N Pierce, G Howard, TE Sauna, ZE AF Yanover, Chen Jain, Nisha Pierce, Glenn Howard, Tom E. Sauna, Zuben E. TI Pharmacogenetics and the immunogenicity of protein therapeutics SO NATURE BIOTECHNOLOGY LA English DT Letter ID FACTOR-VIII; RISK-FACTORS; IMMUNE-RESPONSES; INHIBITORS; PREVENTION; HEMOPHILIA; PREDICTION C1 [Yanover, Chen] Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. [Jain, Nisha] US FDA, Clin Review Branch, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Pierce, Glenn] Biogen Idec Hemophilia, Waltham, MA USA. [Howard, Tom E.] Vet Affairs Greater Los Angeles Healthcare Syst, Dept Pathol & Lab Med, Los Angeles, CA USA. [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Yanover, C (reprint author), Fred Hutchinson Canc Res Ctr, Program Computat Biol, 1124 Columbia St, Seattle, WA 98104 USA. EM Zuben.Sauna@fda.hhs.gov RI Yanover, Chen/A-3754-2012 OI Yanover, Chen/0000-0003-3663-4286 NR 20 TC 13 Z9 13 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2011 VL 29 IS 10 BP 870 EP 873 DI 10.1038/nbt.2002 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 838FQ UT WOS:000296273000009 PM 21997623 ER PT J AU Myers, MJ AF Myers, Michael J. TI Molecular identification of animal species in food: Transition from research laboratories to the regulatory laboratories SO VETERINARY JOURNAL LA English DT Editorial Material ID PCR; FISH C1 US FDA, Ctr Vet Med, Div Appl Vet Res, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Div Appl Vet Res, Laurel, MD 20708 USA. EM Michael.myers@fda.hhs.gov NR 16 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1090-0233 J9 VET J JI Vet. J. PD OCT PY 2011 VL 190 IS 1 BP 7 EP 8 DI 10.1016/j.tvjl.2011.01.013 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 838CA UT WOS:000296263000003 PM 21333569 ER PT J AU He, Z Cui, L Patterson, TA Paule, MG AF He, Zhen Cui, Li Patterson, Tucker A. Paule, Merle G. TI Defining the Phosphodiesterase Superfamily Members in Rat Brain Microvessels SO ACS CHEMICAL NEUROSCIENCE LA English DT Article DE Brain microvessel; phosphodiesterase; microarrays; Immunofluorescent labeling; rat ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASES; ENDOTHELIAL-CELLS; GLOBAL-ISCHEMIA; CEREBRAL-ARTERY; NITRIC-OXIDE; 4D PDE4D; CAMP; PERMEABILITY; INHIBITORS; SILDENAFIL AB Eleven phosphodiesterase (PDE) families are known, each having several different isoforms and splice variants. Recent evidence indicates that expression of individual PDE family members is tissue-specific. Little is known concerning detailed PDE component expression in brain microvessels where the blood-brain-barrier and the local cerebral blood flow are thought to be regulated by PDEs. The present study attempted to identify PDE family members that are expressed in brain microvessels. Adult male F344 rats were sacrificed and blocks of the cerebral cortex and infratentorial areas were dissected. Microvessels were isolated using a filtration method, and total RNA was extracted. RNA quality and quantity were determined using an Agilent bioanalyzer. The isolated cortical and infratentorial microvessel total RNA amounts were 2720 +/- 750 ng (n = 2) and 250 40 ng (n = 2), respectively. Microarrays with 22 000 transcripts demonstrated that there were 16 PDE transcripts in the PDE superfamily,. exhibiting quantifiable density in the microvessels. An additional immunofluorescent study verified that PDE4D (cAMP-specific) and PDESA (cGMP-specific) were colocalized with RECA-1 (an endothelial marker) in the cerebral cortex using both F344 rats and Sprague Dawley rats (n = 3-6/strain). In addition, PDE4D and PDE5A were found to be colocalized with alpha-smooth muscle actin which delineates cerebral arteries and arterioles as well as pericytes. In conclusion, a filtration method followed by microarray analyses allows PDE components to be identified in brain microvessels, and confirmed that PDE4D and PDESA are the primary forms expressed in rat brain microvessels. C1 [He, Zhen; Patterson, Tucker A.; Paule, Merle G.] Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Jefferson, AR 72079 USA. [Cui, Li] Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. RP He, Z (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Off Room 53D-203N,HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM zhen.he@fda.hhs.gov FU NCTR [P00710] FX The present study was partially supported by NCTR under Protocol # P00710. NR 50 TC 7 Z9 7 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-7193 J9 ACS CHEM NEUROSCI JI ACS Chem. Neurosci. PD OCT PY 2011 VL 2 IS 10 BP 600 EP 607 DI 10.1021/cn2000487 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences & Neurology GA 837MQ UT WOS:000296208300007 PM 22860158 ER PT J AU Hammad, TA Pinheiro, SP Neyarapally, GA AF Hammad, Tarek A. Pinheiro, Simone P. Neyarapally, George A. TI Secondary use of randomized controlled trials to evaluate drug safety: a review of methodological considerations SO CLINICAL TRIALS LA English DT Review ID CLINICAL-TRIALS; SUBGROUP ANALYSIS; POSTMARKETING SURVEILLANCE; CUMULATIVE METAANALYSIS; MYOCARDIAL-INFARCTION; CARDIOVASCULAR EVENTS; PATIENT-LEVEL; DOUBLE-BLIND; RISK; QUALITY AB Background Randomized clinical trials (RCTs) are often positioned at the top of evidence hierarchies. Meta-analyses of RCTs aim to integrate the state of knowledge on a given scientific question, particularly for rare drug-related outcomes. However, although RCTs are valuable tools in our armamentarium, they are rarely designed to evaluate drug safety and are thus susceptible to limitations that may hamper the ability of both RCTs and meta-analyses to fully characterize the safety profiles of drugs. Their potential limitations might be exacerbated in the study of rare outcomes, often encountered in drug safety assessment, when even minor deviations from the intended randomization could impact the stability of the risk estimates. Purpose This article considers the methodological caveats of both RCTs and meta-analyses of RCTs pertinent to the study of drug-related harms. It is intended to stimulate discussion about the impact of these caveats on interpreting findings of RCTs and meta-analyses for drug safety, which would foster more robust, critical evaluations, and thus enhance clinical and regulatory decision-making. Methods Pertinent issues that can influence the interpretation of drug-related harms discussed in this article were based on authors' expertise and review of the literature. Results Investigators and clinicians should be cognizant of the potential limitations of the secondary use of RCTs and meta-analyses in the assessment of drug-related harms and, when applicable, should consider potential remedies to overcome these limitations. Limitations Only few practical examples are included in the article due to the fact that many of the discussed caveats are not examined and/or reported in many publications. In addition, the confidential nature of data reviewed at a regulatory agency forestalls an in depth discussion of examples pertaining to specific drugs. Furthermore, our ability to quantify the extent of encountering, or the actual impact of, the caveats addressed in this review on the RCTs findings is limited. It is worth noting that the mere encounter of a given caveat does not mean that it will obviate the utility of drug safety information from a given trial. The extent of its impact is expected to vary based on the specifics of the trial, the drugs studied, the indications, and the nature of the adverse events. Conclusions Although some of the limitations described are inherent in RCTs, some of the sources of bias highlighted in this article could be minimized by careful RCT design, planned follow-up, and improved collection of information on adverse events. As future research sheds more light on pertinent knowledge gaps and issues, the ability to maximize the use of RCTs and meta-analyses of RCTs to address drug safety questions of interest will be greatly enhanced. Clinical Trials 2011; 8: 559-570. http://ctj.sagepub.com C1 [Hammad, Tarek A.; Pinheiro, Simone P.; Neyarapally, George A.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hammad, TA (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 22,Room 24, Silver Spring, MD USA. EM tarek.hammad@fda.hhs.gov NR 91 TC 15 Z9 15 U1 0 U2 2 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 OCT PY 2011 VL 8 IS 5 BP 559 EP 570 DI 10.1177/1740774511419165 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 835FI UT WOS:000296020500002 PM 21878445 ER PT J AU Buckley, LA Chapman, K Burns-Naas, LA Todd, MD Martin, PL Lansita, JA AF Buckley, Lorrene A. Chapman, Kathryn Burns-Naas, Leigh Ann Todd, Marque D. Martin, Pauline L. Lansita, Janice A. TI Considerations Regarding Nonhuman Primate Use in Safety Assessment of Biopharmaceuticals SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE nonhuman primate; safety assessment; monoclonal antibodies; biopharmaceuticals ID MONOCLONAL-ANTIBODIES; TOXICITY; THERAPEUTICS; TOXICOLOGY; TRENDS AB Selection of a pharmacologically responsive species can represent a major challenge in designing nonclinical safety assessment programs for many biopharmaceuticals (eg, monoclonal antibodies (mAbs)). Frequently, the only relevant species for nonclinical testing of mAbs is the non-human primate (NHP). This situation, coupled with a rapidly increasing number of mAb drugs in development, has resulted in a significant increase in the number of NHPs used in nonclinical safety assessment. Apart from ethical considerations related to responsible animal use, there is a clear need for more efficient and innovative approaches to drug discovery and development; these factors drive the need to investigate alternative approaches and strategies for the safety assessment. This review summarizes important scientific and regulatory perspectives derived from presentations and audience discussions in an educational forum at the 2010 annual American College of Toxicology meeting regarding opportunities for employing alternative approaches to minimize NHP use in mAb drug development. C1 [Buckley, Lorrene A.] Eli Lilly & Co, Indianapolis, IN 46225 USA. [Chapman, Kathryn] Natl Ctr Replacement Refinement & Reduct Anim Res, London, England. [Burns-Naas, Leigh Ann; Todd, Marque D.] Pfizer Inc, La Jolla, CA USA. [Martin, Pauline L.] Centocor R&D, Radnor, PA USA. [Lansita, Janice A.] US FDA, Silver Spring, MD USA. RP Buckley, LA (reprint author), Eli Lilly & Co, Indianapolis, IN 46225 USA. EM buckleyla@lilly.com NR 30 TC 10 Z9 11 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD OCT PY 2011 VL 30 IS 5 BP 583 EP 590 DI 10.1177/1091581811415875 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 835GJ UT WOS:000296023600014 PM 22013138 ER PT J AU Kelman, A Soong, YA Dupuy, N Shafer, D Richbourg, W Johnson, K Brown, T Kestler, E Li, Y Zheng, J McDermott, P Meng, JH AF Kelman, Alina Soong, Yee-Ann Dupuy, Nicole Shafer, Daniel Richbourg, William Johnson, Kourtney Brown, Twain Kestler, Edward Li, Yi Zheng, Jie McDermott, Patrick Meng, Jianghong TI Antimicrobial Susceptibility of Staphylococcus aureus from Retail Ground Meats SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; ANIMAL ORIGIN; INFECTIONS; MRSA; RESISTANCE; EMERGENCE; PRODUCTS; DATABASE; STRAINS; HUMANS AB The aim of this study was to characterize antimicrobial resistance in Staphylococcus aureus, including methicillin-resistant S. ant-ens (MRSA), recovered from raw retail meat products purchased in the Washington, D.C., area. From March to August 2008, 694 samples of ground beef (n = 198), ground pork (n = 300), and ground turkey (a = 196) were collected by random sampling from stores of three grocery chains. In total, 200 S. aureus isolates (29%) were recovered by direct plating. When tested for susceptibility to 22 antimicrobials, 69% of the S. aureus isolates were resistant to tetracycline, 26% to penicillin, 17% to ampicillin, 13% to methicillin, 8% to erythromycin, 4.5% to clindamycin, 1.5% to gentamicin, and 0.5% to chloramphenicol, oxacillin, cefoxitin, or quinupristin-dalfopristin. However, 27% of the isolates were susceptible to all tested antimicrobials. More turkey and pork isolates were resistant to ampicillin, penicillin, and tetracycline than were beef isolates (P < 0.05). Additionally, 17% of the turkey and 17% of the pork isolates were resistant to methicillin (MIC >= 16 mu g/ml), whereas no beef isolates were resistant to the antimicrobial agent. A single MRSA (methicillin MIC > 32 mu g/ml) isolate containing the mecA gene with additional resistance to erythromycin, clindamycin, oxacillin plus 2% NaCl, cefoxitin, ampicillin, penicillin, quinupristin-dalfopristin, tetracycline, and gentamicin was recovered from one pork sample. The presence of antimicrobial-resistant S. amens, coupled with the relative lack of such studies in the United States, suggests that further investigations on MRSA in the food supply are needed despite the low rate of MRSA found in this particular study. C1 [Li, Yi; Zheng, Jie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Kelman, Alina; Soong, Yee-Ann; Dupuy, Nicole; Shafer, Daniel; Richbourg, William; Johnson, Kourtney; Brown, Twain; Kestler, Edward] Univ Maryland, Gemstone Program, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [McDermott, Patrick] US FDA, Ctr Vet Med, Laurel, MD 20780 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; FDA; University of Maryland FX We thank Sherry Ayers, Althea Glenn, and Dr. Shaohua Zhao at the FDA for technical training and advice. This work was supported in part by funding from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the FDA, and from the Gemstone Program of the University of Maryland. NR 31 TC 13 Z9 15 U1 1 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 J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2011 VL 74 IS 10 BP 1625 EP 1629 DI 10.4315/0362-028X.JFP-10-571 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 836AC UT WOS:000296077400007 PM 22004808 ER PT J AU Yang, BW Xi, ML Wang, X Cui, SH Yue, TL Hao, HS Wang, Y Cui, Y Alali, WQ Meng, JH Walls, I Wong, DML Doyle, MP AF Yang, Baowei Xi, Meili Wang, Xin Cui, Shenghui Yue, Tianli Hao, Hongshan Wang, Yin Cui, Yue Alali, W. Q. Meng, Jianghong Walls, Isabel Wong, D. M. Lo Fo Doyle, M. P. TI Prevalence of Salmonella on Raw Poultry at Retail Markets in China SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CHICKEN CARCASSES; PRODUCTS; CAMPYLOBACTER; MEAT; CONTAMINATION; OUTBREAKS; SURVIVAL; ETHIOPIA; SEROVARS; DENMARK AB Data regarding Salmonella on raw poultry are very limited in China. The objective of this study was to determine the prevalence of Salmonella on raw poultry at the retail level in six provinces and two national cities in China. Whole chicken carcasses (n = 1,152) were collected from three types of retail markets (large, small, and wet). All samples were analyzed for the presence of Salmonella by using the U.S. Department of Agriculture, Food Safety Inspection Service method. Of 1,152 chicken samples, overall Salmonella prevalence was 52.2%. The highest prevalence was observed in Guangxi Province (65.3%), next in Guangdong Province (64.6%), and then in Beijing (63.9%), Shaanxi Province (50.7%), Henan Province (47.9%), Shanghai (44.4%), and Fujian Province (42.4%), and lowest prevalence was observed in Sichuan Province (38.9%). Salmonella prevalence was significantly different among the six provinces and two national cities. Salmonella prevalence was highest in the wet markets (54.4%) compared with the large markets (50.3%) and the small markets (52.1%), but differences were not significant (P > 0.05). Good manufacturing practices, good agricultural practices, and hazard analysis critical control point systems for Salmonella control in poultry production at the farm, processing, and retail level should be implemented. C1 [Alali, W. Q.; Doyle, M. P.] Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. [Yang, Baowei; Xi, Meili; Wang, Xin; Yue, Tianli; Hao, Hongshan; Wang, Yin; Cui, Yue; Meng, Jianghong] NW A&F Univ, Coll Food Sci, Yangling 712100, Peoples R China. [Cui, Shenghui] State Food & Drug Adm, Beijing 100050, 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. [Walls, Isabel] Natl Inst Food & Agr, USDA, Washington, DC 20250 USA. [Wong, D. M. Lo Fo] WHO, CH-1211 Geneva 27, Switzerland. RP Alali, WQ (reprint author), Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. EM walali@uga.edu OI Walls, Isabel/0000-0002-9643-8845 FU University of Georgia; NWAFU; WHO Global Foodborne Infections Network FX The research work was supported by the project "Data Collection for Salmonella in Raw Poultry in China" of the University of Georgia and NWAFU, in collaboration with the WHO Global Foodborne Infections Network. We thank Dr. Shuangkui Du at NWAFU for data analysis. NR 30 TC 33 Z9 37 U1 1 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 J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2011 VL 74 IS 10 BP 1724 EP 1728 DI 10.4315/0362-028X.JFP-11-215 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 836AC UT WOS:000296077400020 PM 22004821 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Pharmacokinetic Allometric Scaling of Oligonucleotides SO NUCLEIC ACID THERAPEUTICS LA English DT Article ID HUMAN DRUG CLEARANCE; OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATE GEM-91; MODIFIED ANTISENSE OLIGONUCLEOTIDE; NECROSIS-FACTOR-ALPHA; PHASE-I TRIAL; INTRAVENOUS-INFUSION; PREDICTION; HUMANS; BCL-2; METABOLISM AB The objective of this study was to evaluate the predictive performance of interspecies scaling of oligonucleotides to predict clearance and volume of distribution at steady state in humans from animal data. The human pharmacokinetic parameters were predicted using 1, 2, or at least 3 animal species. The results of the study indicated that the pharmacokinetic parameters of oligonucleotides can be predicted with reasonable accuracy in humans when at least 3 animal species are employed. On the other hand, allometric scaling based on 1 or 2 species or fixed coefficient or fixed exponent can be erratic and unreliable. Further work should be conducted in this direction. C1 [Mahmood, Iftekhar] US FDA, Off Blood Review & Res OBRR, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res OBRR, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 30 TC 3 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 2159-3337 J9 NUCLEIC ACID THER JI Nucl. Acid Ther. PD OCT PY 2011 VL 21 IS 5 BP 315 EP 321 DI 10.1089/nat.2011.0299 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Research & Experimental Medicine GA 837UZ UT WOS:000296231700132 PM 21916609 ER PT J AU Tock, CL Turner, LR Altiner, A Batra, P Booher, SL Coelho, SG Warner, JA Therrien, JP Turner, ML Miller, SA Beer, JZ Kraemer, KH Udey, MC Vogel, JC Terunuma, A AF Tock, Christine L. Turner, Lexa R. Altiner, Ahmet Batra, Priya Booher, Susan L. Coelho, Sergio G. Warner, Jennifer A. Therrien, Jean-Philippe Turner, Maria L. Miller, Sharon A. Beer, Janusz Z. Kraemer, Kenneth H. Udey, Mark C. Vogel, Jonathan C. Terunuma, Atsushi TI Transcriptional signatures of full-spectrum and non-UVB-spectrum solar irradiation in human skin SO PIGMENT CELL & MELANOMA RESEARCH LA English DT Letter ID SUNSCREENS; PROTECTION C1 [Tock, Christine L.; Turner, Lexa R.; Altiner, Ahmet; Batra, Priya; Booher, Susan L.; Warner, Jennifer A.; Therrien, Jean-Philippe; Turner, Maria L.; Kraemer, Kenneth H.; Udey, Mark C.; Vogel, Jonathan C.; Terunuma, Atsushi] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Coelho, Sergio G.; Miller, Sharon A.; Beer, Janusz Z.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Terunuma, A (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, Bldg 10, Bethesda, MD 20892 USA. EM atsushi@mail.nih.gov FU Intramural NIH HHS [ZIA BC004517-35] NR 5 TC 2 Z9 2 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1755-1471 J9 PIGM CELL MELANOMA R JI Pigment Cell Melanoma Res. PD OCT PY 2011 VL 24 IS 5 BP 972 EP 974 DI 10.1111/j.1755-148X.2011.00899.x PG 3 WC Oncology; Cell Biology; Dermatology SC Oncology; Cell Biology; Dermatology GA 835SZ UT WOS:000296057600013 PM 21848663 ER PT J AU Drossman, DA Chang, L Bellamy, N Gallo-Torres, HE Lembo, A Mearin, F Norton, NJ Whorwell, P AF Drossman, Douglas A. Chang, L. Bellamy, N. Gallo-Torres, H. E. Lembo, A. Mearin, F. Norton, N. J. Whorwell, P. TI Severity in Irritable Bowel Syndrome: A Rome Foundation Working Team Report SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID QUALITY-OF-LIFE; ILLNESS SEVERITY; CONTROLLED-TRIAL; HEALTH-STATUS; GASTROINTESTINAL DISORDERS; ABDOMINAL-PAIN; PRIMARY-CARE; IBS PATIENTS; SYMPTOMS; HYPNOTHERAPY AB OBJECTIVES: The concept of severity in irritable bowel syndrome (IBS) is clinically recognized and operative in diagnostic decision making and treatment planning. Yet, there is no consensus on its definition, and there are limited data on the prevalence of severity subgroups, its medical and psychosocial determinants, and its association with other health status measures. The aims of the Rome Foundation Working Team Committee were to summarize current research, to develop a consensus of understanding on this concept, and to make recommendations for its use in research and clinical care. METHODS: In 2006, a multinational committee of clinical investigators with expertise in IBS and/or psychometric research methods undertook a systematic review of the literature relating to severity in IBS. Owing to limited data, the Foundation commissioned three clinical studies to better characterize the concept of severity in IBS, and summary information and recommendations for future research and clinical care were developed. RESULTS: The main findings were: (i) severity in IBS is defined as a biopsychosocial composite of patient-reported gastrointestinal and extraintestinal symptoms, degree of disability, and illness-related perceptions and behaviors; (ii) both visceral and central nervous system physiological factors affect severity; as severity increases, the central nervous system provides a greater contribution; (iii) severity is related to and influences health-related quality of life and health behaviors and also guides diagnostic and therapeutic clinical decision making; (iv) severity can be subcategorized into clinically meaningful subgroups as mild (similar to 40 %), moderate (similar to 35 %), and severe (similar to 25 %), and this provides a working model for use in future research and clinical care. CONCLUSIONS: Future work is required to understand more precisely the factors contributing to severity and to develop a valid patient-reported instrument to measure severity in IBS. C1 [Drossman, Douglas A.] UNC Ctr Funct GI & Motil Disorders, Chapel Hill, NC 27599 USA. [Chang, L.] UCLA Ctr Neurobiol Stress, Los Angeles, CA USA. [Bellamy, N.] Univ Queensland, Ctr Natl Res Disabil & Rehabil Med, Brisbane, Qld, Australia. [Gallo-Torres, H. E.] US FDA, Div Gastrointestinal & Coagulat Drug Prod, Bethesda, MD 20014 USA. [Lembo, A.] Harvard Univ, Beth Israel Deaconess Med Ctr, Cambridge, MA 02138 USA. [Mearin, F.] Ctr Med Teknon, Inst Funct & Motor Digest Disorders, Barcelona, Spain. [Norton, N. J.] Int Fdn Funct Gastrointestinal Disorders, Milwaukee, WI USA. [Whorwell, P.] Univ Manchester, Wythenshawe Hosp, Dept Gastroenterol, Manchester, Lancs, England. RP Drossman, DA (reprint author), UNC Ctr Funct GI & Motil Disorders, Bioinformat Bldg,CB 7080, Chapel Hill, NC 27599 USA. EM drossman@med.unc.edu FU Astra Zeneca; Ironwood; Takeda Pharmaceuticals; Rose Pharma; Shire; Novartis Pharma; GSK; Rotta Research; Procter Gamble; Danone Research; Astellas Pharma; Ironwood Pharmaceuticals; Sucampo Pharmaceuticals; Movetis UK; Almirall FX Drossman receives grant support from Astra Zeneca, Ironwood, and Takeda Pharmaceuticals and has served as a consultant for Astra Zeneca, Ironwood, Lexicon, Prometheus, Sucampo, and Takeda Pharmaceuticals. Chang receives grant support from Rose Pharma, Shire, and Takeda Pharmaceuticals and has served as a consultant for GlaxoSmithKline, Ironwood, Forest, Movetis/Shire, Novo Nordisk, Salix, Takeda Pharmaceuticals, Ocera, Movetis, and Prometheus. Lembo has served as a consultant for Astra Zeneca, GSK, Ironwood, Prometheus, and Salix, Pharmaceuticals and Aryx therapeutics. Mearin has served as a consultant for Almirall, Astra Zeneca, Menarin, and Solvay Pharmaceuticals. Ms Norton has served as a consultant for Degge Group Ltd and American Medical Systems. Whorwell is an advisory board member or has received research funding from Novartis Pharma, GSK, Rotta Research, Procter & Gamble, Danone Research, Astellas Pharma, Ironwood Pharmaceuticals, Sucampo Pharmaceuticals, Movetis UK, Almirall. NR 41 TC 56 Z9 62 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2011 VL 106 IS 10 BP 1749 EP 1759 DI 10.1038/ajg.2011.201 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 834AB UT WOS:000295926600003 PM 21747417 ER PT J AU Puig, M Tosh, KW Schramm, LM Grajkowska, LT Kirschman, KD Tami, C Beren, J Rabin, RL Verthelyi, D AF Puig, Montserrat Tosh, Kevin W. Schramm, Lynnsie M. Grajkowska, Lucja T. Kirschman, Kevin D. Tami, Cecilia Beren, Joel Rabin, Ronald L. Verthelyi, Daniela TI TLR9 and TLR7 mediate distinct type I IFN responses in humans and non-human primates SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Puig, Montserrat; Tosh, Kevin W.; Grajkowska, Lucja T.; Tami, Cecilia; Verthelyi, Daniela] Ctr Drug Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. [Schramm, Lynnsie M.; Kirschman, Kevin D.; Rabin, Ronald L.] Lab Bacterial Parasite & Allergen Prod, Bethesda, MD 20892 USA. [Beren, Joel] US FDA, Ctr Biol Evaluat & Res, Div Vet Sci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 9 EP 9 DI 10.1016/j.cyto.2011.07.319 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800023 ER PT J AU Verthelyi, D Pedras-Vasconcelos, J Butts, C Jones, Y Puig, M Wang, V Trinchieri, G Tami, C AF Verthelyi, Daniela Pedras-Vasconcelos, Joao Butts, Cherie Jones, Yava Puig, Montserrat Wang, Vivian Trinchieri, Giorgio Tami, Cecilia TI Innate immune response modulators control inflammation and improve survival in viral encephalitis SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Verthelyi, Daniela; Pedras-Vasconcelos, Joao; Butts, Cherie; Puig, Montserrat; Wang, Vivian; Tami, Cecilia] FDA, Div Therapeut Prot, Off Biotechnol, CDER, Jefferson, AR USA. [Verthelyi, Daniela; Jones, Yava; Trinchieri, Giorgio] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 11 EP 11 DI 10.1016/j.cyto.2011.07.329 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800030 ER PT J AU Zoon, KC Nakashima, H Miyake, K Clark, C Bekisz, J Baron, S Husain, SR Puri, RK AF Zoon, Kathryn C. Nakashima, Hideyuki Miyake, Kotaro Clark, Christopher Bekisz, Joseph Baron, Samuel Husain, Syed R. Puri, Raj K. TI Combination therapy with IFN-alpha plus IFN-gamma and monocytes mediates synergistic antitumor effects against established human ovarian and melanoma tumors in mouse models SO CYTOKINE LA English DT Meeting Abstract CT 9th Joint Meeting of the International-Cytokine-Society/International-Society-for-Interferon-and- Cytokine-Research CY OCT 09-12, 2011 CL Florence, ITALY SP Int Cytokine Soc, Int Society Interferon & Cytokine Res C1 [Zoon, Kathryn C.; Nakashima, Hideyuki; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Zoon, Kathryn C.; Miyake, Kotaro; Clark, Christopher; Bekisz, Joseph; Baron, Samuel] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 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 1043-4666 J9 CYTOKINE JI Cytokine PD OCT PY 2011 VL 56 IS 1 SI SI BP 102 EP 102 DI 10.1016/j.cyto.2011.07.397 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 827OM UT WOS:000295437800347 ER PT J AU Kachko, A Zubkova, I Kochneva, G Wells, F Frey, SE Major, ME AF Kachko, Alla Zubkova, Iryna Kochneva, Galina Wells, Frances Frey, Sharon E. Major, Marian E. TI ANTIBODIES TO A PUTATIVE FUSION LOOP IN HEPATITIS C VIRUS E2 ARE CROSS NEUTRALIZING AND PREFERENTIALLY INDUCED BY RECOMBINANT PROTEINS AND SYNTHETIC PEPTIDES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Kachko, Alla; Zubkova, Iryna; Wells, Frances; Major, Marian E.] CBER FDA, LHV, Bethesda, MD USA. [Kochneva, Galina] SRC Vector, Lab Viral Hepatitis, Koltsov, Russia. [Frey, Sharon E.] St Louis Univ, Sch Med, Div Infect Dis & Immunol, St Louis, MO USA. RI Kochneva, Galina/B-7356-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 379A EP 379A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002037 ER PT J AU Shin, EC Park, SH Nascimbeni, M Major, ME Rice, CM Rehermann, B AF Shin, Eui-Cheol Park, Su-Hyung Nascimbeni, Michelina Major, Marian E. Rice, Charles M. Rehermann, Barbara TI THE PERCENTAGE OF HEPATITIS C VIRUS-SPECIFIC CD127+MEMORY T CELLS IN THE ACUTE PHASE T CELL RESPONSE PREDICTS THE OUTCOME OF HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Shin, Eui-Cheol; Park, Su-Hyung; Nascimbeni, Michelina; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD USA. [Shin, Eui-Cheol] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Major, Marian E.] US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 380A EP 380A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002040 ER PT J AU Vega, M Vuppalanchi, R Bonkovsky, HL Reddy, KR Talwalkar, JA Seeff, LB Serrano, J Navarro, VJ AF Vega, Maricruz Vuppalanchi, Raj Bonkovsky, Herbert L. Reddy, K. Rajender Talwalkar, Jayant A. Seeff, Leonard B. Serrano, Jose Navarro, Victor J. TI THE US DRUG INDUCED LIVER INJURY NETWORK: ESTABLISHMENT OF AN HERBAL AND DIETARY SUPPLEMENT (HDS) REPOSITORY SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Vega, Maricruz; Navarro, Victor J.] Thomas Jefferson Univ, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. [Vuppalanchi, Raj] Indiana Univ, Indianapolis, IN 46204 USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Reddy, K. Rajender] Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. [Talwalkar, Jayant A.] Mayo Clin, Rochester, MN USA. [Seeff, Leonard B.] US FDA, Bethesda, MD 20014 USA. [Serrano, Jose] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 528A EP 529A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578002341 ER PT J AU Liu, J Jadhav, PR Amur, S Fleischer, RD Hammerstrom, T Lewis, LL 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 D. Hammerstrom, Thomas Lewis, Linda L. Naeger, Lisa O'Rear, Jules Pacanowski, Michael Robertson, Sarah Seo, Shirley Soon, Greg Birnkrant, Debra TI RESPONSE GUIDED TELAPREVIR THERAPY IN PRIOR RELAPSERS?: THE ROLE OF BRIDGING DATA FROM PREVIOUSLY TREATED AND UNTREATED SUBJECTS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Jiang; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Amur, Shashi; Pacanowski, Michael; Robertson, Sarah; Seo, Shirley] US FDA, Div Clin Pharmacol, Silver Spring, MD USA. [Fleischer, Russell D.; Lewis, Linda L.; Naeger, Lisa; O'Rear, Jules; Birnkrant, Debra] US FDA, Div Antiviral Drug Prod, Silver Spring, MD USA. [Hammerstrom, Thomas; Soon, Greg] US FDA, Div Biometr 4, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 797A EP 798A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003160 ER PT J AU Florian, JA 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 A. 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 REGIMENS FOR LATE RESPONDERS AND NULL RESPONDERS: THE ROLE OF BRIDGING DATA BETWEEN PREVIOUSLY TREATED AND UNTREATED SUBJECTS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Florian, Jeffry A.; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Amur, Shashi; Ayala, Ruben; Pacanowski, Michael; 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 Drug Prod, Silver Spring, MD USA. [Soon, Greg; Zeng, Wen] US FDA, Div Biometr, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 819A EP 820A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003201 ER PT J AU Liu, J Florian, JA Birnkrant, D Murray, J Jadhav, PR AF Liu, Jiang Florian, Jeffry A. Birnkrant, Debra Murray, Jeffrey Jadhav, Pravin R. TI INTERFERON RESPONSIVENESS DOES NOT CHANGE IN PREVIOUSLY TREATED SUBJECTS: IMPLICATIONS FOR DRUG DEVELOPMENT AND CLINICAL DECISIONS SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Liu, Jiang; Florian, Jeffry A.; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Birnkrant, Debra; Murray, Jeffrey] US FDA, Div Antiviral Drug Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 834A EP 834A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003229 ER PT J AU Hsu, CS Liu, CH Chen, HC Hsu, SJ Chen, DS Kao, JH AF Hsu, Ching-Sheng Liu, Chen-Hua Chen, Hung-Chia Hsu, Shih-Jer Chen, Ding-Shinn Kao, Jia-Horng TI ASSOCIATION OF IL28B GENOTYPES WITH SERUM LIPID PROFILES AND EARLY VIRAL KINETICS IN CHRONIC HEPATITIS C PATIENTS TREATED WITH PEGYLATED INTERFERON PLUS RIBAVIRIN SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Hsu, Ching-Sheng] Buddhist Tzu Chi Gen Hosp, Taipei, Taiwan. [Hsu, Ching-Sheng; Liu, Chen-Hua; Hsu, Shih-Jer; Chen, Ding-Shinn; Kao, Jia-Horng] Natl Taiwan Univ Hosp, Taipei, Taiwan. [Chen, Hung-Chia] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 835A EP 835A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578003231 ER PT J AU Florian, J Chen, JM Jadhav, PR Murray, J Birnkrant, D AF Florian, Jeffry Chen, Jianmeng Jadhav, Pravin R. Murray, Jeffrey Birnkrant, Debra TI CONSIDERATION OF NEW ENDPOINTS FOR REGULATORY APPROVAL AND DOSE SELECTION OF HEPATITIS C THERAPIES SO HEPATOLOGY LA English DT Meeting Abstract CT 62nd Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases (AASLD) CY NOV 04-08, 2011 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 [Florian, Jeffry; Chen, Jianmeng; Jadhav, Pravin R.] US FDA, Div Pharmacometr, Silver Spring, MD USA. [Murray, Jeffrey; Birnkrant, Debra] US FDA, Div Antiviral Drug Prod, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2011 VL 54 SU 1 BP 1444A EP 1444A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 829KG UT WOS:000295578004760 ER PT J AU Abrams, JY Schonberger, LB Belay, ED Maddox, RA Leschek, EW Mills, JL Wysowski, DK Fradkin, JE AF Abrams, Joseph Y. Schonberger, Lawrence B. Belay, Ermias D. Maddox, Ryan A. Leschek, Ellen W. Mills, James L. Wysowski, Diane K. Fradkin, Judith E. TI Lower Risk of Creutzfeldt-Jakob Disease in Pituitary Growth Hormone Recipients Initiating Treatment after 1977 SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID UNITED-STATES; CONTAMINATION; THERAPY; TIME AB Context: Creutzfeldt-Jakob disease (CJD) caused by contaminated cadaveric pituitary-derived human GH (hGH) has been responsible for hundreds of deaths worldwide. Studies of U. S. National Hormone and Pituitary Program (NHPP) hGH recipients have found CJD only in patients treated before 1977, when a new purification procedure with column chromatography was implemented for hGH extraction. Objective: Our objective was to provide updated information on transmission of CJD to NHPP hGH recipients and determine whether recipients of hGH produced after 1977 had a significantly lower CJD risk than pre-1977 recipients. Patients: A total of 5570 NHPP hGH recipients were included in the study: 2099 in the pre-1977 cohort and 3471 in the post-1977 cohort. Main Outcome Measure: We used probability distribution functions to determine whether the observed number of CJD cases in the post-1977 cohort was significantly fewer than expected if the CJD risk was equal to that of the pre-1977 cohort, controlling for treatment duration and follow-up time. Results: All 22 CJD cases (diagnosed from 1984-2009) occurred in the pre-1977 hGH recipients. Almost half (47.9%) of pre-1977 recipients had a treatment duration of at least 5 yr compared with only 13.8% for post-1977 recipients. Based on the rates present in the pre-1977 cohort, the probability of observing no cases in the post-1977 cohort by chance alone was low (P = 0.0019). Conclusions: Risk of acquiring CJD was significantly lower for post-1977 NHPP hGH recipients than for pre-1977 recipients, suggesting that the new purification procedure in 1977 may have greatly reduced or eliminated CJD agent in hGH. (J Clin Endocrinol Metab 96: E1666-E1669, 2011) C1 [Abrams, Joseph Y.; Schonberger, Lawrence B.; Belay, Ermias D.; Maddox, Ryan A.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Leschek, Ellen W.; Fradkin, Judith E.] NIDDK, Bethesda, MD 20817 USA. [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Wysowski, Diane K.] US FDA, Silver Spring, MD 20993 USA. RP Abrams, JY (reprint author), Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd NE,CDC Mailstop A30, Atlanta, GA 30333 USA. EM JAbrams@cdc.gov RI Belay, Ermias/A-8829-2013 NR 12 TC 5 Z9 5 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 2011 VL 96 IS 10 BP E1666 EP E1669 DI 10.1210/jc.2011-1357 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 833JC UT WOS:000295879600016 PM 21816775 ER PT J AU Ali, MM Amialchuk, A Dwyer, DS AF Ali, Mir M. Amialchuk, Aliaksandr Dwyer, Debra S. TI Social Network Effects in Contraceptive Behavior Among Adolescents SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE adolescent contraception use; peer measurements; peer influence ID UNINTENDED PREGNANCY; ALCOHOL-CONSUMPTION; SEXUAL-ACTIVITY; UNITED-STATES; ATTITUDES; INTERCOURSE AB Objective: To quantify empirically the role of peer social networks in contraceptive behavior among adolescents. Method: Using longitudinal data from a nationally representative sample of adolescents, the authors use a multivariate structural model with school-level fixed effects to account for the problems of contextual effects, correlated effects, and peer selection to reduce the potential impact of biases from the estimates of peer influence. The peer group measures are drawn not only from the nominations of close friends but also from classmates. Contraception use among the peer groups was constructed using the peers' own reports of their contraceptive behavior. Results: Controlling for parental characteristics and other demographic variables, the authors find that a 10% increase in the proportion of classmates who use contraception increases the likelihood of individual contraception use by approximately 5%. They also find evidence that the influence of close friends diminishes after accounting for unobserved environmental confounders. Conclusion: The findings of this study support the findings in the literature that peer effects are important determinants of contraception use even after controlling for potential biases in the data. Effective policy aimed at increasing contraception use among adolescents should consider these peer effects. C1 [Ali, Mir M.; Amialchuk, Aliaksandr] Univ Toledo, Dept Econ, Toledo, OH 43606 USA. [Dwyer, Debra S.] SUNY Stony Brook, Sch Hlth Technol & Management, Stony Brook, NY 11794 USA. [Dwyer, Debra S.] SUNY Stony Brook, Dept Econ, Stony Brook, NY 11794 USA. RP Ali, MM (reprint author), US FDA, Off Regulat Policy & Social Sci, College Pk, MD 20740 USA. EM mir.ali@fda.hhs.gov FU National Institute of Child Health and Human Development [P01-HD31921] FX This research uses data from Add Health, a program project designed by J. Richard Udry, Peter S. Bearman and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add Health, Carolina Population Center, 123 W. Franklin Street, Chapel Hill, NC 27516-2524 (addhealth@unc.edu). NR 34 TC 8 Z9 8 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 2011 VL 32 IS 8 BP 563 EP 571 DI 10.1097/DBP.0b013e318231cf03 PG 9 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 832TF UT WOS:000295830000001 PM 21918469 ER PT J AU Freed, M de Zwart, JA Hariharan, P Myers, MR Badano, A AF Freed, Melanie de Zwart, Jacco A. Hariharan, Prasanna Myers, Matthew R. Badano, Aldo TI Development and characterization of a dynamic lesion phantom for the quantitative evaluation of dynamic contrast-enhanced MRI SO MEDICAL PHYSICS LA English DT Article DE dynamic phantom; DCE-MRI; breast imaging ID SPOILED GRADIENT-ECHO; MYOCARDIAL-PERFUSION; DIAGNOSTIC-ACCURACY; BREAST MRI; PARAMETERS; SEQUENCES; RESONANCE; DTPA; STANDARDIZATION; QUANTIFICATION AB Purpose: To develop a dynamic lesion phantom that is capable of producing physiological kinetic curves representative of those seen in human dynamic contrast-enhanced MRI (DCE-MRI) data. The objective of this phantom is to provide a platform for the quantitative comparison of DCE-MRI protocols to aid in the standardization and optimization of breast DCE-MRI. Methods: The dynamic lesion consists of a hollow, plastic mold with inlet and outlet tubes to allow flow of a contrast agent solution through the lesion over time. Border shape of the lesion can be controlled using the lesion mold production method. The configuration of the inlet and outlet tubes was determined using fluid transfer simulations. The total fluid flow rate was determined using x-ray images of the lesion for four different flow rates (0.25, 0.5, 1.0, and 1.5 ml/s) to evaluate the resultant kinetic curve shape and homogeneity of the contrast agent distribution in the dynamic lesion. High spatial and temporal resolution x-ray measurements were used to estimate the true kinetic curve behavior in the dynamic lesion for benign and malignant example curves. DCE-MRI example data were acquired of the dynamic phantom using a clinical protocol. Results: The optimal inlet and outlet tube configuration for the lesion molds was two inlet molds separated by 30 degrees and a single outlet tube directly between the two inlet tubes. X-ray measurements indicated that 1.0 ml/s was an appropriate total fluid flow rate and provided truth for comparison with MRI data of kinetic curves representative of benign and malignant lesions. DCE-MRI data demonstrated the ability of the phantom to produce realistic kinetic curves. Conclusions: The authors have constructed a dynamic lesion phantom, demonstrated its ability to produce physiological kinetic curves, and provided estimations of its true kinetic curve behavior. This lesion phantom provides a tool for the quantitative evaluation of DCE-MRI protocols, which may lead to improved discrimination of breast cancer lesions. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3633911] C1 [Freed, Melanie; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [de Zwart, Jacco A.] Natl Inst Neurol Disorders & Stroke, Lab Funct & Mol Imaging, Adv MRI Sect, NIH, Bethesda, MD 20892 USA. [Hariharan, Prasanna; Myers, Matthew R.] US FDA, Div Solid & Fluid Mech, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Freed, M (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU FDA's Office of Women Health; Center for Devices and Radiological Health; NINDS/NIH FX The authors wish to thank Han Wen (NIH/NHLBI) for providing MRI scan time, Hellmut Merkle (NIH/NINDS) for providing noise reduction filters for the fluid pump, Eugene O'Bryan (FDA) for help with setting up the timing circuit and his tireless material acquisition efforts, and Randy Bidinger (FDA) and Bruce Fleharty (FDA) for machining of a variety of experimental components. The authors also acknowledge funding from the FDA's Office of Women Health. This project was supported in part by an appointment to the Research Participation Program at the Center for Devices and Radiological Health 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 was sponsored, in part, by the Intramural Research Program of NINDS/NIH. NR 33 TC 8 Z9 8 U1 0 U2 5 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 OCT PY 2011 VL 38 IS 10 BP 5601 EP 5611 DI 10.1118/1.3633911 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 829WU UT WOS:000295617400035 PM 21992378 ER PT J AU Popescu, LM AF Popescu, Lucretiu M. TI Nonparametric signal detectability evaluation using an exponential transformation of the FROC curve SO MEDICAL PHYSICS LA English DT Article DE medical image processing; nonparametric statistics; phantoms; sensitivity analysis ID FREE-RESPONSE; OBSERVER-PERFORMANCE; MODEL; LOCALIZATION; ROC; SYSTEMS; IMAGES; METHODOLOGY; MAMMOGRAPHY; ACCURACY AB Purpose: To develop an efficient nonparametric method for evaluation the detectability of signals at unknown locations in images, as a mean for image quality assessment. Methods: We use the free-response methodology that allows the image observer to mark and score all locations found as suspicious in an image, summarizing these results in a free-response operating characteristic (FROC) curve. However, unlike the relative (or receiver) operating characteristic (ROC), or the localization ROC (LROC), the FROC curve has an undefined, theoretically infinite, right side limit. Therefore area under the FROC curves cannot be directly used as an overall performance index, as the area under the curve is for ROC or LROC. We circumvent this drawback by using a transformation of the abscissa that leads to a finite integration range. By applying an exponential transformation we derive a nonparametric estimator for such a metric, and we study its properties by deriving analytical expressions for the mean and standard deviation in conditions of scores independence. Results: A comparative study with other related nonparametric estimators for ROC, LROC, and alternative FROC (AFROC) method is presented. Conclusions: The new nonparametric estimator has sensitivity and scalability properties that make it particularly advantageous for signal detectability evaluation in phantom experiments using model observers. (C) American Association of Physicists in Medicine. [DOI: 10.1118/1.3633938] C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Popescu, LM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM lucretiu.popescu@fda.hhs.gov NR 35 TC 13 Z9 13 U1 0 U2 6 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 OCT PY 2011 VL 38 IS 10 BP 5690 EP 5702 DI 10.1118/1.3633938 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 829WU UT WOS:000295617400041 PM 21992384 ER PT J AU Wang, HG Word, BR Lyn-Cook, BD AF Wang, Honggang Word, Beverly R. Lyn-Cook, Beverly D. TI Enhanced Efficacy of Gemcitabine by Indole-3-carbinol in Pancreatic Cell Lines: The Role of Human Equilibrative Nucleoside Transporter 1 SO ANTICANCER RESEARCH LA English DT Article DE hENT1; gemcitabine; cytotoxicity; I3C; pancreatic cancer ID GROWTH-FACTOR RECEPTOR; CHRONIC LYMPHOCYTIC-LEUKEMIA; TO-MESENCHYMAL TRANSITION; CANCER-CELLS; COMPARING GEMCITABINE; TRANSCRIPTION FACTOR; CARCINOMA-CELLS; DOWN-REGULATION; LUNG-CANCER; PHASE-III AB Pancreatic cancer patients treated with gemcitabine (2',2'-difluorodeoxycytidine) can eventually develop resistance. Recently, published data from our laboratory demonstrated enhanced efficacy of gemcitabine with the dietary agent, indole-3-carbinol (I3C). The current study examined the possible mechanism for this I3C-enhanced efficacy. Several pancreatic cell lines (BxPC-3, Mia Paca-2, PL-45, AsPC-1 and PANC-1) were examined for modulation of human equilibrative nucleoside transporter 1 (hENT1) expression, the major transporter for gemcitabine, by I3C alone and combined with gemcitabine. I3C significantly (p<0.01) up-regulated hENT1 expression in several cell lines. Gemcitabine alone showed no effect on hENT1 expression. However, combining gemcitabine with I3C further increased hENT1 expression. Cell viability assays revealed no effect of I3C on normal cells, hTERT-HPNE. hENT1-specific inhibitor, nitrobenzylthioinosine, significantly abrogated I3C-induced gemcitabine cytotoxicity, further demonstrating its specificity. This study demonstrates that upregulation of hENT1 expression may be a novel mechanism involved in the additive effect of I3C and gemcitabine. C1 [Lyn-Cook, Beverly D.] US FDA, Off Regulatory Act, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Lyn-Cook, BD (reprint author), US FDA, Off Regulatory Act, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM beverly.lyn-cook@fda.hhs.gov NR 50 TC 6 Z9 6 U1 0 U2 4 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD OCT PY 2011 VL 31 IS 10 BP 3171 EP 3180 PG 10 WC Oncology SC Oncology GA 830PA UT WOS:000295667700009 PM 21965724 ER PT J AU Young, FE AF Young, Frank E. TI Assessing the Impact of Biotech Regulation SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Article C1 [Young, Frank E.] US FDA, Rockville, MD 20857 USA. EM frankcosmos@aol.com 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 1935-472X J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD OCT 1 PY 2011 VL 31 IS 17 BP 27 EP 29 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 831BO UT WOS:000295703900007 ER PT J AU Trehy, ML Brown, DJ Woodruff, JT Westenberger, BJ Nychis, WG Reuter, N Schier, JG Vagi, SJ Hwang, RJ AF Trehy, Michael L. Brown, Daniel J. Woodruff, Jeffrey T. Westenberger, Benjamin J. Nychis, William G. Reuter, Nicholas Schier, Joshua G. Vagi, Sara J. Hwang, Rong-Jen TI Determination of Levamisole in Urine by Gas Chromatography-Mass Spectrometry SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID CHIRAL STATIONARY PHASES; COCAINE; AGRANULOCYTOSIS; PLASMA C1 [Trehy, Michael L.; Woodruff, Jeffrey T.; Westenberger, Benjamin J.] US FDA, CDER, DPA, St Louis, MO 63101 USA. [Brown, Daniel J.] US FDA, ORA, Reg Field Off, Detroit, MI 48207 USA. [Nychis, William G.] US FDA, CDER, Off Compliance, Silver Spring, MD 20993 USA. [Reuter, Nicholas] US PHS, SAMHSA, Rockville, MD 20857 USA. [Schier, Joshua G.; Vagi, Sara J.] CDC, NCEH, EHHE, HSB MS F57, Atlanta, GA 30341 USA. [Hwang, Rong-Jen] New Mexico DH, Albuquerque, NM 87196 USA. RP Trehy, ML (reprint author), US FDA, CDER, DPA, 1114 Market St, St Louis, MO 63101 USA. RI Schier, Joshua/F-9861-2013 NR 14 TC 6 Z9 6 U1 0 U2 7 PU PRESTON PUBL INC PI NILES PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2011 VL 35 IS 8 BP 545 EP 550 PG 6 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 829HL UT WOS:000295569100003 PM 22004673 ER PT J AU Chen, YL Reese, DH AF Chen, Yanling Reese, David H. TI The Retinol Signaling Pathway in Mouse Pluripotent P19 Cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE STEM CELL; RETINOL; HOMEOBOX; SIGNALING; PLURIPOTENT ID EMBRYONAL CARCINOMA-CELLS; VITAMIN-A-DEFICIENCY; BINDING-PROTEINS; GENE-EXPRESSION; HUMAN TISSUES; NEURAL DIFFERENTIATION; ACID; BETA; IDENTIFICATION; NEUROGENESIS AB atRA (all-trans-retinoic acid), the active metabolite of retinol (vitamin A), is essential for embryogenesis and maintenance of cellular phenotype in adults. Chemicals that interfere with the metabolism of retinol to atRA, therefore, are a human health concern. During development of a screen for disruptors of this signaling pathway, we investigated whether the mouse pluripotent P19 cell metabolizes retinol to atRA and thus can be used in a cell-based screen for disruptors of the pathway. We found that retinol induced the identical pattern of homeobox gene expression as atRA and its precursor, retinal. Retinol was 160-fold less potent than atRA as an inducer, however. In spite of its lower potency, increased Hoxa1 gene expression was detected 30 min after retinol exposure and increased 40-fold by 2 h. Rdh10 and Aldh1a2/Raldh2, which together convert retinol to atRA in the embryo, were the predominant alcohol and aldehyde dehydrogenases expressed in P19 cells. The cell expressed high mRNA levels of retinol binding proteins, Rbp1 and Rbp4, and the 13,14-dihydroretinol saturase, Retsat. It also expressed all Rar and Rxr isotypes, Crabp1&2, the three Cyp26 genes, and both beta-carotene-cleaving genes, Bcmo1 and Bco2. The basal expression levels and retinol responsiveness of 25 pathway-related genes were quantitated by RT-qPCR. A test of the Aldh1a2 inhibitor, citral, showed that the disruption of the pathway was easily detected and quantitated showing that the P19 cell provides an in vitro model system for identifying and exploring the mechanism of action of chemicals that interfere with this critical cellular pathway. J. Cell. Biochem. 112: 2865-2872, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Chen, Yanling; Reese, David H.] US FDA, Div Mol Biol, Laurel, MD 20708 USA. RP Reese, DH (reprint author), US FDA, Div Mol Biol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM david.reese@fda.hhs.gov NR 50 TC 12 Z9 13 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT PY 2011 VL 112 IS 10 BP 2865 EP 2872 DI 10.1002/jcb.23200 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 829YP UT WOS:000295623300023 PM 21618588 ER PT J AU Ducatez, MF Cai, ZP Peiris, M Guan, Y Ye, ZP Wan, XF Webby, RJ AF Ducatez, Mariette F. Cai, Zhipeng Peiris, Malik Guan, Yi Ye, Zhiping Wan, Xiu-Feng Webby, Richard J. TI Extent of Antigenic Cross-Reactivity among Highly Pathogenic H5N1 Influenza Viruses SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE-GENETICS; A VIRUS; VACCINE; ANTIBODIES; HEMAGGLUTININ; PROTECTION; CHALLENGE; IMMUNITY; FERRETS AB Highly pathogenic H5N1 avian influenza viruses emerged in 1996 and have since evolved so extensively that a single strain can no longer be used as a prepandemic vaccine or diagnostic reagent. We therefore sought to identify the H5N1 strains that may best serve as cross-reactive diagnostic reagents. We compared the cross-reactivity of 27 viruses of clades 0, 1, 2.1, 2.2, 2.3, and 4 and of four computationally designed ancestral H5N1 strains by hemagglutination inhibition (HI) and microneutralization (MN) assays. Antigenic cartography was used to analyze the large quantity of resulting data. Cartographs of HI titers with chicken red blood cells were similar to those of MN titers, but HI with horse red blood cells decreased antigenic distances among the H5N1 strains studied. Thus, HI with horse red blood cells seems to be the assay of choice for H5N1 diagnostics. Whereas clade 2.2 antigens were able to detect antibodies raised to most of the tested H5N1 viruses (and clade 2.2-specific antisera detected most of the H5N1 antigens), ancestral strain A exhibited the widest reactivity pattern and hence was the best candidate diagnostic reagent for broad detection of H5N1 strains. C1 [Ducatez, Mariette F.; Webby, Richard J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Cai, Zhipeng; Wan, Xiu-Feng] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA. [Peiris, Malik; Guan, Yi] Univ Hong Kong, Dept Microbiol, State Key Lab Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China. [Peiris, Malik; Guan, Yi] Shantou Univ, Int Inst Infect & Immun, Shantou 515031, Guangdong, Peoples R China. [Ye, Zhiping] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Webby, RJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM richard.webby@stjude.org FU National Institute of Allergy and Infectious Disease, National Institute of Health, Department of Health and Human Services [HHSN266200700005C]; American Lebanese Syrian Associated Charities (ALSAC); National Institutes of Health (NIH) [1RC1AI086830] FX This study was supported by contract HHSN266200700005C from the National Institute of Allergy and Infectious Disease, National Institute of Health, Department of Health and Human Services, and by the American Lebanese Syrian Associated Charities (ALSAC). Z.C. and X.-F.W. were supported by grant 1RC1AI086830 from the National Institutes of Health (NIH) to X.-F.W. NR 26 TC 17 Z9 17 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD OCT PY 2011 VL 49 IS 10 BP 3531 EP 3536 DI 10.1128/JCM.01279-11 PG 6 WC Microbiology SC Microbiology GA 826NK UT WOS:000295360700014 PM 21832017 ER PT J AU Hume-Smith, KM Groth, AD Rishniw, M Walter-Grimm, LA Plunkett, SJ Maggs, DJ AF Hume-Smith, Karen M. Groth, Allyson D. Rishniw, Mark Walter-Grimm, Linda A. Plunkett, Signe J. Maggs, David J. TI Anaphylactic events observed within 4 h of ocular application of an antibiotic-containing ophthalmic preparation: 61 cats (1993-2010) SO JOURNAL OF FELINE MEDICINE AND SURGERY LA English DT Article ID POLYMYXIN-B; HIND-PAW; BACITRACIN; OINTMENT; CULTURE; EDEMA AB This study describes signalment, history, antibiotic administered, clinical signs observed, therapy, and outcome of anaphylactic events within 4 h following ophthalmic administration of an antibiotic to cats. Data came from survey responses (45 cats) or Federal Drug Administration reports (16 cats). Cat age (7 weeks-19 years), breed, and gender ranged widely. Most were healthy (87%) prior to anaphylaxis. Ophthalmic antibiotics commonly were administered for conjunctival (65%) or corneal (11%) disease, or ocular lubrication (7%) and contained bacitracin, neomycin, and polymyxin B (44%), or oxytetracycline and polymyxin B (21%). Polymyxin B was present in all cases. Vaccines or other drugs were also administered to 51% of cats. In 56% cases, anaphylaxis occurred within 10 min of drug application. Most (82%) cats survived. Although a causal association was not proved, ophthalmic antibiotic administration preceded anaphylaxis in all cats. Like other drugs, ophthalmic antibiotics should be used only when indicated. (C) 2011 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved. C1 [Maggs, David J.] Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, VM Surg & Radiol Sci, Davis, CA 95616 USA. [Hume-Smith, Karen M.; Groth, Allyson D.] Univ Calif Davis, Sch Vet Med, Vet Med Teaching Hosp, Davis, CA 95616 USA. [Rishniw, Mark] Vet Informat Network, Davis, CA 95616 USA. [Walter-Grimm, Linda A.] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Plunkett, Signe J.] Emergency Anim Clin, Phoenix, AZ 85021 USA. RP Maggs, DJ (reprint author), Univ Calif Davis, Sch Vet Med, Dept Surg & Radiol Sci, VM Surg & Radiol Sci, 2112 Tupper Hall, Davis, CA 95616 USA. EM djmaggs@ucdavis.edu RI Walter-Grimm, Linda/A-6348-2012 NR 29 TC 5 Z9 5 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1098-612X J9 J FELINE MED SURG JI J. Feline Med. Surg. PD OCT PY 2011 VL 13 IS 10 BP 744 EP 751 DI 10.1016/j.jfms.2011.06.007 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 831BJ UT WOS:000295703400010 PM 21906985 ER PT J AU Sweet, MP Fillinger, MF Morrison, TM Abel, D AF Sweet, Matthew P. Fillinger, Mark F. Morrison, Tina M. Abel, Dorothy TI The influence of gender and aortic aneurysm size on eligibility for endovascular abdominal aortic aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the New-England-Society-for-Vascular-Surgery CY SEP 23-26, 2010 CL Rockport, ME SP New England Soc Vasc Surg ID PROSPECTIVE CLINICAL-TRIAL; OPEN SURGICAL REPAIR; STENT GRAFT; REPORTING STANDARDS; MULTICENTER TRIAL; UNITED-STATES; SURVEILLANCE; ANGULATION; MORTALITY; SYSTEM AB Objectives: The purpose of this study was to compare the eligibility of men and women with infrarenal abdominal aortic aneurysms (AAAs) for on-label endovascular aneurysm repair (EVAR) as part of the clinician-Food & Drug Administration (FDA) collaborative effort, the Characterization of Human Aortic Anatomy Project (CHAP). Methods: Computed tomography (CT) scans with 3D reconstruction from a single institution obtained between July 1996 and December 2009, including standardized measurements by a blinded third-party (M2S, West Lebanon, NH) were examined. For inclusion, abdominal aortic aneurysm (AAA) had to be infrarenal, unrepaired, and >5 cm, or 4 cm to 5 cm if the orthogonal sac diameter was more than twice the aortic diameter at the renal level. Scans were included regardless of subsequent EVAR, open repair, or lack of treatment. One thousand sixty-three unique, unrepaired AAAs were analyzed. Results: Neck length, diameter, and angulation differ for women (P < .001) even after adjustment for patient age and AAA size. EVAR eligibility based on device Instructions for Use (IFU) criterion is affected by gender. Neck length <15 mm was found in 47% of men and 63% of women. Neck angulation exceeding 60 degrees was found in 12% of men and 26% of women. Minimum iliac diameter of 6 mm was found in 35% of men and 55% of women. Only 32% of men and 12% of women met all three neck criterion and had iliac lumen diameters >6 mm. Logistic regression modeling shows that older patient age (odds ratio [OR], 0.84 per decade), increased aneurysm diameter (OR, 0.70 per cm), and female gender (OR, 0.4) are each independently associated with decreased odds of meeting all device IFU neck criterion (P < .05). EVAR eligibility by neck criterion does not decline significantly until AAA size exceeds 5.5 cm in women and 6.5 cm in men. Conclusion: Women are significantly less likely to meet device IFU criterion for EVAR. Aortic neck criteria and iliac access are important for men and women, but more women than men fail to meet IFU criterion. Devices that accommodate shorter infrarenal AAA neck length will have the greatest impact on expanding on-label EVAR regardless of gender. Lower profile devices and those that accommodate higher neck angulation are expected to expand EVAR eligibility further for women. EVAR eligibility is unlikely to be lost as AAAs enlarge to 5.5 cm in women and 6.5 cm in men. Observation of small AAAs until they reach the standard threshold size for repair should not compromise EVAR eligibility. ( J Vase Surg 2011;54:931-7.) C1 [Fillinger, Mark F.; Morrison, Tina M.; Abel, Dorothy] Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, Lebanon, NH 03756 USA. [Sweet, Matthew P.; Fillinger, Mark F.] US FDA, Rockville, MD 20857 USA. RP Fillinger, MF (reprint author), Dartmouth Hitchcock Med Ctr, Vasc Surg Sect, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Mark.F.Fillinger@hitchcock.org NR 33 TC 51 Z9 53 U1 1 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 OCT PY 2011 VL 54 IS 4 BP 931 EP 937 DI 10.1016/j.jvs.2011.02.054 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 829FA UT WOS:000295562800001 PM 21658895 ER PT J AU Abdel-Rahman, A Anyangwe, N Carlacci, L Casper, S Danam, RP Enongene, E Erives, G Fabricant, D Gudi, R Hilmas, CJ Hines, F Howard, P Levy, D Lin, Y Moore, RJ Pfeiler, E Thurmond, TS Turujman, S Walker, NJ AF Abdel-Rahman, Ali Anyangwe, Njwen Carlacci, Louis Casper, Steve Danam, Rebecca P. Enongene, Evaristus Erives, Gladys Fabricant, Daniel Gudi, Ramadevi Hilmas, Corey J. Hines, Fred Howard, Paul Levy, Dan Lin, Ying Moore, Robert J. Pfeiler, Erika Thurmond, T. Scott Turujman, Saleh Walker, Nigel J. TI The Safety and Regulation of Natural Products Used as Foods and Food Ingredients SO TOXICOLOGICAL SCIENCES LA English DT Article DE botanicals; dietary supplements; food; food ingredients; safety; regulation ID CHINESE HERBS NEPHROPATHY; GREEN TEA; STEVIA-REBAUDIANA; ARISTOLOCHIC ACID; REBAUDIOSIDE-A; EPIGALLOCATECHIN GALLATE; DIETARY-SUPPLEMENTS; RATS; STEVIOSIDE; EXTRACT AB The use of botanicals and dietary supplements derived from natural substances as an adjunct to an improved quality of life or for their purported medical benefits has become increasingly common in the United States. This review addresses the safety assessment and regulation of food products containing these substances by the U.S. Food and Drug Administration (FDA). The issue of safety is particularly critical given how little information is available on the toxicity of some of these products. The first section uses case studies for stevia and green tea extracts as examples of how FDA evaluates the safety of botanical and herbal products submitted for consideration as Generally Recognized as Safe under the Federal Food, Drug, and Cosmetics Act. The 1994 Dietary Supplement Health Education Act (DSHEA) created a regulatory framework for dietary supplements. The article also discusses the regulation of this class of dietary supplements under DSHEA and addresses the FDA experience in analyzing the safety of natural ingredients described in pre-market safety submissions. Lastly, we discuss an ongoing interagency collaboration to conduct safety testing of nominated dietary supplements. C1 [Danam, Rebecca P.; Erives, Gladys; Thurmond, T. Scott] US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 21029 USA. [Abdel-Rahman, Ali; Anyangwe, Njwen; Carlacci, Louis; Casper, Steve; Enongene, Evaristus; Fabricant, Daniel; Gudi, Ramadevi; Hilmas, Corey J.; Hines, Fred; Levy, Dan; Lin, Ying; Moore, Robert J.; Turujman, Saleh] US FDA, Div Dietary Supplement Programs, Off Nutr Labeling & Dietary Supplements, College Pk, MD 21029 USA. [Howard, Paul] US FDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Pfeiler, Erika] US FDA, Off Commissioner, Off Chief Scientist, Laurel, MD 20708 USA. [Walker, Nigel J.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Thurmond, TS (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 265, College Pk, MD 21029 USA. EM scott.thurmond@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 55 TC 38 Z9 43 U1 2 U2 62 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2011 VL 123 IS 2 BP 333 EP 348 DI 10.1093/toxsci/kfr198 PG 16 WC Toxicology SC Toxicology GA 828VW UT WOS:000295532900002 PM 21821733 ER PT J AU Shpyleva, SI Muskhelishvili, L Tryndyak, VP Koturbash, I Tokar, EJ Waalkes, MP Beland, FA Pogribny, IP AF Shpyleva, Svitlana I. Muskhelishvili, Levan Tryndyak, Volodymyr P. Koturbash, Igor Tokar, Erik J. Waalkes, Michael P. Beland, Frederick A. Pogribny, Igor P. TI Chronic Administration of 2-Acetylaminofluorene Alters the Cellular Iron Metabolism in Rat Liver SO TOXICOLOGICAL SCIENCES LA English DT Article DE 2-acetylaminofluorene; carcinogenesis; iron metabolism; liver; rat ID HEPATOCELLULAR-CARCINOMA; HEPATIC IRON; REGULATORY GENES; TRANSFERASE-P; CANCER; HEPCIDIN; HEPATOCARCINOGENESIS; CARCINOGENESIS; EXPRESSION; DISEASE AB Dysregulated intracellular iron homeostasis has been found not only in rodent and human hepatocellular carcinomas but also in several preneoplastic pathological states associated with hepatocarcinogenesis; however, the precise underlying mechanisms of metabolic iron disturbances in preneoplastic liver and the role of these disturbances remain unexplored. In the present study, using an in vivo model of rat hepatocarcinogenesis induced by 2-acetylaminofluorene, we found extensive alterations in cellular iron metabolism at preneoplastic stages of liver carcinogenesis. These were characterized by a substantial decrease in the levels of cytoplasmic non-heme iron in foci of initiated hepatocytes and altered expression of the major genes responsible for the proper maintenance of intracellular iron homeostasis. Gene expression analysis revealed that the decreased intracellular levels of iron in preneoplastic foci might be attributed to increased iron export from the cells, driven by upregulation of ferroportin (Fpn1), the only known non-heme iron exporter. Likewise, increased Fpn1 gene expression was found in vitro in TRL1215 rat liver cells with an acquired malignant phenotype, suggesting that upregulation of Fpn1 might be a specific feature of neoplastically transformed cells. Other changes observed in vivo included the downregulation of hepcidin (Hamp) gene, a key regulator of Fpn1, and this was accompanied by decreased levels of CCAAT/enhancer binding proteins alpha and beta, especially at the Hamp promoter. In conclusion, our results demonstrate the significance of altered intracellular iron metabolism in the progression of liver carcinogenesis and suggest that correction of these alterations could possibly affect liver cancer development. C1 [Shpyleva, Svitlana I.; Tryndyak, Volodymyr P.; Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Shpyleva, Svitlana I.; Tryndyak, Volodymyr P.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, UA-03022 Kiev, Ukraine. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Waalkes, Michael P.] NIEHS, Inorgan Toxicol Grp, Natl Toxicol Program, Res Triangle Pk, NC 27713 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Bldg 14C,Off 101, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH) FX National Toxicology Program, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH). NR 42 TC 3 Z9 3 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2011 VL 123 IS 2 BP 433 EP 440 DI 10.1093/toxsci/kfr193 PG 8 WC Toxicology SC Toxicology GA 828VW UT WOS:000295532900011 PM 21785164 ER PT J AU Oakley, MS Gerald, N McCutchan, TF Aravind, L Kumar, S AF Oakley, Miranda S. Gerald, Noel McCutchan, Thomas F. Aravind, L. Kumar, Sanjai TI Clinical and molecular aspects of malaria fever SO TRENDS IN PARASITOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM; FEBRILE TEMPERATURES; HOST ERYTHROCYTE; CEREBRAL MALARIA; PARASITES; GLYCOSYLPHOSPHATIDYLINOSITOL; RESPONSES; PIGMENT; RECEPTORS; INFECTION AB Although clinically benign, malaria fever is thought to have significant relevance in terms of parasite growth and survival and its virulence which in turn may alter the clinical course of illness. In this article, the historical literature is reviewed, providing some evolutionary perspective on the genesis and biological relevance of malaria fever, and the available molecular data on the febrile-temperature-inducible parasite factors that may contribute towards the regulation of parasite density and alteration of virulence in the host is also discussed. The potential molecular mechanisms that could be responsible for the induction and regulation of cyclical malaria fevers caused by different species of Plasmodiurn are also discussed. C1 [Gerald, Noel; McCutchan, Thomas F.; Kumar, Sanjai] US FDA, Div Emerging Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. [Oakley, Miranda S.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, Div Emerging Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. EM sanjai.kumar@fda.hhs.gov NR 49 TC 12 Z9 12 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD OCT PY 2011 VL 27 IS 10 BP 442 EP 449 DI 10.1016/j.pt.2011.06.004 PG 8 WC Parasitology SC Parasitology GA 831RN UT WOS:000295748900005 PM 21795115 ER PT J AU Kawai, VK Grijalva, CG Arbogast, PG Curtis, JR Solomon, DH Delzell, E Chen, L Ouellet-Hellstrom, R Herrinton, L Liu, LY Mitchel, EF Stein, CM Griffin, MR AF Kawai, Vivian K. Grijalva, Carlos G. Arbogast, Patrick G. Curtis, Jeffrey R. Solomon, Daniel H. Delzell, Elizabeth Chen, Lang Ouellet-Hellstrom, Rita Herrinton, Lisa Liu, Liyan Mitchel, Edward F., Jr. Stein, C. Michael Griffin, Marie R. TI Changes in Cotherapies After Initiation of Disease-Modifying Antirheumatic Drug Therapy in Patients With Rheumatoid Arthritis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID RANDOMIZED CONTROLLED-TRIALS; PRESCRIPTION MEDICATIONS; CLINICAL-PRACTICE; PAIN; POPULATION; RISK; METHOTREXATE; EFFICACY; GLUCOCORTICOIDS; LEFLUNOMIDE AB Objective. We hypothesized that initiation of a new disease-modifying antirheumatic drug (DMARD) for treatment of rheumatoid arthritis (RA) would decrease the use of corticosteroids, nonsteroidal antiinflammatory drugs (NSAIDs), and narcotics. Methods. Using administrative databases, we assembled 4 retrospective cohorts of RA patients (1998-2005) and identified 5 groups initiating DMARD regimens: methotrexate (MTX) with (new MTX) or without (first MTX) use of other nonbiologic DMARDs in the previous year; new hydroxychloroquine (HCQ) and/or sulfasalazine (SSZ; new HCQ/SSZ) and new leflunomide (new LEF), both with previous use of MTX; and new tumor necrosis factor alpha (TNF alpha) antagonists (new anti-TNF). We compared within-person differences in any use of cotherapies (> 1 prescription) between the 6 months before and the 6-12 months after DMARD initiation. Results. Among 32,476 DMARD initiators, the prevalence of corticosteroid, NSAID, and narcotic use increased by 15%, 5%, and 6%, respectively, in the 6 months before initiation compared to the previous 6 months, suggesting worsening of the disease. In the 6-12 months after initiation for most initiator groups, more patients stopped using corticosteroids and NSAIDs than started, with overall decreases of 8.9% (95% confidence interval [95% CI] 8.4-9.4%) for corticosteroids and 12.9% (95% CI 12.3-13.4%) for NSAIDs. The proportion of narcotic users changed little (overall decrease of 2.5%; 95% CI 1.9-3.0%). Conclusion. Use of all 3 cotherapies increased in the 6 months before initiation of new DMARD regimens for RA. Use of corticosteroids and NSAIDs decreased modestly 6-12 months after initiation, but there was only a very small decrease in narcotic use. These differential changes require further study. C1 [Griffin, Marie R.] Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37232 USA. [Griffin, Marie R.] VA Tennessee Valley Hlth Care Syst, Midsouth Geriatr Res Educ & Clin Ctr, Nashville, TN USA. [Curtis, Jeffrey R.; Delzell, Elizabeth; Chen, Lang] Univ Alabama, Birmingham, AL USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ouellet-Hellstrom, Rita] US FDA, Silver Spring, MD USA. [Herrinton, Lisa; Liu, Liyan] Kaiser Permanente No Calif, Oakland, CA USA. RP Griffin, MR (reprint author), Vanderbilt Univ, Sch Med, Dept Prevent Med, Suite 2600,1500 21st Ave S, Nashville, TN 37232 USA. EM marie.griffin@vanderbilt.edu FU Agency for Healthcare Research and Quality [U18-HSO17919-01, R01HS018517]; NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases [5P60AR56116, 5T32GM007569-33]; Abbott; Centocor; Pfizer; BMS; Amgen; Consortium of Rheumatology Researchers of North America, Roche/Genentech; UCB; Procter Gamble; Rocky Mountain Poison and Drug Center; McNeil FX Supported by the Agency for Healthcare Research and Quality (grant U18-HSO17919-01), the NIH National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant 5P60AR56116), and the NIH (grant 5T32GM007569-33). Dr. Gurtis's work was supported by the Agency for Healthcare Research and Quality (grant R01HS018517) and the NIH (grant AR053351).; Dr. Curtis has received consultant fees, speaking fees, and/or honoraria (less than $10,000 each) from Abbott, Centocor, Pfizer, and BMS, and (more than $10,000 each) from Amgen, Consortium of Rheumatology Researchers of North America, Roche/Genentech, and UCB. Dr. Delzell has received research support from Amgen. Dr. Solomon has received research support from Abbott and Amgen. Dr. Herrinton has received research support from Centocor, Genentech, and Procter & Gamble. Dr. Griffin has received consultant fees, speaking fees and/or honoraria (less than $10,000 each) from Rocky Mountain Poison and Drug Center funded by McNeil. NR 40 TC 7 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2011 VL 63 IS 10 BP 1415 EP 1424 DI 10.1002/acr.20550 PG 10 WC Rheumatology SC Rheumatology GA 825FA UT WOS:000295255200008 PM 22121511 ER PT J AU Wong, HL Rabkin, CS Shu, XO Pfeiffer, RM Cai, Q Ji, BT Yang, G Li, HL Rothman, N Gao, YT Zheng, W Chow, WH AF Wong, Hui-Lee Rabkin, Charles S. Shu, Xiao-Ou Pfeiffer, Ruth M. Cai, Qiuyin Ji, Bu-Tian Yang, Gong Li, Hong-Lan Rothman, Nathaniel Gao, Yu-Tang Zheng, Wei Chow, Wong-Ho TI Systemic cytokine levels and subsequent risk of gastric cancer in Chinese Women SO CANCER SCIENCE LA English DT Article ID HELICOBACTER-PYLORI INFECTION; NECROSIS-FACTOR-ALPHA; ELEVATED LEVELS; INTERLEUKIN-6; HEALTH; POPULATION; REPRODUCIBILITY; POLYMORPHISMS; INFLAMMATION; METASTASIS AB Although control of the host cytokine network is known to influence gastric cancer susceptibility, the specific inflammatory responses in gastric carcinogenesis remain unclear. We prospectively examined the relationships between gastric cancer risk and plasma levels of interleukin (IL)-1 beta, IL-6, IL-8 and tumor necrosis factor (TNF)-alpha in a nested case control study within The Shanghai Women's Health Study. Two controls were matched to each case on the basis of age, menopausal status, and sample collection parameters. The associations between gastric cancer risk and tertiles of cytokine levels were estimated by odds ratios (OR) and 95% confidence intervals (CI) from conditional logistic regression, adjusting for education. During a median follow-up period of 4 years (range 0.1-8 years), 141 women developed gastric cancer and were matched to 282 cancer-free study participants. Elevated levels of plasma IL-6 were associated with an increased risk of gastric cancer (P-trend = 0.04). Risk increased 70% (OR = 1.7; 95% CI 1.0, 3.0) for women in the highest tertile (>4 pg/mL) of IL-6 compared with those in the lowest tertile (<1.8 pg/mL). The association between gastric cancer risk and IL-6 was stronger after 4 years of follow-up (OR = 2.6 [95% CI 1.0, 6.7] for highest versus lowest tertile) compared with an OR of 1.4 (95% CI 0.7, 2.9) for those diagnosed within 1-4 years of follow-up. No associations were observed with the other pro-inflammatory cytokines examined, namely IL-1 beta, IL-8, and TNF-alpha. Systemic plasma IL-6 levels may inform long-term gastric cancer risk. This novel finding awaits confirmation in future studies with sequential plasma collection. (Cancer Sci 2011; 102: 1911-1915) C1 [Wong, Hui-Lee] US FDA, Silver Spring, MD USA. [Rabkin, Charles S.; Pfeiffer, Ruth M.; Ji, Bu-Tian; Rothman, Nathaniel; Chow, Wong-Ho] NCI, US NIH, Rockville, MD USA. [Shu, Xiao-Ou; Cai, Qiuyin; Yang, Gong; Zheng, Wei] Vanderbilt Univ, Nashville, TN USA. [Li, Hong-Lan; Gao, Yu-Tang] Shanghai Canc Inst, Shanghai, Peoples R China. RP Wong, HL (reprint author), US FDA, Silver Spring, MD USA. EM huilee.wong@fda.hhs.gov FU National Institutes of Health [R37 CA70867]; Intramural Research Program [N02 CP1101066]; Vanderbilt-Ingram Cancer Center [P30 CA68485] FX The work was supported by a grant from the National Institutes of Health (R37 CA70867) and an Intramural Research Program contract (N02 CP1101066). The authors thank the Shanghai residents who participated in the study and the research staff of the Shanghai Women's Health Study. The authors also thank Regina Courtney for plasma sample preparation at the Survey and Biospecimen Shared Resources supported, in part, by the Vanderbilt-Ingram Cancer Center (P30 CA68485). NR 31 TC 10 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2011 VL 102 IS 10 BP 1911 EP 1915 DI 10.1111/j.1349-7006.2011.02033.x PG 5 WC Oncology SC Oncology GA 826CK UT WOS:000295328800010 PM 21740481 ER PT J AU Goldblatt, D Plikaytis, BD Akkoyunlu, M Antonello, J Ashton, L Blake, M Burton, R Care, R Durant, N Feavers, I Fernsten, P Fievet, F Giardina, P Jansen, K Katz, L Kierstead, L Lee, L Lin, J Maisonneuve, J Nahm, MH Raab, J Romero-Steiner, S Rose, C Schmidt, D Stapleton, J Carlone, GM AF Goldblatt, D. Plikaytis, B. D. Akkoyunlu, M. Antonello, J. Ashton, L. Blake, M. Burton, R. Care, R. Durant, N. Feavers, I. Fernsten, P. Fievet, F. Giardina, P. Jansen, K. Katz, L. Kierstead, L. Lee, L. Lin, J. Maisonneuve, J. Nahm, M. H. Raab, J. Romero-Steiner, S. Rose, C. Schmidt, D. Stapleton, J. Carlone, G. M. TI Establishment of a New Human Pneumococcal Standard Reference Serum, 007sp SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; IMMUNOGLOBULIN G1; ANTIBODY UNITS; LOT 89-S(F); ASSIGNMENT; POLYSACCHARIDES; QUANTITATION AB Lot 89SF has been the reference standard serum pool used in pneumococcal enzyme-linked immunosorbent assays (ELISAs) since 1990. In 2005, it was estimated that there remained between 2 and 5 years' supply of lot 89SF. Since lot 89SF was the reference standard used in the evaluation of the seven-valent pneumococcal conjugate vaccine Prevnar (PCV7), the link to clinical efficacy would be severed if stocks became completely depleted. Furthermore, demonstration of immune responses comparable to those elicited by PCV7 is a licensure approach used for new pneumococcal conjugate vaccines, so a replacement reference standard was required. A total of 278 volunteers were immunized with the 23-valent unconjugated polysaccharide vaccine Pneumovax II, and a unit of blood was obtained twice within 120 days following immunization. Plasma was prepared, pooled, and confirmed to be free from hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV. The pooled serum was poured at 6 ml per vial into 15,333 vials and lyophilized. Immunological bridging of 007sp to 89SF was used to establish equivalent reference values for 13 pneumococcal capsular serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F) by five independent laboratories. Antibody concentrations in 007sp were established relative to the lot 89SF reference preparation using the WHO reference ELISA. Subsequently, 12 existing WHO calibration sera had concentrations reassigned for 13 pneumococcal serotypes using new serum 007sp as the reference, and these were compared to concentrations relative to the original reference serum. Agreement was excellent for the 12 WHO calibration sera. The 007sp preparation has replaced 89SF as the pneumococcal reference standard. Sufficient quantity of this new preparation is available such that, with judicious use, it should be available for at least 25 years. C1 [Goldblatt, D.] UCL, Inst Child Hlth, Immunobiol Unit, London WC1N 1EH, England. [Plikaytis, B. D.; Romero-Steiner, S.; Rose, C.; Schmidt, D.; Carlone, G. M.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Akkoyunlu, M.; Blake, M.; Lee, L.] US FDA, CBER, Bethesda, MD 20014 USA. [Burton, R.; Lin, J.; Nahm, M. H.] Univ Alabama, Huntsville, AL 35899 USA. [Fernsten, P.; Giardina, P.; Jansen, K.] Pfizer Vaccine Res, Pearl River, NY USA. [Durant, N.; Fievet, F.] GlaxoSmithKline Biol, Rixensart, Belgium. [Care, R.; Feavers, I.] Natl Inst Biol Stand & Controls, Potters Bar, Herts, England. [Kierstead, L.; Raab, J.] PPD Vaccines & Biol Lab, Wayne, PA USA. [Antonello, J.] Sharp & Dohme Corp, Merck, West Point, PA USA. [Maisonneuve, J.] PATH, Seattle, WA USA. [Katz, L.] Mississippi Valley Reg Blood Ctr, Davenport, IA USA. [Stapleton, J.] Univ Iowa, Iowa City, IA USA. RP Goldblatt, D (reprint author), UCL, Inst Child Hlth, Immunobiol Unit, 30 Guilford St, London WC1N 1EH, England. EM d.goldblatt@ich.ucl.ac.uk RI Goldblatt, David/C-5972-2008; Akkoyunlu, Mustafa/I-5712-2012; OI Goldblatt, David/0000-0002-0769-5242; Romero-Steiner, Sandra/0000-0003-4128-7768; Nahm, Moon/0000-0002-6922-1042 FU CBER [06-0093]; USFDA; NIAID; Basic and Clinical Approaches to Controlling Human Respiratory Pathogens [N01-AI-30040] FX This study (study protocol no. 06-0093) was sponsored by CBER, USFDA, and NIAID and supported in part by Basic and Clinical Approaches to Controlling Human Respiratory Pathogens (N01-AI-30040 to J.S.). NR 10 TC 26 Z9 29 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2011 VL 18 IS 10 BP 1728 EP 1736 DI 10.1128/CVI.05252-11 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 826NQ UT WOS:000295361300018 PM 21852547 ER PT J AU Von Tungeln, LS Zhou, T Woodling, KA Doerge, DR Greenlees, KJ Beland, FA AF Von Tungeln, Linda S. Zhou, Tong Woodling, Kellie A. Doerge, Daniel R. Greenlees, Kevin J. Beland, Frederick A. TI Benzocaine-induced methemoglobinemia in an acute-exposure rat model SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Benzocaine; Tricaine methanesulfonate; Methemoglobin; Rats ID TROUT ONCORHYNCHUS-MYKISS; TOPICAL BENZOCAINE; RAINBOW-TROUT; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TEMPERATURE; ELIMINATION; EXPERIENCE; ENDOSCOPY AB Tricaine methanesulfonate, a sedative for temporarily immobilizing fish, has a 21-day withdrawal time. Benzocaine has been proposed as an alternative sedative because a withdrawal period may not be required. Since benzocaine is known to induce methemoglobinemia, the potential for orally administered benzocaine to induce methemoglobin was assessed in rats. Sprague-Dawley rats were given a single gavage administration of 64 mg benzocaine hydrochloride per kg bw and then euthanized at intervals up to 120 min. Plasma levels of benzocaine were relatively low at all times, whereas methemoglobin peaked at 24 min. Additional rats were orally gavaged with 0-1024 mg benzocaine hydrochloride per kg bw and euthanized after 24 min. Plasma levels of benzocaine increased from 0.01 mu M at 2 mg per kg bw to 2.9 mu M at 1024 mg per kg bw. Methemoglobin levels did not differ from controls at doses up to 32 mg per kg bw in females and 64 mg per kg bw in males, whereupon the value increased to similar to 80% at 1024 mg per kg bw. These data were used to estimate the potential impact of benzocaine residues in fish and suggest that the consumption of fish treated with benzocaine hydrochloride will not cause methemoglobinemia in humans. Published by Elsevier Ltd. C1 [Von Tungeln, Linda S.; Woodling, Kellie A.; Doerge, Daniel R.; Beland, Frederick A.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zhou, Tong; Greenlees, Kevin J.] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. RP Beland, FA (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, HFT-110, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov NR 24 TC 1 Z9 1 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD OCT PY 2011 VL 49 IS 10 BP 2530 EP 2535 DI 10.1016/j.fct.2011.06.048 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 824ZW UT WOS:000295241700006 PM 21726594 ER PT J AU Dabrazhynetskaya, A Volokhov, DV David, SW Ikonomi, P Brewer, A Chang, A Chizhikov, V AF Dabrazhynetskaya, A. Volokhov, D. V. David, S. W. Ikonomi, P. Brewer, A. Chang, A. Chizhikov, V. TI Preparation of reference strains for validation and comparison of mycoplasma testing methods SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE detection; microbial contamination; optimisation; polymerase chain reaction; rapid methods ID MORPHOLOGY; STORAGE; GROWTH; INFECTIONS; LAIDLAWII; BIOLOGY; FROZEN AB Aims: To optimize growth conditions for preparation of stocks of mycoplasma reference strains to obtain highly viable and disperse samples with low ratios of genomic copy (GC) number to that of colony forming units (CFU). These stocks are required for assessment of relative limits of detection (LOD) of alternative nucleic acid testing (NAT)-based methods in comparison to the conventional microbiological methods. Methods and Results: A kinetics study was used to assess the changes in ratios between the numbers of GC and CFU at different growth phases of six different mycoplasma cultures Acholeplasma laidlawii, Mycoplasma gallisepticum, Mycoplasma arginini, Mycoplasma fermentans, Mycoplasma orale and Mycoplasma pneumoniae. All tested mycoplasmas demonstrated low GC/CFU ratios (<= 10) within the log and early stationary growth phases. A significant increase in GC/CFU ratios was observed at the very late stationary and death phases, when the titre of cultures has declined. Similar patterns of GC/CFU profiles were observed for A. laidlawii and Myc. gallisepticum co-cultured with suspension of Chinese hamster ovary (CHO) cells. Conclusions: Tested mycoplasma strains harvested at the exponential-early stationary phases of growth demonstrated the lowest GC/CFU ratios and low propensity to form filamentous structures or aggregates under proposed conditions and can be used for the preparation of a mycoplasma reference panel for methods comparability study. Significance and Impact of the Study: This study shows that the preparation and use of viable mycoplasma reference strains with low CG/CFU ratios is the most reliable way to adequately evaluate the LOD of alternative NAT-based mycoplasma testing methods. C1 [Dabrazhynetskaya, A.] US FDA, Lab Methods Dev, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ikonomi, P.; Brewer, A.] Amer Type Culture Collect ATCC, Manassas, VA USA. [Chang, A.] BioReliance Corp, Rockville, MD USA. RP Dabrazhynetskaya, A (reprint author), US FDA, Lab Methods Dev, Div Viral Prod, Off Vaccine Res & Review,Ctr Biol Evaluat & Res, HFM 470,1401 Rockville Pike, Rockville, MD 20852 USA. EM alena.dabrazhynetskaya@fda.hhs.gov NR 30 TC 5 Z9 5 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD OCT PY 2011 VL 111 IS 4 BP 904 EP 914 DI 10.1111/j.1365-2672.2011.05108.x PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 827LE UT WOS:000295429200012 PM 21794032 ER PT J AU Wu, WW Wang, GH Insel, PA Hsiao, CT Zou, SG Maudsley, S Martin, B Shen, RF AF Wu, Wells W. Wang, Guanghui Insel, Paul A. Hsiao, Cheng-Te Zou, Sige Maudsley, Stuart Martin, Bronwen Shen, Rong-Fong TI Identification of Proteins and Phosphoproteins Using Pulsed Q Collision Induced Dissociation (PQD) SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article DE Pulsed Q collision induced dissociation (PQD); Linear ion trap; Triple quadrupole (QqQ); Protein identification ID TRAP MASS-SPECTROMETER; QUADRUPOLE ION-TRAP; ELECTRON-TRANSFER DISSOCIATION; ITRAQ; QUANTIFICATION; PHOSPHOPEPTIDES; FRAGMENTATION; EXCITATION; SPECTRA AB Pulsed Q collision induced dissociation (PQD) was developed to facilitate detection of low-mass reporter ions from labeling reagents (e.g., iTRIQ) in peptide quantification using an LTQ mass spectrometer (MS). Despite the large number of linear ion traps worldwide, the use and optimization of PQD for protein identification have been limited, in part due to less effective ion fragmentation relative to the collision induced dissociation (CID). PQD expands the m/z coverage of fragment ions to the lower m/z range by circumventing the typical low mass cut-off of an ion trap MS. Since database searching relies on the matching between theoretical and observed spectra, it is not clear how ion intensity and peak number might affect the outcomes of a database search. In this report, we systematically evaluated the attributes of PQD mass spectra, performed intensity optimization, and assessed the benefits of using PQD on the identification of peptides and phosphopeptides from an LTQ. Based on head-to-head comparisons between CID (higher intensity) and PQD (better m/z coverage), peptides identified using PQD generally have Xcorr scores lower than those using CID. Such score differences were considerably diminished by the use of 0.1% m-nitrobenzyl alcohol (m-NBA) in mobile phases. The ion intensities of both CID and PQD were adversely affected by increasing m/z of the precursor, with PQD more sensitive than CID. In addition to negating the 1/3 rule, PQD enhances direct bond cleavage and generates patterns of fragment ions different from those of CID, particularly for peptides with a labile functional group (e.g., phosphopeptides). The higher energy fragmentation pathway of PQD on peptide fragmentation was further compared to those of CID and the quadrupole-type activation in parallel experiments. C1 [Wu, Wells W.; Martin, Bronwen; Shen, Rong-Fong] NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. [Wang, Guanghui] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA. [Insel, Paul A.] Univ Calif San Diego, Dept Pharmacol & Med, La Jolla, CA 92093 USA. [Hsiao, Cheng-Te; Zou, Sige] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Maudsley, Stuart] NIA, Receptor Pharmacol Unit, NIH, Baltimore, MD 21224 USA. [Shen, Rong-Fong] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shen, RF (reprint author), NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. EM rongfong.shen@fda.hhs.gov FU National Institute on Aging and National Heart, Lung, and Blood Institute, National Institutes of Health (NIH) FX The authors acknowledge support for this work by the Intramural Research Programs of National Institute on Aging and National Heart, Lung, and Blood Institute, National Institutes of Health (NIH). They acknowledge the following for technical advice: Dr. Howard Jaffe, NINDS, NIH; Drs. Jae C. Schwartz, Mike W. Senko, and John E. P. Syka of ThermoFisher Scientific Inc. NR 25 TC 5 Z9 5 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD OCT PY 2011 VL 22 IS 10 BP 1753 EP 1762 DI 10.1007/s13361-011-0197-6 PG 10 WC Biochemical Research Methods; Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 822ZC UT WOS:000295088400009 PM 21952889 ER PT J AU Woo, EJ AF Woo, Emily Jane TI Expanded Indication for Recombinant Human Bone Morphogenetic Protein 2 SO SPINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Woo, EJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 2 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 1 PY 2011 VL 36 IS 21 BP 1817 EP 1817 DI 10.1097/BRS.0b013e31822e6028 PG 1 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 825YK UT WOS:000295318000025 PM 22046613 ER PT J AU Bjornsdottir-Butler, K Jones, JL Benner, RA Burkhardt, W AF Bjornsdottir-Butler, Kristin Jones, Jessica L. Benner, Ronald A., Jr. Burkhardt, William, III TI Quantification of total and specific gram-negative histamine-producing bacteria species in fish using an MPN real-time PCR method SO FOOD MICROBIOLOGY LA English DT Article DE Histamine; Histidine decarboxylase; Real-time PCR; MPN; Bacteria; Fish ID HISTIDINE-DECARBOXYLASE; FORMING BACTERIA; IDENTIFICATION; ALBACORE; TUNA; ENUMERATION; PATHOGENS; OYSTERS; GENES AB Quantification of histamine-producing bacteria (HPB) is necessary in order to elucidate the role that HPB play in scombrotoxin (histamine) fish poisoning. We report here the evaluation of a real-time PCR method for the quantification of total and specific Gram-negative HPB species in fish using a most probable number (MPN) format. The species-specific real-time PCR assay was 100% inclusive for independently detecting Morganella morganii, Enterobacter aerogenes, Raoultella planticola/ornithinolytica and Photobacterium damselae and did not cross react with other histamine- or non- histamine-producing bacteria. The efficiency of the reactions in the absence and presence of Spanish mackerel enrichment containing 1 x 10(6) CFU/ml of background microflora were 93-104 and 92-99%, respectively. The MPN-real-time PCR assay accurately quantified total and specific HPB in spiked mahi-mahi (Coryphaena hippurus) and Spanish mackerel (Scomberomorus maculates) samples. These methods were used to quantify total and specific HPB in naturally contaminated, decomposing mahi-mahi, Spanish mackerel and tuna (Thunnus albacores) samples. The results of this study indicate that MPN-real-time PCR assays can be used to accurately enumerate total and specific HPB in fish samples. These assays can be applied to assess the effectiveness of mitigation strategies and understand the relationship between HPB and histamine production in decomposing fish. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Bjornsdottir-Butler, Kristin; Jones, Jessica L.; Benner, Ronald A., Jr.; Burkhardt, William, III] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Bjornsdottir-Butler, K (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM Kristin.Butler@fda.hhs.gov NR 36 TC 8 Z9 8 U1 1 U2 11 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 OCT PY 2011 VL 28 IS 7 BP 1284 EP 1292 DI 10.1016/j.fm.2011.05.006 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 825DY UT WOS:000295252300006 PM 21839377 ER PT J AU Beaubrun, JJG Gopinath, G Kothary, MH Franco, A Curtis, SK Eribo, BE Tall, BD AF Beaubrun, Junia Jean-Gilles Gopinath, Gopal Kothary, Mahendra H. Franco, Augusto Curtis, Sherill K. Eribo, Broderick E. Tall, Ben D. TI Influence of iron-chelated growth conditions on outer membrane protein production and virulence of Vibrio tubiashii SO FOOD MICROBIOLOGY LA English DT Article DE Vibrio tubiashii; Outer membrane protein; HutA; Fur ID SIDEROPHORE BIOSYNTHESIS; FUR GENE; ACQUISITION; VULNIFICUS; CHOLERAE; BACTERIA; PARAHAEMOLYTICUS; METALLOPROTEASE; EXPRESSION; CLONING AB Growth of two Vibrio tubiashii strains under iron-chelated conditions resulted in the production of a hydroxymate-like siderophore, and expression of outer membrane proteins with homologies to proteins in Vibrio cholerae and Vibrio vulnificus which were not seen in cells grown under non-chelated growth conditions. PCR analysis using primers based on Listonella anguillarum's ferric uptake Repressor protein (fur) gene detected a 316 bp fur gene homolog which also had sequence homology to the fur genes of V. cholerae and V. vulnificus. V tubiashii cultured under iron-chelated growth conditions induced a greater fluid accumulation (FA) response in suckling mice than cells which were cultured under iron non-chelated growth conditions. Our observations that V. tubiashii possesses a fur-like gene homolog and expresses unique OMPs, a hydroxymate-like siderophore, and produces an increased fluid accumulation response in suckling mice when grown under iron-chelated condition support previous findings that V. tubiashii may have the essential components for the survival and establishment of infections and this report represents the first observations of competent iron acquisition system in V. tubiashii which is similar to those produced by other marine vibrios, many of which are pathogenic for humans. Published by Elsevier Ltd. C1 [Beaubrun, Junia Jean-Gilles; Gopinath, Gopal; Kothary, Mahendra H.; Franco, Augusto; Curtis, Sherill K.; Tall, Ben D.] Ctr Food Safety & Appl Nutr, US FDA, Div Virulence Assessment, OARSA,MOD Facil Virulence Mech Branch 1, Laurel, MD 20708 USA. [Eribo, Broderick E.] Howard Univ, Washington, DC 20050 USA. RP Beaubrun, JJG (reprint author), Ctr Food Safety & Appl Nutr, US FDA, Div Virulence Assessment, OARSA,MOD Facil Virulence Mech Branch 1, HFS 025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM junia.jean-gillesbeaubrun@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 28 TC 2 Z9 3 U1 0 U2 6 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 OCT PY 2011 VL 28 IS 7 BP 1409 EP 1413 DI 10.1016/j.fm.2011.04.003 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 825DY UT WOS:000295252300022 ER PT J AU Chen, Y Kumar, N Siddique, N AF Chen, Yi Kumar, Nishant Siddique, Nusrat TI Development and Evaluation of a Real-Time Polymerase Chain Reaction Assay Targeting iap for the Detection of Listeria monocytogenes in Select Food Matrices SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID INTERNAL AMPLIFICATION CONTROL; QUANTITATIVE PCR; INNOCUA STRAINS; QUANTIFICATION; GENE; RNA; PROTEIN; CELLS; ENRICHMENT; BINDING AB Listeria monocytogenes is an intracellular foodborne pathogen that has been associated with severe human illnesses. Various rapid detection methods have been developed for the specific detection of this pathogen. In the present study, a real-time quantitative polymerase chain reaction (PCR) assay targeting iap, a gene encoding extracellular protein p60, was developed for L. monocytogenes. The PCR efficiency is above 85% and the limit of detection (LOD) is 30 copies of genome per reaction for all strains tested. The assay exhibited 100% inclusivity and exclusivity rates. The detection of L. monocytogenes in five food matrices, whole milk, soft cheese, turkey deli meat, smoked salmon, and alfalfa sprouts, was evaluated with and without enrichment. Without enrichment, the LOD for all food matrices were 4 x 10(3) CFU/mL food enrichment mix for whole milk and 4 x 10(4) CFU/mL for all other foods. With 24 h incubation in Buffered Listeria Enrichment Broth, the LOD was 3 CFU/25 g food for whole milk, turkey deli meat, and smoked salmon and 9 CFU/25 g food for soft cheese and alfalfa sprouts. With 48 h incubation, the LOD was 3 CFU/25 g food for all matrices. This quantitative PCR appears to be a promising alternative for rapid detection of L. monocytogenes in select foods. C1 [Chen, Yi; Kumar, Nishant; Siddique, Nusrat] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM yi.chen@fda.hhs.gov RI Zhou, Tian/J-7175-2012 NR 29 TC 7 Z9 7 U1 0 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 OCT PY 2011 VL 8 IS 10 BP 1063 EP 1069 DI 10.1089/fpd.2010.0820 PG 7 WC Food Science & Technology SC Food Science & Technology GA 823WR UT WOS:000295158500002 PM 21612427 ER PT J AU Chen, Y Strain, EA Allard, M Brown, EW AF Chen, Y. Strain, E. A. Allard, M. Brown, E. W. TI Genome Sequence of Cronobacter sakazakii E899, a Strain Associated with Human Illness SO JOURNAL OF BACTERIOLOGY LA English DT Article AB Cronobacter has caused numerous illnesses in neonates, infants, and children. Here we report the draft genome of Cronobacter sakazakii E899. Whole-genome sequence analysis of Cronobacter strains provides a tool for understanding the genomic regions specific to each individual species. C1 [Chen, Y.; Allard, M.; Brown, E. W.] US FDA, Div Microbiol, CFSAN, College Pk, MD 20740 USA. [Strain, E. A.] US FDA, Div Math, CFSAN, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, Div Microbiol, CFSAN, 5100 Paint Branch Pkwy,HFS 712, College Pk, MD 20740 USA. EM yi.chen@fda.hhs.gov RI Zhou, Tian/J-7175-2012 FU U.S. Food and Drug Administration FX This project was supported by U.S. Food and Drug Administration Foods Program intramural funds. NR 6 TC 2 Z9 3 U1 0 U2 1 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 OCT PY 2011 VL 193 IS 20 BP 5861 EP 5861 DI 10.1128/JB.05913-11 PG 1 WC Microbiology SC Microbiology GA 825FJ UT WOS:000295256100032 PM 21952538 ER PT J AU Pan, HM Feng, JH Cerniglia, CE Chen, HZ AF Pan, Hongmiao Feng, Jinhui Cerniglia, Carl E. Chen, Huizhong TI Effects of Orange II and Sudan III azo dyes and their metabolites on Staphylococcus aureus SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Staphylococcus aureus; Orange II; Sudan III; Metabolite; Cell growth and viability ID HUMAN INTESTINAL MICROFLORA; ENTEROCOCCUS-FAECALIS; AZOREDUCTASE AZOA; ESCHERICHIA-COLI; MOLECULAR CHARACTERIZATION; MASS-SPECTROMETRY; CRYSTAL-STRUCTURE; IN-VITRO; REDUCTION; DEGRADATION AB Azo dyes are widely used in the plastic, paper, cosmetics, food, and pharmaceutical industries. Some metabolites of these dyes are potentially genotoxic. The toxic effects of azo dyes and their potential reduction metabolites on Staphylococcus aureus ATCC BAA 1556 were studied. When the cultures were incubated with 6, 18, and 36 mu g/ml of Orange II and Sudan III for 48 h, 76.3, 68.5, and 61.7% of Orange II and 97.8, 93.9, and 75.8% of Sudan III were reduced by the bacterium, respectively. In the presence of 36 mu g/ml Sudan III, the cell viability of the bacterium decreased to 61.9% after 48 h of incubation, whereas the cell viability of the control culture without the dye was 71.5%. Moreover, the optical density of the bacterial cultures at 10 h decreased from 0.74 to 0.55, indicating that Sudan III is able to inhibit growth of the bacterium. However, Orange II had no significant effects on either cell growth or cell viability of the bacterium at the tested concentrations. 1-Amino-2-naphthol, a metabolite common to Orange II and Sudan III, was capable of inhibiting cell growth of the bacterium at 1 mu g/ml and completely stopped bacterial cell growth at 24-48 mu g/ml. On the other hand, the other metabolites of Orange II and Sudan III, namely sulfanilic acid, p-phenylenediamine, and aniline, showed no significant effects on cell growth. p-Phenylenediamine exhibited a synergistic effect with 1-amino-2-naphthol on cell growth inhibition. All of the dye metabolites had no significant effects on cell viability of the bacterium. C1 [Pan, Hongmiao; Feng, Jinhui; Cerniglia, Carl E.; Chen, Huizhong] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM huizhong.chen@fda.hhs.gov FU Office of Women's Health; National Center for Toxicological Research, United States Food and Drug Administration; Oak Ridge Institute for Science and Education; US Department of Energy; US Food and Drug Administration FX We thank Drs. Huanli Liu, Rajesh Nayak, and Robin Stingley for their critical review of the manuscript, Dr. Mark Hart for strain ATCC BAA 1556, and Ohgew Kweon for helpful discussions. This study was funded by the Office of Women's Health and the National Center for Toxicological Research, United States Food and Drug Administration, and supported in part by appointments (HP and JF) to the Postgraduate Research Fellowship Program 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 views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 51 TC 10 Z9 12 U1 1 U2 17 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 OCT PY 2011 VL 38 IS 10 BP 1729 EP 1738 DI 10.1007/s10295-011-0962-3 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 823AN UT WOS:000295093300011 PM 21451978 ER PT J AU Cohen, E Agrawal, A Connors, M Hansen, B Charkhkar, H Pfefer, J AF Cohen, Ethan Agrawal, Anant Connors, Megan Hansen, Barry Charkhkar, Hamid Pfefer, Joshua TI Optical coherence tomography imaging of retinal damage in real time under a stimulus electrode SO JOURNAL OF NEURAL ENGINEERING LA English DT Article ID SUPRACHOROIDAL-TRANSRETINAL STIMULATION; SOURCE-DENSITY ANALYSIS; ELECTRICAL-STIMULATION; GANGLION-CELLS; RABBIT RETINA; DEVELOPMENTAL NEUROTOXICITY; AUDITORY-NERVE; CHARGE-DENSITY; GLIAL-CELLS; ACTIVATION AB We have developed a novel method to study the effects of electrical stimulation of the local retina directly under an epiretinal stimulus electrode in real time. Using optical coherence tomography (OCT) and a superfused retinal eyecup preparation, we obtained high-resolution images of the rabbit retina directly under an optically transparent saline-filled fluoropolymer stimulation tube electrode. During OCT imaging, 50 Hz trains of biphasic current pulses 1 ms/phase (23-749 mu C cm(-2) ph(-1)) were applied to the retinal surface for 5 min. After imaging, the stimulated regions were stained with the dye propidium iodide (PI) to reveal cytotoxic damage. Pulse train stimulation at 44-133 mu C cm(-2) ph(-1) had little effect on the retina; however, trains >= 442 mu C cm(-2) ph(-1) caused increases in the reflectance of the inner plexiform layer (IPL) and edema. The damage seen in retinal OCT images matched the pattern observed in histological sections, and in the PI staining. With pulse trains >= 442 mu C cm(-2) ph(-1), rapid increases in the reflectivity of the IPL could be observed under the stimulus electrode. Below the electrode, we observed a ring-like pattern of retinal detachment in the subretinal space. The OCT imaging method may be useful for analyzing overstimulation of neuronal tissue by electrodes in many brain regions. C1 [Cohen, Ethan; Agrawal, Anant; Hansen, Barry; Pfefer, Joshua] White Oak Fed Res Ctr, CDRH FDA, Off Sci & Engn Labs, Div Phys, White Oak, MD USA. [Connors, Megan] Univ Maryland, Dept Elect Engn, College Pk, MD 20742 USA. [Charkhkar, Hamid] George Mason Univ, Dept Elect Engn, Fairfax, VA 22030 USA. RP Cohen, E (reprint author), White Oak Fed Res Ctr, CDRH FDA, Off Sci & Engn Labs, Div Phys, White Oak, MD USA. EM ethan.cohen@fda.hhs.gov RI Pfefer, Josh/I-9055-2012; OI COHEN, ETHAN/0000-0001-6365-2266; Charkhkar, Hamid/0000-0001-5485-5969 NR 53 TC 11 Z9 11 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD OCT PY 2011 VL 8 IS 5 AR 056017 DI 10.1088/1741-2560/8/5/056017 PG 13 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 822VV UT WOS:000295079200018 PM 21934187 ER PT J AU Allen, CE Schmitt, MP AF Allen, Courtni E. Schmitt, Michael P. TI Novel Hemin Binding Domains in the Corynebacterium diphtheriae HtaA Protein Interact with Hemoglobin and Are Critical for Heme Iron Utilization by HtaA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCUS; CELL-SURFACE PROTEIN; STAPHYLOCOCCUS-AUREUS; BACTERIAL PATHOGENS; TRANSPORT-SYSTEM; BROAD-SPECTRUM; ACQUISITION; IDENTIFICATION; SIDEROPHORE; METHEMOGLOBIN AB The human pathogen Corynebacterium diphtheriae utilizes hemin and hemoglobin as iron sources for growth in iron-depleted environments. The use of hemin iron in C. diphtheriae involves the dtxR- and iron-regulated hmu hemin uptake locus, which encodes an ABC hemin transporter, and the surface-anchored hemin binding proteins HtaA and HtaB. Sequence analysis of HtaA and HtaB identified a conserved region (CR) of approximately 150 amino acids that is duplicated in HtaA and present in a single copy in HtaB. The two conserved regions in HtaA, designated CR1 and CR2, were used to construct glutathione S-transferase (GST) fusion proteins (GST-CR1 and GST-CR2) to assess hemin binding by UV-visual spectroscopy. These studies showed that both domains were able to bind hemin, suggesting that the conserved sequences are responsible for the hemin binding property previously ascribed to HtaA. HtaA and the CR2 domain were also shown to be able to bind hemoglobin (Hb) by the use of an enzyme-linked immunosorbent assay (ELISA) method in which Hb was immobilized on a microtiter plate. The CR1 domain exhibited a weak interaction with Hb in the ELISA system, while HtaB showed no significant binding to Hb. Competitive binding studies demonstrated that soluble hemin and Hb were able to inhibit the binding of HtaA and the CR domains to immobilized Hb. Moreover, HtaA was unable to bind to Hb from which the hemin had been chemically removed. Alignment of the amino acid sequences of CR domains from various Corynebacterium species revealed several conserved residues, including two highly conserved tyrosine (Y) residues and one histidine (H) residue. Site-directed mutagenesis studies showed that Y361 and H412 were critical for the binding to hemin and Hb by the CR2 domain. Biological assays showed that Y361 was essential for the hemin iron utilization function of HtaA. Hemin transfer experiments demonstrated that HtaA was able to acquire hemin from Hb and that hemin bound to HtaA could be transferred to HtaB. These findings are consistent with a proposed mechanism of hemin uptake in C. diphtheriae in which hemin is initially obtained from Hb by HtaA and then transferred between surface-anchored proteins, with hemin ultimately transported into the cytosol by an ABC transporter. C1 [Allen, Courtni E.; Schmitt, Michael P.] US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM michael.schmitt@fda.hhs.gov NR 48 TC 17 Z9 17 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 OCT PY 2011 VL 193 IS 19 BP 5374 EP 5385 DI 10.1128/JB.05508-11 PG 12 WC Microbiology SC Microbiology GA 819LE UT WOS:000294826200036 PM 21803991 ER PT J AU Bogdanove, AJ Koebnik, R Lu, H Furutani, A Angiuoli, SV Patil, PB Van Sluys, MA Ryan, RP Meyer, DF Han, SW Aparna, G Rajaram, M Delcher, AL Phillippy, AM Puiu, D Schatz, MC Shumway, M Sommer, DD Trapnell, C Benahmed, F Dimitrov, G Madupu, R Radune, D Sullivan, S Jha, G Ishihara, H Lee, SW Pandey, A Sharma, V Sriariyanun, M Szurek, B Vera-Cruz, CM Dorman, KS Ronald, PC Verdier, V Dow, JM Sonti, RV Tsuge, S Brendel, VP Rabinowicz, PD Leach, JE White, FF Salzberg, SL AF Bogdanove, Adam J. Koebnik, Ralf Lu, Hong Furutani, Ayako Angiuoli, Samuel V. Patil, Prabhu B. Van Sluys, Marie-Anne Ryan, Robert P. Meyer, Damien F. Han, Sang-Wook Aparna, Gudlur Rajaram, Misha Delcher, Arthur L. Phillippy, Adam M. Puiu, Daniela Schatz, Michael C. Shumway, Martin Sommer, Daniel D. Trapnell, Cole Benahmed, Faiza Dimitrov, George Madupu, Ramana Radune, Diana Sullivan, Steven Jha, Gopaljee Ishihara, Hiromichi Lee, Sang-Won Pandey, Alok Sharma, Vikas Sriariyanun, Malinee Szurek, Boris Vera-Cruz, Casiana M. Dorman, Karin S. Ronald, Pamela C. Verdier, Valerie Dow, J. Maxwell Sonti, Ramesh V. Tsuge, Seiji Brendel, Volker P. Rabinowicz, Pablo D. Leach, Jan E. White, Frank F. Salzberg, Steven L. TI Two New Complete Genome Sequences Offer Insight into Host and Tissue Specificity of Plant Pathogenic Xanthomonas spp. SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ORYZAE PV.-ORYZAE; 2-COMPONENT SIGNAL-TRANSDUCTION; CAMPESTRIS PATHOVAR CAMPESTRIS; GYP DOMAIN PROTEIN; OUTER-MEMBRANE; III EFFECTORS; RESISTANCE GENE; DI-GMP; HYPERSENSITIVE RESPONSE; ARABIDOPSIS-THALIANA AB Xanthomonas is a large genus of bacteria that collectively cause disease on more than 300 plant species. The broad host range of the genus contrasts with stringent host and tissue specificity for individual species and pathovars. Whole-genome sequences of Xanthomonas campestris pv. raphani strain 756C and X. oryzae pv. oryzicola strain BLS256, pathogens that infect the mesophyll tissue of the leading models for plant biology, Arabidopsis thaliana and rice, respectively, were determined and provided insight into the genetic determinants of host and tissue specificity. Comparisons were made with genomes of closely related strains that infect the vascular tissue of the same hosts and across a larger collection of complete Xanthomonas genomes. The results suggest a model in which complex sets of adaptations at the level of gene content account for host specificity and subtler adaptations at the level of amino acid or noncoding regulatory nucleotide sequence determine tissue specificity. C1 [Bogdanove, Adam J.; Meyer, Damien F.; Trapnell, Cole] Iowa State Univ, Dept Plant Pathol, 351 Bessey Hall, Ames, IA 50011 USA. [Koebnik, Ralf; Szurek, Boris; Verdier, Valerie] Inst Rech Dev, UMR RPB IRD CIRAD UM2, F-34394 Montpellier 5, France. [Lu, Hong; Brendel, Volker P.] Iowa State Univ, Dept Genet Cell & Dev Biol, Ames, IA 50011 USA. [Furutani, Ayako] Natl Inst Agrobiol Sci, Dept Genet Resources, Tsukuba, Ibaraki 3058602, Japan. [Furutani, Ayako] Ibaraki Univ, Ctr Gene Res, Ami, Ibaraki 3000393, Japan. [Angiuoli, Samuel V.; Delcher, Arthur L.; Phillippy, Adam M.; Puiu, Daniela; Schatz, Michael C.; Sommer, Daniel D.; Salzberg, Steven L.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Patil, Prabhu B.; Sharma, Vikas] CSIR, Inst Microbial Technol, Chandigarh 160036, India. [Van Sluys, Marie-Anne; Ishihara, Hiromichi; Leach, Jan E.] Colorado State Univ, Dept Bioagr Sci & Pest Management, Ft Collins, CO 80523 USA. [Van Sluys, Marie-Anne] IB USP, Dept Bot, Sao Paulo, Brazil. [Ryan, Robert P.; Dow, J. Maxwell] Univ Coll Cork, BioSci Inst, BIOMERIT Res Ctr, Cork, Ireland. [Meyer, Damien F.] INRA, CIRAD, Control Emerging & Exot Anim Dis, Prise Deau 97170, Petit Bourg, Guadeloupe. [Han, Sang-Wook; Lee, Sang-Won; Sriariyanun, Malinee; Ronald, Pamela C.] Univ Calif Davis, Dept Plant Pathol, Davis, CA 95616 USA. [Aparna, Gudlur; Jha, Gopaljee; Pandey, Alok; Sonti, Ramesh V.] CSIR, Ctr Cellular & Mol Biol, Hyderabad, Andhra Pradesh, India. [Aparna, Gudlur] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA. [Rajaram, Misha; Dorman, Karin S.; Brendel, Volker P.] Iowa State Univ, Dept Stat, Ames, IA 50011 USA. [Rajaram, Misha] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Phillippy, Adam M.] Natl Biodef Anal & Countermeasures Ctr, Frederick, MD 21702 USA. [Schatz, Michael C.] Cold Spring Harbor Lab, Simons Ctr Quantitat Biol, Cold Spring Harbor, NY 11724 USA. [Shumway, Martin] NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Trapnell, Cole] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Benahmed, Faiza; Dimitrov, George; Madupu, Ramana; Radune, Diana; Sullivan, Steven; Rabinowicz, Pablo D.] Inst Genom Res, Rockville, MD 20850 USA. [Benahmed, Faiza] US FDA, Div Food & Anim Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Sullivan, Steven] NYU, Ctr Genom & Syst Biol, New York, NY 10003 USA. [Jha, Gopaljee] CSIR, Inst Himalayan Bioresouce Technol, Palampur, Himachal Prades, India. [Ishihara, Hiromichi] Okayama Univ, Grad Sch Nat Sci & Technol, Dept Chem Mat, Okayama 7008530, Japan. [Lee, Sang-Won] Kyung Hee Univ, Dept Plant Mol Syst Biotechnol, Yongin 446701, South Korea. [Lee, Sang-Won] Kyung Hee Univ, Crop Biotech Inst, Yongin 446701, South Korea. [Vera-Cruz, Casiana M.] Int Rice Res Inst, Plant Breeding Genet & Biotechnol Div, Manila, Philippines. [Tsuge, Seiji] Kyoto Prefectural Univ, Plant Pathol Lab, Sakyo Ku, Kyoto 6068522, Japan. [Delcher, Arthur L.; Rabinowicz, Pablo D.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Rabinowicz, Pablo D.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [White, Frank F.] Kansas State Univ, Dept Plant Pathol, Manhattan, KS 66506 USA. [Salzberg, Steven L.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Bogdanove, AJ (reprint author), Iowa State Univ, Dept Plant Pathol, 351 Bessey Hall, Ames, IA 50011 USA. EM ajbog@iastate.edu RI Van Sluys, Marie-Anne/A-8483-2012; MEYER, Damien/G-2607-2013; Salzberg, Steven/F-6162-2011; IB/USP, Botanica/Q-7627-2016; 2, INCT/G-6506-2013; Bioetanol, Inct/I-1068-2013; Angiuoli, Samuel/H-7340-2014; Lu, Hong/F-2744-2015; Gudlur, Aparna/J-9646-2015; Sriariyanun, Malinee/B-6767-2016; Verdier, Valerie/K-1004-2016; Koebnik, Ralf/J-5627-2014 OI Jha, Gopaljee/0000-0002-3965-3135; Angiuoli, Samuel/0000-0001-9525-4350; Ryan, Rober/0000-0002-7353-0913; Dorman, Karin/0000-0003-3650-0018; Van Sluys, Marie-Anne/0000-0002-6506-2734; MEYER, Damien/0000-0003-2735-176X; Salzberg, Steven/0000-0002-8859-7432; IB/USP, Botanica/0000-0002-4192-3747; Lu, Hong/0000-0002-4026-4292; Gudlur, Aparna/0000-0001-8753-183X; Sriariyanun, Malinee/0000-0002-3088-9256; Verdier, Valerie/0000-0001-5425-9454; Koebnik, Ralf/0000-0002-4419-0542 FU USDA-NSF [20043560015022] FX This work was supported by the USDA-NSF Microbial Genome Sequencing Program (award CSREES 20043560015022). NR 109 TC 85 Z9 94 U1 3 U2 35 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2011 VL 193 IS 19 BP 5450 EP 5464 DI 10.1128/JB.05262-11 PG 15 WC Microbiology SC Microbiology GA 819LE UT WOS:000294826200044 PM 21784931 ER PT J AU Garcia, MC Amankwa-Sakyi, M Flynn, TJ AF Garcia, Martha C. Amankwa-Sakyi, Margaret Flynn, Thomas J. TI Cellular glutathione in fatty liver in vitro models SO TOXICOLOGY IN VITRO LA English DT Article DE Fatty liver; Glutathione; NAFLD; Oxidative stress; Obesity ID ACIDS SENSITIZE HEPATOCYTES; OXIDATIVE STRESS; NONALCOHOLIC STEATOHEPATITIS; LIPID-PEROXIDATION; DISEASE; STEATOSIS; LIPOTOXICITY; CELLS; MECHANISMS; RESISTANCE AB The range of non-alcoholic fatty liver disease (NAFLD) includes simple hepatic steatosis, the inflammatory non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. The accumulation of specific lipids in hepatocytes has been associated with oxidative stress and progression of the disease. Elevated serum free fatty acids and hepatocyte lipotoxicity can be studied in an in vitro cellular model. For this purpose, we cultured the human liver cell line, HepG2/C3A, in medium supplemented with increasing amounts of oleic acid (08:1) and evaluated oxidative stress by measuring the content of the cellular antioxidant, glutathione (GSH). We observed a dose-dependent steatosis, as determined by Nile Red staining, with concurrent increases of GSH; similar findings were also observed in cultured human hepatocytes. Cells cultured with palmitic acid (C16:0) or the combination oleic/palmitic acids (2:1 ratio) also exhibited a dose-dependent increase of GSH; however palmitic-supplemented cultures did not sustain the GSH increase after 24 h. We also detected an increase in the formation of lipid peroxides (LPO) indicating that the increase of GSH was a cellular mechanism that may be related to the high exposure of fatty acids. The results of this in vitro study suggest an antioxidant response against fat overloading and indicate potential differences in response to specific fatty acid-induced hepatic steatosis and associated lipotoxicity. Published by Elsevier Ltd. C1 [Garcia, Martha C.] US FDA, MOD Labs 1, Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD 20708 USA. [Amankwa-Sakyi, Margaret] US FDA, Ctr Food Safety & Appl Nutr, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP Garcia, MC (reprint author), US FDA, MOD Labs 1, Ctr Food Safety & Appl Nutr, Div Toxicol, HFS-025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM martha.garcia@fda.hhs.gov; Margaret.Amankwa-Sakyi@fda.hhs.gov; thomas.flynn@fda.hhs.gov OI Flynn, Thomas/0000-0002-7248-0643 FU FDA FX The authors would like to express their thanks to Ms. Erica Hoagland for her technical assistance. The assistance of Michael W. O'Donnell with statistical analysis is also appreciated. The research was support in part through funding from the FDA Commissioner's Fellowship Program to MCG. NR 34 TC 13 Z9 14 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0887-2333 J9 TOXICOL IN VITRO JI Toxicol. Vitro PD OCT PY 2011 VL 25 IS 7 BP 1501 EP 1506 DI 10.1016/j.tiv.2011.05.011 PG 6 WC Toxicology SC Toxicology GA 822RF UT WOS:000295066600032 PM 21620948 ER PT J AU Sutter, DE Summers, AM Keys, CE Taylor, KL Frasch, CE Braun, LE Fattom, AI Bash, MC AF Sutter, Deena E. Summers, Amy M. Keys, Christine E. Taylor, Kimberly L. Frasch, Carl E. Braun, LoRanee E. Fattom, Ali I. Bash, Margaret C. TI Capsular serotype of Staphylococcus aureus in the era of community-acquired MRSA SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Staphylococcus aureus; MRSA; pediatric; community acquired; capsule ID PANTON-VALENTINE LEUKOCIDIN; UNITED-STATES; TEICHOIC-ACIDS; GENETIC-LOCI; INFECTIONS; POLYSACCHARIDE; PNEUMONIA; VIRULENCE; MODEL; SKIN AB Capsular polysaccharide (CP) plays an important role in the pathogenicity and immunogenicity of Staphylococcus aureus, yet the common serotypes of S. aureus isolated from US pediatric patients have not been reported. We investigated capsular serotype as well as methicillin susceptibility, presence of Panton-Valentine leukocidin (PVL), and clonal relatedness of pediatric S. aureus isolates. Clinical isolates were tested for methicillin susceptibility, presence of mecA, lukS-PV and lukF-PV, cap5 and cap8 genes by PCR, and for capsular or surface polysaccharide expression (CP5, CP8, or 336 polysaccharide) by agglutination. Genetic relatedness was determined by pulsed-field gel electrophoresis. All S. aureus isolates encoded cap5 or cap8. Sixty-nine percent of 2004-2005 isolates were methicillin-susceptible (MSSA) and most expressed a detectable capsule. The majority of MRSA isolates (82%) were unencapsulated, exposing an expressed cell wall techoic acid antigen 336. Pulsed-field type USA300 were MRSA, PVL-positive, unencapsulated strains that were associated with deep skin infections and recurrent disease. Over half (58%) of all isolates from invasive pediatric dermatologic infections were USA300. All pediatric isolates contained either capsule type 5 or capsule type 8 genes, and roughly half of the S. aureus clinical disease isolates from our population were diverse MSSA-encapsulated strains. The majority of the remaining pediatric clinical disease isolates were unencapsulated serotype 336 strains of the PVL(1) USA300 community-associated-MRSA clone. C1 [Sutter, Deena E.; Frasch, Carl E.; Bash, Margaret C.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Summers, Amy M.] Walter Reed Army Med Ctr, Dept Pathol, Washington, DC 20307 USA. [Keys, Christine E.; Fattom, Ali I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Taylor, Kimberly L.] Nabi Biopharmaceut, Rockville, MD USA. [Sutter, Deena E.; Braun, LoRanee E.; Bash, Margaret C.] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. RP Sutter, DE (reprint author), Brooke Army Med Ctr, Dept Pediat, 3851 Roger Brooke Dr, Ft Sam Houston, TX 78234 USA. EM deena.sutter@amedd.army.mil NR 34 TC 15 Z9 15 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD OCT PY 2011 VL 63 IS 1 BP 16 EP 24 DI 10.1111/j.1574-695X.2011.00822.x PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 820TQ UT WOS:000294928900003 PM 21631600 ER PT J AU Sauna, ZE Kimchi-Sarfaty, C AF Sauna, Zuben E. Kimchi-Sarfaty, Chava TI Understanding the contribution of synonymous mutations to human disease SO NATURE REVIEWS GENETICS LA English DT Review ID TRANSFER-RNA-SYNTHETASE; CODING-SEQUENCE EVOLUTION; GENOME-WIDE ASSOCIATION; P-GLYCOPROTEIN ABCB1; ESCHERICHIA-COLI; MESSENGER-RNA; CODON USAGE; SECONDARY STRUCTURE; GENE-EXPRESSION; PROTEIN THERAPEUTICS AB Synonymous mutations-sometimes called 'silent' mutations-are now widely acknowledged to be able to cause changes in protein expression, conformation and function. The recent increase in knowledge about the association of genetic variants with disease, particularly through genome-wide association studies, has revealed a substantial contribution of synonymous SNPs to human disease risk and other complex traits. Here we review current understanding of the extent to which synonymous mutations influence disease, the various molecular mechanisms that underlie these effects and the implications for future research and biomedical applications. C1 [Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Sauna, ZE (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM zuben.sauna@fda.hhs.gov; chava.kimchi-sarfaty@fda.hhs.gov FU Laboratory of Hemostasis; Center for Biologics Evaluation and Research, US Food and Drug Administration FX We thank B. Golding for helpful discussions and G. S. Pandey for comments and help in the manuscript preparation. The assistance of E. Ayalp and I. Kimchi in generating the table in box 1 and J. Sauna for the illustrations in figure 1 is gratefully acknowledged. This work was supported by funds from the Laboratory of Hemostasis (C.K.-S.) and the Center for Biologics Evaluation and Research, US Food and Drug Administration's Modernization of Science programme (Z.E.S.). The findings and conclusions in this article have not been formally disseminated by the US Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 93 TC 261 Z9 270 U1 3 U2 54 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2011 VL 12 IS 10 BP 683 EP 691 DI 10.1038/nrg3051 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 820ZL UT WOS:000294944500009 PM 21878961 ER PT J AU Wokovich, AM Shen, MY Doub, WH Machado, SG Buhse, LF AF Wokovich, Anna M. Shen, Meiyu Doub, William H. Machado, Stella G. Buhse, Lucinda F. TI Evaluating elevated release liner adhesion of a transdermal drug delivery system (TDDS): A study of Daytrana (TM) methylphenidate transdermal system SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE Adhesion; liner; methylphenidate; release liner; patch; transdermal delivery system ID 90-DEGREES PEEL ADHESION AB Background: Complaints from healthcare providers that the adhesive on the Daytrana (TM) methylphenidate transdermal drug delivery system (TDDS) adhered to the release liner to such an extent that the release liner could not be removed prompted this study. Daytrana (TM) has a packaging system consisting of a moisture-permeable pouch contained within a sealed tray containing a desiccant; the tray is impermeable to ambient moisture. The objective of this project was to determine if the Daytrana (TM) packaging system influenced the difficulty in removing the release liner. Method: Both a sealed tray and an open tray containing sealed pouches were placed into an environmental chamber at 25 degrees C and 60% relative humidity for 30 days; afterwards, release liner removal testing using a peel angle of 90 degrees and a peel speed of 300 mm/min was performed. Results: TDDS from open chamber trays required less force to remove the release liner than did TDDS from closed chamber trays. For the 10 mg/9 h TDDS and the 15 mg/9 h TDDS (the dosages examined), there were substantial differences in release liner removal force between an old lot and a new lot for closed chamber trays but not for open chamber trays. Conclusion: The results demonstrate that for this particular TDDS, storage conditions such as humidity influence release liner adhesion. This project also demonstrates that, to ensure adequate product quality, adhesion needs to become an important design parameter, and the design of a TDDS should consider the ability to remove the release liner under anticipated storage conditions. C1 [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. [Shen, Meiyu; Machado, Stella G.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wokovich, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. EM anna.wokovich@fda.hhs.gov FU FDA Center for Drug Evaluation and Research (CDER) FX The authors thank the FDA Center for Drug Evaluation and Research (CDER) Regulatory Science and Review Enhancement (RSR) program for funding this project. This project relates with post-market product quality and safety issues, one of CDER's FY 2008 priorities. This article reflects the current thinking and experience of the authors. 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. The views presented in this article do not necessarily reflect those of Food and Drug Administration policy; this is not a policy document and should not be used in lieu of regulations, published FDA guidances or direct discussions with the agency. 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. The information presented in this article is publically available; references are provided in the text. NR 35 TC 3 Z9 3 U1 0 U2 6 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PD OCT PY 2011 VL 37 IS 10 BP 1217 EP 1224 DI 10.3109/03639045.2011.565773 PG 8 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 819WD UT WOS:000294862600010 PM 21438703 ER PT J AU Ali, MI Luttrell, RG AF Ali, M. I. Luttrell, R. G. TI Susceptibility of Helicoverpa zea and Heliothis virescens (Lepidoptera: Noctuidae) to Vip3A insecticidal protein expressed in VipCot (TM) cotton SO JOURNAL OF INVERTEBRATE PATHOLOGY LA English DT Article DE Helicoverpa zea; Heliothis virescens; LC(50); MIC(50); Vip3A; Susceptibility ID BASE-LINE SUSCEPTIBILITY; EUROPEAN CORN-BORER; BACILLUS-THURINGIENSIS TOXIN; RESISTANCE MANAGEMENT; TRANSGENIC COTTON; CRYSTAL PROTEINS; POPULATIONS; PESTS; ENDOTOXIN; TOXICITY AB Susceptibility of laboratory and field colonies of Helicoverpa zea (Boddie) and Heliothis virescens F. to Vip3A insecticidal protein was studied in diet incorporation and diet overlay assays from 2004 to 2008. Responses of field populations were compared to paired responses of University of Arkansas laboratory susceptible H. zea (LabZA) and H. virescens (LabVR) colonies. After 7 d of exposure, observations were made on number of dead larvae (M) and the number of larvae alive but remaining as first instars (L1). Regression estimates using M (LC(50)) and M plus L1 (MIC(50)) data were developed for laboratory and field populations. Susceptibility of laboratory and field populations exposed to Vip3A varied among different batches of protein used over the study period. Within the same batch of Vip3A protein, susceptibilities of laboratory colonies of both species (LabZA and LabVR) were similar. Field colonies were significantly more susceptible to Vip3A than the respective reference colonies of both species. Within field populations, susceptibility to Vip3A varied up to 75-fold in H. zea and 132-fold in H. virescens in LC(50) estimates. Variabilities in MIC(50)s were up to 59- and 11-fold for H. zea and H. virescens, respectively. Published by Elsevier Inc. C1 [Ali, M. I.; Luttrell, R. G.] Univ Arkansas, Dept Entomol, Div Agr, Fayetteville, AR 72701 USA. RP Ali, MI (reprint author), FDA ORA, Arkansas Reg Lab, 3900 NCTR Rd,Bldg 26, Jefferson, AR 72079 USA. EM Ibrahim.Ali@fda.hhs.gov FU Syngenta Biotechnology, Raleigh, NC FX This research was supported by financial contributions from Syngenta Biotechnology, Raleigh, NC. We acknowledge R. Kurtz, A. Crespo, A. McCaffery and D. O'Reilly of Syngenta Biotechnology for their cooperation in providing the Vip3A protein for the study. We thank students and employees of the University of Arkansas for their assistance in rearing insects and conducting assays. Sakuntala Sivasupramaniam, Shank Palekar, Ryan Jackson and Ryan Kurtz are acknowledged for critical reviews of earlier drafts of this manuscript. NR 36 TC 6 Z9 6 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-2011 J9 J INVERTEBR PATHOL JI J. Invertebr. Pathol. PD OCT PY 2011 VL 108 IS 2 BP 76 EP 84 DI 10.1016/j.jip.2011.06.013 PG 9 WC Zoology SC Zoology GA 819NY UT WOS:000294834800002 PM 21767545 ER PT J AU Lucas, PW Schmit, JM Peterson, QP West, DC Hsu, DC Novotny, CJ Dirikolu, L Churchwell, MI Doerge, DR Garrett, LD Hergenrother, PJ Fan, TM AF Lucas, Pamela W. Schmit, Joanna M. Peterson, Quinn P. West, Diana C. Hsu, Danny C. Novotny, Chris J. Dirikolu, Levent Churchwell, Mona I. Doerge, Daniel R. Garrett, Laura D. Hergenrother, Paul J. Fan, Timothy M. TI Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Procaspase-3 activation; Novel anticancer strategy; Pharmacokinetic modeling; Comparative and translational oncology; Non-Hodgkin's lymphoma ID APOPTOSIS PROTEIN FAMILY; NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMAS; VETERINARY-MEDICINE; SPECIAL SERIES; CANCER; INHIBITOR; DEATH; CASPASE-3; EXPRESSION AB PAC-1 is a preferential small molecule activator of procaspase-3 and has potential to become a novel and effective anticancer agent. The rational development of PAC-1 for translational oncologic applications would be advanced by coupling relevant in vitro cytotoxicity studies with pharmacokinetic investigations conducted in large mammalian models possessing similar metabolism and physiology as people. In the present study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 h that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 +/- 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 h in duration. Using the dog as a large mammalian model, PAC-1 can be safely administered as an intravenous CRI while achieving predicted in vitro cytotoxic concentrations. C1 [Lucas, Pamela W.; Schmit, Joanna M.; Garrett, Laura D.; Fan, Timothy M.] Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA. [Churchwell, Mona I.; Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [West, Diana C.; Hsu, Danny C.; Hergenrother, Paul J.] Univ Illinois, Dept Chem, Urbana, IL 61801 USA. [Peterson, Quinn P.; Novotny, Chris J.; Hergenrother, Paul J.] Univ Illinois, Dept Biochem, Urbana, IL 61801 USA. [Dirikolu, Levent] Univ Illinois, Dept Vet Biosci, Urbana, IL 61802 USA. RP Fan, TM (reprint author), Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA. EM hergenro@illinois.edu; t-fan@illinois.edu FU Office of the Vice President for Technology and Economic Development at the University of Illinois; National Institutes of Health [R01-CA120439]; NIH (Ruth L. Kirschstein National Research Service) [1 T32 GM070421]; Medicinal Chemistry Division of the American Chemical Society; Ruth L. Kirschstein National Research Service [F31-CA130138-01 S1] FX This work is supported in part by the Office of the Vice President for Technology and Economic Development at the University of Illinois, and the National Institutes of Health (R01-CA120439, PJH). QPP was supported by a Chemistry-Biology Interface Training Grant from the NIH (Ruth L. Kirschstein National Research Service Award 1 T32 GM070421) and by a predoctoral fellowship from the Medicinal Chemistry Division of the American Chemical Society. DCW was partially supported by Ruth L. Kirschstein National Research Service Award F31-CA130138-01 S1. We thank Mrs. Holly Pondenis and Mr. Ian Sprandel for helping with in vitro laboratory experiments, and Mrs. Rebecca Kamerer and Nancy George for aiding canine pharmacokinetic experiments. The views presented in this article do not necessarily reflect those of the U. S. Food and Drug Administration. NR 37 TC 16 Z9 16 U1 0 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2011 VL 29 IS 5 BP 901 EP 911 DI 10.1007/s10637-010-9445-z PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 811PC UT WOS:000294223500020 PM 20499133 ER PT J AU Chowdhury, BA Seymour, SM Levenson, MS AF Chowdhury, Badrul A. Seymour, Sally M. Levenson, Mark S. TI Adding LABAs to Inhaled Glucocorticoids for Asthma REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD USA. RP Chowdhury, BA (reprint author), US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 29 PY 2011 VL 365 IS 13 BP 1261 EP 1261 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 825YO UT WOS:000295318400030 ER PT J AU Mattison, DR Plant, TM Lin, HM Chen, HC Chen, JJ Twaddle, NC Doerge, D Slikker, W Patton, RE Hotchkiss, CE Callicott, RJ Schrader, SM Turner, TW Kesner, JS Vitiello, B Petibone, DM Morris, SM AF Mattison, Donald R. Plant, Tony M. Lin, Hui-Min Chen, Hung-Chia Chen, James J. Twaddle, Nathan C. Doerge, Daniel Slikker, William, Jr. Patton, Ralph E. Hotchkiss, Charlotte E. Callicott, Ralph J. Schrader, Steven M. Turner, Terry W. Kesner, James S. Vitiello, Benedetto Petibone, Dayton M. Morris, Suzanne M. TI Pubertal delay in male nonhuman primates (Macaca mulatta) treated with methylphenidate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE attention deficit hyperactivity disorder; developmental delay; male puberty ID FOLLICLE-STIMULATING-HORMONE; INHIBIN-B; LUTEINIZING-HORMONE; GONADOTROPIN; TESTOSTERONE; SECRETION; RELEASE; SERTOLI; LEPTIN; RATS AB Juvenile male rhesus monkeys treated with methylphenidate hydrochloride (MPH) to evaluate genetic and behavioral toxicity were observed after 14 mo of treatment to have delayed pubertal progression with impaired testicular descent and reduced testicular volume. Further evaluation of animals dosed orally twice a day with (i) 0.5 mL/kg of vehicle (n = 10), (ii) 0.15 mg/kg of MPH increased to 2.5 mg/kg (low dose, n = 10), or (iii) 1.5 mg/kg of MPH increased to 12.5 mg/kg (high dose, n = 10) for a total of 40 mo revealed that testicular volume was significantly reduced (P < 0.05) at months 15 to 19 and month 27. Testicular descent was significantly delayed (P < 0.05) in the high-dose group. Significantly lower serum testosterone levels were detected in both the low-(P = 0.0017) and high-dose (P = 0.0011) animals through month 33 of treatment. Although serum inhibin B levels were increased overall in low-dose animals (P = 0.0328), differences between groups disappeared by the end of the study. Our findings indicate that MPH administration, beginning before puberty, and which produced clinically relevant blood levels of the drug, impaired pubertal testicular development until similar to 5 y of age. It was not possible to resolve whether MPH delayed the initiation of the onset of puberty or reduced the early tempo of the developmental process. Regardless, deficits in testicular volume and hormone secretion disappeared over the 40-mo observation period, suggesting that the impact of MPH on puberty is not permanent. C1 [Mattison, Donald R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. [Plant, Tony M.] Univ Pittsburgh, Magee Womens Res Inst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. [Lin, Hui-Min; Chen, Hung-Chia; Chen, James J.; Twaddle, Nathan C.; Doerge, Daniel; Slikker, William, Jr.; Petibone, Dayton M.; Morris, Suzanne M.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Patton, Ralph E.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hotchkiss, Charlotte E.; Callicott, Ralph J.] Bionet Corp, Jefferson, AR 72079 USA. [Schrader, Steven M.; Turner, Terry W.; Kesner, James S.] NIOSH, Div Appl Res & Technol, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA. [Vitiello, Benedetto] NIMH, Bethesda, MD 20892 USA. RP Mattison, DR (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. EM mattisod@mail.nih.gov RI Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 FU Eunice Kennedy Shriver National Institute for Child Health; Development/National Institutes of Health; National Center for Toxicological Research/Food and Drug Administration; National Center for Toxicological Research; National Institute for Occupational Safety and Health; Oak Ridge Institute for Science and Education; National Institute for Child Health and Human Development; National Institutes of Health [R01 HD 013254] FX This work was supported by an InterAgency Agreement between the Eunice Kennedy Shriver National Institute for Child Health and Development/National Institutes of Health and the National Center for Toxicological Research/Food and Drug Administration; an Interagency Agreement between the National Center for Toxicological Research and the National Institute for Occupational Safety and Health; an Interagency Agreement between the Oak Ridge Institute for Science and Education and the National Center for Toxicological Research/Food and Drug Administration (H.-M. L. and H.-C. C.); intramural funds from the National Institute for Child Health and Human Development (to D. R. M.); and National Institutes of Health Grant R01 HD 013254 (to T. M. P.). NR 21 TC 16 Z9 17 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 27 PY 2011 VL 108 IS 39 BP 16301 EP 16306 DI 10.1073/pnas.1102187108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 825FB UT WOS:000295255300038 PM 21930929 ER PT J AU Griffiths, HH Whitehouse, IJ Baybutt, H Brown, D Kellett, KAB Jackson, CD Turner, AJ Piccardo, P Manson, JC Hooper, NM AF Griffiths, Heledd H. Whitehouse, Isobel J. Baybutt, Herbert Brown, Debbie Kellett, Katherine A. B. Jackson, Carolyn D. Turner, Anthony J. Piccardo, Pedro Manson, Jean C. Hooper, Nigel M. TI Prion Protein Interacts with BACE1 Protein and Differentially Regulates Its Activity toward Wild Type and Swedish Mutant Amyloid Precursor Protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-SECRETASE CLEAVAGE; ALZHEIMERS-DISEASE; PLAQUE-FORMATION; CLEAVING ENZYME; MUTATION; APP; PATHOGENESIS; OLIGOMERS; BRAIN; MICE AB In Alzheimer disease amyloid-beta (A beta) peptides derived from the amyloid precursor protein (APP) accumulate in the brain. Cleavage of APP by the beta-secretase BACE1 is the rate-limiting step in the production of A beta. We have reported previously that the cellular prion protein (PrP(C)) inhibited the action of BACE1 toward human wild type APP (APP(WT)) in cellular models and that the levels of endogenous murine A beta were significantly increased in PrP(C)-null mouse brain. Here we investigated the molecular and cellular mechanisms underlying this observation. PrP(C) interacted directly with the prodomain of the immature Golgi-localized form of BACE1. This interaction decreased BACE1 at the cell surface and in endosomes where it preferentially cleaves APP(WT) but increased it in the Golgi where it preferentially cleaves APP with the Swedish mutation (APP(Swe)). In transgenic mice expressing human APP with the Swedish and Indiana familial mutations (APP(Swe,Ind)), PrP(C) deletion had no influence on APP proteolytic processing, A beta plaque deposition, or levels of soluble A beta or A beta oligomers. In cells, although PrP(C) inhibited the action of BACE1 on APP(WT), it did not inhibit BACE1 activity toward APP(Swe). The differential subcellular location of the BACE1 cleavage of APP(Swe) relative to APP(WT) provides an explanation for the failure of PrP(C) deletion to affect A beta accumulation in APP(Swe,Ind) mice. Thus, although PrP(C) exerts no control on cleavage of APP(Swe) by BACE1, it has a profound influence on the cleavage of APP(WT), suggesting that PrP(C) may be a key protective player against sporadic Alzheimer disease. C1 [Griffiths, Heledd H.; Whitehouse, Isobel J.; Kellett, Katherine A. B.; Jackson, Carolyn D.; Turner, Anthony J.; Hooper, Nigel M.] Univ Leeds, Inst Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England. [Baybutt, Herbert; Brown, Debbie; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, Roslin Inst, Roslin EH25 9PS, Midlothian, Scotland. [Baybutt, Herbert; Brown, Debbie; Piccardo, Pedro; Manson, Jean C.] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin EH25 9PS, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hooper, NM (reprint author), Univ Leeds, Inst Mol & Cellular Biol, Fac Biol Sci, Leeds LS2 9JT, W Yorkshire, England. EM n.m.hooper@leeds.ac.uk FU NIAID [Y1-AI-4893-02]; Medical Research Council of Great Britain [G9824728, G0802189]; Alzheimer's Research Trust of Great Britain [PG2008/2]; Food and Drug Administration Agreement [224-05-1307] FX This work was supported, in whole or in part, by National Institutes of Health Agreement Y1-AI-4893-02 from the NIAID. This work was also supported by Medical Research Council of Great Britain Grants G9824728 and G0802189, Alzheimer's Research Trust of Great Britain Grant PG2008/2, and Food and Drug Administration Agreement 224-05-1307. NR 40 TC 35 Z9 35 U1 0 U2 5 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 SEP 23 PY 2011 VL 286 IS 38 BP 33489 EP 33500 DI 10.1074/jbc.M111.278556 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 821IR UT WOS:000294968800066 PM 21795680 ER PT J AU Gu, SX Gupta, R Kyprianou, I AF Gu, Songxiang Gupta, Rajiv Kyprianou, Iacovos TI Computational high-resolution heart phantoms for medical imaging and dosimetry simulations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID CARDIAC MR; LEFT-VENTRICLE; SEGMENTATION; MODELS; IMAGES; DISEASE AB Cardiovascular disease in general and coronary artery disease (CAD) in particular, are the leading cause of death worldwide. They are principally diagnosed using either invasive percutaneous transluminal coronary angiograms or non-invasive computed tomography angiograms (CTA). Minimally invasive therapies for CAD such as angioplasty and stenting are rendered under fluoroscopic guidance. Both invasive and non-invasive imaging modalities employ ionizing radiation and there is concern for deterministic and stochastic effects of radiation. Accurate simulation to optimize image quality with minimal radiation dose requires detailed, gender-specific anthropomorphic phantoms with anatomically correct heart and associated vasculature. Such phantoms are currently unavailable. This paper describes an open source heart phantom development platform based on a graphical user interface. Using this platform, we have developed seven high-resolution cardiac/coronary artery phantoms for imaging and dosimetry from seven high-quality CTA datasets. To extract a phantom from a coronary CTA, the relationship between the intensity distribution of the myocardium, the ventricles and the coronary arteries is identified via histogram analysis of the CTA images. By further refining the segmentation using anatomy-specific criteria such as vesselness, connectivity criteria required by the coronary tree and image operations such as active contours, we are able to capture excellent detail within our phantoms. For example, in one of the female heart phantoms, as many as 100 coronary artery branches could be identified. Triangular meshes are fitted to segmented high-resolution CTA data. We have also developed a visualization tool for adding stenotic lesions to the coronaries. The male and female heart phantoms generated so far have been cross-registered and entered in the mesh-based Virtual Family of phantoms with matched age/gender information. Any phantom in this family, along with user-defined stenoses, can be used to obtain clinically realistic projection images with the Monte Carlo code penMesh for optimizing imaging and dosimetry. C1 [Gu, Songxiang; Kyprianou, Iacovos] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Gupta, Rajiv] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gu, SX (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM songxiang.gu@fda.hhs.gov; rgupta1@partners.org; iacovos.kyprianou@fda.hhs.gov FU FDA; National Institute of Biomedical Imaging and Bioengineering of the National Institute of Health; Food and Drug Administration Office of Women's Health FX Dr Songxiang Gu was supported in part by a grant from the FDA Critical Path. Dr Kyprianou's research was supported in part by the National Institute of Biomedical Imaging and Bioengineering of the National Institute of Health and by the Food and Drug Administration Office of Women's Health. Special gratitude is expressed for the help and recommendations of Dr Rongping Zeng, Dr Aldo Badano, Dr Kyle Myers, Dr Andreu Badal-Soler, Dr Camille Vidal and Mr Samir Abboud. NR 46 TC 8 Z9 8 U1 1 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD SEP 21 PY 2011 VL 56 IS 18 BP 5845 EP 5864 DI 10.1088/0031-9155/56/18/005 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 818WT UT WOS:000294787300007 PM 21852725 ER PT J AU Golden, JW Zaitseva, M Kapnick, S Fisher, RW Mikolajczyk, MG Ballantyne, J Golding, H Hooper, JW AF Golden, Joseph W. Zaitseva, Marina Kapnick, Senta Fisher, Robert W. Mikolajczyk, Malgorzata G. Ballantyne, John Golding, Hana Hooper, Jay W. TI Polyclonal antibody cocktails generated using DNA vaccine technology protect in murine models of orthopoxvirus disease SO VIROLOGY JOURNAL LA English DT Article DE Smallpox; vaccinia immunoglobulin; monoclonal antibody; passive protection; DNA vaccine; polyclonal antibody; bioluminescence ID NEUTRALIZING MONOCLONAL-ANTIBODIES; INTRANASAL POXVIRUS CHALLENGE; LETHAL RESPIRATORY CHALLENGE; OUTER-MEMBRANE PROTEINS; 2 INFECTIOUS FORMS; SMALLPOX VACCINE; VIRUS CHALLENGE; PROGRESSIVE VACCINIA; NONHUMAN-PRIMATES; IMMUNE GLOBULIN AB Background: Previously we demonstrated that DNA vaccination of nonhuman primates (NHP) with a small subset of vaccinia virus (VACV) immunogens (L1, A27, A33, B5) protects against lethal monkeypox virus challenge. The L1 and A27 components of this vaccine target the mature virion (MV) whereas A33 and B5 target the enveloped virion (EV). Results: Here, we demonstrated that the antibodies produced in vaccinated NHPs were sufficient to confer protection in a murine model of lethal Orthopoxvirus infection. We further explored the concept of using DNA vaccine technology to produce immunogen-specific polyclonal antibodies that could then be combined into cocktails as potential immunoprophylactic/therapeutics. Specifically, we used DNA vaccines delivered by muscle electroporation to produce polyclonal antibodies against the L1, A27, A33, and B5 in New Zealand white rabbits. The polyclonal antibodies neutralized both MV and EV in cell culture. The ability of antibody cocktails consisting of anti-MV, anti-EV, or a combination of anti-MV/EV to protect BALB/c mice was evaluated as was the efficacy of the anti-MV/EV mixture in a mouse model of progressive vaccinia. In addition to evaluating weight loss and lethality, bioimaging technology was used to characterize the spread of the VACV infections in mice. We found that the anti-EV cocktail, but not the anti-MV cocktail, limited virus spread and lethality. Conclusions: A combination of anti-MV/EV antibodies was significantly more protective than anti-EV antibodies alone. These data suggest that DNA vaccine technology could be used to produce a polyclonal antibody cocktail as a possible product to replace vaccinia immune globulin. C1 [Golden, Joseph W.; Hooper, Jay W.] USA, Div Virol, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. [Zaitseva, Marina; Kapnick, Senta; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Fisher, Robert W.; Mikolajczyk, Malgorzata G.] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Ballantyne, John] Aldevron LLC, Fargo, ND USA. RP Hooper, JW (reprint author), USA, Div Virol, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. EM jay.hooper@amedd.army.mil OI Hooper, Jay/0000-0002-4475-0415 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [IAA 224-06-1322, IAA Y1-AI-9426-02] FX We thank Matthew Josleyn, Andrew Wells and Leslie Jones for their technical assistance in completing this work. We thank Michael Merchlinsky and Jerry P. Weir for providing IHD-J-Luc vaccinia virus. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the U. S. Army or the Department of Defense. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles state in the Guide for the Care and Use of Laboratory Animals, National Research Council, 1996. The facilities where this research was conducted are fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International. 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 IAA Y1-AI-9426-02, Appendix A120 B.19. NR 82 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 1743-422X J9 VIROL J JI Virol. J. PD SEP 20 PY 2011 VL 8 AR 441 DI 10.1186/1743-422X-8-441 PG 18 WC Virology SC Virology GA 832XG UT WOS:000295843300001 PM 21933385 ER PT J AU Ravichandran, V Major, EO Ibe, C Monaco, MC Girisetty, MKH Hewlett, IK AF Ravichandran, Veerasamy Major, Eugen O. Ibe, Carol Monaco, Maria Chiara Girisetty, Mohan Kumar Haleyur Hewlett, Indira K. TI Susceptibility of human primary neuronal cells to Xenotropic Murine Leukemia Virus-related (XMRV) virus infection SO VIROLOGY JOURNAL LA English DT Article DE XMRV infection; Primary neuronal cells; Non-neuronal cells; Nuclear factors ID JC VIRUS; PROGENITOR CELLS; BONE-MARROW; PATHWAY AB Background: Xenotropic Murine Leukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study, we investigated the susceptibility of primary neuronal cell types to infection with XMRV. Findings: We observed that the human primary progenitors, progenitor-derived neurons, and progenitor-derived astrocytes supported XMRV multiplication. Interestingly, both progenitors and progenitor-derived neurons were more susceptible compared with progenitor-derived astrocytes. In addition, XMRV-infected Jurkat cells were able to transmit infection to neuronal cells. Conclusions: These data suggest that neuronal cells are susceptible for XMRV infection. C1 [Ravichandran, Veerasamy; Girisetty, Mohan Kumar Haleyur; Hewlett, Indira K.] US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Major, Eugen O.; Ibe, Carol; Monaco, Maria Chiara] NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Hewlett, IK (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM indira.hewlett@fda.hhs.gov RI Haleyur Giri Setty, Mohan Kumar/F-5841-2014 OI Haleyur Giri Setty, Mohan Kumar/0000-0001-6423-1420 NR 9 TC 8 Z9 9 U1 0 U2 2 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 SEP 20 PY 2011 VL 8 AR 443 DI 10.1186/1743-422X-8-443 PG 4 WC Virology SC Virology GA 832XG UT WOS:000295843300003 PM 21933387 ER PT J AU Zidan, AS Rahman, Z Khan, MA AF Zidan, Ahmed S. Rahman, Ziyaur Khan, Mansoor A. TI Product and process understanding of a novel pediatric anti-HIV tenofovir niosomes with a high-pressure homogenizer SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Tenofovir; Niosomes; Microfluidization; Factorial design; Characterization ID VESICLES NIOSOMES; DRUG-DELIVERY; IN-VITRO; LIPOSOMES; NANOPARTICLES; FORMULATION; ABSORPTION; DESIGN; SKIN AB A variety of factors were systemically evaluated in order to establish the characteristics of the niosomes obtained with a high-pressure homogenizer. The vesicular sizing parameters, electrical properties, drug entrapment data and drug release characteristics were investigated using two groups of factors. The first group presented the physical process variables such as pressure of the homogenizer and the times that the samples were processed (cycles). The second group encompassed the compositional variables such as the drug loading, surfactant chain length, cholesterol level and the level of the charge imparting agent. The obtained data showed that the drug distributed within both the aqueous and lipid phases of the formed niosomes. Saturation-like behaviors for both the effect of homogenization cycles on the produced size and the effect of the pressure on the size homogeneity were recorded. In contrast to the drug entrapment and conductivity of the niosomal suspension, the vesicular size parameters as well as the zeta potential were inversely proportional with the homogenization parameters. Drug release was significantly affected by the compositional factors rather than the physical ones. The current study demonstrated the usefulness of the microfluidization for the production and further scale-up of anti-HIV niosomes with very small mean vesicular sizes. Published by Elsevier B.V. C1 [Khan, Mansoor A.] US FDA, Div Prod Qual Res, CDER, OPS,OTR, Silver Spring, MD 20993 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Dept Pharmaceut & Ind Pharm, Zagazig, Egypt. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, CDER, OPS,OTR, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012; OI Rahman, Ziyaur/0000-0002-0402-825X FU Oak Ridge Institute for Science and Education (ORISE); National Institute of Health (IAA) [Y1-HD-0052-01] FX The authors would like to acknowledge the Oak Ridge Institute for Science and Education (ORISE) for its support with a research postdoctoral fellowship. This work was supported in part by a funding from the National Institute of Health (IAA, Y1-HD-0052-01). NR 40 TC 15 Z9 15 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD SEP 18 PY 2011 VL 44 IS 1-2 BP 93 EP 102 DI 10.1016/j.ejps.2011.06.012 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 823GB UT WOS:000295109400012 PM 21726640 ER PT J AU Miller, HI AF Miller, Henry I. TI FDA Thumps Industry, Patients Feel the Pain SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] Competit Enterprise Inst, Washington, DC USA. [Miller, Henry I.] US FDA, Off Biotechnol, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. EM henry.miller@stanford.edu 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 1935-472X J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD SEP 15 PY 2011 VL 31 IS 16 BP 6 EP + PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 825EA UT WOS:000295252500002 ER PT J AU Gerald, NJ Majam, V Mahajan, B Kozakai, Y Kumar, S AF Gerald, Noel J. Majam, Victoria Mahajan, Babita Kozakai, Yukiko Kumar, Sanjai TI Protection from Experimental Cerebral Malaria with a Single Dose of Radiation-Attenuated, Blood-Stage Plasmodium berghei Parasites SO PLOS ONE LA English DT Article ID FALCIPARUM MALARIA; LIVER STAGE; IMMUNITY; VACCINE; BRAIN; MICE; SPOROZOITES; CELLS; ACCUMULATION; IMMUNIZATION AB Background: Whole malaria parasites are highly effective in inducing immunity against malaria. Due to the limited success of subunit based vaccines in clinical studies, there has been a renewed interest in whole parasite-based malaria vaccines. Apart from attenuated sporozoites, there have also been efforts to use live asexual stage parasites as vaccine immunogens. Methodology and Results: We used radiation exposure to attenuate the highly virulent asexual blood stages of the murine malaria parasite P. berghei to a non-replicable, avirulent form. We tested the ability of the attenuated blood stage parasites to induce immunity to parasitemia and the symptoms of severe malaria disease. Depending on the mouse genetic background, a single high dose immunization without adjuvant protected mice from parasitemia and severe disease (CD1 mice) or from experimental cerebral malaria (ECM) (C57BL/6 mice). A low dose immunization did not protect against parasitemia or severe disease in either model after one or two immunizations. The protection from ECM was associated with a parasite specific antibody response and also with a lower level of splenic parasite-specific IFN-gamma production, which is a mediator of ECM pathology in C57BL/6 mice. Surprisingly, there was no difference in the sequestration of CD8+ T cells and CD45+ CD11b+ macrophages in the brains of immunized, ECM-protected mice. Conclusions: This report further demonstrates the effectiveness of a whole parasite blood-stage vaccine in inducing immunity to malaria and explicitly demonstrates its effectiveness against ECM, the most pathogenic consequence of malaria infection. This experimental model will be important to explore the formulation of whole parasite blood-stage vaccines against malaria and to investigate the immune mechanisms that mediate protection against parasitemia and cerebral malaria. C1 [Gerald, Noel J.; Majam, Victoria; Mahajan, Babita; Kozakai, Yukiko; Kumar, Sanjai] US FDA, Div Emerging Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Gerald, NJ (reprint author), US FDA, Div Emerging Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM sanjai.kumar@fda.hhs.gov FU Food and Drug Administration FX This work was supported by intramural funding from the Food and Drug Administration and no external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 3 Z9 3 U1 1 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD SEP 15 PY 2011 VL 6 IS 9 AR e24398 DI 10.1371/journal.pone.0024398 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 822JR UT WOS:000295041700030 PM 21935405 ER PT J AU Doerge, DR Twaddle, NC Vanlandingham, M Brown, RP Fisher, JW AF Doerge, Daniel R. Twaddle, Nathan C. Vanlandingham, Michelle Brown, Ronald P. Fisher, Jeffrey W. TI Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Bisphenol A; Pregnancy; Placental transfer; Mass spectrometry; Pharmacokinetics ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; REPRODUCTIVE TOXICITY; PLACENTAL-TRANSFER; PROTEIN-BINDING; DISPOSITION; PHARMACOKINETICS; GLUCURONIDATION; EXPOSURE; SAMPLES AB Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of >90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 mu g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 mu g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral administration, and fetal age are critical in reducing exposures to the fetus. Published by Elsevier Inc. C1 [Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Fisher, Jeffrey W.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Brown, Ronald P.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU NCTR/FDA [FDA 224-07-0007, NIH Y1ES1027]; National Institute of Environmental Health Sciences FX This research was supported in part by an Interagency Agreement (FDA 224-07-0007; NIH Y1ES1027) between NCTR/FDA and the National Institute of Environmental Health Sciences/National Toxicology Program. The authors are grateful to Dr. John F. Young for helpful discussions. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration, NR 58 TC 53 Z9 53 U1 3 U2 29 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 SEP 15 PY 2011 VL 255 IS 3 BP 261 EP 270 DI 10.1016/j.taap.2011.07.009 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 822CK UT WOS:000295021100004 PM 21820460 ER PT J AU Sommers, CD Keire, DA AF Sommers, Cynthia D. Keire, David A. TI Detection of Possible Economically Motivated Adulterants in Heparin Sodium and Low Molecular Weight Heparins with a Colorimetric Microplate Based Assay SO ANALYTICAL CHEMISTRY LA English DT Article ID OVERSULFATED CHONDROITIN SULFATE; ANTICOAGULANT ACTIVITY; GLYCOSAMINOGLYCANS; CONTAMINANTS; PRODUCTS AB Recently, we described a 96-well plate format assay for visual detection of oversulfated chondroitin sulfate A (OSCS) contamination in heparin samples based on a water-soluble cationic polythiophene polymer (3-(2-(N-(N'-methylimidazole))ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion of heparin. Here, we establish the specificity of the LPTP/heparinase test with a unique set of reagents that define the structural requirements for significant LPTP chemosensor color change. For example, we observed a biphasic behavior of larger shifts to the red in the UV absorbance spectra with decreasing average molecular weight of heparin chains with a break below 12-mer chain lengths. In addition, the oversulfation of chondroitin sulfate A (CSA) to a partially (PSCS) or fully (OSCS) sulfated form caused progressively less red shift of LPTP solutions. Furthermore, glycosaminoglycans (GAGs) containing glucuronic acid caused distinct spectral patterns compared to iduronic acid containing GAGs. We applied the LPTP/heparinase test to detection of OSCS (>= 0.03% (w/w) visually or 0.01% using a plate reader) in 10 mu g amounts of low molecular weight heparins (LMWHs; i.e. dalteparin, tinzaparin, or enoxaparin). Furthermore, because other oversulfated GAGs are possible economically motivated adulterants (EMAs) in heparin sodium, we tested the capacity of the LPTP/heparinase assay to detect oversulfated dermatan sulfate (OSDS), heparin (OSH), and heparan sulfate (OSHS). These potential EMAs were visually detectable at a level of similar to 0.1% when spiked into heparin sodium. We conclude that the LPTP/heparinase test visually detects oversulfated GAGs in heparin sodium and LMWHs in a format potentially amenable to high-throughput screening. C1 [Sommers, Cynthia D.; Keire, David A.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Keire, DA (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. EM David.Keire@fda.hhs.gov NR 22 TC 13 Z9 13 U1 2 U2 32 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 SEP 15 PY 2011 VL 83 IS 18 BP 7102 EP 7108 DI 10.1021/ac201412z PG 7 WC Chemistry, Analytical SC Chemistry GA 818XM UT WOS:000294790000027 PM 21819047 ER PT J AU Park, YP Choi, SC Kiesler, P Gil-Krzewska, A Borrego, F Weck, J Krzewski, K Coligan, JE AF Park, Yuk Pheel Choi, Seung-Chul Kiesler, Patricia Gil-Krzewska, Aleksandra Borrego, Francisco Weck, Jennifer Krzewski, Konrad Coligan, John E. TI Complex regulation of human NKG2D-DAP10 cell surface expression: opposing roles of the gamma(c) cytokines and TGF-beta 1 SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; CD8(+) T-CELLS; NK CELLS; IN-VIVO; CYTOMEGALOVIRUS-INFECTION; NKG2D RECEPTOR; CUTTING EDGE; TGF-BETA; INTERLEUKIN-2; CANCER AB Natural killer (NK) cells help protect the host against viral infections and tumors. NKG2D is a vital activating receptor, also expressed on subsets of T cells, whose ligands are up-regulated by cells in stress. Ligation of NKG2D leads to phosphorylation of the associated DAP10 adaptor protein, thereby activating immune cells. Understanding how the expression of NKG2D-DAP10 is regulated has implications for immunotherapy. We show that IL-2 and TGF-beta 1 oppositely regulate NKG2D-DAP10 expression by NK cells. IL-2 stimulation increases NKG2D surface expression despite a decrease in NKG2D mRNA levels. Stimulation with IL-2 results in a small increase of DAP10 mRNA and a large up-regulation of DAP10 protein synthesis, indicating that IL-2-mediated effects are mostly posttranscriptional. Newly synthesized DAP10 undergoes glycosylation that is required for DAP10 association with NKG2D and stabilization of NKG2D expression. TGF-beta 1 has an opposite and dominant effect to IL-2. TGF-beta 1 treatment decreases DAP10, as its presence inhibits the association of RNA polymerase II with the DAP10 promoter, but not NKG2D mRNA levels. This leads to the down-regulation of DAP10 expression and, as a consequence, NKG2D protein as well. Finally, we show that other gamma(c) cytokines act similarly to IL-2 in up-regulating DAP10 expression and NKG2D-DAP10 surface expression. (Blood. 2011; 118(11):3019-3027) C1 [Park, Yuk Pheel; Choi, Seung-Chul; Kiesler, Patricia; Gil-Krzewska, Aleksandra; Weck, Jennifer; Krzewski, Konrad; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. RP Coligan, JE (reprint author), 12441 Parklawn Dr,Twinbrook II,Rm 205, Rockville, MD 20852 USA. EM jcoligan@niaid.nih.gov NR 50 TC 34 Z9 35 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 2011 VL 118 IS 11 BP 3019 EP 3027 DI 10.1182/blood-2011-04-346825 PG 9 WC Hematology SC Hematology GA 821DU UT WOS:000294955900019 PM 21816829 ER PT J AU Kim, DH Shi, DX Ilev, IK AF Kim, Do-Hyun Shi, Dexiu Ilev, Ilko K. TI Alternative method for measuring effective focal length of lenses using the front and back surface reflections from a reference plate SO APPLIED OPTICS LA English DT Article ID CONFOCAL MICROSCOPY; OPTICAL-SYSTEMS; INTERFEROMETRY; PHASE AB We present a simple method for measuring the effective focal length without determining the location of principle plane of the lens. The method is based on the measurement of confocal backreflection axial responses from the front and back surfaces of a reference plate with known refractive index and thickness. We proved the concept by measuring the effective focal lengths of thin singlet lenses and complex microscope objectives. The theoretical limit of measurement precision varies depending on the numerical aperture of the lens. This method can provide an alternative focal length measurement method for complex lenses or lenses that are permanently attached to other structures. Measurement errors were analyzed theoretically and improvements in measurement accuracy were discussed. (C) 2011 Optical Society of America C1 [Kim, Do-Hyun; Shi, Dexiu; Ilev, Ilko K.] US FDA, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov NR 17 TC 4 Z9 4 U1 0 U2 2 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD SEP 10 PY 2011 VL 50 IS 26 BP 5163 EP 5168 DI 10.1364/AO.50.005163 PG 6 WC Optics SC Optics GA 818CJ UT WOS:000294726700015 PM 21946999 ER PT J AU Zhao, YW Xia, QS Yin, JJ Lin, G Fu, PP AF Zhao, Yuewei Xia, Qingsu Yin, Jun Jie Lin, Ge Fu, Peter P. TI Photoirradiation of dehydropyrrolizidine alkaloids-Formation of reactive oxygen species and induction of lipid peroxidation SO TOXICOLOGY LETTERS LA English DT Article DE Dehydropyrrolizidine alkaloids; Photoirradiation; UVA light; Reactive oxygen species; Lipid peroxidation ID DNA ADDUCT FORMATION; HEPATOTOXIC PYRROLIZIDINE ALKALOIDS; METABOLIC-ACTIVATION; SINGLET OXYGEN; DIETARY-SUPPLEMENTS; IN-VIVO; MASS-SPECTROMETRY; MEDICINAL-PLANTS; RIDDELLIINE; LASIOCARPINE AB Pyrrolizidine alkaloid (PA)-containing plants are widespread in the world and are probably the most common poisonous plants affecting livestock, wildlife, and human. PAs require metabolic activation to generate pyrrolic metabolites (dehydro-PAs) that bind cellular protein and DNA, leading to hepatotoxicity and genotoxicity, including tumorigenicity. In this study we report that UVA photoirradiation of a series of dehydro-PAs, e.g., dehydromonocrotaline, dehydroriddelliine, dehydroretrorsine, dehydrosenecionine, dehydroseneciphylline, dehydrolasiocarpine, dehydroheliotrine, and dehydroretronecine (DHR) at 0-70J/cm(2) in the presence of a lipid, methyl linoleate, resulted in lipid peroxidation in a light dose-responsive manner. When irradiated in the presence of sodium azide, the level of lipid peroxidation decreased; lipid peroxidation was enhanced when methanol was replaced by deuterated methanol. These results suggest that singlet oxygen is a photo-induced product. When irradiated in the presence of superoxide dismutase, the level of lipid peroxidation decreased, indicating that lipid peroxidation is also mediated by superoxide. Electron spin resonance (ESR) spin trapping studies confirmed that both singlet oxygen and superoxide anion radical were formed during photoirradiation. These results indicate that UVA photoirradiation of dehydro-PAs generates reactive oxygen species (ROS) that mediated the initiation of lipid peroxidation. UVA irradiation of the parent PAs and other PA metabolites, including PA N-oxides, under similar experimental conditions did not produce lipid peroxidation. It is known that PAs induce skin cancer and are secondary (hepatogenous) photosensitization agents. Our results suggest that dehydro-PAs are the active metabolites responsible for skin cancer formation and PA-induced secondary photosensitization. Published by Elsevier Ireland Ltd. C1 [Zhao, Yuewei; Xia, Qingsu; 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. [Lin, Ge] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU NCTR FX We thank Drs. William Melchior and Frederick A. Beland for critical review of this manuscript and Dr. Lining Cai of Bioytanex Co. for mass spectral measurements of the pyrrolic metabolites and Dr. Qiangen Wu for the statistical analysis of data. We also thank a gift of riddelliine from Dr. Po-Chuen Chan, of lasiocarpine from Dr. John A. Edgar, and of senecionine and seneciphylline from Dr. Russell J. Molyneur. This research was supported in part by appointment (Y. Zhao) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. NR 43 TC 14 Z9 14 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 10 PY 2011 VL 205 IS 3 BP 302 EP 309 DI 10.1016/j.toxlet.2011.06.020 PG 8 WC Toxicology SC Toxicology GA 816DI UT WOS:000294578500011 PM 21723383 ER PT J AU Weisz, A Ito, Y AF Weisz, Adrian Ito, Yoichiro TI Performance comparison of three types of high-speed counter-current chromatographs for the separation of components of hydrophilic and hydrophobic color additives SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 6th International Conference on Countercurrent Chromatography CY JUL 28-30, 2010 CL Univ Lyon, La Doua Campus, Lyon, FRANCE SP French Assoc Separat Sci HO Univ Lyon, La Doua Campus DE High-speed counter-current chromatography; J-type coil planet centrifuge; Cross-axis coil planet centrifuge; Multilayer-coil column; Spiral-tube assembly column; HPLC; Color additives; FD&C Blue No. 2; D&C Red No. 17; Sudan II ID BLUE NO 2; SUBSIDIARY COLORS; FD; IDENTIFICATION; PURIFICATION; APPARATUS AB The performance of three types of high-speed counter-current chromatography (HSCCC) instruments was assessed for their use in separating components in hydrophilic and hydrophobic dye mixtures. The HSCCC instruments compared were: (i) a J-type coil planet centrifuge (CPC) system with a conventional multilayer-coil column, (ii) a J-type CPC system with a spiral-tube assembly-coil column, and (iii) a cross-axis CPC system with a multilayer-coil column. The hydrophilic dye mixture consisted of a sample of FD&C Blue No. 2 that contained mainly two isomeric components, 5,5'- and 5,7'-disulfonated indigo, in the ratio of similar to 7:1. The hydrophobic dye mixture consisted of a sample of D&C Red No. 17 (mainly Sudan III) and Sudan II in the ratio of similar to 4:1. The two-phase solvent systems used for these separations were 1-butanol/1.3 M HCl and hexane/acetonit rile. Each of the three instruments was used in two experiments for the hydrophilic dye mixture and two for the hydrophobic dye mixture, for a total of 12 experiments. In one set of experiments, the lower phase was used as the mobile phase, and in the second set of experiments, the upper phase was used as the mobile phase. The results suggest that: (a) use of a J-type instrument with either a multilayer-coil column or a spiral-tube assembly column, applying the lower phase as the mobile phase, is preferable for separating the hydrophilic components of FD&C Blue No. 2; and (b) use of a J-type instrument with multilayer-coil column, while applying either the upper phase or the lower phase as the mobile phase, is preferable for separating the hydrophobic dye mixture of D&C Red No. 17 and Sudan II. Published by Elsevier B.V. C1 [Weisz, Adrian] USA Food & Drug Adm, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), USA Food & Drug Adm, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov FU Intramural NIH HHS [ZIA HL005107-02] NR 26 TC 6 Z9 6 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 9 PY 2011 VL 1218 IS 36 BP 6156 EP 6164 DI 10.1016/j.chroma.2010.12.034 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 815JZ UT WOS:000294523200022 PM 21215406 ER PT J AU Hsu, AP Sampaio, EP Khan, J Calvo, KR Lemieux, JE Patel, SY Frucht, DM Vinh, DC Auth, RD Freeman, AF Olivier, KN Uzel, G Zerbe, CS Spalding, C Pittaluga, S Raffeld, M Kuhns, DB Ding, L Paulson, ML Marciano, BE Gea-Banacloche, JC Orange, JS Cuellar-Rodriguez, J Hickstein, DD Holland, SM AF Hsu, Amy P. Sampaio, Elizabeth P. Khan, Javed Calvo, Katherine R. Lemieux, Jacob E. Patel, Smita Y. Frucht, David M. Vinh, Donald C. Auth, Roger D. Freeman, Alexandra F. Olivier, Kenneth N. Uzel, Gulbu Zerbe, Christa S. Spalding, Christine Pittaluga, Stefania Raffeld, Mark Kuhns, Douglas B. Ding, Li Paulson, Michelle L. Marciano, Beatriz E. Gea-Banacloche, Juan C. Orange, Jordan S. Cuellar-Rodriguez, Jennifer Hickstein, Dennis D. Holland, Steven M. TI Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; MYELOID-LEUKEMIA; HAPLOINSUFFICIENCY AB The syndrome of monocytopenia, B-cell and NK-cell lymphopenia, and mycobacterial, fungal, and viral infections is associated with myelodysplasia, cytogenetic abnormalities, pulmonary alveolar proteinosis, and myeloid leukemias. Both autosomal dominant and sporadic cases occur. We identified 12 distinct mutations in GATA2 affecting 20 patients and relatives with this syndrome, including recur-rent missense mutations affecting the zinc finger-2 domain (R398W and T354M), suggesting dominant interference of gene function. Four discrete insertion/deletion mutations leading to frame shifts and premature termination implicate haploin-sufficiency as a possible mechanism of action as well. These mutations were found in hematopoietic and somatic tissues, and several were identified in families, indicating germline transmission. Thus, GATA2 joins RUNX1 and CEBPA not only as a familial leukemia gene but also as a cause of a complex congenital immunodeficiency that evolves over decades and combines predisposition to infection and myeloid malignancy. (Blood. 2011;118(10):2653-2655) C1 [Hsu, Amy P.; Sampaio, Elizabeth P.; Vinh, Donald C.; Freeman, Alexandra F.; Olivier, Kenneth N.; Uzel, Gulbu; Zerbe, Christa S.; Spalding, Christine; Ding, Li; Paulson, Michelle L.; Marciano, Beatriz E.; Cuellar-Rodriguez, Jennifer; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. [Khan, Javed] NCI, Oncogen Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Calvo, Katherine R.] Warren Grant Magnuson Clin Canc Ctr, Hematol Sect, Dept Lab Med, Bethesda, MD USA. [Lemieux, Jacob E.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Patel, Smita Y.] Univ Oxford, John Radcliffe Hosp, Oxford OX3 9DU, England. [Frucht, David M.; Auth, Roger D.] Fed Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Pittaluga, Stefania; Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Kuhns, Douglas B.; Paulson, Michelle L.] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Gea-Banacloche, Juan C.; Hickstein, Dennis D.] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. [Orange, Jordan S.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov RI Calvo, Katherine/A-8109-2009; OI orange, jordan/0000-0001-7117-7725; Calvo, Katherine/0000-0002-0771-4191; VINH, DONALD/0000-0003-1347-7767 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health (contract HHSN261200800001E). NR 18 TC 176 Z9 178 U1 2 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD SEP 8 PY 2011 VL 118 IS 10 BP 2653 EP 2655 DI 10.1182/blood-2011-05-356352 PG 3 WC Hematology SC Hematology GA 819BX UT WOS:000294801500008 PM 21670465 ER PT J AU Setty, MKHG Devadas, K Ragupathy, V Ravichandran, V Tang, SX Wood, O Gaddam, DS Lee, S Hewlett, IK AF Setty, Mohan Kumar Haleyur Giri Devadas, Krishnakumar Ragupathy, Viswanath Ravichandran, Veerasamy Tang, Shixing Wood, Owen Gaddam, Durga Sivacharan Lee, Sherwin Hewlett, Indira K. TI XMRV: Usage of Receptors and potential Co-receptors SO VIROLOGY JOURNAL LA English DT Article ID CELL-SURFACE RECEPTOR; LEUKEMIA VIRUSES; GAMMARETROVIRUSES AB Background: XMRV is a gammaretrovirus first identified in prostate tissues of Prostate Cancer (PC) patients and later in the blood cells of patients with Chronic Fatigue Syndrome (CFS). Although XMRV is thought to use XPR1 for cell entry, it infects A549 cells that do not express XPR1, suggesting usage of other receptors or co-receptors. Methods: To study the usage of different receptors and co-receptors that could play a role in XMRV infection of lymphoid cells and GHOST (GFP-Human osteosarcoma) cells expressing CD4 along with different chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture supernatants and cells were tested for XMRV replication using real time quantitative PCR. Results: Infection and replication of XMRV was seen in a variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of XMRV replication varied in different cell lines showing differential replication in different cell lines. However, replication in A549 which lacks XPR1 expression was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied in GHOST cell lines expressing CD4 and each of the co-receptors CCR1-CCR8 and bob. There was significant replication of XMRV in CCR3 and Bonzo although it is much lower when compared to DU145, A549 and LNCaP. Conclusion: XMRV replication was observed in GHOST cells that express CD4 and each of the chemokine receptors ranging from CCR1-CCR8 and BOB suggesting that infectivity in hematopoietic cells could be mediated by use of these receptors. C1 [Setty, Mohan Kumar Haleyur Giri; Devadas, Krishnakumar; Ragupathy, Viswanath; Ravichandran, Veerasamy; Tang, Shixing; Wood, Owen; Gaddam, Durga Sivacharan; Lee, Sherwin; Hewlett, Indira K.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hewlett, IK (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM indira.hewlett@fda.hhs.gov RI Haleyur Giri Setty, Mohan Kumar/F-5841-2014 OI Haleyur Giri Setty, Mohan Kumar/0000-0001-6423-1420 FU CPATH FDA FX We thank NIH AIDS Reagent Program for Ghost cell lines. We thank Dr. Xue Wang, Dr. Mingjie Zhang, Dr. Robin Biswas, and Dr. Chintamani D. Atreya for critical review of the article. This work was supported by funds from CPATH FDA. 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. NR 14 TC 4 Z9 4 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 SEP 6 PY 2011 VL 8 AR 423 DI 10.1186/1743-422X-8-423 PG 4 WC Virology SC Virology GA 830EB UT WOS:000295639100001 PM 21896167 ER PT J AU Voss, KA Riley, RT Jackson, LS Jablonski, JE Bianchini, A Bullerman, LB Hanna, MA Ryu, D AF Voss, Kenneth A. Riley, Ronald T. Jackson, Lauren S. Jablonski, Joseph E. Bianchini, Andreia Bullerman, Lloyd B. Hanna, Milford A. Ryu, Dojin TI Extrusion cooking with glucose supplementation of fumonisin-contaminated corn grits protects against nephrotoxicity and disrupted sphingolipid metabolism in rats SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Extrusion cooking; Fumonisin; In vivo toxicity; Sphinganine; Sphinganine 1-phosphate ID SINGLE-SCREW EXTRUSION; NEURAL-TUBE DEFECTS; FUSARIUM-MONILIFORME; B6C3F(1) MICE; B-1; TOXICITY; CARCINOGENICITY; ACCUMULATION; PRODUCT; KIDNEY AB Scope: Fumonisin B1 (FB1) is a mycotoxin found in maize and maize-based foods. It causes animal diseases and is a suspected risk factor for cancer and birth defects in humans. Extrusion cooking reduces FB1 concentrations in maize however toxicity caused by unknown degradation or FB1-matrix reaction products might persist. Methods and results: To test the efficacy of extrusion to reduce FB1 toxicity, Fusarium verticillioides fermented corn (= maize) grits (Batch-1=9.7 ppm FB1; Batch-2=50 ppm FB1) were extruded without (Batch-1E; Batch-2E) or with 10% glucose supplementation (Batch-1EG; Batch-2EG). FB1 concentrations were reduced 64% (Batch-2E) to 94% (Batch-1EG) after cooking. When the uncooked and processed grits were fed (50% w/w in rodent chow) to rats for up to 8 weeks, FB1 intakes averaged 354, 103, and 25.1 cg/kg body weight/day for Batch-1, Batch-1E and Batch-1EG and 1804, 698, and 222 cg/kg body weight/day for the Batch-2, Batch-2E and Batch-2EG, respectively. Nephrotoxicity including apoptotic lesions and elevated sphingoid base concentrations decreased in a dose-dependent manner in groups fed Batch-1, Batch-1E, Batch-2, Batch-2E, or Batch-2EG and was absent in the Batch-1EG group. Conclusion: Extrusion cooking, especially with glucose supplementation, is potentially useful to reduce FB1 concentrations and toxicity of FB1-contaminated maize. C1 [Voss, Kenneth A.; Riley, Ronald T.] ARS, USDA, Toxicol & Mycotoxin Res Unit, Russell Res Ctr, Athens, GA 30605 USA. [Jackson, Lauren S.; Jablonski, Joseph E.] FDA Natl Ctr Food Safety & Technol, Summit Argo, IL USA. [Bianchini, Andreia; Bullerman, Lloyd B.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. [Ryu, Dojin] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. RP Voss, KA (reprint author), ARS, USDA, Toxicol & Mycotoxin Res Unit, Russell Res Ctr, 950 Coll Stn Rd, Athens, GA 30605 USA. EM Ken.Voss@ars.usda.gov FU National Research Initiative of the USDA Cooperative State Research, Education and Extension Service [2005-35201-16329] FX This study was supported in part by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service, grant #2005-35201-16329 The expert technical assistance of M. Vongkunthong, N. Stewart, J. Showker and E. Wray are gratefully acknowledged. We thank S. Bush and colleagues in the Pathology Department, University of Georgia College of Veterinary Medicine, Athens, GA for the clinical laboratory procedures. The pioneering work of S. Hendrich, P. Murphy and colleagues on the use of reducing sugars as a fumonisin detoxification strategy is acknowledged. References to their investigations are subsumed in the cited literature. NR 33 TC 11 Z9 11 U1 1 U2 21 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1613-4125 EI 1613-4133 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD SEP PY 2011 VL 55 SU 2 SI SI BP S312 EP S320 DI 10.1002/mnfr.201100067 PG 9 WC Food Science & Technology SC Food Science & Technology GA 931VF UT WOS:000303246700017 PM 21648070 ER PT J AU Pontone, GM Palanci, J Bienvenu, OJ Liang, KY Nestadt, G Rabins, PV Williams, JR Marsh, L AF Pontone, Gregory M. Palanci, Justin Bienvenu, O. Joseph Liang, Kung-Yee Nestadt, Gerald Rabins, Peter V. Williams, James R. Marsh, Laura TI Familial Aggregation of Panic Disturbances in Parkinson's Disease SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID ATTACK-LIKE EPISODES; ANXIETY DISORDERS; EARLY-ONSET; HETEROGENEITY; COMORBIDITY; PREVALENCE; POPULATION; SUBTYPES; THERAPY; SAMPLE AB Panic disorder has an elevated prevalence in Parkinson's disease (PD). To explore the basis for this co-occurrence, the familial aggregation of panic disorder was examined in patients with PD. Probands and relatives of patients with PD and panic disorder (PD-PANIC; N=20, N=115) and control probands with PD and no active psychiatric illness (PD-NA; N=17, N=108) were interviewed by phone, using a structured interview to determine panic status. Lifetime prevalence of panic and "panic-like" disorders was higher in PD-PANIC than in PD-NA relatives. Panic and "panic-like" disorders are familial disorders in PD. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23:417-424) C1 [Pontone, Gregory M.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurol & Neurol Sci, Baltimore, MD USA. US FDA, Silver Spring, MD USA. Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Pontone, GM (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. EM gponton1@jhmi.edu FU National Institutes of Health [K23 MH64543, R01-MH069666]; Forest Research Institute; Parkinson's Disease Foundation/Parkinson Study Group; APA; Eli Lilly; Michael I Fox Foundation; Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins [NIH-P50-NS-58377]; Age-Related Cognitive Disorders Training Grant [NIH-5T32-AG-027668-02]; Donna Jeanne Gault Baumann Fund FX Authors report the following grants:; Gregory Pontone: Grants: National Institutes of Health, Forest Research Institute, Parkinson's Disease Foundation/Parkinson Study Group.; O. Joseph Bienvenu: Grant: National institutes of Health (K23 MH64543), Contracts (research): APA. Kung-Yee Liang, Gerald Nestadt, Peter V. Rabins: Grants: National institutes of Health; L. Marsh: Advisory Boards, National Parkinson Foundation, American Parkinson's Disease Association; Grants, National Institutes of Health, Forest Research Institute, Eli Lilly, Michael I Fox Foundation; Employment: Michael E. DeBakey Veterans Affairs Medical Center, Baylor College of Medicine; Royalties: Taylor and Francis/Informa.; This work was supported by: NIH grants R01-MH069666, the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins (NIH-P50-NS-58377) 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, M.D.), and the Donna Jeanne Gault Baumann Fund. NR 41 TC 1 Z9 1 U1 2 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2011 VL 23 IS 4 BP 417 EP 424 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 875GT UT WOS:000299019100008 PM 22231313 ER PT J AU Garra, BS AF Garra, Brian S. TI Elastography Current Status, Future Prospects, and Making It Work for You SO ULTRASOUND QUARTERLY LA English DT Review DE elastography; elasticity; ultrasound; acoustic radiation force impulse; shear velocity; breast cancer; cirrhosis ID PROSTATE-CANCER DETECTION; REAL-TIME ELASTOGRAPHY; ULTRASOUND ELASTOGRAPHY; SONOGRAPHIC ELASTOGRAPHY; TRANSIENT ELASTOGRAPHY; IN-VIVO; DIFFERENTIAL-DIAGNOSIS; VENOUS THROMBOSIS; LIVER FIBROSIS; LYMPH-NODES AB Elastography has emerged as a useful adjunct tool for ultrasound diagnosis. Elastograms are images of tissue stiffness and may be in color, grayscale, or a combination of the two. The first and most common application of elastography is for the diagnosis of breast lesions where studies have shown an area under the receiver operating characteristic curve of 0.88 to 0.95 for distinguishing cancer from benign lesions. The technique is also useful for the diagnosis of complex cysts, although different scanners may vary in how they display such lesions. Recent advances in elastography include quantification using strain ratios, acoustic radiation force impulse imaging, and shear wave velocity estimation. These are useful not only for characterizing focal masses but also for diagnosing diffuse organ diseases such as liver cirrhosis. Other near terrn potential applications for elastography include characterization of thyroid nodules and lymph node evaluation for metastatic disease. Prostate cancer detection is also a potential application, but obtaining high-quality elastograms may be difficult. This area is evolving. Other promising applications include atheromatous plaque and arterial wall evaluation, venous thrombus evaluation, graft rejection, and monitoring of tumor ablation therapy. When contemplating the acquisition of a system with elastography in this rapidly evolving field, a clear picture of the manufacturer's plans for future upgrades (including quantification) should be obtained. C1 [Garra, Brian S.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Garra, Brian S.] Washington DC Vet Affairs Med Ctr, Dept Radiol, Washington, DC USA. RP Garra, BS (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4102, Silver Spring, MD 20993 USA. EM brian.garra@fda.hhs.gov NR 47 TC 64 Z9 71 U1 3 U2 30 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-8771 J9 ULTRASOUND Q JI Ultrasound Q. PD SEP PY 2011 VL 27 IS 3 BP 177 EP 186 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 854XF UT WOS:000297527400006 PM 21873855 ER PT J AU Sharma, HS Muresanu, DF Sharma, A Ali, SF AF Sharma, H. S. Muresanu, D. F. Sharma, A. Ali, S. F. TI Breakdown of the blood-brain barrier in drug abuse and neurodegenerative disorders: nanoparticles as therapeutic option? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 24th Congress Meeting of European-College-of-Neuropsychopharmacology CY SEP 03-07, 2011 CL Paris, FRANCE SP European Coll Neuropsychopharmacol ID HYPERTHERMIA C1 [Sharma, H. S.; Sharma, A.] Univ Uppsala Hosp, Dept Surg Sci, Uppsala, Sweden. [Muresanu, D. F.] Univ Med & Pharm, Dept Neurol, Cluj Napoca, Romania. [Ali, S. F.] US FDA, NCTR, Dept Neurochem, Jefferson, AR USA. RI Sharma, Hari/G-4508-2016 NR 3 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD SEP PY 2011 VL 21 SU 3 BP S208 EP S209 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 852US UT WOS:000297383600065 ER PT J AU Haas, DW Kuritzkes, DR Ritchie, MD Amur, S Gage, BF Maartens, G Masys, D Fellay, J Phillips, E Ribaudo, HJ Freedberg, KA Petropoulos, C Manolio, TA Gulick, RM Haubrich, R Kim, P Dehlinger, M Abebe, R Telenti, A AF Haas, David W. Kuritzkes, Daniel R. Ritchie, Marylyn D. Amur, Shashi Gage, Brian F. Maartens, Gary Masys, Dan Fellay, Jacques Phillips, Elizabeth Ribaudo, Heather J. Freedberg, Kenneth A. Petropoulos, Christos Manolio, Teri A. Gulick, Roy M. Haubrich, Richard Kim, Peter Dehlinger, Marjorie Abebe, Rahel Telenti, Amalio CA Participants Workshop Pharmacogeno TI Pharmacogenomics of HIV Therapy: Summary of a Workshop Sponsored by the National Institute of Allergy and Infectious Diseases SO HIV CLINICAL TRIALS LA English DT Article DE HIV therapy; pharmacogenetics; pharmacogenomics; workshop ID SINGLE-NUCLEOTIDE POLYMORPHISMS; ANTIRETROVIRAL THERAPY; PLASMA-CONCENTRATIONS; HIV-1-INFECTED INDIVIDUALS; SLCO1B1 POLYMORPHISMS; EFAVIRENZ; HYPERSENSITIVITY; NEVIRAPINE; CYP2B6; ABACAVIR AB Approximately 1 million people in the United States and over 30 million worldwide are living with human immunodeficiency virus type 1 (HIV-1). While mortality from untreated infection approaches 100%, survival improves markedly with use of contemporary antiretroviral therapies (ART). In the United States, 25 drugs are approved for treating HIV-1, and increasing numbers are available in resource-limited countries. Safe and effective ART is a cornerstone in the global struggle against the acquired immunodeficiency syndrome. Variable responses to ART are due at least in part to human genetic variants that affect drug metabolism, drug disposition, and off-site drug targets. Defining effects of human genetic variants on HIV treatment toxicity, efficacy, and pharmacokinetics has far-reaching implications. In 2010, the National Institute of Allergy and Infectious Diseases sponsored a workshop entitled, Pharmacogenomics A Path Towards Personalized HIV Care. This article summarizes workshop objectives, presentations, discussions, and recommendations derived from this meeting. C1 [Haas, David W.; Ritchie, Marylyn D.; Masys, Dan] Vanderbilt Univ, Sch Med, Nashville, TN 37204 USA. [Kuritzkes, Daniel R.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kuritzkes, Daniel R.; Freedberg, Kenneth A.] Harvard Univ, Sch Med, Boston, MA USA. [Amur, Shashi] US FDA, Silver Spring, MD USA. [Gage, Brian F.] Washington Univ, St Louis, MO USA. [Maartens, Gary] Univ Cape Town, ZA-7925 Cape Town, South Africa. [Fellay, Jacques; Telenti, Amalio] Univ Lausanne, Lausanne, Switzerland. [Phillips, Elizabeth] Murdoch Univ, Royal Perth Hosp, Sir Charles Gairdner Hosp, Perth, WA, Australia. [Phillips, Elizabeth] Univ Western Australia, Perth, WA 6009, Australia. [Ribaudo, Heather J.] Harvard Univ, Sch Publ Hlth, Stat Data Anal Ctr, Boston, MA 02115 USA. [Freedberg, Kenneth A.] Massachussetts Gen Hosp, Boston, MA USA. [Petropoulos, Christos] Monogram Biosci, San Francisco, CA USA. [Manolio, Teri A.] Natl Genome Res Inst, NIH, Bethesda, MD USA. [Gulick, Roy M.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Haubrich, Richard] Univ Calif San Diego, San Diego, CA 92103 USA. [Kim, Peter; Dehlinger, Marjorie] NIAID, NIH, Bethesda, MD 20892 USA. [Abebe, Rahel] Henry M Jackson Fdn DAIDS, Bethesda, MD USA. RP Haas, DW (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Hlth 1 Hundred Oaks,719 Thompson Lane,, Nashville, TN 37204 USA. EM david.w.haas@vanderbilt.edu RI Ritchie, Marylyn/C-1114-2012; Maartens, Gary/F-3836-2014; Fellay, Jacques/A-6681-2009 OI Maartens, Gary/0000-0003-3080-6606; Fellay, Jacques/0000-0002-8240-939X FU National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [HHSN272200800014C]; Bristol Myers Squibb; Boehringer Ingelheim; Merck; Gilead Sciences; Abbott; Avexa; Boehringer-Ingelheim; Gilead; GlaxoSmithKline (GSK); Oncolys; Roche; Siemens; Tobira; Vertex; ViiV; Viro-Statics; VIRxSYS; ViiV Australia; Merck Pty Ltd; Tibotec; Pfizer; Bristol-Myers Squibb; GSK; Monogram; GlaxoSmithKline; National Institute of Allergy and Infectious Diseases; NIH Office of AIDS Research; AIDS Clinical Trials Group [AI68636, AI38858, AI68634, AI38855]; Swiss National Foundation [324730-124943, HL097036, AI64086, AI36214, AI69432]; CHRP [MC08-SD-700, AI069472, HL065962, AI077505, AI42006, AI085736]; [AI069439]; [RR024975]; [AI54999]; [AI51966]; [RR024996]; [RR69419] FX The views expressed in written conference materials or publications and by speakers and moderators at HHS-sponsored conferences do not necessarily reflect the official policies of the US Department of Health and Human Services nor does mention of trade names, commercial practices, or organizations imply endorsement by the US Government. This project has been funded in whole or in part with federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. HHSN272200800014C.; David W. Haas: Principal Investigator for research grants to Vanderbilt from Bristol Myers Squibb, Boehringer Ingelheim, Merck, Gilead Sciences. Daniel Kuritzkes: Consultant to and/or received research support from Abbott, Avexa, Boehringer-Ingelheim, Gilead, GlaxoSmithKline (GSK), Merck, Oncolys, Roche, Siemens, Tobira, Vertex, ViiV, Viro-Statics and VIRxSYS. Marylyn D. Ritchie: Consultant for Boehringer Ingelheim. Elizabeth Phillips: Honoraria and consulting fees from ViiV Australia, Merck Pty Ltd, and Tibotec. Christos Petropoulos: Employee of Monogram Biosciences, South San Francisco, CA. Roy M. Gulick: Ad hoc consultant for Bristol-Myers, Gilead, GSK, MedImmune, ViiV, and Virostatics, and as Principal Investigator for research grants to Weill Cornell from Merck and Pfizer. Richard Haubrich: Received honoraria or consultant fees from Abbott, Bristol-Myers Squibb, Gilead Sciences, GSK, Merck, Monogram, Pfizer, Roche, Tibotec, and ViiV and research support (to UCSD) from Abbott, GlaxoSmithKline, Merck, Pfizer, and ViiV. No potential conflicts of interest: Shashi Amur, Brian Gage, Gary Maartens, Dan Masys, Jacques Fellay, Heather J. Ribaudo, Kenneth A. Freedberg, Ten A. Manolio, Peter Kim, Marjorie Dehlinger, Rahel Abebe, and Amalio Telenti.; The workshop entitled, Pharmacogenomics - A Path Towards Personalized HIV Care, was supported by the National Institute of Allergy and Infectious Diseases and the NIH Office of AIDS Research. This work was supported in part by the AIDS Clinical Trials Group (grants AI68636, AI38858, AI68634, and AI38855). Participants were also supported by the following: grants AI069439, RR024975, and AI54999 (DWH); AI51966 (RMG); RR024996 (Cornell CTSC); RR69419 (CTU); Swiss National Foundation 324730-124943 (AT); HL097036 (BFG); AI64086, AI36214, AI69432, and CHRP MC08-SD-700 (RH); AI069472 (DK); HL065962 and AI077505 (MDR); AI42006 and AI085736 (KAF). NR 34 TC 8 Z9 9 U1 0 U2 4 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD SEP-OCT PY 2011 VL 12 IS 5 BP 277 EP 285 DI 10.1310/hct1205-277 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 847UT UT WOS:000296998700006 PM 22180526 ER PT J AU Garofolo, F Rocci, ML Dumont, I Martinez, S Lowes, S Woolf, E van Amsterdam, P Bansal, S Barra, ACG Bauer, R Booth, BP Carrasco-Triguero, M DeSilva, B Dunn, J Gallicano, K Gouty, D Ho, S Hucker, R Jemal, M Katori, N Le Blaye, O Lee, J Li, WK Michael, S Nehls, C Nicholson, R Ormsby, E Tang, D Viswanathan, CT Weiner, R Young, G AF Garofolo, Fabio Rocci, Mario L., Jr. Dumont, Isabelle Martinez, Suzanne Lowes, Steve Woolf, Eric van Amsterdam, Peter Bansal, Surendra Gomes Barra, Ariadna Cristina Bauer, Ronald Booth, Brian P. Carrasco-Triguero, Montserrat DeSilva, Binodh Dunn, John Gallicano, Keith Gouty, Dominique Ho, Stacy Hucker, Richard Jemal, Mohammed Katori, Noriko Le Blaye, Olivier Lee, Jean Li, Wenkui Michael, Steve Nehls, Corey Nicholson, Robert Ormsby, Eric Tang, Daniel Viswanathan, C. T. Weiner, Russell Young, Graeme TI 2011 White Paper on Recent Issues in Bioanalysis and Regulatory Findings from Audits and Inspections SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; GLOBAL HARMONIZATION; CALIBRATION; GUIDANCE; STABILITY; COUNCIL AB The 5th Workshop on Recent Issues in Bioanalysis (WRIB) was organized by the Calibration and Validation Group as a 2-day full immersion workshop for pharmaceutical companies, CROs and regulatory agencies to discuss, review, share perspectives, provide potential solutions and agree upon a consistent approach to recent issues in the bioanalysis of both small and large molecules. High quality, better compliance to regulations and scientific excellence are the foundation of this workshop. As in the previous editions of this significant event, recommendations were made and a consensus was reached among panelists and attendees, including industry leaders and regulatory experts representing the global bioanalytical community, on many 'hot' topics in bioanalysis. This 2011 White Paper is based on the conclusions from this workshop, and aims to provide a practical reference guide on those topics. C1 [Garofolo, Fabio; Dumont, Isabelle; Martinez, Suzanne] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [Rocci, Mario L., Jr.] ICON Dev Solut, Whitesboro, NY USA. [Lowes, Steve] Advion BioServ Inc, Ithaca, NY USA. [Woolf, Eric] Merck Res Labs, West Point, PA USA. [van Amsterdam, Peter] Abbott Healthcare Prod BV, Weesp, Netherlands. [Bansal, Surendra] Hoffmann La Roche, Nutley, NJ USA. [Gomes Barra, Ariadna Cristina; Katori, Noriko] ANVISA, Brasilia, DF, Brazil. [Bauer, Ronald] AGES PharmMed, Vienna, Austria. [Booth, Brian P.; Viswanathan, C. T.] US FDA, CDER, Silver Spring, MD USA. [Carrasco-Triguero, Montserrat] Genentech Inc, San Francisco, CA 94080 USA. [DeSilva, Binodh; Jemal, Mohammed] Bristol Myers Squibb Co, Princeton, NJ USA. [Dunn, John] GlaxoSmithKline Res & Dev Ltd, Res Triangle Pk, NC USA. [Gallicano, Keith] Watson Labs, Corona, CA USA. [Gouty, Dominique] Intertek, San Diego, CA USA. [Ho, Stacy] Genzyme Corp, Waltham, MA USA. [Hucker, Richard] Pfizer, Sandwich, Kent, England. Japan MHLW NIHS, Tokyo, Japan. [Le Blaye, Olivier] AFSSAPS, St Denis, France. [Lee, Jean] Amgen Inc, Thousand Oaks, CA 91320 USA. [Li, Wenkui] Novartis Inst Biomed Res, E Hanover, NJ USA. [Michael, Steve] Covance, Madison, WI USA. [Nehls, Corey] PPD, Middleton, WI USA. [Nicholson, Robert] PPD, Richmond, VA USA. [Ormsby, Eric] Hlth Canada TPD, Ottawa, ON, Canada. [Tang, Daniel] Frontage Labs, Shanghai, Peoples R China. [Weiner, Russell] Merck Res Labs, Rahway, NJ USA. [Young, Graeme] GlaxoSmithKline Res & Dev Ltd, Ware, Herts, England. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com FU US FDA; Brazil ANVISA; European Medicines Agency; Health Canada TPD; France AFSSAPS; Japan MHLW-NIHS; Austria AGES PharmMed; European Bioanalysis Forum; Pharma Medica Research; GYROS; WIL Reseach Company; Cetero Research; Intertek Pharmaceutical Services; Algorithme Pharma; Bruker; Waters; iStudy Reporter Bioanalytics; AB Sciex; Zef Scientific; Tandem Labs; Advion, Worldwide Clinical Trials; PRA International; mSpec Group; ICON; Celerion; Parker Balston; Peak Scientific; Bioanalysis Journal; KCAS, Thermo Scientific; MPI Research; PPD; ICF FX On Behalf of the Calibration and Validation Group (CVG), F Garofolo would like to thank: US FDA, Brazil ANVISA, European Medicines Agency, Health Canada TPD, France AFSSAPS, Japan MHLW-NIHS and Austria AGES PharmMed for supporting this workshop. Binodh DeSilva (Bristol-Myers Squibb [BMS]) and CT Viswanathan (FDA) for cochairing the workshop. All the workshop attendees and CVG members who have sent comments and suggestions to complete this White Paper. Speakers/panelists: Peter van Amsterdam (Abbott), Surendra Bansal (Hoffmann-La Roche), Ariadna Cristina Gomes Barra (ANVISA/LIKA-UFPE), Ronald Bauer (AGES), Brian P Booth (FDA), Montserrat Carrasco-Triguero (Genentech), Binodh DeSilva (BMS), John Dunn (GlaxoSmithKline), Keith Gallicano (Watson), Dominique Gouty (Intertek), Stacy Ho (Genzyme), Richard Hucker (Pfizer), Mohammed Jemal (BMS), Noriko Katori (Japan MHLW-NIHS), Olivier Le Blaye (AFSSAPS), Jean Lee (Amgen), Steve Lowes (Advion), Wenkui Li (Novartis), Steve Michael (Covance), Corey Nehls (PPD), Robert Nicholson (PPD), Eric Ormsby (TPD), Mario L Rocci Jr (ICON), Daniel Tang (Frontage), CT Viswanathan (FDA), Russell Weiner (Merck), Eric Woolf (Merck) and Graeme Young (GlaxoSmithKline). Isabelle Dumont and Suzanne Martinez (Algorithme Pharma) for collecting the Workshop minutes and preparing the first draft of this White Paper. Natasha Savoie (Algorithme Pharma) for actively participating in the revision of this White Paper. Wei Garofolo (Database Director, CVG) for the logistic organization of the event. Supporting Bioanalytical Group: European Bioanalysis Forum. Workshop sustaining sponsors: Pharma Medica Research, GYROS, WIL Reseach Company, Cetero Research, Intertek Pharmaceutical Services, Algorithme Pharma, Bruker, Waters, iStudy Reporter Bioanalytics, AB Sciex, Zef Scientific, Tandem Labs, Advion, Worldwide Clinical Trials, PRA International, mSpec Group, ICON, Celerion, Parker Balston, Peak Scientific, Bioanalysis Journal, KCAS, Thermo Scientific, MPI Research, PPD, ICF. Media Partner: Future Science Group. NR 19 TC 46 Z9 47 U1 0 U2 6 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD SEP PY 2011 VL 3 IS 18 BP 2081 EP 2096 DI 10.4155/BIO.11.192 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 846RB UT WOS:000296919800011 PM 21942519 ER PT J AU Hoerner, R Feldpausch, J Gray, RL Curry, S Islam, Z Goldy, T Klein, F Tadese, T Rice, J Mozola, M Hammack, T Marrow, T Fernandez, MC AF Hoerner, Rebecca Feldpausch, Jill Gray, R. Lucas Curry, Stephanie Islam, Zahidul Goldy, Tim Klein, Frank Tadese, Theodros Rice, Jennifer Mozola, Mark Hammack, Thomas Marrow, Todd Cristina Fernandez, Maria TI Reveal (R) Salmonella 2.0 Test for Detection of Salmonella spp. in Foods and Environmental Samples SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Reveal Salmonella 2.0 is an improved version of the original Reveal Salmonella lateral flow immunoassay and is applicable to the detection of Salmonella enterica serogroups A-E in a variety of food and environmental samples. A Performance Tested Method(SM) validation study was conducted to compare performance of the Reveal 2.0 method with that of the U.S. Department of Agriculture-Food Safety and Inspection Service or U.S. Food and Drug Administration/Bacteriological Analytical Manual reference culture methods for detection of Salmonella spp. in chicken carcass rinse, raw ground turkey, raw ground beef, hot dogs, raw shrimp, a ready-to-eat meal product, dry pet food, ice cream, spinach, cantaloupe, peanut butter, stainless steel surface, and sprout irrigation water. In a total of 17 trials performed internally and four trials performed in an independent laboratory, there were no statistically significant differences in performance of the Reveal 2.0 and reference culture procedures as determined by Chi-square analysis, with the exception of one trial with stainless steel surface and one trial with sprout irrigation water where there were significantly more positive results by the Reveal 2.0 method. Considering all data generated in testing food samples using enrichment procedures specifically designed for the Reveal method, overall sensitivity of the Reveal method relative to the reference culture methods was 99%. In testing environmental samples, sensitivity of the Reveal method relative to the reference culture method was 164%. For select foods, use of the Reveal test in conjunction with reference method enrichment resulted in overall sensitivity of 92%. There were no unconfirmed positive results on uninoculated control samples in any trials for specificity of 100%. In inclusivity testing, 102 different Salmonella serovars belonging to serogroups A E were tested and 99 were consistently positive in the Reveal test. In exclusivity testing of 33 strains of non-salmonellae representing 14 genera, 32 were negative when tested with Reveal following nonselective enrichment, and the remaining strain was found to be substantially inhibited by the enrichment media used with the Reveal method. Results of ruggedness testing showed that the Reveal test produces accurate results even with substantial deviation in sample volume or device development time. C1 [Hoerner, Rebecca; Feldpausch, Jill; Gray, R. Lucas; Curry, Stephanie; Islam, Zahidul; Goldy, Tim; Klein, Frank; Tadese, Theodros; Rice, Jennifer; Mozola, Mark] Neogen Corp, Lansing, MI 48912 USA. [Hammack, Thomas] US FDA, College Pk, MD 20740 USA. [Marrow, Todd] Univ Guelph, Guelph, ON 8J7, Canada. [Cristina Fernandez, Maria] ANMAT Minist Hlth, RA-1419 Buenos Aires, DF, Argentina. RP Mozola, M (reprint author), Neogen Corp, 620 Lesher Pl, Lansing, MI 48912 USA. EM mmozola@neogen.com NR 6 TC 3 Z9 5 U1 0 U2 5 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1467 EP 1480 DI 10.5740/jaoacint.11-051 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300010 PM 22165011 ER PT J AU Tebbs, RS Balachandran, P Wong, LY Zoder, P Furtado, MR Petrauskene, OV Cao, YX Chen, Y Donnelly, C Ryser, E AF Tebbs, Robert S. Balachandran, Priya Wong, Lily Y. Zoder, Patrick Furtado, Manohar R. Petrauskene, Olga V. Cao, Yanxiang Chen, Yi Donnelly, Catherine Ryser, Elliott TI Evaluation of Applied Biosystems MicroSEQ (R) Real-Time PCR System for Detection of Listeria monocytogenes in Food SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Increasingly, more food companies are relying on molecular methods, such as PCR, for pathogen detection due to their improved simplicity, sensitivity, and rapid time to results. This report describes the validation of a new Real-Time PCR method to detect Listeria monocytogenes in nine different food matrixes. The complete system consists of the MicroSEQ (R) L. monocylogenes Detection Kit, sample preparation, the Applied Biosystems 7500 Fast Real-Time PCR instrument, and RapidFinder (TM) Express software. Two sample preparation methods were validated: the PrepSEQ (R) Nucleic Acid extraction kit and the PrepSEQ Rapid Spin sample preparation kit. The test method was compared to the ISO 11290-1 reference method using an unpaired-study design to detect L. monocytogenes in roast beef, cured bacon, lox (smoked salmon), lettuce, whole cow's milk, dry infant formula, ice cream, salad dressing, and mayonnaise. The MicroSEQ L. monocytogenes Detection Kit and the ISO 11290-1 reference method showed equivalent detection based on Chi-square analysis for all food matrixes when the samples were prepared using either of the two sample preparation methods. An independent validation confirmed these findings on smoked salmon and whole cow's milk. The MicroSEQ kit detected all 50 L. monocytogenes strains tested, and none of the 30 nontargeted bacteria strains. C1 [Tebbs, Robert S.; Balachandran, Priya; Wong, Lily Y.; Zoder, Patrick; Furtado, Manohar R.; Petrauskene, Olga V.; Cao, Yanxiang] Life Technol Corp, Foster City, CA 94404 USA. [Chen, Yi] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Donnelly, Catherine] Univ Vermont, Dept Nutr & Food Sci, Burlington, VT 05405 USA. [Ryser, Elliott] Michigan State Univ, E Lansing, MI 48824 USA. RP Tebbs, RS (reprint author), Life Technol Corp, 850 Lincoln Ctr Dr, Foster City, CA 94404 USA. EM Robert.Tebbs@lifetech.com FU Q Laboratories FX We thank Max Brevnov (Life Technologies, Inc.) for early developmental work on food sample preparation; Michael Schumaker (Life Technologies, Inc.) for coordination of real-time PCR assay lyophilization; and Q Laboratories for its support with internal validation studies. NR 10 TC 3 Z9 3 U1 1 U2 7 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1481 EP 1489 DI 10.5740/jaoacint.11-052 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300011 PM 22165012 ER PT J AU Bao, L Oles, CJ White, KD Sapp, C Trucksess, MW AF Bao, Lei Oles, Carolyn J. White, Kevin D. Sapp, Chelsea Trucksess, Mary W. TI Use of a Multifunctional Column for the Determination of Deoxynivalenol in Grains, Grain Products, and Processed Foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID WHOLE WHEAT-FLOUR; LIQUID-CHROMATOGRAPHY; UV DETECTION; WHITE FLOUR; CLEANUP; NIVALENOL; CEREAL; BRAN AB Deoxynivalenol (DON), also known as vomitoxin, belongs to a class of naturally occurring mycotoxins produced by Fusarium spp. DON, 12, 13-epoxy-3,7 trihydroxytrichothec-9-en-8-one, is one of the most frequently detected mycotoxins in agricultural commodities worldwide. A method consisting of extraction, filtration, column cleanup, and RP-HPLC-UV separation and quantitation was validated for the determination of DON in grains (rice and barley), grain products (whole wheat flour, white flour, wheat germ, and wheat bran), and processed foods (bread, breakfast cereals, and pretzels). A 25 g test portion was extracted with 100 mL acetonitrile-water (84 + 16, v/v). After blending for 3 min, the supernatant was applied to a multifunctional column (MycoSep 225). The purified filtrate (2 mL) was evaporated to dryness and redissolved in the mobile phase. The toxins were then subjected to RP-HPLC-UV analysis. The accuracy and repeatability characteristics of the method were determined. Recoveries of DON added at levels ranging from 0.5 to 1.5 mu g/g for all test matrixes were from 75 to 98%. SD and RSD(r) ranged from 0.7 to 11.6% and 0.9 to 12.7%, respectively. Within-laboratory HorRat values were from 0.1 to 0.7 for all matrixes analyzed. The method was found to meet AOAC method performance criteria for grains, grain products, and processed foods. The identity of DON in naturally contaminated test sample extracts was confirmed by HPLC/MS/MS analysis. C1 [Bao, Lei; Oles, Carolyn J.; White, Kevin D.; Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD USA. [Sapp, Chelsea] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Microbiol, College Pk, MD USA. RP Bao, L (reprint author), Shan Dong Exit Entry Inspect & Quarantine Bur Chi, 70 Qutang Xia Rd, Qing Dao City 266001, Peoples R China. EM baoleiqd@yahoo.com.cn FU Center for Food Safety and Applied Nutrition FX This project 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 FDA. We would like to thank Jeanne I. Rader for her support and guidance. NR 12 TC 4 Z9 4 U1 1 U2 16 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1506 EP 1512 DI 10.5740/jaoacint.10-477 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300013 PM 22165014 ER PT J AU Iha, MH Barbosa, CB Favaro, RMD Trucksess, MW AF Iha, Maria Helena Barbosa, Cynara Baltazar Duarte Favaro, Rosa Maria Trucksess, Mary W. TI Chromatographic Method for the Determination of Aflatoxin M-1 in Cheese, Yogurt, and Dairy Beverages SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; M1 DETERMINATION; MILK; TURKEY; M(1); CARCINOGENICITY; PRODUCTS; SAMPLES; RATS AB The aim of this work was to develop and validate a method to determine aflatoxin M-1 (AFM(1)) in cheese, yogurt, and dairy beverages. The method consisted of aqueous methanol extraction, immunoaffinity column purification and isolation, RPLC separation, and fluorescence detection. The four types of cheese samples were classified according to moisture and fat content. The mean recoveries were 71% for cheese at spiked levels from 100 to 517 ng/kg, and 76% for yogurt and dairy beverages spiked at levels from 66 to 260 ng/kg. The mean RSDs were 5.9% for cheese, and 10% for yogurt and dairy beverages. The LOD was 3 ng/kg and the LOQ was 10 ng/kg for all test commodities. To test the applicability of the developed method, a small survey of the presence of AFM(1) in cheese, yogurt, and dairy beverages purchased in Ribeirao Preto-SP, Brazil, was conducted. AFM(1) was detected (>3 ng/kg) in all samples. Twenty cheese samples (83%) were contaminated with ARM(1) in the range of 13-304 ng/kg. In yogurt and dairy beverages, the contamination was lower (13-22 ng/kg) in five samples (42%). The results indicated that the method is adequate for the determination of AFM(1), in these four types of cheese, as well as in yogurt and dairy beverages. C1 [Iha, Maria Helena; Barbosa, Cynara Baltazar; Duarte Favaro, Rosa Maria] Inst Adolfo Lutz Registro, Lab Ribeirao Preto, BR-14085410 Ribeirao Preto, SP, Brazil. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, Div Bioanalyt Chem, College Pk, MD USA. RP Iha, MH (reprint author), Inst Adolfo Lutz Registro, Lab Ribeirao Preto, Rua Minas 877, BR-14085410 Ribeirao Preto, SP, Brazil. EM mhiha@ial.sp.gov.br FU FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) FX We are grateful to FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo) for financial support. NR 25 TC 9 Z9 9 U1 2 U2 10 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1513 EP 1518 DI 10.5740/jaoac.int.10-432 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300014 PM 22165015 ER PT J AU Trombley, A Fan, T LaBudde, R Shephard, GS Trucksess, MW Ziemer, W AF Trombley, Arthur Fan, Titan LaBudde, Robert Shephard, Gordon S. Trucksess, Mary W. Ziemer, Wayne TI Aflatoxin Plate Kit SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The level of total aflatoxin contamination was analyzed in naturally contaminated and spiked samples of corn and peanut using the Aflatoxin Plate Kit. This kit is an enzyme-linked immunosorbent assay (ELISA) suitable for rapid testing of grains and peanuts. The assay was evaluated for ruggedness and linearity of the standard curve. The test kit results were then statistically evaluated for accuracy, precision, and correlation to a validated H PLC method (AOAC 994.08). The results were verified by an independent laboratory. C1 [Trombley, Arthur; Fan, Titan] Beacon Analyt Syst Inc, Saco, ME 04072 USA. [LaBudde, Robert] Least Cost Formulat Ltd, Virginia Beach, VA 23464 USA. [Shephard, Gordon S.] S African MRC, Tygerberg, South Africa. [Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trombley, A (reprint author), Beacon Analyt Syst Inc, 82 Ind Pk Rd, Saco, ME 04072 USA. EM art@beaconkits.com OI Shephard, Gordon Seymour/0000-0002-1267-9036 NR 3 TC 1 Z9 1 U1 0 U2 6 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1519 EP 1530 DI 10.5740/jaoacint.10-482 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300015 PM 22165016 ER PT J AU Harp, BP Belai, N Barrows, JN AF Harp, Bhakti Petigara Belai, Nebebech Barrows, Julie N. TI Ultra-Performance Liquid Chromatographic Determination of Manufacturing Intermediates and Subsidiary Colors in D&C Red No. 34 and Its Lakes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An ultra-performance liquid chromatography (U PLC) method was developed to determine the manufacturing intermediates and subsidiary colors in the monosulfo monoazo color additive D&C Red No. 34 and its lakes. This method is currently used for batch certification of the color additives by the U.S. Food and Drug Administration to ensure that each lot meets published specifications for coloring drugs and cosmetics. The new UPLC method has replaced an HPLC method for determining the intermediates and a TLC method for determining the subsidiary colors. The intermediates are 2-amino-1-naphthalenesulfonic acid (Tobias acid) and 3-hydroxy-2-naphthalenecarboxylic acid (3-hydroxy-2-naphthoic acid). Subsidiary colors are positional isomers of the major dye component or related compounds containing lower numbers of substituent groups. The analytes are identified by comparison of their UPLC retention times and UV or visible absorption spectra with those of standards. Validation studies showed that peak area calibrations for the analytes were generally linear (R >0.999), and recoveries were 98-103%. The LODs were 0.002-0.02%, and the RSDs at the specification levels were 0.7-2.2%. Survey analyses of 12 samples of certified D&C Red No. 34 straight colors and lakes from six domestic and foreign manufacturers yielded results for the intermediates by UPLC and HPLC that were consistent within experimental error. The UPLC analyses yielded results for the subsidiary colors that were consistently lower than results previously obtained by TLC, which we attribute to limitations of the TLC method. The new UPLC method provides sharper peaks, better peak separation, and faster analysis times than the formerly used HPLC method and is more accurate, much faster, and much less labor-intensive than the formerly used TLC method. C1 [Harp, Bhakti Petigara; Belai, Nebebech; Barrows, Julie N.] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Harp, BP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM bhakti.petigara@fda.hhs.gov NR 7 TC 2 Z9 2 U1 0 U2 6 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1548 EP 1554 DI 10.5740/jaoacint.10-474 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300018 PM 22165019 ER PT J AU Whittaker, P AF Whittaker, Paul TI Identification of Six Species in the New Genus Cronobacter (Enterobacter sakazakii) from Culture Using Gas Chromatographic Analysis of Fatty Acid Methyl Esters SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PROFILES AB Capillary GC with flame ionization detection (FID) was used to determine the cellular fatty acid (CFA) profiles of six species in the new genus Cronobacter (Enterobacter sakazakii). The six different species are C. sakazakii, C. malonaticus, C. dublinensis, C. muytjensii, C. turicensis, and C. genomospecies. For GC-FID analysis, whole cell fatty acid methyl esters (FAMEs) from cells cultured on brain heart infusion (BHI) agar at 35 degrees C for 24 h were obtained by saponification, methylation, and extraction into hexane-methyl tert-butyl ether. A data set for 57 strains of Cronobacter species was prepared using fatty acid profiles from two or three replicates prepared on different days. Major fatty acids of the Cronobacter strains evaluated in this study were straight-chain C(12:0), C(14:0), C(16:0), and unsaturated C(18:1) omega 7c, summed C(16:1) omega 7c/C(16:1) w6c, and summed C(14:0) 3-OH/iso-C(16:1), and C(17:0) omega cyclo 7-8. The CFA profiles for the Cronobacter species are similar, but there are several fatty acids-C(12:0), C(14:0), C(16:0), C(18:1) omega 7c, and summed C(16:1) omega 7C/C(16:1) omega 6c-that differ significantly among these six species. Analysis of FAMEs from Cronobacter strains grown on BHI agar by a rapid GC-FID method is a sensitive procedure for the identification of these organisms, and this analytical method provides a procedure for the differentiation of strains from closely related Cronobacter species. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 12 TC 0 Z9 0 U1 0 U2 9 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 SEP-OCT PY 2011 VL 94 IS 5 BP 1581 EP 1584 DI 10.5740/jaoacint.10-451 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300023 PM 22165024 ER PT J AU Gratz, SR Ciolino, LA Mohrhaus, AS Gamble, BM Gracie, JM Jackson, DS Roetting, JP McCauley, HA Heitkemper, DT Fricke, FL Krol, WJ Arsenault, TL White, JC Flottmeyer, MM Johnson, YS AF Gratz, Samuel R. Ciolino, Laura A. Mohrhaus, Angela S. Gamble, Bryan M. Gracie, Jill M. Jackson, David S. Roetting, John P., II McCauley, Heather A. Heitkemper, Douglas T. Fricke, Fred L. Krol, Walter J. Arsenault, Terri L. White, Jason C. Flottmeyer, Michele M. Johnson, Yoko S. TI Screening and Determination of Polycyclic Aromatic Hydrocarbons in Seafoods Using QuEChERS-Based Extraction and High-Performance Liquid Chromatography with Fluorescence Detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TOXIC EQUIVALENCY FACTORS; OIL-SPILL; PESTICIDE-RESIDUES; EXXON-VALDEZ; EDIBLE OILS; CRUDE-OIL; GULF; FISH; IDENTIFICATION; METABOLITES AB A rapid, sensitive, and accurate method for the screening and determination of polycyclic aromatic hydrocarbons (PAHs) in edible seafood is described. The method uses quick, easy, cheap, effective, rugged, and safe (QuEChERS)-based extraction and HPLC with fluorescence detection (FLD). The method was developed and validated in response to the massive Deepwater Horizon oil spill in the Gulf of Mexico. Rapid and highly sensitive PAH screening methods are critical tools needed for oil spill response; they help to assess when seafood is safe for harvesting and consumption. Sample preparation involves SPE of edible Seafood portions with acetonitrile, followed by the addition of salts to induce water partitioning. After centrifugation, a portion of the acetonitrile layer is filtered prior to analysis via HPLC-FLD. The chromatographic method uses a polymeric C-18 stationary phase designed for PAH analysis with gradient elution, and it resolves 15 U.S. Environmental Protection Agency priority parent PAHs in fewer than 20 min. The procedure was validated in three laboratories for the parent PAHs using spike recovery experiments at PAH fortification levels ranging from 25 to 10 000 mu g/kg in oysters, shrimp, crab, and finfish, with recoveries ranging from 78 to 99%. Additional validation was conducted for a series of alkylated homologs of naphthalene, dibenzothiophene, and phenanthrene, with recoveries ranging from 87 to 128%. Method accuracy was further assessed based on analysis of National Institute of Standards and Technology Standard Reference Material 1974b. The method provides method detection limits in the sub to low ppb (mu g/kg) range, and practical LOQs in the low ppb (mu g/kg) range for most of the PAH compounds studied. C1 [Gratz, Samuel R.; Ciolino, Laura A.; Mohrhaus, Angela S.; Gamble, Bryan M.; Gracie, Jill M.; Jackson, David S.; Roetting, John P., II; McCauley, Heather A.; Heitkemper, Douglas T.; Fricke, Fred L.] US FDA, FCC, Cincinnati, OH 45237 USA. [Krol, Walter J.; Arsenault, Terri L.; White, Jason C.] Connecticut Agr Expt Stn, Dept Analyt Chem, New Haven, CT 06504 USA. [Flottmeyer, Michele M.; Johnson, Yoko S.] Minnesota Dept Agr, Lab Serv, St Paul, MN 55155 USA. RP Gratz, SR (reprint author), US FDA, FCC, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM Samuel.gratz@fda.hhs.gov NR 38 TC 18 Z9 19 U1 2 U2 50 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2011 VL 94 IS 5 BP 1601 EP 1616 DI 10.5740/jaoacint.11-035 PG 16 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 838DZ UT WOS:000296268300026 PM 22165027 ER PT J AU Flood, AB Nicolalde, RJ Demidenko, E Williams, BB Shapiro, A Wiley, AL Swartz, HM AF Flood, Ann Barry Nicolalde, Roberto J. Demidenko, Eugene Williams, Benjamin B. Shapiro, Alla Wiley, Albert L., Jr. Swartz, Harold M. TI A framework for comparative evaluation of dosimetric methods to triage a large population following a radiological event SO RADIATION MEASUREMENTS LA English DT Article DE Biodosimetry; Comparative effectiveness; Models ID BIOLOGICAL DOSIMETRY; BIODOSIMETRY APPLICATIONS; IONIZING-RADIATION; MEDICAL-MANAGEMENT; GAMMA-H2AX FOCI; DOSE ASSESSMENT; NIH ROADMAP; EPR; LYMPHOCYTES; RECOMMENDATIONS AB Background: To prepare for a possible major radiation disaster involving large numbers of potentially exposed people, it is important to be able to rapidly and accurately triage people for treatment or not, factoring in the likely conditions and available resources. To date, planners have had to create guidelines for triage based on methods for estimating dose that are clinically available and which use evidence extrapolated from unrelated conditions. Current guidelines consequently focus on measuring clinical symptoms (e.g., time-to-vomiting), which may not be subject to the same verification of standard methods and validation processes required for governmental approval processes of new and modified procedures. Biodosimeters under development have not yet been formally approved for this use. Neither set of methods has been tested in settings involving large-scale populations at risk for exposure. Objective: To propose a framework for comparative evaluation of methods for such triage and to evaluate biodosimetric methods that are currently recommended and new methods as they are developed. Methods: We adapt the NIH model of scientific evaluations and sciences needed for effective translational research to apply to biodosimetry for triaging very large populations following a radiation event. We detail criteria for translating basic science about dosimetry into effective multi-stage triage of large populations and illustrate it by analyzing 3 current guidelines and 3 advanced methods for biodosimetry. Conclusions: This framework for evaluating dosimetry in large populations is a useful technique to compare the strengths and weaknesses of different dosimetry methods. It can help policy-makers and planners not only to compare the methods' strengths and weaknesses for their intended use but also to develop an integrated approach to maximize their effectiveness. It also reveals weaknesses in methods that would benefit from further research and evaluation. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Flood, Ann Barry; Nicolalde, Roberto J.; Demidenko, Eugene; Williams, Benjamin B.; Swartz, Harold M.] Dartmouth Med Sch, Dartmouth Phys Based Biodosimetry Ctr Med C, Hanover, NH 03768 USA. [Shapiro, Alla] Food & Drug Adm FDA, Rockville, MD USA. [Wiley, Albert L., Jr.] Oak Ridge Inst Sci & Educ ORISE, Oak Ridge, TN USA. RP Flood, AB (reprint author), Dartmouth Med Sch, Dartmouth Phys Based Biodosimetry Ctr Med C, Hanover, NH 03768 USA. EM Ann.B.Flood@Dartmouth.Edu; Roberto.J.Nicolalde@Dartmouth.Edu; Eugene.Demidenko@Dartmouth.Edu; Benjamin.B.Williams@Dartmouth.Edu; Alla.Shapiro@fda.hhs.gov; Albert.Wiley@orise.orau.gov; Harold.M.Swartz@Dartmouth.Edu FU National Institute of Allergy and Infectious Diseases [NIH-U19AI091173] FX This work was supported by a grant from the National Institute of Allergy and Infectious Diseases: NIH-U19AI091173. We would like to acknowledge the research assistance of Liliana Ma and Karen Wai. NR 38 TC 18 Z9 19 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD SEP PY 2011 VL 46 IS 9 SI SI BP 916 EP 922 DI 10.1016/j.radmeas.2011.02.019 PG 7 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 835MA UT WOS:000296039300036 PM 21949481 ER PT J AU Inselman, AL Hansen, DK Lee, HY Nakamura, N Ning, BT Monteiro, JP Varma, V Kaput, J AF Inselman, Amy L. Hansen, Deborah K. Lee, Hyung-yul Nakamura, Noriko Ning, Baitang Monteiro, Jacqueline Pontes Varma, Vijayalakshmi Kaput, Jim TI Assessment of research models for testing gene-environment interactions SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Review DE Inbred strain; Embryonic stem cells (ESCs); Induced pluripotent stem cells (iPSCs); Adult stem cell; Genome wide association studies (GWAS); Individual risk factor ID PLURIPOTENT STEM-CELLS; GENOME-WIDE ASSOCIATION; QUANTITATIVE TRAIT LOCI; MOUSE MODELS; BONE-MARROW; COLLABORATIVE CROSS; COMPLEX TRAITS; NEURAL DIFFERENTIATION; NUTRIGENOMICS RESEARCH; LACTASE PERSISTENCE AB Throughout the last century, possible effects of exposure to toxicants, nutrients or drugs were examined primarily by studies of groups or populations. Individual variation in responses was acknowledged but could not be analyzed due to lack of information or tools to analyze individual genetic make-ups and lifestyle factors such as diet and activity. The Human Genome, Haplotype Map, 1000Genomes, and Human Variome Projects are identifying and cataloging the variation found within humans. Advances in DNA sequencing technologies will soon permit the characterization of individual genomes in clinical and basic research studies, thus allowing associations to be made between an individual genotype and the response to a particular exposure. Such knowledge and tools have generated a significant challenge for scientists: to design and conduct research studies that account for individual genetic variation. However, before these studies are done in humans, they will be performed in various in vivo and in vitro models. The advantages and disadvantages of some of the model test systems that are being used or developed in relation to individual genetic make-up and responses to xenobiotics are discussed. (C) 2011 Elsevier B.V. All rights reserved. C1 [Inselman, Amy L.; Hansen, Deborah K.; Lee, Hyung-yul; Nakamura, Noriko; Ning, Baitang; Varma, Vijayalakshmi; Kaput, Jim] US FDA, Div Personalized Nutr & Med, NCTR, Jefferson, AR 72079 USA. [Monteiro, Jacqueline Pontes] Univ Sao Paulo, Fac Nutr & Metab, Fac Med, Dept Pediat, BR-14049900 Ribeirao Preto, SP, Brazil. RP Inselman, AL (reprint author), US FDA, Div Personalized Nutr & Med, NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM amy.inselman@fda.hhs.gov RI Monteiro, Jacqueline/F-6987-2012 NR 132 TC 3 Z9 3 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP PY 2011 VL 668 SU 1 BP S108 EP S116 DI 10.1016/j.ejphar.2011.05.084 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 842LA UT WOS:000296599700014 PM 21816149 ER PT J AU Zou, XJ Liu, F Zhang, X Patterson, TA Callicott, R Liu, SL Hanig, JP Paule, MG Slikker, W Wang, C AF Zou, Xiaoju Liu, Fang Zhang, Xuan Patterson, Tucker A. Callicott, Ralph Liu, Shuliang Hanig, Joseph P. Paule, Merle G. Slikker, William, Jr. Wang, Cheng TI Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Nitrous oxide (N(2)O); Isoflurane (ISO); Developmental neurotoxicity; Rhesus monkey ID INDUCED APOPTOSIS; CELL-DEATH; KETAMINE; EXPOSURE; RECEPTOR; CULTURE; BRAIN; NEURODEGENERATION; SUSCEPTIBILITY; NEUROTOXICITY AB The combination of nitrous oxide gas (N(2)O) and isoflurane (ISO) vapor is commonly used in pediatric surgical procedures for human infants and children to produce unconsciousness and analgesia. Because of obvious limitations it is difficult to thoroughly explore the effects of pediatric anesthetic agents on neurons in human infants or children. Due to the complexity of the primate brain, the monkey is often the animal model of choice for developmental neurotoxicology experiments, and it is in the rhesus monkey that the phenomenon of interest (anesthetic-induced neuronal cell death in the brain) has been previously reported. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA)-type glutamate receptors or potentiate gamma-aminobutyric acid (GABA) receptors can trigger widespread apoptotic cell death in rodents. The present study was performed to determine whether prolonged exposure of developing nonhuman primates to a clinically relevant combination of nitrous oxide and isoflurane produces neuronal damage. Postnatal day (PND) 5-6 rhesus monkeys were exposed to N(2)O (70%) or ISO (1.0%) alone, or N(2)O plus ISO for 8 h. Inhalation of the combination of 70% N(2)O + 1% ISO produces a surgical plane of anesthesia. Six hours after completion of anesthetic administration the monkeys were examined for neurotoxic effects. No significant neurotoxic effects were observed for the monkeys exposed to N(2)O or ISO alone. However, neuronal damage was apparent when N(2)O was combined with ISO as indicated by increased numbers of caspase-3-, Silver staining- and Fluoro-Jade C-positive cells in the frontal cortex, temporal gyrus and hippocampus. Electron micrographs indicated typical swelling of the cytoplasm and nuclear condensation in the frontal cortex. These data suggest that prolonged exposure to inhaled anesthetics (a combination of N(2)O and ISO) in the developing rhesus monkey results in neuronal damage, and that the cell death observed is apoptotic and necrotic in nature. Published by Elsevier Inc. C1 [Zou, Xiaoju; Liu, Fang; Zhang, Xuan; Patterson, Tucker A.; Liu, Shuliang; Paule, Merle G.; Slikker, William, Jr.; Wang, Cheng] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Callicott, Ralph] Bionetics Corp, Jefferson, AR 72079 USA. [Hanig, Joseph P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, C (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, HFT-132, Jefferson, AR 72079 USA. EM Cheng.wang@fda.hhs.gov RI Liu, Shuliang/J-4696-2014 FU National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA); Center for Drug Evaluation and Research (CDER)/FDA; National Institute of Child Health and Human Development (NICHD) FX This work was supported by the National Center for Toxicological Research (NCTR)/U.S. Food and Drug Administration (FDA), the Center for Drug Evaluation and Research (CDER)/FDA, and the National Institute of Child Health and Human Development (NICHD). NR 24 TC 54 Z9 57 U1 0 U2 6 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 SEP-OCT PY 2011 VL 33 IS 5 BP 592 EP 597 DI 10.1016/j.ntt.2011.06.003 PG 6 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 841VY UT WOS:000296544500009 PM 21708249 ER PT J AU Sathyamoorthy, V Datta, AR Lee, CJ Kothary, MH McCardell, BA Tall, BD AF Sathyamoorthy, Venugopal Datta, Atin R. Lee, Clara J. Kothary, Mahendra H. McCardell, Barbara A. Tall, Ben D. TI Cloning and partial characterization of a novel hemolysin gene of Vibrio tubiashii and the development of a PCR-based detection assay SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Article DE Vibrio tubiashii; ribA gene; hemolysin ID JUVENILE BIVALVE MOLLUSKS; GTP-CYCLOHYDROLASE-II; BACILLARY NECROSIS; ESCHERICHIA-COLI; RAINBOW-TROUT; VULNIFICUS; VIRULENCE; DISEASE; PARAHAEMOLYTICUS; METALLOPROTEASE AB Vibrio tubiashii expresses virulence factors, such as a vulnificolysin-like hemolysin or cytolysin and a zinc metalloprotease, similar to those of other pathogenic vibrios. In this study, we report the cloning of a novel hemolysin gene of V tubiashii in Escherichia coli. A V. tubiashii gene library was screened for hemolytic activity on sheep blood agar. Three hemolytic clones pGem:hly1, pGem:hly2, and pGem:hly3 were sequenced, and the sequences showed a strong homology to the ribA gene coding for guanosine triphosphate cyclohydrolase II (GCH II), required for riboflavin biosynthesis and reported to be responsible for hemolytic activity in Helicobacter pylori. The plasmids pGem:hly1 and pGem:hly3 when introduced into E. coli BSV18 (ribA18::Tn5) were able to restore growth of strain BSV18 in a medium without riboflavin and also produced hemolytic activity on blood agar. PCR primers based on the cloned hly-ribA sequence were tested using 23 different Vibrio strains representing 10 different species. Amplification of ribA gene locus only occurred with V. tubiashii strains. In summary, our results indicate that we have cloned a ribA homolog of V tubiashii that imparts hemolytic activity to E. coli clones, and primers based on this gene locus might be useful as a species-specific identification tool for V. tubiashii. C1 [Sathyamoorthy, Venugopal; Datta, Atin R.; Lee, Clara J.; Kothary, Mahendra H.; McCardell, Barbara A.; Tall, Ben D.] US FDA, MOD I Facil, Virulence Mech Branch,Ctr Food Safety & Appl Nutr, Div Virulence Assessment,Off Appl Res & Safety As, Laurel, MD 20708 USA. RP Sathyamoorthy, V (reprint author), US FDA, MOD I Facil, Virulence Mech Branch,Ctr Food Safety & Appl Nutr, Div Virulence Assessment,Off Appl Res & Safety As, HFS 025,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Venugopal.Sathyamoorthy@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 23 TC 1 Z9 1 U1 2 U2 7 PU CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS PI OTTAWA PA 65 AURIGA DR, SUITE 203, OTTAWA, ON K2E 7W6, CANADA SN 0008-4166 EI 1480-3275 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD SEP PY 2011 VL 57 IS 9 BP 714 EP 721 DI 10.1139/W11-058 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 834VQ UT WOS:000295992700003 PM 21854089 ER PT J AU Ratcliffe, BC Skelley, PE AF Ratcliffe, Brett C. Skelley, Paul E. TI DESCRIPTION OF THE LARVA OF HOMOPHILEURUS INTEGER (BURMEISTER, 1847) (COLEOPTERA: SCARABAEIDAE: DYNASTINAE: PHILEURINI), WITH NOTES ON BIOLOGY AND A KEY TO THE KNOWN LARVAE OF NEW WORLD PHILEURINI SO COLEOPTERISTS BULLETIN LA English DT Article DE scarab beetle; third instar; distribution; morphology; termites AB The larva of Homophileurus integer (Burmeister, I 847) (Coleoptera: Scarabaeidae: Dynastinae: Phileurini) is described for the first time and accompanied by notes on its biology based on specimens from Suriname. An updated key to the known third-stage larvae of American Phileurini is provided. C1 [Ratcliffe, Brett C.] Univ Nebraska, Lincoln, NE 68588 USA. [Skelley, Paul E.] Florida State Collect Arthropods, FDACS DPI, Gainesville, FL 32614 USA. RP Ratcliffe, BC (reprint author), Univ Nebraska, W436 Nebraska Hall, Lincoln, NE 68588 USA. EM bratcliffe1@unl.edu; Paul.Skelley@freshfromflorida.com FU NSF [DEB 0716899] FX For assistance in the field, PES thanks Anielkoemar Gangadin and Conrad Gillett (National Zoological Collection of Suriname, University of Suriname, Paramaribo) and William Warner (Chandler, AZ). The Suriname Forest Service is acknowledged for providing the export permit. Rudi Scheffrahn (University of Florida, Fort Lauderdale REC, Ft. Lauderdale, FL) provided the identification of the termites. Conrad Gillett graciously provided some of the images used in this paper. We are grateful to Angie Fox (University of Nebraska State Museum) for arranging and labeling the plates and two anonymous reviewers for constructive suggestions. This is Florida Department of Agriculture and Consumer Services, Division of Plant Industry, Entomology Contribution No. 1200. This project was supported, in part, by an NSF Biotic Surveys and Inventory grant (DEB 0716899) to B. C. Ratcliffe and R. D. Cave. NR 11 TC 3 Z9 7 U1 0 U2 0 PU COLEOPTERISTS SOC PI ATHENS PA UNIV GEORGIA, 413 BIOLOGICAL SCIENCES BUILDING, ATHENS, GA 30602-2603 USA SN 0010-065X EI 1938-4394 J9 COLEOPTS BULL JI Coleopt. Bull. PD SEP PY 2011 VL 65 IS 3 BP 297 EP 304 PG 8 WC Entomology SC Entomology GA 838DH UT WOS:000296266500011 ER PT J AU Laughren, TP Gobburu, J Temple, RJ Unger, EF Bhattaram, A Dinh, PV Fossom, L Hung, HMJ Klimek, V Lee, JE Levin, RL Lindberg, CY Mathis, M Rosloff, BN Wang, SJ Wang, YN Yang, PL Yu, B Zhang, HX Zhang, L Zineh, I AF Laughren, Thomas P. Gobburu, Jogarao Temple, Robert J. Unger, Ellis F. Bhattaram, Atul Dinh, Phillip V. Fossom, Linda Hung, H. M. James Klimek, Violetta Lee, Jee Eun Levin, Robert L. Lindberg, Cheri Y. Mathis, Mitchell Rosloff, Barry N. Wang, Sue-Jane Wang, Yaning Yang, Peiling Yu, Bei Zhang, Huixia Zhang, Li Zineh, Issam TI Vilazodone: Clinical Basis for the US Food and Drug Administration's Approval of a New Antidepressant SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; SUICIDALITY; BUPROPION; EFFICACY AB Objective: Vilazodone was recently approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). The purpose of this review is to summarize the FDA's approach to its review of the clinical pharmacology and the clinical efficacy and safety data for this new drug application, important issues in its decision-making, and its conclusions. Data Sources:The data sources for this review were the original raw data sets for all clinical trials included in the development program for vilazodone, as well as the sponsor's original analyses of these data. Study Selection: Data were available from 24 human trials involving vilazodone, and included a total of 2,898 human subjects exposed to 1 or more doses of this drug. Data Extraction:The FDA had access to original raw data sets for these trials. Results: Vilazodone is effective in treating MDD at a dose of 40 mg/d, but it needs to be incrementally adjusted to this dose to minimize gastrointestinal symptoms. It needs to be taken with food to ensure adequate plasma concentrations. Vilazodone's profile of adverse events is similar to that seen with selective serotonin reuptake inhibitors. No dose adjustment is needed based on age, gender, or renal or hepatic impairment. It is recommended that the vilazodone dose be reduced to 20 mg when it is taken with strong cytochrome P450 (CYP) 3A4 inhibitors, eg, ketoconazole. Vilazodone is not expected to have important effects on the clearance of other drugs that are cytochrome P450 substrates. Conclusions: Vilazodone is a new treatment for MDD, but it is unknown whether it has any advantages compared to other drugs in the antidepressant class. J Clin Psychiatry 2011;72(9):1166-1173 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Laughren, Thomas P.; Fossom, Linda; Klimek, Violetta; Levin, Robert L.; Lindberg, Cheri Y.; Mathis, Mitchell; Rosloff, Barry N.] US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Gobburu, Jogarao; Bhattaram, Atul; Lee, Jee Eun; Wang, Yaning; Yu, Bei; Zhang, Huixia; Zhang, Li; Zineh, Issam] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Temple, Robert J.; Unger, Ellis F.] US FDA, Off Drug Evaluat I, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Dinh, Phillip V.; Hung, H. M. James; Wang, Sue-Jane; Yang, Peiling] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Laughren, TP (reprint author), US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM thomas.laughren@fda.hhs.gov RI Zhang, Jinny/C-4794-2012 NR 10 TC 28 Z9 29 U1 1 U2 12 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2011 VL 72 IS 9 BP 1166 EP 1173 DI 10.4088/JCP.11r06984 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 828LO UT WOS:000295502700002 PM 21951984 ER PT J AU Khin, NA Chen, YF Yang, Y Yang, PL Laughren, TP AF Khin, Ni A. Chen, Yeh-Fong Yang, Yang Yang, Peiling Laughren, Thomas P. TI Failure Rate and "Professional Subjects" in Clinical Trials of Major Depressive Disorder Reply SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter C1 [Khin, Ni A.; Laughren, Thomas P.] US FDA, Div Psychiat Prod, Off Drug Evaluat I, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Chen, Yeh-Fong; Yang, Yang; Yang, Peiling] US FDA, Div Biometr I, Off Biostat, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Khin, NA (reprint author), US FDA, Div Psychiat Prod, Off Drug Evaluat I, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM ni.khin@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD SEP PY 2011 VL 72 IS 9 BP 1284 EP 1285 DI 10.4088/JCP.11lr07229a PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 828LO UT WOS:000295502700020 ER PT J AU Gomila, M Tvrzova, L Teshim, A Sedlacek, I Gonzalez-Escalona, N Zdrahal, Z Sedo, O Gonzalez, JF Bennasar, A Moore, ERB Lalucat, J Murialdo, SE AF Gomila, Margarita Tvrzova, Ludmila Teshim, Andrea Sedlacek, Ivo Gonzalez-Escalona, Narjol Zdrahal, Zbynek Sedo, Ondrej Froilan Gonzalez, Jorge Bennasar, Antonio Moore, Edward R. B. Lalucat, Jorge Murialdo, Silvia E. TI Achromobacter marplatensis sp nov., isolated from a pentachlorophenol-contaminated soil SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID HUMAN CLINICAL-SAMPLES; DENITRIFICANS RUGER; RECLASSIFICATION; PIECHAUDII AB A polyphasic taxonomic approach was applied to the study of a Gram-negative bacterium (B2(T)) isolated from soil by selective enrichment with pentachlorophenol. 16S rRNA gene sequence analysis of strain B2(T) showed that the strain belongs to the genus Achromobacter within the Betaproteobacteria. The 16S rRNA gene sequence displayed more than 99% similarity to the sequences of the type strains of all species of Achromobacter, with the highest sequence similarity to those of Achromobacter spanius CCM 7183(T) and A. piechaudii CCM 2986(T) (99.8%). On the basis of phylogenetic analysis, genomic DNA-DNA relatedness and phenotypic characteristics, including chemotaxonomic (cellular fatty acid profile) analysis, a novel species is proposed, Achromobacter marplatensis sp. nov., with the type strain B2(T) (=CCM 7608(T) =CCUG 56371(T) =CECT 7342(T)). C1 [Gomila, Margarita; Bennasar, Antonio; Lalucat, Jorge] Univ Illes Balears, Dept Biol, Palma De Mallorca 07122, Illes Balears, Spain. [Gomila, Margarita; Bennasar, Antonio; Lalucat, Jorge] Inst Mediterrani Estudis Avancats CSIC UIB, Palma De Mallorca 07122, Illes Balears, Spain. [Tvrzova, Ludmila; Teshim, Andrea] Masaryk Univ, Fac Sci, Dept Expt Biol, Div Microbiol, Brno 60200, Czech Republic. [Sedlacek, Ivo] Masaryk Univ, Fac Sci, Dept Expt Biol, Czech Collect Microorganisms, Brno 60200, Czech Republic. [Gonzalez-Escalona, Narjol] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Zdrahal, Zbynek; Sedo, Ondrej] Masaryk Univ, Fac Sci, Dept Expt Biol, Div Funct Genom & Prote, Brno 62500, Czech Republic. [Froilan Gonzalez, Jorge; Murialdo, Silvia E.] Univ Nacl Mar del Plata, RA-7600 Buenos Aires, Argentina. [Bennasar, Antonio] Inst Univ Invest Ciencies Salut IUNICS UIB, Palma De Mallorca 07122, Spain. [Moore, Edward R. B.] Sahlgrens Univ Hosp, CCUG, Dept Clin Bacteriol, Gothenburg, Sweden. [Moore, Edward R. B.] Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden. RP Gomila, M (reprint author), Univ Illes Balears, Dept Biol, Palma De Mallorca 07122, Illes Balears, Spain. EM marga.gomila@uib.es RI Zdrahal, Zbynek/D-9491-2012; Sedo, Ondrej/D-9868-2012; Lalucat, Jorge/K-1127-2014; Gomila, Margarita/H-3314-2015; Bennasar, Antonio/I-4469-2015; OI Lalucat, Jorge/0000-0002-8350-6087; Gomila, Margarita/0000-0001-8725-190X; Bennasar, Antonio/0000-0002-2221-3248; Moore, Edward/0000-0001-7693-924X; Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU Agencia-Pict, Argentina [13-03246]; National University of Mar del Plata; Pla Balear de Recerca i Desenvolupament Tecnologic de les Illes Balears (PRIB); Ministry of Education, Youth and Sport of the Czech Republic [MSM0021622415, MSM0021622413, MSM0021622416]; Universitat de les Illes Balears, Institut Mediterrani d'Estudis Avancats (CSIC-UIB); Masaryk University; North Carolina State University FX This research was supported by Agencia-Pict, Argentina (grant 13-03246), and the National University of Mar del Plata. The work of M. G., A. B. and J. L. was supported by the Pla Balear de Recerca i Desenvolupament Tecnologic de les Illes Balears (PRIB). The MALDI-TOF MS and ribotyping analyses were supported by projects of the Ministry of Education, Youth and Sport of the Czech Republic (MSM0021622415, MSM0021622413 and MSM0021622416). Support from the Universitat de les Illes Balears, Institut Mediterrani d'Estudis Avancats (CSIC-UIB), Masaryk University and North Carolina State University is greatly appreciated. The authors acknowledge the technical expertise of the CCUG staff for CFA analyses. NR 20 TC 17 Z9 17 U1 0 U2 9 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD SEP PY 2011 VL 61 BP 2231 EP 2237 DI 10.1099/ijs.0.025304-0 PN 9 PG 7 WC Microbiology SC Microbiology GA 827MJ UT WOS:000295432300036 PM 20952547 ER PT J AU Barb, AW Freedberg, DI Battistel, MD Prestegard, JH AF Barb, Adam W. Freedberg, Daron I. Battistel, Marcos D. Prestegard, James H. TI NMR detection and characterization of sialylated glycoproteins and cell surface polysaccharides SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE N-acetylneuraminic acid; Sialic acid; Carbohydrate; Pulse sequence; In vivo NMR; Isotopic labeling ID NUCLEAR-MAGNETIC-RESONANCE; SIALIC-ACID; GLYCOSYLATION; ASSIGNMENTS; PROTEINS; ANTIGENS; GLYCANS; SYSTEM; CANCER; MUCIN AB Few solution NMR pulse sequences exist that are explicitly designed to characterize carbohydrates (glycans). This is despite the essential role carbohydrate motifs play in cell-cell communication, microbial pathogenesis, autoimmune disease progression and cancer metastasis, and despite that fact that glycans, often shed to extra-cellular fluids, can be diagnostic of disease. Here we present a suite of two dimensional coherence experiments to measure three different correlations (H3-C2, H3-C1, and C1-C2) on sialic acids, a group of nine-carbon carbohydrates found on eukaryotic cell surfaces that often play a key role in disease processes. The chemical shifts of the H3, C2, and C1 nuclei of sialic acids are sensitive to carbohydrate linkage, linkage conformation, and ionization state of the C1 carboxylate. The experiments reported include rigorous filter elements to enable detection and characterization of isotopically labeled sialic acids with high sensitivity in living cells and crude isolates with minimal interference from unwanted signals arising from the similar to 1% (13)C-natural abundance of cellular metabolites. Application is illustrated with detection of sialic acids on living cells, in unpurified mixtures, and at the terminus of the N-glycan on the 55 kDa immunoglobulin G Fc. C1 [Barb, Adam W.; Prestegard, James H.] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Freedberg, Daron I.; Battistel, Marcos D.] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Rockville, MD 20852 USA. RP Prestegard, JH (reprint author), Univ Georgia, Complex Carbohydrate Res Ctr, 315 Riverbend Rd, Athens, GA 30602 USA. EM jpresteg@ccrc.uga.edu FU National Institutes of Health [RO1GM033225, P41RR005351, F32AR058084] FX We thank Dr. Eric Vimr (U. Illinois) for the E. coli EV239 cells, and Dr. Yizhou Liu and Dr. Xu Wang for helpful discussions regarding pulse sequence design. This work was financially supported by the grants RO1GM033225 and P41RR005351 from the National Institutes of Health. A. W. B. was supported by a NIH Kirschstein National Research Service Award (F32AR058084). The content of this work is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 33 TC 7 Z9 7 U1 2 U2 13 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD SEP PY 2011 VL 51 IS 1-2 BP 163 EP 171 DI 10.1007/s10858-011-9550-0 PG 9 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 834TX UT WOS:000295988100016 PM 21947924 ER PT J AU Wang, SJ Blume, JD AF Wang, Sue-Jane Blume, Jeffrey D. TI An evidential approach to non-inferiority clinical trials SO PHARMACEUTICAL STATISTICS LA English DT Article DE constancy assumption; likelihood ratio; misleading evidence; non-inferiority margin; strength of evidence ID ACTIVE-CONTROL TRIALS; LONGITUDINAL DATA-ANALYSIS; PLACEBO-CONTROLLED TRIALS; STATISTICAL EVIDENCE; ALTERNATIVE FOUNDATION; MYOCARDIAL-INFARCTION; ISSUES; DESIGN; MODELS; METAANALYSIS AB We present likelihood methods for defining the non-inferiority margin and measuring the strength of evidence in non-inferiority trials using the 'fixed-margin' framework. Likelihood methods are used to (1) evaluate and combine the evidence from historical trials to define the non-inferiority margin, (2) assess and report the smallest non-inferiority margin supported by the data, and (3) assess potential violations of the constancy assumption. Data from six aspirin-controlled trials for acute coronary syndrome and data from an active-controlled trial for acute coronary syndrome, the Organisation to Assess Strategies for Ischemic Syndromes (OASIS-2) trial, are used for illustration. The likelihood framework offers important theoretical and practical advantages when measuring the strength of evidence in non-inferiority trials. Besides eliminating the influence of sample spaces and prior probabilities on the 'strength of evidence in the data', the likelihood approach maintains good frequentist properties. Violations of the constancy assumption can be assessed in the likelihood framework when it is appropriate to assume a unifying regression model for trial data and a constant control effect including a control rate parameter and a placebo rate parameter across historical placebo controlled trials and the non-inferiority trial. In situations where the statistical non-inferiority margin is data driven, lower likelihood support interval limits provide plausibly conservative candidate margins. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. [Blume, Jeffrey D.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37212 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, CDER, HFD-700,WO 21,Mail Stop Room 3562,10903 New Hamps, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 50 TC 5 Z9 5 U1 0 U2 12 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD SEP-OCT PY 2011 VL 10 IS 5 SI SI BP 440 EP 447 DI 10.1002/pst.513 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 833HE UT WOS:000295873100009 PM 21928286 ER PT J AU Mokhtari, N AF Mokhtari, Nahid TI New paradigm in medicine - The secrets of quantum field SO CLINICAL BIOCHEMISTRY LA English DT Meeting Abstract C1 [Mokhtari, Nahid] US FDA, Ctr Drug Evaluat & Res, Gaithersburg, MD 20878 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 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD SEP PY 2011 VL 44 IS 13 SU S BP S31 EP S31 DI 10.1016/j.clinbiochem.2011.08.1026 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 827OK UT WOS:000295437600089 ER PT J AU Boehmer, JL DeGrasse, JA Lancaster, VA McFarland, MA Callahan, JH Ward, JL AF Boehmer, Jamie L. DeGrasse, Jeffrey A. Lancaster, Vicki A. McFarland, Melinda A. Callahan, John H. Ward, Jeffrey L. TI Evaluation of protein expression in bovine bronchoalveolar fluid following challenge with Mannheimia haemolytica SO PROTEOMICS LA English DT Article DE Animal proteomics; Antimicrobial protein; Bovine bronchoalveolar fluid; MS/MS; Nanoflow LC ID ACUTE-PHASE PROTEIN; ALPHA-TRYPSIN INHIBITOR; ANTIMICROBIAL PEPTIDES; RESPIRATORY-DISEASE; PROTEOMIC ANALYSIS; LAVAGE FLUID; CATTLE; TRACT AB Proteomics analysis of bovine bronchoalveolar fluid (BAF) following induction of pneumonia with Mannheimia haemolytica using nanoflow liquid chromatography coupled with tandem mass spectrometry (nanoLC-MS/MS) resulted in the identification of 88 unique proteins. Proteins detected in BAF included antimicrobial peptides (AMPs), complement factors, acute-phase proteins, protease inhibitors, and proteins involved in oxidation-reduction. Notwithstanding biological variation, differences in relative protein abundance, determined using normalized peptide counts, were detected for select proteins in BAF from genuinely infected versus sham-infected animals. To demonstrate the applicability of using normalized peptide counts to assess protein expression trends, LC-MS/MS data for the acute-phase protein haptoglobin (HPT) were compared with ELISA data, and statistical evaluation of the relationship between the data revealed a strong measure of association. Differences were detected between sham-and genuinely infected animals for haptoglobin, as well as the AMPs cathelicidin-1 and cathelicidin-4, and inter-alpha-trypsin inhibitor heavy chain-4, a fairly novel protein involved in the acute phase response. Though the small sample size limited the scope of the inferences, the results indicate the likely importance of AMPs and acute-phase proteins during respiratory infection, and provide additional information regarding potential mechanisms involved in the bovine mucosal barrier defense. C1 [Boehmer, Jamie L.; Ward, Jeffrey L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [DeGrasse, Jeffrey A.; McFarland, Melinda A.; Callahan, John H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Lancaster, Vicki A.] US FDA, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. RP Boehmer, JL (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM jamie.boehmer@fda.hhs.gov RI McFarland, Melinda/A-1866-2013; DeGrasse, Jeffrey/J-1151-2014 OI DeGrasse, Jeffrey/0000-0003-3178-6301 NR 31 TC 12 Z9 12 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1615-9853 J9 PROTEOMICS JI Proteomics PD SEP PY 2011 VL 11 IS 18 BP 3685 EP 3697 DI 10.1002/pmic.201000710 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 831FG UT WOS:000295713500011 PM 21800424 ER PT J AU Zhao, YW Xia, QS Yin, JJ Yu, HT Fu, PP AF Zhao, Yuewei Xia, Qingsu Yin, Jun-Jie Yu, Hongtao Fu, Peter P. TI Photoirradiation of polycyclic aromatic hydrocarbon diones by UVA light leading to lipid peroxidation SO CHEMOSPHERE LA English DT Article DE Lipid peroxidation; PAH-diones; Reactive oxygen species; UVA light; Electron spin resonance ID GENOTOXIC ENVIRONMENTAL-POLLUTANTS; SINGLET OXYGEN; RETINYL PALMITATE; DNA-DAMAGE; QUINONES; EXPOSURE; INDUCTION; RADICALS; AZULENE; 1-HYDROXYPYRENE AB Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous genotoxic environmental pollutants and potentially pose a health risk to humans. In most if not all cases. PAHs in the environment can be oxidized into their corresponding PAH-diones. This process is considered a detoxification pathway with regard to tumorigenicity. Nevertheless, photo-induced toxicological activity of PAH-diones has not been systematically investigated. In this study, we show that 27 potential environmental PAH-diones induced lipid peroxidation, in a dose (light) response manner, when irradiated with UVA at 7 and 21 J cm(-2). Photoirradiation in the presence of sodium azide, deuterated methanol, or superoxide dismutase revealed that lipid peroxidation is mediated by reactive oxygen species. Electron spin resonance (ESR) spin trapping studies supported this observation. These results suggest that UVA photoirradiation of PAH-diones generates reactive oxygen species and induces lipid peroxidation. Published by Elsevier Ltd. C1 [Zhao, Yuewei; Xia, Qingsu; 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. [Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. RP Zhao, YW (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM yuewei.zhao@fda.hhs.gov RI Yin, Jun Jie /E-5619-2014 FU NCTR; US Department of Energy; FDA FX We thank Drs. Frederick A. Be land for critical review of this manuscript. This research was supported in part by appointment (Y. Zhao) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. NR 81 TC 7 Z9 7 U1 4 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD SEP PY 2011 VL 85 IS 1 BP 83 EP 91 DI 10.1016/j.chemosphere.2011.05.040 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 825UO UT WOS:000295307800012 PM 21680011 ER PT J AU Nelson, CP Patton, GW Arvidson, K Lee, H Twaroski, ML AF Nelson, Chad P. Patton, Geoffrey W. Arvidson, Kirk Lee, Helen Twaroski, Michelle L. TI Assessing the toxicity of polymeric food-contact substances SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE Food-contact substance; Polymers; Oligomers; Regulatory; Toxicology ID NATIONAL-TOXICOLOGY-PROGRAM; THYMIDINE KINASE LOCUS; MOUSE LYMPHOMA-CELLS; HAMSTER EMBRYO CELL; IN-VITRO; BISPHENOL-A; STRAND BREAKS; CHROMOSOMAL-ABERRATIONS; CHEMICAL MUTAGENESIS; POLYVINYL-ALCOHOL AB The US Food and Drug Administration's Office of Food Additive Safety in the Center for Food Safety and Applied Nutrition conducts safety assessments of food additives, including food-contact substances such as polymeric and oligomeric materials that have the potential to migrate to food. Traditionally, little toxicity testing has been conducted on the low-molecular weight oligomeric fraction (<1000 Da) of these food-contact substances. At lower exposures (<= 150 mu g/person/day), safety has been assessed based on the use of toxicity data on the monomeric components of these polymers as a sufficiently conservative approach for addressing the concern for genetic toxicity and carcinogenicity of the low-molecular weight oligomers (LMWOs). This paper discusses this assumption relative to the available data on these substances and their monomeric components in the context of exposures of <= 150 mu g/person/day with emphasis on the evaluation of the potential genetic toxicity of these compounds. In most instances, data are available on either the monomers or the monomers' structural class to conservatively address the potential genetic toxicity of the LMWOs. Caveats to this generalization are also discussed. The assessment of LMWOs is important because they can be one of the primary migrants to food from a polymeric food-contact substance. Published by Elsevier Ltd. C1 [Patton, Geoffrey W.; Arvidson, Kirk; Lee, Helen; Twaroski, Michelle L.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notificat, College Pk, MD 20740 USA. [Nelson, Chad P.] US FDA, Off Commissioner, Off Foods, Silver Spring, MD 20993 USA. RP Patton, GW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Food Contact Notificat, 5100 Paint Branch Pkwy,HFS 275, College Pk, MD 20740 USA. EM geoffrey.patton@fda.hhs.gov NR 99 TC 3 Z9 3 U1 2 U2 14 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 2011 VL 49 IS 9 BP 1877 EP 1897 DI 10.1016/j.fct.2011.06.054 PG 21 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 824FU UT WOS:000295188600001 PM 21723908 ER PT J AU Chancey, C Winkelman, V Silberstein, E Taylor, D Rios, M AF Chancey, C. Winkelman, V. Silberstein, E. Taylor, D. Rios, M. TI Partition of HCV in Whole Blood Specimens from Infected Donors Confirms Suitability of Plasma for NAT Screening SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Chancey, C.; Silberstein, E.; Taylor, D.; Rios, M.] US FDA, DETTD, CBER, Bethesda, MD 20014 USA. [Winkelman, V.] MDL, Tempe, AZ USA. EM caren.chancey@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 16A EP 16A PG 1 WC Hematology SC Hematology GA 822YC UT WOS:000295085500037 ER PT J AU Menis, M Izurieta, H Anderson, SA Holness, L Gibbs, JM Kropp, G Worrall, CM MaCurdy, T Kelman, JA Ball, R AF Menis, M. Izurieta, H. Anderson, S. A. Holness, L. Gibbs, J. M. Kropp, G. Worrall, C. M. MaCurdy, T. Kelman, J. A. Ball, R. TI TRALI Occurrence Trends Among the Inpatient US Elderly, as Recorded by Diagnosis Code in 2007-2010 SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Menis, M.; Izurieta, H.; Anderson, S. A.; Holness, L.; Ball, R.] US FDA, CBER, Rockville, MD 20857 USA. [Gibbs, J. M.; Kropp, G.; MaCurdy, T.] Acumen LLC, Burlingame, CA USA. [Worrall, C. M.; Kelman, J. A.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. EM Mikhail.Menis@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 126A EP 127A PG 2 WC Hematology SC Hematology GA 822YC UT WOS:000295085500317 ER PT J AU Freimanis, GL Sedegah, MY Owusu-Ofori, S Kumar, S Allain, J AF Freimanis, G. L. Sedegah, M. Y. Owusu-Ofori, S. Kumar, S. Allain, J. TI Transfusion-Transmitted Malaria in Adult Semi-Immune Patients from Hyperendemic Area SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Freimanis, G. L.; Allain, J.] Univ Cambridge, Cambridge, England. [Sedegah, M. Y.; Kumar, S.] Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD USA. [Owusu-Ofori, S.] Komfo Anokye Teaching Hosp, Transfus Med Unit, Kumasi, Ghana. EM glf31@cam.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 196A EP 196A PG 1 WC Hematology SC Hematology GA 822YC UT WOS:000295085500503 ER PT J AU Anez, G Chancey, C Espina, LM Stramer, SL Rios, M AF Anez, G. Chancey, C. Espina, L. M. Stramer, S. L. Rios, M. TI Dengue Virus Bound to Red Blood Cells of Viremic Blood Donors Retains Its Infectivity in Cell Culture SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Anez, G.; Chancey, C.; Espina, L. M.; Rios, M.] CBER FDA, Lab Emerging Pathogens DETTD OBRR, Bethesda, MD USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA. EM German.Anez@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 205A EP 205A PG 1 WC Hematology SC Hematology GA 822YC UT WOS:000295085500525 ER PT J AU Anez, G Chancey, C Taylor, D Rios, M AF Anez, G. Chancey, C. Taylor, D. Rios, M. TI Development of RNA International Standards for Dengue Virus Types SO TRANSFUSION LA English DT Meeting Abstract CT AABB Annual Meeting and CTTXPO CY OCT 22-25, 2011 CL San Diego, CA SP AABB C1 [Anez, G.; Chancey, C.; Taylor, D.; Rios, M.] CBER FDA, Lab Emerging Pathogens DETTD OBRR, Bethesda, MD USA. EM German.Anez@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2011 VL 51 SU 3 SI SI BP 209A EP 209A PG 1 WC Hematology SC Hematology GA 822YC UT WOS:000295085500535 ER PT J AU Zhang, YB Xu, Y Li, ZG Chen, T Lantz, SM Howard, PC Paule, MG Slikker, W Watanabe, F Mustafa, T Biris, AS Ali, SF AF Zhang, Yongbin Xu, Yang Li, Zhiguang Chen, Tao Lantz, Susan M. Howard, Paul C. Paule, Merle G. Slikker, William, Jr. Watanabe, Fumiya Mustafa, Thikra Biris, Alexandru S. Ali, Syed F. TI Mechanistic Toxicity Evaluation of Uncoated and PEGylated Single-Walled Carbon Nanotubes in Neuronal PC12 Cells SO ACS NANO LA English DT Article DE single-walled carbon nanotubes; functionalization; toxicity; reactive oxygen species; gene expression ID IN-VITRO; OXIDATIVE STRESS; PULMONARY TOXICITY; RAMAN-SPECTROSCOPY; PARTICLE-SIZE; LIVING CELLS; MICE; NANOPARTICLES; DELIVERY; DRUG AB We investigated and compared the concentration-dependent cytotoxicity of single-walled carbon nanotubes (SWCNTs) and SWCNTs functionalized with polyethylene glycol (SWCNT-PEGS) in neuronal PC12 cells at the biochemical, cellular, and gene expressional levels. SWCNTs elicited cytotoxicity in a concentration-dependent manner, and SWCNT-PEGs exhibited less cytotoxic potency than uncoated SWCNTs. Reactive oxygen species (ROS) were generated In both a concentration- and surface coating-dependent manner after exposure to these nanomaterials, Indicating different oxidative stress mechanisms. More specifically, gene expression analysis showed that the genes involved In oxidoreductases and antioxidant activity, nucleic acid or lipid metabolism, and mitochondria dysfunction were highly represented. Interestingly, alteration of the genes is also surface coating-dependent with a good correlation with the biochemical data. These findings suggest that surface functionalization of SWCNTs decreases ROS-mediated toxicological response in vitro. C1 [Xu, Yang; Watanabe, Fumiya; Mustafa, Thikra; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Zhang, Yongbin; Li, Zhiguang; Chen, Tao; Lantz, Susan M.; Howard, Paul C.; Paule, Merle G.; Slikker, William, Jr.; Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Biris, AS (reprint author), Univ Arkansas, Nanotechnol Ctr, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM asbiris@ualr.edu; Syed.Ali@fda.hhs.gov RI Biris, Alexandru/A-8507-2010 FU U.S. Army Telemedicine and Advanced Research Center FX This research was supported in part by an appointment (Y.Z.) to the Research Participation Program at the National Center for Toxicological Research administered by the Oak Ridge Institute of Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. Portions of these studies were conducted using the Nanotechnology Core Facility (NanoCore) located at the U.S. Food & Drug Administration's National Center for Toxicological Research (NCTR) and Office of Regulatory Affairs Arkansas Regional Laboratory (ORA/ARL) campus. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. The financial support of the U.S. Army Telemedicine and Advanced Research Center program is highly appreciated. The editorial assistance of Dr. Marinelle Ringer is also acknowledged. NR 76 TC 82 Z9 83 U1 2 U2 45 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD SEP PY 2011 VL 5 IS 9 BP 7020 EP 7033 DI 10.1021/nn2016259 PG 14 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 824FI UT WOS:000295187400030 PM 21866971 ER PT J AU Hall, S AF Hall, S. TI SAXITOXINS AND DOMOIC ACID: IMPACTS AND MANAGEMENT SO JOURNAL OF PHYCOLOGY LA English DT Meeting Abstract C1 [Hall, S.] US FDA, Rockville, MD 20857 USA. EM sherwood.hall@fda.hhs.gov NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3646 J9 J PHYCOL JI J. Phycol. PD SEP PY 2011 VL 47 SU 2 SI SI BP S4 EP S4 PG 1 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 822ZO UT WOS:000295090200014 ER PT J AU Su, ZQ Li, ZG Chen, T Li, QZ Fang, H Ding, D Ge, WG Ning, BT Hong, HX Perkins, RG Tong, WD Shi, LM AF Su, Zhenqiang Li, Zhiguang Chen, Tao Li, Quan-Zhen Fang, Hong Ding, Don Ge, Weigong Ning, Baitang Hong, Huixiao Perkins, Roger G. Tong, Weida Shi, Leming TI Comparing Next-Generation Sequencing and Microarray Technologies in a Toxicological Study of the Effects of Aristolochic Acid on Rat Kidneys SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; RNA-SEQ; DIFFERENTIAL EXPRESSION; READ ALIGNMENT; REPRODUCIBILITY; TOOL; NORMALIZATION; CONSISTENCY; ULTRAFAST AB RNA-Seq has been increasingly used for the quantification and characterization of transcriptomes. The ongoing development of the technology promises the more accurate measurement of gene expression. However, its benefits over widely accepted microarray technologies have not been adequately assessed, especially in toxicogenomics studies. The goal of this study is to enhance the scientific community's understanding of the advantages and challenges of RNA-Seq in the quantification of gene expression by comparing analysis results from RNA-Seq and microarray data on a toxicogenomics study. A typical toxicogenomics study design was used to compare the performance of an RNA-Seq approach (Illumina Genome Analyzer II) to a microarray-based approach (Affymetrix Rat Genome 230 2.0 arrays) for detecting differentially expressed genes (DEGs) in the kidneys of rats treated with aristolochic acid (AA), a carcinogenic and nephrotoxic chemical most notably used for weight loss. We studied the comparability of the RNA-Seq and microarray data in terms of absolute gene expression, gene expression patterns, differentially expressed genes, and biological interpretation. We found that RNA-Seq was more sensitive in detecting genes with low expression levels, while similar gene expression patterns were observed for both platforms. Moreover, although the overlap of the DEGs was only 40-50%, the biological interpretation was largely consistent between the RNA-Seq and microarray data. RNA-Seq maintained a consistent biological interpretation with time-tested microarray platforms while generating more sensitive results. However, there is clearly a need for future investigations to better understand the advantages and limitations of RNA-Seq in toxicogenomics studies and environmental health research. C1 [Su, Zhenqiang; Fang, Hong; Ding, Don] FDAs Natl Ctr Toxicol Res, ICF Int, Jefferson, AR 72079 USA. [Li, Zhiguang; Chen, Tao; Ge, Weigong; Ning, Baitang; Hong, Huixiao; Perkins, Roger G.; Tong, Weida; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Li, Quan-Zhen] Univ Texas SW Med Ctr Dallas, Genom & Microarray Core Facil, Dallas, TX 75390 USA. RP Su, ZQ (reprint author), FDAs Natl Ctr Toxicol Res, ICF Int, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM zhenqiang.su@fda.hhs.gov; leming.shi@gmail.com RI Su, Zhenqiang/H-3914-2012 NR 31 TC 49 Z9 51 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X EI 1520-5010 J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD SEP PY 2011 VL 24 IS 9 BP 1486 EP 1493 DI 10.1021/tx200103b PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 822OV UT WOS:000295058900008 PM 21834575 ER PT J AU Hill, K Rowers, LR AF Hill, Kenneth Rowers, Louis R., III TI US Public Health Service Commissioned Corps Pharmacist Promoting and Advancing Pharmaceutical Services Abroad SO MILITARY MEDICINE LA English DT Editorial Material C1 [Hill, Kenneth] US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Seattle, WA 98121 USA. [Rowers, Louis R., III] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hill, K (reprint author), US Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, 2201 6th Ave,Suite 865, Seattle, WA 98121 USA. NR 4 TC 0 Z9 0 U1 1 U2 2 PU ASSOC MILITARY SURG US PI BETHESDA PA 9320 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0026-4075 J9 MIL MED JI Milit. Med. PD SEP PY 2011 VL 176 IS 9 BP 974 EP 975 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 821KU UT WOS:000294974700005 PM 21987952 ER PT J AU Donnelly, RP Dickensheets, H O'Brien, TR AF Donnelly, Raymond P. Dickensheets, Harold O'Brien, Thomas R. TI Interferon-lambda and therapy for chronic hepatitis C virus infection SO TRENDS IN IMMUNOLOGY LA English DT Review ID REGULATORY FACTOR FAMILY; IFN-LAMBDA; GENETIC-VARIATION; DENDRITIC CELLS; DIFFERENTIAL EXPRESSION; ANTIVIRAL RESPONSES; VIRAL-INFECTION; INTERLEUKIN 28B; III IFN; NON-A AB Interferon (IFN)-alpha, a type-I IFN, is widely used to treat chronic hepatitis C virus infection, but the broad expression of IFN-alpha receptors often leads to adverse reactions in many organs. Here, we examine IFN-lambda, a type-III IFN, as a therapeutic alternative to IFN-alpha. Like IFN-alpha, IFN-lambda also induces antiviral activity in hepatocytes, but might induce fewer adverse reactions because its receptor is largely restricted to cells of epithelial origin. We also discuss the recent discovery of single nucleotide polymorphisms (SNPs) near the human IFN-lambda 3 gene, IL28B, that correlate strongly with the ability to achieve a sustained virological response to therapy with pegylated IFN-alpha plus ribavirin in patients with chronic hepatitis C. C1 [Donnelly, Raymond P.; Dickensheets, Harold] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [O'Brien, Thomas R.] NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM Raymond.Donnelly@fda.hhs.gov FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. NR 64 TC 37 Z9 39 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD SEP PY 2011 VL 32 IS 9 BP 443 EP 450 DI 10.1016/j.it.2011.07.002 PG 8 WC Immunology SC Immunology GA 820XT UT WOS:000294940100007 PM 21820962 ER PT J AU Wen, Z Pollock, K Nichols, J Waser, P AF Wen, Zhi Pollock, Kenneth Nichols, James Waser, Peter TI Augmenting Superpopulation Capture-Recapture Models with Population Assignment Data SO BIOMETRICS LA English DT Article DE Assignment procedures; Capture-recapture; Genetic assignment test; Immigration; Kangaroo rat; Resampling approach; Robust design; Superpopulation ID POLLOCKS ROBUST DESIGN; INTERPOPULATION DISPERSAL; TEMPORARY EMIGRATION; MULTILOCUS GENOTYPES; KANGAROO RATS; IMMIGRATION AB Ecologists applying capture-recapture models to animal populations sometimes have access to additional information about individuals' populations of origin (e. g., information about genetics, stable isotopes, etc.). Tests that assign an individual's genotype to its most likely source population are increasingly used. Here we show how to augment a superpopulation capture-recapture model with such information. We consider a single superpopulation model without age structure, and split each entry probability into separate components due to births in situ and immigration. We show that it is possible to estimate these two probabilities separately. We first consider the case of perfect information about population of origin, where we can distinguish individuals born in situ from immigrants with certainty. Then we consider the more realistic case of imperfect information, where we use genetic or other information to assign probabilities to each individual's origin as in situ or outside the population. We use a resampling approach to impute the true population of origin from imperfect assignment information. The integration of data on population of origin with capture-recapture data allows us to determine the contributions of immigration and in situ reproduction to the growth of the population, an issue of importance to ecologists. We illustrate our new models with capture-recapture and genetic assignment data from a population of banner-tailed kangaroo rats Dipodomys spectabilis in Arizona. C1 [Wen, Zhi] US FDA, Off Biostat & Epidemiol, Ctr Biol Res & Evaluat, Rockville, MD 20850 USA. [Pollock, Kenneth] Murdoch Univ, Ctr Fish & Fisheries Res, Murdoch, WA 6150, Australia. [Nichols, James] US Geol Survey, Patuxent Wildlife Res Ctr, Laurel, MD 20708 USA. [Waser, Peter] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP Wen, Z (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Res & Evaluat, Rockville, MD 20850 USA. EM zhiwenislucky@gmail.com FU NSF [DEB 0816925] FX We thank the NSF for support (DEB 0816925). NR 30 TC 4 Z9 4 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2011 VL 67 IS 3 BP 691 EP 700 DI 10.1111/j.1541-0420.2010.01522.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 819XE UT WOS:000294866800002 PM 21155745 ER PT J AU Proschan, M Brittain, E Kammerman, L AF Proschan, Michael Brittain, Erica Kammerman, Lisa TI Minimize the Use of Minimization with Unequal Allocation SO BIOMETRICS LA English DT Article DE Adaptive randomization; Analyze as you randomize; Asymptotics; Minimization; Permuted block randomization; Permutation test; Randomization; Rerandomization test; Temporal trend; Unequal allocation ID CLINICAL-TRIALS; RANDOMIZATION AB Minimization as an alternative to randomization is gaining popularity for small clinical trials. In response to critics' questions about the proper analysis of such a trial, proponents have argued that a rerandomization approach, akin to a permutation test with conventional randomization, can be used. However, they add that this computationally intensive approach is not necessary because its results are very similar to those of a t-test or test of proportions unless the sample size is very small. We show that minimization applied with unequal allocation causes problems that challenge this conventional wisdom. C1 [Proschan, Michael; Brittain, Erica] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Kammerman, Lisa] US FDA, Div Biometr 3, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Proschan, M (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr,Room 5140, Bethesda, MD 20892 USA. EM ProschaM@niaid.nih.gov NR 14 TC 15 Z9 15 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2011 VL 67 IS 3 BP 1135 EP 1141 DI 10.1111/j.1541-0420.2010.01545.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 819XE UT WOS:000294866800048 PM 21281276 ER PT J AU Landmon, C Retersdorf, E AF Landmon, Chad Retersdorf, Elizabeth TI Advocating for Biosimilar Approval Standards Under BPCI SO BIOPHARM INTERNATIONAL LA English DT Editorial Material C1 [Landmon, Chad; Retersdorf, Elizabeth] Axinn Veltrop & Harkrider LLP, FDA Practice Grp, New York, NY 10036 USA. RP Landmon, C (reprint author), Axinn Veltrop & Harkrider LLP, FDA Practice Grp, New York, NY 10036 USA. EM cal@avhlaw.com; epr@avhlaw.com NR 1 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI DULUTH PA 131 W 1ST STREET, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD SEP PY 2011 VL 24 IS 9 BP 57 EP + PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 820WR UT WOS:000294937300022 ER PT J AU Miller, VA Ittenbach, RF Harris, D Reynolds, WW Beauchamp, TL Luce, MF Nelson, RM AF Miller, Victoria A. Ittenbach, Richard F. Harris, Diana Reynolds, William W. Beauchamp, Tom L. Luce, Mary Frances Nelson, Robert M. TI The Decision Making Control Instrument to Assess Voluntary Consent SO MEDICAL DECISION MAKING LA English DT Article DE voluntariness; decision making control; informed consent; ethics ID BLIND CONTROLLED EXPERIMENT; SELF-EFFICACY SCALE; INFORMED-CONSENT; INDIVIDUAL AUTONOMY; VALIDATION; THERAPY AB Background. The decision to participate in a research intervention or to undergo medical treatment should be both informed and voluntary. Objective. The aim of the present study was to develop an instrument to measure the perceived voluntariness of parents making decisions for their seriously ill children. Methods. A total of 219 parents completed questionnaires within 10 days of making such a decision at a large, urban tertiary care hospital for children. Parents were presented with an experimental form of the Decision Making Control Instrument (DMCI), a measure of the perception of voluntariness. Data obtained from the 28-item form were analyzed using a combination of both exploratory and confirmatory factor analytic techniques. Results. The 28 items were reduced to 9 items representing 3 oblique dimensions: Self-Control, Absence of Control, and Others' Control. The hypothesis that the 3-factor covariance structure of our model was consistent with that of the data was supported. Internal consistency for the scale as a whole was high (0.83); internal consistency for the subscales ranged from 0.68 to 0.87. DMCI scores were associated with measures of affect, trust, and decision self-efficacy, supporting the construct validity of the new instrument. Conclusion. The DMCI is an important new tool that can be used to inform our understanding of the voluntariness of treatment and research decisions in medical settings. C1 [Miller, Victoria A.] Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, Philadelphia, PA 19104 USA. [Harris, Diana] Univ Penn, Sch Med, Ctr Integrat Genet Healthcare Technol, Philadelphia, PA 19104 USA. [Ittenbach, Richard F.] Cincinnati Childrens Hosp, Med Ctr, Div Biostat & Epidemiol, Cincinnati, OH USA. [Reynolds, William W.] Richard Stockton Coll New Jersey, Galloway, NJ USA. [Beauchamp, Tom L.] Georgetown Univ, Kennedy Inst Eth, Washington, DC 20057 USA. [Luce, Mary Frances] Duke Univ, Fuqua Sch Business, Durham, NC 27706 USA. [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. RP Miller, VA (reprint author), Childrens Hosp Philadelphia, Dept Anesthesiol & Crit Care Med, 34th St & Civ Ctr Blvd,CHOP N Room 1425, Philadelphia, PA 19104 USA. EM millerv@email.chop.edu RI Ittenbach, Richard/Q-1806-2015 FU National Science Foundation [SES-0527618]; National Institutes of Health/National Cancer Institute [R21CA118377-01A1] FX Received February 9, 2010, from Department of Anesthesiology and Critical Care Medicine, the Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine (VAM); Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center (RFI); Center for the Integration of Genetic Healthcare Technologies, University of Pennsylvania School of Medicine (DH); Richard Stockton College of New Jersey (WWR); Kennedy Institute of Ethics, George-town University (TLB); the Fuqua School of Business, Duke University (MFL); and Office of Pediatric Therapeutics, Office of the Commissioner, Food and Drug Administration (RMN). Financial support for this study was provided entirely by grants from the National Science Foundation (SES-0527618; Drs Nelson, Luce, and Beauchamp) and the National Institutes of Health/National Cancer Institute (R21CA118377-01A1; Dr Nelson) and an Institutional Development Grant to the Center for Research Integrity, Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia. The funding agreements ensured the authors' independence in designing the study, interpreting the data, writing, and publishing the report. The work reported in this article was conducted prior to Dr Nelson joining the US Food and Drug Administration and does not represent the views and/or policies of the Food and Drug Administration or the Department of Health and Human Services. Revision accepted for publication December 26, 2010. NR 35 TC 12 Z9 13 U1 1 U2 8 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD SEP-OCT PY 2011 VL 31 IS 5 SI SI BP 730 EP 741 DI 10.1177/0272989X11398666 PG 12 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 820HV UT WOS:000294897200007 PM 21402793 ER PT J AU Zhang, GD Brown, EW Gonzalez-Escalona, N AF Zhang, Guodong Brown, Eric W. Gonzalez-Escalona, Narjol TI Comparison of Real-Time PCR, Reverse Transcriptase Real-Time PCR, Loop-Mediated Isothermal Amplification, and the FDA Conventional Microbiological Method for the Detection of Salmonella spp. in Produce SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; RAPID DETECTION; UNITED-STATES; SENSITIVE DETECTION; FOODBORNE ILLNESS; MESSENGER-RNA; WATER SAMPLES; QUANTIFICATION; ENTERICA; IDENTIFICATION AB Contamination of foods, especially produce, with Salmonella spp. is a major concern for public health. Several methods are available for the detection of Salmonella in produce, but their relative efficiency for detecting Salmonella in commonly consumed vegetables, often associated with outbreaks of food poisoning, needs to be confirmed. In this study, the effectiveness of three molecular methods for detection of Salmonella in six produce matrices was evaluated and compared to the FDA microbiological detection method. Samples of cilantro (coriander leaves), lettuce, parsley, spinach, tomato, and jalapeno pepper were inoculated with Salmonella serovars at two different levels (10(5) and < 10(1) CFU/25 g of produce). The inoculated produce was assayed by the FDA Salmonella culture method (Bacteriological Analytical Manual) and by three molecular methods: quantitative real-time PCR (qPCR), quantitative reverse transcriptase real-time PCR (RT-qPCR), and loop-mediated isothermal amplification (LAMP). Comparable results were obtained by these four methods, which all detected as little as 2 CFU of Salmonella cells/25 g of produce. All control samples (not inoculated) were negative by the four methods. RT-qPCR detects only live Salmonella cells, obviating the danger of false-positive results from nonviable cells. False negatives (inhibition of either qPCR or RT-qPCR) were avoided by the use of either a DNA or an RNA amplification internal control (IAC). Compared to the conventional culture method, the qPCR, RT-qPCR, and LAMP assays allowed faster and equally accurate detection of Salmonella spp. in six high-risk produce commodities. C1 [Zhang, Guodong; Brown, Eric W.; Gonzalez-Escalona, Narjol] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Gonzalez-Escalona, N (reprint author), US FDA, CFSAN, 5100 Paint Branch Pkwy HFS 712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU FDA FX This project was supported by the FDA Foods Program Intramural Funds. NR 47 TC 32 Z9 33 U1 3 U2 39 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 SEP PY 2011 VL 77 IS 18 BP 6495 EP 6501 DI 10.1128/AEM.00520-11 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 817RJ UT WOS:000294691400022 PM 21803916 ER PT J AU Feng, PCH Jinneman, K Scheutz, F Monday, SR AF Feng, Peter C. H. Jinneman, Karen Scheutz, Flemming Monday, Steven R. TI Specificity of PCR and Serological Assays in the Detection of Escherichia coli Shiga Toxin Subtypes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MULTIPLEX PCR; CLINICAL PROFILES; VARIANTS; STRAINS; IDENTIFICATION; ASSOCIATION; O157-H7; HUMANS; STEC; GENE AB Specificity analysis for stx or Stx subtypes in Escherichia coli showed that the PCR assays we tested did not detect stx(1d) and stx(2f), and some also missed stx(2b) and stx(2g). Most of the serological assays examined did not detect Stx2c, Stx2e, Stx2f, and Stx2g, and some strain-to-strain variation in reactivity was observed for Stx2b. C1 [Feng, Peter C. H.; Monday, Steven R.] US FDA, Div Microbiol, College Pk, MD 20740 USA. [Jinneman, Karen] US FDA, Pacific Reg Lab NW, Bothell, WA USA. [Scheutz, Flemming] WHO Collaborating Ctr Reference & Res Escherichia, Copenhagen, Denmark. RP Feng, PCH (reprint author), US FDA, Div Microbiol, HFS-711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov OI Scheutz, Flemming/0000-0002-3931-4846 NR 23 TC 39 Z9 39 U1 0 U2 7 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 SEP PY 2011 VL 77 IS 18 BP 6699 EP 6702 DI 10.1128/AEM.00370-11 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 817RJ UT WOS:000294691400048 PM 21803918 ER PT J AU Degheidy, HA Venzon, DJ Farooqui, MZH Abbasi, F Arthur, DC Wilson, WH Wiestner, A Stetler-Stevenson, MA Marti, GE AF Degheidy, Heba A. Venzon, David J. Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Diane C. Wilson, Wyndham H. Wiestner, Adrian Stetler-Stevenson, M. A. Marti, Gerald E. TI Methodological Comparison of Two Anti-ZAP-70 Antibodies SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE chronic lymphocytic leukemia; ZAP-70 score; flow cytometry; 1E7.2/AF488; SBZAP/PE ID CHRONIC LYMPHOCYTIC-LEUKEMIA; FLOW-CYTOMETRIC MEASUREMENT; ZAP-70 PROTEIN EXPRESSION; GENE MUTATION STATUS; CELLS; CD38 AB Background: ZAP-70 expression is a stage independent prognostic marker in CLL. However, interlaboratory variation is large, and there is neither a consensus nor a regulatory approved methodology. Methods: Two anti-ZAP70 clones (1E7.2 and SBZAP) were compared in 45 untreated CLL patients. Nine different methods for ZAP-70 expression analysis were evaluated: M1, isotype control to determine negative; M2, internal residual T-cell to determine positive; M3, normal donor (ND) T-cell to determine positive; M4, internal T-cell/clone ratio; M5, ND residual T-cell/clone ratio; M6, clone/normal remaining B-cell ratio; M7, clone/ND B-cell ratio; M8, CLL-Z score; M9, modified CLL-Z score. A scoring system was designed integrating both 1E7.2 and SBZAP clones to assign ZAP-70 expression. Results: The correlation coefficients for the four selected highest statistically significant methods were as follows (M1 = 0.71, M3 = 0.72, M7 = 0.67, and M9 = 0.64). These four methods were used to generate a combined score. The two reagents showed agreement using the designed scoring system for 37/45 samples (82%), and 8/45 (18%) showed equivocal result with one of the two clones. Seven of the eight equivocal samples were resolved using the scoring system. Conclusions: Four of the nine methods of analysis were compared for each reagent. The use of two independent ZAP-70 reagents increases analytical certitude and the scoring method aids in the resolution of equivocal results. The combined use of two reagents, four methods of analysis, and a scoring method allowed for assignment of ZAP-70 expression in 44/45 samples (98%) tested and improved performance of this important prognostic assay. Published 2011 Wiley-Liss, Inc.(dagger) C1 [Marti, Gerald E.] US FDA, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapies,CBER,NIH, Bethesda, MD 20892 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Arthur, Diane C.; Stetler-Stevenson, M. A.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Wilson, Wyndham H.] NCI, Metab Branch, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapies,CBER,NIH, Bdg 29B,Rm 1NN010,8800 Rockville Pike, Bethesda, MD 20892 USA. EM gemarti@mac.com FU NHLBI, NIH FX The authors acknowledge the nursing and data management skills of Susan Soto and Therese White in this study. In addition, we acknowledge the friendly support provided by the Phlebotomy Service (Department of Transfusion Medicine, NIH). This research was supported in part, by the Intramural Research Program of the NHLBI, NIH. NR 22 TC 4 Z9 4 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2011 VL 80B IS 5 BP 300 EP 308 DI 10.1002/cyto.b.20591 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 817OX UT WOS:000294684800004 PM 21472849 ER PT J AU Degheidy, HA Venzon, DJ Farooqui, MZH Abbasi, F Arthur, DC Wilson, WW Wiestner, A Stetler-Stevenson, MA Marti, GE AF Degheidy, Heba A. Venzon, David J. Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Diane C. Wilson, Wyndham W. Wiestner, Adrian Stetler-Stevenson, M. A. Marti, Gerald E. TI Improved ZAP-70 Assay Using Two Clones, Multiple Methods of Analysis and Clinical Correlation SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE chronic lymphocytic leukemia; ZAP-70; CLL score system; flow cytometry; prognostic marker ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GENE MUTATION STATUS; CD38 EXPRESSION; DISEASE PROGRESSION; FLOW-CYTOMETRY; FLUDARABINE; DIAGNOSIS; CLL; CHEMOIMMUNOTHERAPY; CYCLOPHOSPHAMIDE AB Introduction: In a companion methodological study, we compared two anti-ZAP-70 clones (1E7.2 AF 488 and SBZAP PE) and four selected methods of analysis. Clinical correlations are required for validation. Methods: Multicolor flow-cytometric evaluation of ZAP-70, CD38, CD69, CD26, CD49d, and CD27 was tested in 45 untreated-CLL patients. Four methods of ZAP-70 expression analysis and a scoring system were designed. A correlation analysis between ZAP-70 score, immunoglobulin heavy chain variable (IGHV) mutational status, fluorescence in situ hybridization, and these biomarkers was undertaken. Results: There is a strong correlation between ZAP-70 expression and IGHV mutational status. The scoring system for a single reagent (P = 0.0006 or 0.0002) favors the use of multiple methods of analysis. The combined score was substantially equivalent (P = 0.0003). There was also a correlation with del 13q14 (P = 0.017) and trisomy12 (P = 0.011). A correlation for CD38 and ZAP-70 score was seen using both 1E7.2 AF488 and SBZAP PE when >= 20% or >= 7% cutoff was used. A positive correlation was seen for CD49d expression using both reagents. CD26 showed a correlation with ZAP-70 expression, but it was dependent upon the method of analysis. CD69 and CD27 showed no statistically significant correlation. Conclusion: In our study population, ZAP-70 expression is the better predictor of the IGHV mutational status. The correlation analysis confirms that the use of four methods of analysis with a single reagent or both reagents is superior to the use of a single method of analysis. The routine use of CD38, CD49d, and CD26 will require standardization. Published 2011 Wiley-Liss, Inc.(dagger) C1 [Degheidy, Heba A.; Abbasi, Fatima; Marti, Gerald E.] US FDA, Div Cellular Tissue & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Arthur, Diane C.; Stetler-Stevenson, M. A.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Wilson, Wyndham W.] NCI, Metab Branch, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies, Off Cellular Tissues & Gene Therapies,CBER,NIH, Bdg 29B,Room 1NN010,8800 Rockville Pike, Bethesda, MD 20892 USA. EM gemarti@mac.com FU NHLBI, NIH FX This research was supported in part, by the Intramural Research Program of the NHLBI, NIH. NR 31 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2011 VL 80B IS 5 BP 309 EP 317 DI 10.1002/cyto.b.20593 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 817OX UT WOS:000294684800005 PM 21472850 ER PT J AU Harris, BD Hanson, C Christy, C Adams, T Banks, A Willis, TS Maciejewski, ML AF Harris, Bradford D. Hanson, Cherissa Christy, Claudia Adams, Tina Banks, Andrew Willis, Tina Schade Maciejewski, Matthew L. TI Strict Hand Hygiene And Other Practices Shortened Stays And Cut Costs And Mortality In A Pediatric Intensive Care Unit SO HEALTH AFFAIRS LA English DT Article ID VENTILATOR-ASSOCIATED PNEUMONIA; HEALTH-CARE; QUALITY IMPROVEMENT; INFECTION-RATES; PREVENTION; GUIDELINE; IMPACT; STATES; TRIAL; RISK AB Efforts to reduce infections acquired during a hospital stay through improvements in the quality of care have had measurable results in many hospital settings. In pediatric intensive care units, the right quality interventions can save lives and money. We found that improving practices of hand hygiene, oral care, and central-line catheter care reduced hospital-acquired infections and improved mortality rates among children admitted to a large pediatric intensive care unit in 2007-09. In addition, on average patients admitted after the quality interventions were fully implemented spent 2.3 fewer days in the hospital, their hospitalization cost $12,136 less, and mortality was 2.3 percentage points lower, compared to patients admitted before the interventions. The projected annual cost savings for the single pediatric intensive care unit studied was approximately $12 million. Given the modest expenses incurred for these improvements-which mainly consisted of posters for an educational campaign, a training "fair," roughly $21 per day for oral care kits, about $0.60 per day for chlorhexidine antiseptic patches, and hand sanitizers attached to the walls outside patients' rooms-this represents a significant return on investment. Used on a larger scale, these quality improvements could save lives and reduce costs for patients, hospitals, and payers around the country, provided that sustained efforts ensure compliance with new protocols and achieve long-lasting changes. C1 [Harris, Bradford D.] US FDA, Silver Spring, MD 20993 USA. [Christy, Claudia] Univ N Carolina, N Carolina Translat & Clin Sci Inst, Chapel Hill, NC USA. [Banks, Andrew] Univ N Carolina, Womens Hosp, Div Operat Efficiency, Chapel Hill, NC 27515 USA. [Banks, Andrew] Univ N Carolina, Childrens Hosp, Div Operat Efficiency, Chapel Hill, NC 27515 USA. [Maciejewski, Matthew L.] Duke Univ, Med Ctr, Div Gen Internal Med, Durham, NC 27710 USA. RP Harris, BD (reprint author), US FDA, Silver Spring, MD 20993 USA. EM bdharrisha@gmail.com FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs; Department of Veterans Affairs [RCS 10-391]; Takeda Pharmaceuticals; Novartis; Surgical Review Corporation FX The two projects described in this article were led by Jordan Erickson and Andrew Banks. Bradford Harris, Kathy Short, Claudia Christy, Tiffany Mabe, and Otis Patterson were involved in the ventilator-associated pneumonia project. Cherissa Hanson, Roger Saunders, Tina Adams, and Doreen Marlowe were involved in the central-line bloodstream infection project. The authors gratefully acknowledge the assistance of Emily Miller Ray and Ashley Prudy, from the Center for Clinical Excellence at the Women's and Children's Hospitals at the University of North Carolina; Glen Spivak and the Department of Operational Efficiency at the Women's and Children's Hospitals at the University of North Carolina; and all of the pediatric intensive care unit staff members who contributed to these efforts. The authors also gratefully acknowledge the helpful comments of David Weber, Tim Carey, and Todd Purves. This work was supported in part by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs. Matthew Maciejewski was also supported by a Research Career Scientist award from the Department of Veterans Affairs (No. RCS 10-391). He has received consultation funds from Takeda Pharmaceuticals, Novartis, and the Surgical Review Corporation, and he owns stock in Amgen. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs, the University of North Carolina at Chapel Hill, or Duke University. NR 29 TC 8 Z9 8 U1 1 U2 6 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP PY 2011 VL 30 IS 9 BP 1751 EP 1761 DI 10.1377/hlthaff.2010.1282 PG 11 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 817KE UT WOS:000294670400018 PM 21900667 ER PT J AU Senior, JR London, WT Slitnick, AI AF Senior, John R. London, W. Thomas Slitnick, Alton I. TI The Australia Antigen and Role of the Late Philadelphia General Hospital in Reducing Post-Transfusion Hepatitis and Sequelae SO HEPATOLOGY LA English DT Editorial Material ID POST-TRANSFUSION HEPATITIS; VIRAL HEPATITIS; ANICTERIC HEPATITIS; DOWNS SYNDROME; DONOR BLOOD; REDUCTION; PARTICLES; LEUKEMIA; SERUM C1 [Senior, John R.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [London, W. Thomas] Fox Chase Canc Ctr, Inst Review Board, Philadelphia, PA 19111 USA. [Slitnick, Alton I.] Drexel Univ, Coll Med, Dept Med, Philadelphia, PA 19104 USA. RP Senior, JR (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.senior@fda.hhs.gov NR 23 TC 3 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2011 VL 54 IS 3 BP 753 EP 756 DI 10.1002/hep.24593 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 818FZ UT WOS:000294738300001 PM 21809361 ER PT J AU Engblom, H Strauss, DG Heden, B Hedstrom, E Jovinge, S Gotberg, M Erlinge, D Wagner, GS Arheden, H AF Engblom, Henrik Strauss, David G. Heden, Bo Hedstrom, Erik Jovinge, Stefan Gotberg, Matthias Erlinge, David Wagner, Galen S. Arheden, Hakan TI The evaluation of an electrocardiographic myocardial ischemia acuteness score to predict the amount of myocardial salvage achieved by early percutaneous coronary intervention Clinical validation with myocardial perfusion single photon emission computed tomography and cardiac magnetic resonance SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT Magnetic and eLectrical Technologies (MALT) Meeting CY FEB 24-25, 2011 CL Maastricht, NETHERLANDS DE Acute myocardial infarction; Myocardial salvage; Reperfusion therapy; Electrocardiography; Magnetic resonance imaging; Myocardial perfusion SPECT ID REPERFUSION THERAPY; INFARCT SIZE; OCCLUSION; QUANTIFICATION; EVOLUTION; ANTERIOR; VOLUME; SPECT; RISK AB Background: The time from symptom onset to reperfusion in acute myocardial infarction (MI) has been shown to be a poor predictor of patient outcome. Acute electrocardiographic (ECG) changes, however, have been shown useful for estimated acuteness of myocardial ischemia using the Anderson-Wilkins ECG ischemia acuteness score (AW-acuteness score). The aim was to study whether acute ischemic ECG changes can predict the amount of salvageable myocardium in patients with acute ST-elevation MI. Methods: Thirty-eight patients treated with primary percutaneous coronary intervention for first-time ST-elevation MI were retrospectively enrolled. Myocardium at risk (MaR) was determined by myocardial perfusion single photon emission computed tomography acutely or by T2-weighted cardiac magnetic resonance after 1 week, at the same time when final MI size was determined by late gadolinium enhancement. Myocardial salvage was calculated as (MaR - MI size)/MaR and compared with AW-acuteness score and time from symptom onset to primary percutaneous coronary intervention. Results: The AW-acuteness score correlated significantly with salvageable myocardium for right coronary artery (RCA) occlusions (r = -0.57; P = .02) but not for left anterior descending artery (LAD) occlusions (r = 0.04; P = .88). Time from symptom onset did not correlate with the amount of salvageable myocardium (LAD, r = 0.04 and P = .87; RCA, r = 0.40 and P = .13). Conclusions: There is a moderate correlation between AW-acuteness score and salvageable myocardium in patients with acute RCA occlusion but not in patients with LAD occlusion. (C) 2011 Elsevier Inc. All rights reserved. C1 [Engblom, Henrik; Strauss, David G.; Heden, Bo; Hedstrom, Erik; Arheden, Hakan] Lund Univ, Dept Clin Physiol, S-22185 Lund, Sweden. [Engblom, Henrik; Strauss, David G.; Heden, Bo; Hedstrom, Erik; Jovinge, Stefan; Gotberg, Matthias; Erlinge, David; Arheden, Hakan] Skane Univ Hosp, S-22185 Lund, Sweden. [Jovinge, Stefan; Gotberg, Matthias; Erlinge, David] Lund Univ, Dept Cardiol, S-22185 Lund, Sweden. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Wagner, Galen S.] Duke Clin Res Inst, Durham, NC USA. RP Arheden, H (reprint author), Lund Univ, Dept Clin Physiol, S-22185 Lund, Sweden. EM hakan.arheden@med.lu.se RI Strauss, David/A-9211-2012 FU Swedish Research Council (Stockholm, Sweden); Swedish Heart Lung Foundation (Stockholm, Sweden); Lund Medical Faculty (Lund, Sweden); Region of Scania (Sweden); Sarnoff Cardiovascular Research Foundation (Boston, MA) FX This work was supported by the Swedish Research Council (Stockholm, Sweden), the Swedish Heart Lung Foundation (Stockholm, Sweden), Lund Medical Faculty (Lund, Sweden), Region of Scania (Sweden), and the Sarnoff Cardiovascular Research Foundation (Boston, MA). NR 21 TC 9 Z9 9 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2011 VL 44 IS 5 BP 525 EP 532 DI 10.1016/j.jelectrocard.2011.03.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 818HH UT WOS:000294742000007 PM 21658711 ER PT J AU Loring, Z Chelliah, S Selvester, RH Wagner, G Strauss, DG AF Loring, Zak Chelliah, Sreetharan Selvester, Ronald H. Wagner, Galen Strauss, David G. TI A detailed guide for quantification of myocardial scar with the Selvester QRS score in the presence of electrocardiogram confounders SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Article; Proceedings Paper CT Magnetic and eLectrical Technologies (MALT) Meeting CY FEB 24-25, 2011 CL Maastricht, NETHERLANDS DE Electrocardiology; Electrophysiology; QRS complex; ECG criteria; Myocardial infarction; Fibrosis; Multimodal cardiac imaging; Risk stratification ID CARDIAC-RESYNCHRONIZATION THERAPY; QUANTITATIVE ANATOMIC FINDINGS; INFARCT SIZE; PROGNOSTIC VALUE; MAGNETIC-RESONANCE; SYSTEM; CONDUCTION AB The Selvester QRS score translates subtle changes in ventricular depolarization measured by the electrocardiogram into information about myocardial scar location and size. This estimated scar has been shown to have a high degree of correlation with autopsy-measured myocardial infarct size. In addition, multiple studies have demonstrated the value of the QRS score in post myocardial infarct patients to provide prognostic information. Recent studies have demonstrated that increasing QRS score is predictive of increased implantable defibrillator shocks for ventricular tachycardia and fibrillation as well as decreased response to cardiac resynchronization therapy. Although QRS scoring has never achieved widespread clinical use, increased interest in patient selection and risk-stratification techniques for implantable defibrillators and cardiac resynchronization therapy has led to renewed interest in QRS scoring and its potential to identify which patients will benefit from device therapy. The QRS score criteria were updated in 2009 to expand their use to a broader population by accounting for the different ventricular depolarization sequences in patients with bundle-branch/fascicular blocks or ventricular hypertrophy. However, these changes also introduced additional complexity and nuance to the scoring procedure. This article provides detailed instructions and examples on how to apply the QRS score criteria in the presence of confounding conduction types to facilitate understanding and enable development and application of automated QRS scoring. Published by Elsevier Inc. C1 [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Loring, Zak] Duke Univ, Sch Med, Durham, NC USA. [Chelliah, Sreetharan; Wagner, Galen] Duke Clin Res Inst, Durham, NC USA. [Selvester, Ronald H.] Mem Hosp, Res Ctr, Long Beach, CA USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO62-1126, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov RI Strauss, David/A-9211-2012 FU NCRR/NIH [TL1RR024126]; Food and Drug Administration Critical Path; Office of Women's Health FX Supported, in part, by Duke University's Clinical and Translational Science Award grant TL1RR024126 from NCRR/NIH (to Z. Loring) and Food and Drug Administration Critical Path and Office of Women's Health grants (to D. Strauss). NR 25 TC 36 Z9 38 U1 1 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 EI 1532-8430 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD SEP-OCT PY 2011 VL 44 IS 5 BP 544 EP 554 DI 10.1016/j.jelectrocard.2011.06.008 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 818HH UT WOS:000294742000010 PM 21872001 ER PT J AU Fein, SB Lando, AM Levy, AS Teisl, MF Noblet, C AF Fein, Sara B. Lando, Amy M. Levy, Alan S. Teisl, Mario F. Noblet, Caroline TI Trends in U.S. Consumers' Safe Handling and Consumption of Food and Their Risk Perceptions, 1988 through 2010 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID DOMESTIC ENVIRONMENT; TELEPHONE SURVEY; BEHAVIORS; ADULTS; NONRESPONSE; KNOWLEDGE AB Although survey results measuring the safety of consumers' food handling and risky food consumption practices have been published for over 20 years, evaluation of trends is impossible because the designs of published studies are not comparable. The Food Safety Surveys used comparable methods to interview U.S. adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling (i.e., cross-contamination prevention) and risky consumption practices (eating raw or undercooked foods from animals) and perceived risk from foodborne illness. Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively, and four indices measuring meat, chicken, and egg cross-contamination, fish cross-contamination, risky consumption, and risk perceptions were analyzed using generalized linear models. The extent of media coverage of food safety issues was also examined. We found a substantial improvement in food handling and consumption practices and an increase in perceived risk from foodborne illness between 1993 and 1998. All indices were stable or declined between 1998 and 2006. Between 2006 and 2010, the two safe food handling practice indices increased significantly, but risk perceptions did not change, and safe consumption declined. Women had safer food handling and consumption practices than men. The oldest and youngest respondents and those with the highest education had the least safe food handling behaviors. Changes in safety of practices over the survey years are consistent with the change in the number of media stories about food safety in the periods between surveys. This finding suggests that increased media attention to food safety issues may raise awareness of food safety hazards and increase vigilance in food handling by consumers. C1 [Fein, Sara B.; Lando, Amy M.; Levy, Alan S.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Teisl, Mario F.; Noblet, Caroline] Univ Maine, Sch Econ, Orono, ME 04469 USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM sara.fein@fda.hhs.gov OI teisl, mario/0000-0002-2021-9208 FU U.S. Food and Drug Administration; U.S. Department of Agriculture Food Safety and Inspection Service FX We thank Katherine Farrow (University of Maine) for supporting the media analysis. Support was provided by the U.S. Food and Drug Administration and the U.S. Department of Agriculture Food Safety and Inspection Service. NR 40 TC 31 Z9 31 U1 0 U2 13 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD SEP PY 2011 VL 74 IS 9 BP 1513 EP 1523 DI 10.4315/0362-028X.JFP-11-017 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 818KN UT WOS:000294750700014 PM 21902921 ER PT J AU Lanasa, MC Allgood, SD Slager, SL Dave, SS Love, C Marti, GE Kay, NE Hanson, CA Rabe, KG Achenbach, SJ Goldin, LR Camp, NJ Goodman, BK Vachon, CM Spector, LG Rassenti, LZ Leis, JF Gockerman, JP Strom, SS Call, TG Glenn, M Cerhan, JR Levesque, MC Weinberg, JB Caporaso, NE AF Lanasa, M. C. Allgood, S. D. Slager, S. L. Dave, S. S. Love, C. Marti, G. E. Kay, N. E. Hanson, C. A. Rabe, K. G. Achenbach, S. J. Goldin, L. R. Camp, N. J. Goodman, B. K. Vachon, C. M. Spector, L. G. Rassenti, L. Z. Leis, J. F. Gockerman, J. P. Strom, S. S. Call, T. G. Glenn, M. Cerhan, J. R. Levesque, M. C. Weinberg, J. B. Caporaso, N. E. TI Immunophenotypic and gene expression analysis of monoclonal B-cell lymphocytosis shows biologic characteristics associated with good prognosis CLL SO LEUKEMIA LA English DT Article DE chronic lymphocytic leukemia; monoclonal B lymphocytosis; immunophenotype; B-cell immunology; gene expression profiling ID VARIABLE-REGION MUTATIONS; CD38 EXPRESSION; ZAP-70 EXPRESSION; PERIPHERAL-BLOOD; NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; SURVIVAL; RECEPTOR; DISEASE AB Monoclonal B-cell lymphocytosis (MBL) is a hematologic condition wherein small B-cell clones can be detected in the blood of asymptomatic individuals. Most MBL have an immunophenotype similar to chronic lymphocytic leukemia (CLL), and 'CLL-like' MBL is a precursor to CLL. We used flow cytometry to identify MBL from unaffected members of CLL kindreds. We identified 101 MBL cases from 622 study subjects; of these, 82 individuals with MBL were further characterized. In all, 91 unique MBL clones were detected: 73 CLL-like MBL (CD5(+)CD20(dim)sIg(dim)), 11 atypical MBL (CD5(+)CD20(+)sIg(+)) and 7 CD5(neg) MBL (CD5(neg)CD20(+)sIg(neg)). Extended immunophenotypic characterization of these MBL subtypes was performed, and significant differences in cell surface expression of CD23, CD49d, CD79b and FMC-7 were observed among the groups. Markers of risk in CLL such as CD38, ZAP70 and CD49d were infrequently expressed in CLL-like MBL, but were expressed in the majority of atypical MBL. Interphase cytogenetics was performed in 35 MBL cases, and del 13q14 was most common (22/30 CLL-like MBL cases). Gene expression analysis using oligonucleotide arrays was performed on seven CLL-like MBL, and showed activation of B-cell receptor associated pathways. Our findings underscore the diversity of MBL subtypes and further clarify the relationship between MBL and other lymphoproliferative disorders. Leukemia (2011) 25, 1459-1466; doi: 10.1038/leu.2011.117; published online 27 May 2011 C1 [Lanasa, M. C.; Allgood, S. D.; Dave, S. S.; Love, C.; Gockerman, J. P.; Weinberg, J. B.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Slager, S. L.; Rabe, K. G.; Achenbach, S. J.; Vachon, C. M.; Cerhan, J. R.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. [Marti, G. E.] US FDA, Cellular & Tissue Therapy Branch, CBER, OCTGC, Rockville, MD 20857 USA. [Kay, N. E.; Call, T. G.] Mayo Clin, Coll Med, Dept Med, Rochester, MN USA. [Hanson, C. A.] Mayo Clin, Coll Med, Dept Pathol, Rochester, MN USA. [Goldin, L. R.] NCI, Genet Epidemiol Branch, Bethesda, MD USA. [Camp, N. J.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT USA. [Goodman, B. K.] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. [Spector, L. G.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Rassenti, L. Z.; Weinberg, J. B.] Moores UCSD Canc Ctr, Dept Med, La Jolla, CA USA. [Leis, J. F.] Mayo Clin, Coll Med, Dept Med, Scottsdale, AZ USA. [Strom, S. S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Glenn, M.] Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. [Levesque, M. C.] Univ Pittsburgh, Med Ctr, Dept Med, Pittsburgh, PA USA. [Caporaso, N. E.] Durham Vet Affairs Med Ctr, Dept Med, Durham, NC USA. RP Lanasa, MC (reprint author), Duke Univ, Med Ctr, Dept Med, DUMC Box 3872,1 Trent Dr,Morris Bldg,Room 25152, Durham, NC 27710 USA. EM mark.lanasa@duke.edu OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU Duke Clinical Oncology Research Clinical Development Program [K12]; Leukemia and Lymphoma Society of America; Harold Bernstein Family Fund; VA Research Service; National Institutes of Health [NCI R03 CA128030, NCI R01 CA95241, NCI U01 CA118444, AI-51445] FX MC Lanasa is supported by the Duke Clinical Oncology Research Clinical Development Program (K12) and is a fellow of the Leukemia and Lymphoma Society of America. This research is supported by the Leukemia and Lymphoma Society of America, the Harold Bernstein Family Fund, the VA Research Service and grants from the National Institutes of Health (NCI R03 CA128030, NCI R01 CA95241 and NCI U01 CA118444). We thank the study research subjects for their willingness to participate in this study and the hematology-oncology nurses and physician assistants for their special help. Flow Cytometry was performed in the Duke Human Vaccine Institute Flow Cytometry Core Facility that is supported by the National Institutes of Health award AI-51445. NR 42 TC 19 Z9 21 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD SEP PY 2011 VL 25 IS 9 BP 1459 EP 1466 DI 10.1038/leu.2011.117 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 817IM UT WOS:000294665400011 PM 21617698 ER PT J AU Wang, YY Meng, FX Arlt, VM Mei, N Chen, T Parsons, BL AF Wang, Yiying Meng, Fanxue Arlt, Volker M. Mei, Nan Chen, Tao Parsons, Barbara L. TI Aristolochic acid-induced carcinogenesis examined by ACB-PCR quantification of H-Ras and K-Ras mutant fraction SO MUTAGENESIS LA English DT Article ID CHINESE HERBS NEPHROPATHY; GENE-EXPRESSION PROFILES; BALKAN ENDEMIC NEPHROPATHY; DNA ADDUCT FORMATION; P53 MUTATIONS; RISK-FACTOR; RATS; CANCER; TUMORS; TISSUE AB Aristolochic acid (AA) is a strong cytotoxic nephrotoxin and carcinogen associated with the development of urothelial cancer in humans. AA induces forestomach, kidney and urothelial tract tumours in rats and mice. This study was conducted to characterise AA's carcinogenic mechanism of action and compare allele-specific competitive blocker-polymerase chain reaction (ACB-PCR)-based early detection of carcinogenic effect using two different tumour-relevant endpoints. H-Ras codon 61 CAA -> CTA mutation was analysed because it is found in rodent forestomach tumours and A:T -> T:A transversion is the predominant mutational specificity induced by AA. K-Ras codon 12 GGT -> GAT mutation was analysed because it is a common spontaneous mutation present in various rodent tissues and may be a useful generic biomarker for carcinogenic effect. DNA samples from Big Blue rats treated with 0, 0.1, 1.0 or 10.0 mg AA/kg body weight (bw) by gavage, 5 days/week for 12 weeks were used in ACB-PCR in order to examine the induction of the two specific mutations. A significant dose-dependent induction of H-Ras mutant fraction (MF) was observed in liver and kidney. Statistically significant correlations were observed between AA-induced DNA adduct levels or cII mutant frequencies (previously measured in the same rats) and H-Ras MF measurements. No correlation between AA dose and K-Ras MF was found in liver or kidney, although there was a significant induction of K-Ras mutation in kidneys exposed to 0.1 mg/kg bw AA relative to controls. Thus, the data establish a straightforward dose-related increase in H-Ras MF due to fixation of AA-induced DNA adducts, whereas the common spontaneous K-Ras mutation showed a non-monotonic dose-response, consistent with loss of non-targeted mutation at cytotoxic doses. C1 [Wang, Yiying; Meng, Fanxue; Mei, Nan; Chen, Tao; Parsons, Barbara L.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Arlt, Volker M.] Inst Canc Res, Sect Mol Carcinogenesis, Sutton SM2 5NG, Surrey, England. RP Wang, YY (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM yiying.wang@fda.hhs.gov OI MEI, NAN/0000-0002-3501-9014 FU U.S. Department of Energy; U.S. Food and Drug Administration (FDA); Association for International Cancer Research (AICR); Cancer Research UK FX This work was supported by an appointment (Y.W.) to the Postgraduate Research Program at the NCTR 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 (FDA). Work at the Institute of Cancer Research was supported by Association for International Cancer Research (AICR) and Cancer Research UK. NR 62 TC 15 Z9 15 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 EI 1464-3804 J9 MUTAGENESIS JI Mutagenesis PD SEP PY 2011 VL 26 IS 5 BP 619 EP 628 DI 10.1093/mutage/ger023 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 815UF UT WOS:000294554600005 PM 21642617 ER PT J AU Teeguarden, JG Calafat, AM Ye, XY Doerge, DR Churchwell, MI Gunawan, R Graham, MK AF Teeguarden, Justin G. Calafat, Antonia M. Ye, Xiaoyum Doerge, Daniel R. Churchwell, Mona I. Gunawan, Rudy Graham, Morgan K. TI Twenty-Four Hour Human Urine and Serum Profiles of Bisphenol A during High-Dietary Exposure SO TOXICOLOGICAL SCIENCES LA English DT Article DE bisphenol A; pharmacokinetics; exposure; biomonitoring; endocrine disruptors; urine; serum ID SPRAGUE-DAWLEY RATS; MASS-SPECTROMETRIC DETERMINATION; HPLC-MS/MS METHOD; LIQUID-CHROMATOGRAPHY; ENVIRONMENTAL PHENOLS; BLOOD-VISCOSITY; WATER-INTAKE; MONKEYS; PHARMACOKINETICS; DISPOSITION AB By virtue of its binding to steroid hormone receptors, bisphenol A (BPA, the unconjugated bioactive monomer) is hypothesized to be estrogenic when present in sufficient quantities in the body, raising concerns that widespread exposure to BPA may impact human health. To better understand the internal exposure of adult humans to BPA and the relationship between the serum and urinary pharmacokinetics of BPA, a clinical exposure study was conducted. Blood and urine samples were collected approximately hourly over a 24-h period from 20 adult volunteers who ingested 100% of one of three specified meals comprising standard grocery store food items for breakfast, lunch, and dinner. The volunteers' average consumption of BPA, estimated from the urinary excretion of total BPA ((TOT)BPA = conjugated BPA + BPA), was 0.27 mu g/kg body weight (range, 0.03-0.86), 21% greater than the 95th percentile of aggregate exposure in the adult U.S. population. A serum time course of (TOT)BPA was observable only in individuals with exposures 1.3-3.9 times higher than the 95th percentile of aggregate U.S. exposure. The (TOT)BPA urine concentration T(max) was 2.75 h (range, 0.75-5.75 h) post-meal, lagging the serum concentration T(max) by similar to 1 h. Serum (TOT)BPA area under the curve per unit BPA exposure was between 21.5 and 79.0 nM center dot h center dot kg/mu g BPA. Serum (TOT)BPA concentrations ranged from less than or equal to limit of detection (LOD, 1.3 nM) to 5.7 nM and were, on average, 42 times lower than urine concentrations. During these high dietary exposures, (TOT)BPA concentrations in serum were undetectable in 83% of the 320 samples collected and BPA concentrations were determined to be less than or equal to LOD in all samples. C1 [Teeguarden, Justin G.; Gunawan, Rudy; Graham, Morgan K.] Pacific NW Natl Lab, Richland, WA 99352 USA. [Calafat, Antonia M.; Ye, Xiaoyum] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Doerge, Daniel R.; Churchwell, Mona I.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Teeguarden, JG (reprint author), Pacific NW Natl Lab, 902 Battelle Blvd, Richland, WA 99352 USA. EM justin.teeguarden@pnl.gov OI Teeguarden, Justin/0000-0003-3817-4391 FU U.S. Enivronmental Protection Agency (EPA) [R83386701] FX U.S. Enivronmental Protection Agency (EPA), through STAR grant (R83386701). NR 36 TC 111 Z9 112 U1 1 U2 54 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2011 VL 123 IS 1 BP 48 EP 57 DI 10.1093/toxsci/kfr160 PG 10 WC Toxicology SC Toxicology GA 815VG UT WOS:000294557500005 PM 21705716 ER PT J AU Ding, W Levy, DD Bishop, ME Lascelles, ELC Kulkarni, R Chang, CW Aidoo, A Manjanatha, MG AF Ding, Wei Levy, Dan D. Bishop, Michelle E. Lascelles, E. Lyn-Cook Kulkarni, Rohan Chang, Ching-We Aidoo, Anane Manjanatha, Mugimane G. TI Methyleugenol Genotoxicity in the Fischer 344 Rat Using the Comet Assay and Pathway-Focused Gene Expression Profiling SO TOXICOLOGICAL SCIENCES LA English DT Article DE Comet assay; gene expression; genotoxicity; methyleugenol; methyl methanesulfonate; oxidative DNA damage ID NATURALLY-OCCURRING ALKENYLBENZENES; UNSCHEDULED DNA-SYNTHESIS; IN-VIVO; METHYL EUGENOL; SAFROLE; LIVER; MICE; ACTIVATION; CHEMICALS; ESTRAGOLE AB Methyleugenol (MEG), a constituent of human food, induces malignant tumors in multiple tissues of rats and mice. Although MEG forms DNA adducts and induces unscheduled DNA synthesis in rat liver, it is negative in many in vitro genetic toxicity assays. In the present study, we evaluated MEG-induced DNA damage in the rat using (1) the alkaline Comet assay, (2) the oxidative Comet assay, and (3) expression profiling of genes associated with DNA damage pathways. Male F344 rats received single oral doses of 400 or 1000 mg/kg body weight (bw) MEG and DNA damage was assessed by the Comet assay in liver, bladder, bone marrow, kidney, and lung 3 h and 24 h later. MEG failed to produce any increase in DNA damage. In addition, rats were given a single oral dose of 2000 mg/kg bw MEG, and Comet assays were performed with liver, bone marrow, and bladder 1, 3, 6, and 8 h later. With one exception (bone marrow at 8 h), no DNA damage was detected. Enzyme-modified Comet assays were conducted in parallel with standard Comet assays in liver. Whereas no MEG-induced DNA damage was detected following formamidopyrimidine DNA glycosylase digestion, digestion with endonuclease III resulted in increases in DNA damage at the 6- and 8-h sampling times. Gene expression analysis on the livers from MEG-exposed rats showed significant reduction in genes associated with DNA repair. The results indicate that MEG induces DNA damage in rat liver and that oxidative DNA damages may be partly responsible for the genotoxicity of MEG in rodents. C1 [Ding, Wei; Bishop, Michelle E.; Lascelles, E. Lyn-Cook; Kulkarni, Rohan; Aidoo, Anane; Manjanatha, Mugimane G.] US FDA, Jefferson Labs, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Levy, Dan D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Chang, Ching-We] US FDA, Jefferson Labs, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Manjanatha, MG (reprint author), US FDA, Jefferson Labs, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. EM mugimane.manjanatha@fda.hhs.gov RI Ding, Wei/L-1503-2014 FU National Center for Toxicological Research FX Research Program at the National Center for Toxicological Research (to W. D.) 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 24 Z9 24 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2011 VL 123 IS 1 BP 103 EP 112 DI 10.1093/toxsci/kfr153 PG 10 WC Toxicology SC Toxicology GA 815VG UT WOS:000294557500010 PM 21659616 ER PT J AU Choi, J Reipa, V Hitchins, VM Goering, PL Malinauskas, RA AF Choi, Jonghoon Reipa, Vytas Hitchins, Victoria M. Goering, Peter L. Malinauskas, Richard A. TI Physicochemical Characterization and In Vitro Hemolysis Evaluation of Silver Nanoparticles SO TOXICOLOGICAL SCIENCES LA English DT Article DE silver nanoparticles; hemolysis; nanoparticle characterization; silver ions ID RISK-ASSESSMENT; NANO-SILVER; NANOMATERIALS; ERYTHROCYTES; NANOSILVER; PARTICLES; TOXICITY AB Silver nanomaterials are increasingly being used as antimicrobial agents in medical devices. This study assessed the in vitro hemolytic potential of unbound silver particles in human blood to determine which physical and chemical particle properties contribute to mechanisms of red blood cell (RBC) damage. Four silver particle powders (two nano-sized and two micron-sized) were dispersed in water and characterized using transmission electron microscopy, dynamic light scattering, surface-enhanced Raman spectroscopy, and zeta potential measurement. Particle size and agglomeration were dependent on the suspension media. Under similar conditions to the hemolysis assay, with the particles added to phosphate buffered saline (PBS) and plasma, the size of the nanoparticles increased compared with particles suspended in water alone due to interaction with chloride ions and plasma proteins. To determine hemolysis response, aqueous particle suspensions were mixed with heparinized human blood diluted in PBS for 3.5 h at 37 degrees C. Both nanoparticle preparations were significantly more hemolytic than micron-sized particles at equivalent mass concentrations > 220 mu g/ml and at estimated surface area concentrations > 10 cm(2)/ml. The presence or absence of surface citrate on nanoparticles showed no significant difference in hemolysis. However, the aqueous nanoparticle preparations released significantly more silver ions than micron-sized particles, which correlated with increased hemolysis. Although significant size changes occurred to the silver particles due to interaction with media components, the higher level of in vitro hemolysis observed with nanoparticles compared with micron-sized particles may be related to their greater surface area, increased silver ion release, and direct interaction with RBCs. C1 [Malinauskas, Richard A.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Choi, Jonghoon; Reipa, Vytas] NIST, Div Biochem Sci, Gaithersburg, MD 20899 USA. RP Malinauskas, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave,Bldg 62,Room 2108, Silver Spring, MD 20993 USA. EM richard.malinauskas@fda.hhs.gov FU Oak Ridge Institute for Science and Education from the United States Food and Drug Administration FX This work was supported by the Oak Ridge Institute for Science and Education through a fellowship from the United States Food and Drug Administration to JC. NR 35 TC 52 Z9 53 U1 6 U2 57 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2011 VL 123 IS 1 BP 133 EP 143 DI 10.1093/toxsci/kfr149 PG 11 WC Toxicology SC Toxicology GA 815VG UT WOS:000294557500013 PM 21652737 ER PT J AU Bosworth, HB Granger, BB Mendys, P Brindis, R Burkholder, R Czajkowski, SM Daniel, JG Ekman, I Ho, M Johnson, M Kimmel, SE Liu, LZ Musaus, J Shrank, WH Buono, EW Weiss, K Granger, CB AF Bosworth, Hayden B. Granger, Bradi B. Mendys, Phil Brindis, Ralph Burkholder, Rebecca Czajkowski, Susan M. Daniel, Jodi G. Ekman, Inger Ho, Michael Johnson, Mimi Kimmel, Stephen E. Liu, Larry Z. Musaus, John Shrank, William H. Buono, Elizabeth Whalley Weiss, Karen Granger, Christopher B. TI Medication adherence: A call for action SO AMERICAN HEART JOURNAL LA English DT Article ID BLOOD-PRESSURE CONTROL; RANDOMIZED CONTROLLED-TRIAL; PRESCRIPTION DRUG LABELS; NURSE FOLLOW-UP; PHYSICIAN COMMUNICATION; TREATMENT OUTCOMES; PATIENT ADHERENCE; ELDERLY-PATIENTS; HEALTH LITERACY; AUTOMATED CALLS AB Poor adherence to efficacious cardiovascular-related medications has led to considerable morbidity, mortality, and avoidable health care costs. This article provides results of a recent think-tank meeting in which various stakeholder groups representing key experts from consumers, community health providers, the academic community, decision-making government officials (Food and Drug Administration, National Institutes of Health, etc), and industry scientists met to evaluate the current status of medication adherence and provide recommendations for improving outcomes. Below, we review the magnitude of the problem of medication adherence, prevalence, impact, and cost. We then summarize proven effective approaches and conclude with a discussion of recommendations to address this growing and significant public health issue of medication nonadherence. (Am Heart J 2011;162:412-24.) C1 [Bosworth, Hayden B.] Durham VAMC, Ctr Hlth Serv Res Primary Care, Durham, NC USA. [Bosworth, Hayden B.] Duke Univ, Sch Nursing, Dept Psychiat & Behav Sci, Durham, NC 27705 USA. [Mendys, Phil] UNC, Sch Pharm, Pfizer, US Med Affairs, Chapel Hill, NC USA. [Mendys, Phil] UNC, Sch Pharm, Div Cardiol, Chapel Hill, NC USA. [Brindis, Ralph] Oakland Kaiser Hosp, Amer Coll Cardiol, San Francisco, CA USA. [Brindis, Ralph] Oakland Kaiser Hosp, Dept Cardiol, San Francisco, CA USA. [Burkholder, Rebecca; Johnson, Mimi] Natl Consumers League, Washington, DC USA. [Czajkowski, Susan M.] Natl Inst Heart Lung & Blood Inst, NIH, Bethesda, MD USA. [Daniel, Jodi G.] US Dept HHS, Office Natl Coordinator Hlth Informat Technol, Washington, DC 20201 USA. [Ekman, Inger] Gothenburg Univ, Sahlgrenska Acad, Ctr Person Ctr Care Long Term Illness GPCC, S-41124 Gothenburg, Sweden. [Ho, Michael] Denver VA Med Ctr, Denver, CO USA. [Kimmel, Stephen E.] Univ Penn, Sch Med, Div Cardiol, Dept Med & Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Liu, Larry Z.] Pfizer Inc, New York, NY USA. [Liu, Larry Z.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Musaus, John; Buono, Elizabeth Whalley] MWV Healthcare, Richmond, VA USA. [Shrank, William H.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pharmacoepidemiol & Pharmacoecon,Dept Med, Boston, MA 02115 USA. [Weiss, Karen] US FDA, Washington, DC 20204 USA. [Granger, Christopher B.] Duke Univ, Div Cardiol, Dept Med, Durham, NC 27705 USA. [Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27705 USA. RP Bosworth, HB (reprint author), Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, 2424 Erwin Rd,Suite 1105,Hock Plaza, Durham, NC 27705 USA. EM hayden.bosworth@duke.edu RI Granger, Christopher/D-3458-2014 OI Granger, Christopher/0000-0002-0045-3291 FU VA HSRD career scientist award [RCS 08-027]; American Heart Association; NIH [UL1RR024128] FX This research is supported by a VA HSRD career scientist award (RCS 08-027) and an Established Investigator Award from the American Heart Association to the first author (H. B. B.). Dr. B. Granger was supported by A NIH funded CTSA grant (UL1RR024128). The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the Department of Veterans Affairs. NR 84 TC 80 Z9 86 U1 7 U2 27 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 SEP PY 2011 VL 162 IS 3 BP 412 EP 424 DI 10.1016/j.ahj.2011.06.007 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 814JU UT WOS:000294447400002 PM 21884856 ER PT J AU Walters-Conte, KB Johnson, DLE Allard, MW Pecon-Slattery, J AF Walters-Conte, Kathryn B. Johnson, Diana L. E. Allard, Marc W. Pecon-Slattery, Jill TI Carnivore-Specific SINEs (Can-SINEs): Distribution, Evolution, and Genomic Impact SO JOURNAL OF HEREDITY LA English DT Article DE carnivore; genome; SINE ID LINKED MYOTUBULAR MYOPATHY; NON-LTR RETROTRANSPOSONS; TRANSFER-RNA; ALU REPEATS; PHYLOGENETIC-RELATIONSHIPS; TRANSPOSABLE ELEMENTS; RETROPOSON ANALYSIS; R2 RETROTRANSPOSON; ORDER CARNIVORA; DOMESTIC DOG AB Short interspersed nuclear elements (SINEs) are a type of class 1 transposable element (retrotransposon) with features that allow investigators to resolve evolutionary relationships between populations and species while providing insight into genome composition and function. Characterization of a Carnivora-specific SINE family, Can-SINEs, has, has aided comparative genomic studies by providing rare genomic changes, and neutral sequence variants often needed to resolve difficult evolutionary questions. In addition, Can-SINEs constitute a significant source of functional diversity with Carnivora. Publication of the whole-genome sequence of domestic dog, domestic cat, and giant panda serves as a valuable resource in comparative genomic inferences gleaned from Can-SINEs. In anticipation of forthcoming studies bolstered by new genomic data, this review describes the discovery and characterization of Can-SINE motifs as well as describes composition, distribution, and effect on genome function. As the contribution of noncoding sequences to genomic diversity becomes more apparent, SIN Es and other transposable elements will play an increasingly large role in mammalian comparative genomics. C1 [Walters-Conte, Kathryn B.] Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. [Johnson, Diana L. E.] George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. [Allard, Marc W.] US FDA, Div Microbiol, College Pk, MD USA. [Pecon-Slattery, Jill] NCI, Lab Genom Div, Frederick, MD 21701 USA. RP Walters-Conte, KB (reprint author), Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. EM kwalt@sas.upenn.edu FU National Cancer institute, National Institutes of Health [N01-CO-12400]; George Washington University FX This project has been supported in part with federal funds from the National Cancer institute, National Institutes of Health, under contract N01-CO-12400. The Robert Weintraub Program in Systematics and Evolution administered by The George Washington University also provided financial support. NR 70 TC 4 Z9 4 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 2011 VL 102 SU 1 BP S2 EP S10 DI 10.1093/jhered/esr051 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 813ME UT WOS:000294370500002 PM 21846743 ER PT J AU Mossoba, MM Chizhikov, V Volokhov, DV Milians, KMD Schoen, B Al-Khaldi, SF AF Mossoba, M. M. Chizhikov, V. Volokhov, D. V. Milians, K. Martinez-Diaz Schoen, B. Al-Khaldi, S. F. TI Identification of Mycoplasmas Using a Fluorophore-Free Microarray and Infrared Chemical Imaging (IRCI) SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Mycoplasma detection; DNA microarrays; Infrared Imaging ID NANOPARTICLE PROBES; ENRICHMENT AB A novel application of mid-infrared chemical imaging (IRCI) for the fluorophore-free detection and identification of mycoplasma species is reported for the first time. The PCR-amplified biotinylated targets hybridized to microarray probes were treated with streptavidin-gold nanoparticles followed by silver enhancement. This modification has the potential to expand the implementation of DNA microarray techniques in laboratories involved in the detection of cell substrates, other biological products, and clinical materials for the presence of mycoplasmas. Published by Elsevier B.V. C1 [Mossoba, M. M.; Milians, K. Martinez-Diaz; Schoen, B.; Al-Khaldi, S. F.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Chizhikov, V.; Volokhov, D. V.] Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 15 TC 2 Z9 2 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD SEP PY 2011 VL 86 IS 3 BP 383 EP 386 DI 10.1016/j.mimet.2011.06.003 PG 4 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 815DX UT WOS:000294507400019 PM 21693139 ER PT J AU Botsis, T Nguyen, MD Woo, EJ Markatou, M Ball, R AF Botsis, Taxiarchis Nguyen, Michael D. Woo, Emily Jane Markatou, Marianthi Ball, Robert TI Text mining for the Vaccine Adverse Event Reporting System: medical text classification using informative feature selection SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID SURVEILLANCE SYSTEM; CATEGORIZATION; IDENTIFICATION; ANAPHYLAXIS; RECORDS; MEDDRA AB Objective The US Vaccine Adverse Event Reporting System (VAERS) collects spontaneous reports of adverse events following vaccination. Medical officers review the reports and often apply standardized case definitions, such as those developed by the Brighton Collaboration. Our objective was to demonstrate a multi-level text mining approach for automated text classification of VAERS reports that could potentially reduce human workload. Design We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (N(pos)=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations. Measurements Classifiers' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman's test; misclassification error rate analysis was also performed. Results Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively). Conclusion Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably. C1 [Botsis, Taxiarchis; Nguyen, Michael D.; Woo, Emily Jane; Ball, Robert] CBER, Off Biostat & Epidemiol, FDA, Rockville, MD 20852 USA. [Botsis, Taxiarchis] Univ Tromso, Dept Comp Sci, Tromso, Norway. [Markatou, Marianthi] Cornell Univ, Dept Stat Sci, New York, NY 10021 USA. [Markatou, Marianthi] IBM TJ Watson Res Ctr, New York, NY USA. RP Botsis, T (reprint author), CBER, Off Biostat & Epidemiol, FDA, Woodmont Off Complex 1,Rm 306N,1401 Rockville Pik, Rockville, MD 20852 USA. EM taxiarchis.botsis@fda.hhs.gov FU Center for Biologics Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration FX This project was supported in part by the appointment of Taxiarchis Botsis 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. We thank all the staff members who participated on the VAERS 2009-H1N1 Influenza Response Team for assisting with the acquisition, review, and analysis of the adverse event report data. NR 48 TC 23 Z9 23 U1 2 U2 22 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP PY 2011 VL 18 IS 5 BP 631 EP 638 DI 10.1136/amiajnl-2010-000022 PG 8 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 816AV UT WOS:000294572000017 PM 21709163 ER PT J AU Taylor, MR AF Taylor, Michael R. TI Will the Food Safety Modernization Act Help Prevent Outbreaks of Foodborne Illness? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Off Deputy Commissioner Foods, Silver Spring, MD 20993 USA. RP Taylor, MR (reprint author), US FDA, Off Deputy Commissioner Foods, Silver Spring, MD 20993 USA. NR 2 TC 8 Z9 8 U1 0 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 1 PY 2011 VL 365 IS 9 AR e18 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 813YC UT WOS:000294405200004 PM 21848454 ER PT J AU Russell, SM Lechner, MG Gong, L Megiel, C Liebertz, DJ Masood, R Correa, AJ Han, J Puri, RK Sinha, UK Epstein, AL AF Russell, Sarah M. Lechner, Melissa G. Gong, Lucy Megiel, Carolina Liebertz, Daniel J. Masood, Rizwan Correa, Adrian J. Han, Jing Puri, Raj K. Sinha, Uttam K. Epstein, Alan L. TI USC-HN2, a new model cell line for recurrent oral cavity squamous cell carcinoma with immunosuppressive characteristics SO ORAL ONCOLOGY LA English DT Article DE Head and neck squamous cell carcinoma (HNSCC); Cell line; Tumor immune tolerance; Myeloid derived suppressor cells (MDSC); Human papillomavirus (HPV) ID STEM-LIKE CELLS; EXPRESSION PROFILES; HEAD; NECK; CANCER; MECHANISMS; EXPANSION; BIOLOGY AB Head and neck squamous cell carcinomas (HNSCC) are common and aggressive tumors that have not seen an improvement in survival rates in decades. These tumors are believed to evade the immune system through a variety of mechanisms and are therefore highly immune modulatory. In order to elucidate their interaction with the immune system and develop new therapies targeting immune escape, new pre-clinical models are needed. A novel human cell line, USC-HN2, was established from a patient biopsy specimen of invasive, recurrent buccal HNSCC and characterized by morphology, heterotransplantation, cytogenetics, phenotype, gene expression, and immune modulation studies and compared to a similar HNSCC cell line; SCCL-MT1. Characterization studies confirmed the HNSCC origin of USC-HN2 and demonstrated a phenotype similar to the original tumor and typical of aggressive oral cavity HNSCC (EGFR(+)CD44v6(+)FABP5(+)Keratin(+) and HPV-). Gene and protein expression studies revealed USC-HN2 to have highly immune-modulatory cytokine production (IL-1 beta, IL-6, IL-8, GM-CSF, and VEGF) and strong regulatory T and myeloid derived suppressor cell (MDSC) induction capacity in vitro. Of note, both USC-HN2 and SCCL-MT1 were found to have a more robust cytokine profile and MDSC induction capacity when compared to seven previously established HNSCC cell lines. Additionally, microarray gene expression profiling of both cell lines demonstrate up-regulation of antigen presenting genes. Because USC-HN2 is therefore highly immunogenic, it also induces strong immune suppression to evade immunologic destruction. Based upon these results, both cell lines provide an excellent model for the development of new suppressor cell-targeted immunotherapies. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Russell, Sarah M.; Lechner, Melissa G.; Gong, Lucy; Megiel, Carolina; Liebertz, Daniel J.; Correa, Adrian J.; Epstein, Alan L.] USC Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. [Masood, Rizwan; Sinha, Uttam K.] USC Keck Sch Med, Dept Otolaryngol, Los Angeles, CA 90033 USA. [Han, Jing; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Epstein, AL (reprint author), USC Keck Sch Med, Dept Pathol, Hoffman Med Res Bldg,Room 205,2011 Zonal Ave, Los Angeles, CA 90033 USA. EM aepstein@usc.edu OI Lechner, Melissa/0000-0002-4744-6566 FU American Tissue Culture Collection, National Institutes of Health [3T32GM067587-07S1]; USC Keck School of Medicine FX The authors thank Lillian Young for performing the IHC studies, James Pang for his assistance with the animal studies, and Victoria Bedell and the City of Hope Cytogenetic Core Facility for performing expert cytogenetic and HPV FISH studies. Grant support: This work was supported by the American Tissue Culture Collection, National Institutes of Health training grant 3T32GM067587-07S1 (M.G.L.) and the USC Keck School of Medicine Dean's Research Fellowship (S.M.R.). NR 28 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD SEP PY 2011 VL 47 IS 9 BP 810 EP 817 DI 10.1016/j.oraloncology.2011.05.015 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 812NG UT WOS:000294299600007 PM 21719345 ER PT J AU Sjolund-Karlsson, M Joyce, K Blickenstaff, K Ball, T Haro, J Medalla, FM Fedorka-Cray, P Zhao, SH Crump, JA Whichard, JM AF Sjolund-Karlsson, Maria Joyce, Kevin Blickenstaff, Karen Ball, Takiyah Haro, Jovita Medalla, Felicita M. Fedorka-Cray, Paula Zhao, Shaohua Crump, John A. Whichard, Jean M. TI Antimicrobial Susceptibility to Azithromycin among Salmonella enterica Isolates from the United States SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID UNCOMPLICATED TYPHOID-FEVER; MULTIDRUG-RESISTANT; DECREASED SUSCEPTIBILITY; SEROTYPE TYPHI; CHILDREN; BREAKPOINTS; PARATYPHI; OFLOXACIN; DIARRHEA; GENES AB Due to emerging resistance to traditional antimicrobial agents, such as ampicillin, trimethoprim-sulfamethoxazole, and chloramphenicol, azithromycin is increasingly used for the treatment of invasive Salmonella infections. In the present study, 696 isolates of non-Typhi Salmonella collected from humans, food animals, and retail meats in the United States were investigated for antimicrobial susceptibility to azithromycin. Seventy-two Salmonella enterica serotype Typhi isolates from humans were also tested. For each isolate, MICs of azithromycin and 15 other antimicrobial agents were determined by broth microdilution. Among the non-Typhi Salmonella isolates, azithromycin MICs among human isolates ranged from 1 to 32 mu g/ml, whereas the MICs among the animal and retail meat isolates ranged from 2 to 16 mu g/ml and 4 to 16 mu g/ml, respectively. Among Salmonella serotype Typhi isolates, the azithromycin MICs ranged from 4 to 16 mu g/ml. The highest MIC observed in the present study was 32 mu g/ml, and it was detected in three human isolates belonging to serotypes Kentucky, Montevideo, and Paratyphi A. Based on our findings, we propose an epidemiological cutoff value (ECOFF) for wild-type Salmonella of <= 16 mu g/ml of azithromycin. The susceptibility data provided could be used in combination with clinical outcome data to determine tentative clinical breakpoints for azithromycin and Salmonella enterica. C1 [Sjolund-Karlsson, Maria] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, CCID NCZVED DFBMD EDLB, Atlanta, GA 30329 USA. [Blickenstaff, Karen; Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD USA. [Ball, Takiyah; Haro, Jovita; Fedorka-Cray, Paula] USDA ARS, Bacterial Epidemiol & Antimicrobial Resistance Re, Athens, GA 30613 USA. RP Sjolund-Karlsson, M (reprint author), Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, CCID NCZVED DFBMD EDLB, 1600 Clifton Rd, Atlanta, GA 30329 USA. EM fwt4@cdc.gov FU CDC; USDA; FDA Center for Veterinary Medicine (FDA-CVM) FX This work was supported by interagency agreements that the CDC and USDA have with the FDA Center for Veterinary Medicine (FDA-CVM). NR 38 TC 26 Z9 26 U1 0 U2 8 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 SEP PY 2011 VL 55 IS 9 BP 3985 EP 3989 DI 10.1128/AAC.00590-11 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 808CW UT WOS:000293953900003 PM 21690279 ER PT J AU Kim, DW Heinze, TM Kim, BS Schnackenberg, LK Woodling, KA Sutherland, JB AF Kim, Dae-Wi Heinze, Thomas M. Kim, Bong-Soo Schnackenberg, Laura K. Woodling, Kellie A. Sutherland, John B. TI Modification of Norfloxacin by a Microbacterium sp Strain Isolated from a Wastewater Treatment Plant SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FUNGUS GLOEOPHYLLUM-STRIATUM; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; N-DESETHYL-METABOLITES; LIQUID-CHROMATOGRAPHY; FLUOROQUINOLONE ENROFLOXACIN; AROMATIC HYDROXYLATION; FLUORESCENCE DETECTION; OXIDATIVE STRESS; SP NOV. AB Antimicrobial residues found in municipal wastewater may increase selective pressure on microorganisms for development of resistance, but studies with mixed microbial cultures derived from wastewater have suggested that some bacteria are able to inactivate fluoroquinolones. Medium containing N-phenylpiperazine and inoculated with wastewater was used to enrich fluoroquinolone-modifying bacteria. One bacterial strain isolated from an enrichment culture was identified by 16S rRNA gene sequence analysis as a Microbacterium sp. similar to a plant growth-promoting bacterium, Microbacterium azadirachtae (99.70%), and a nematode pathogen, "M. nematophilum" (99.02%). During growth in medium with norfloxacin, this strain produced four metabolites, which were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) analyses as 8-hydroxynorfloxacin, 6-defluoro-6-hydroxynorfloxacin, desethylene norfloxacin, and N-acetylnorfloxacin. The production of the first three metabolites was enhanced by ascorbic acid and nitrate, but it was inhibited by phosphate, amino acids, mannitol, formate, and thiourea. In contrast, N-acetylnorfloxacin was most abundant in cultures supplemented with amino acids. This is the first report of defluorination and hydroxylation of a fluoroquinolone by an isolated bacterial strain. The results suggest that some bacteria may degrade fluoroquinolones in wastewater to metabolites with less antibacterial activity that could be subject to further degradation by other microorganisms. C1 [Kim, Dae-Wi; Kim, Bong-Soo; Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.; Woodling, Kellie A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Schnackenberg, Laura K.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov RI Kim, Bong-Soo/L-4779-2013 OI Kim, Bong-Soo/0000-0003-1243-8280 FU National Center for Toxicological Research FX This research was supported in part by an appointment to the Research Participation Program (D.-W.K. and B.-S.K.) at the National Center for Toxicological 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 56 TC 14 Z9 15 U1 3 U2 23 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 SEP PY 2011 VL 77 IS 17 BP 6100 EP 6108 DI 10.1128/AEM.00545-11 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 811JP UT WOS:000294205700032 PM 21724893 ER PT J AU Amidon, KS Langguth, P Lennernas, H Yu, L Amidon, GL AF Amidon, K. S. Langguth, P. Lennernas, H. Yu, L. Amidon, G. L. TI Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID INTESTINAL PERMEABILITY; DRUGS; BIOAVAILABILITY; CACO-2; BCS; FDA AB The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard. C1 [Amidon, G. L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Amidon, K. S.] Iowa State Univ, Dept World Languages & Cultures, Ames, IA USA. [Langguth, P.] Johannes Gutenberg Univ Mainz, Dept Biopharm & Pharmaceut Technol, Mainz, Germany. [Lennernas, H.] Uppsala Univ, Dept Pharm, Uppsala, Sweden. [Yu, L.] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM glamidon@umich.edu RI Yu, Lawrence/L-6280-2016; OI Amidon, Kevin/0000-0003-3941-4414 FU Alexander von Humboldt Foundation; NIH [GM 037188] FX G.L.A. gratefully acknowledges the Alexander von Humboldt Foundation and NIH GM 037188 for support of this work. NR 24 TC 25 Z9 26 U1 1 U2 17 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 SEP PY 2011 VL 90 IS 3 BP 467 EP 470 DI 10.1038/clpt.2011.109 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 811WM UT WOS:000294247900023 PM 21775984 ER PT J AU Menon-Andersen, D Yu, B Madabushi, R Bhattaram, V Hao, W Uppoor, RS Mehta, M Lesko, L Temple, R Stockbridge, N Laughren, T Gobburu, JV AF Menon-Andersen, D. Yu, B. Madabushi, R. Bhattaram, V. Hao, W. Uppoor, R. S. Mehta, M. Lesko, L. Temple, R. Stockbridge, N. Laughren, T. Gobburu, J. V. TI Essential Pharmacokinetic Information for Drug Dosage Decisions: A Concise Visual Presentation in the Drug Label SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB A critical issue in labeling is to succinctly communicate, in a manner that is readily understandable and actionable, changes in systemic exposure that affect drug dosing. Current practices in labeling make it difficult for prescribers to locate the most important information influencing their dosing decisions. In this report, we propose the use of forest plots for communicating the pharmacokinetic consequences of intrinsic and extrinsic factors in a concise and readily interpretable manner. C1 [Menon-Andersen, D.; Yu, B.; Madabushi, R.; Bhattaram, V.; Hao, W.; Uppoor, R. S.; Mehta, M.; Lesko, L.; Gobburu, J. V.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Temple, R.; Stockbridge, N.; Laughren, T.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Gobburu, JV (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Jogarao.Gobburu@fda.hhs.gov NR 6 TC 7 Z9 7 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 SEP PY 2011 VL 90 IS 3 BP 471 EP 474 DI 10.1038/clpt.2011.149 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 811WM UT WOS:000294247900024 PM 21796114 ER PT J AU Stockbridge, N AF Stockbridge, Norman TI ABPM PART OF FDA REVIEWS SO DRUG INFORMATION JOURNAL LA English DT Letter C1 US FDA, Div Cardiovasc & Renal Prod, CDER, Rockville, MD 20857 USA. RP Stockbridge, N (reprint author), US FDA, Div Cardiovasc & Renal Prod, CDER, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD SEP PY 2011 VL 45 IS 5 BP 567 EP 567 PG 1 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 811FR UT WOS:000294191800003 ER PT J AU Davidson, VJ Ravel, A Nguyen, TN Fazil, A Ruzante, JM AF Davidson, Valerie J. Ravel, Andre Nguyen, To N. Fazil, Aamir Ruzante, Juliana M. TI Food-Specific Attribution of Selected Gastrointestinal Illnesses: Estimates from a Canadian Expert Elicitation Survey SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FOODBORNE PATHOGENS; BRITISH-COLUMBIA; BURDEN AB The study used a structured expert elicitation survey to derive estimates of food-specific attribution for nine illnesses caused by enteric pathogens in Canada. It was based on a similar survey conducted in the United States and focused on Campylobacter spp., Escherichia coli O157:H7, Listeria monocytogenes, nontyphoidal Salmonella enterica, Shigella spp., Vibrio spp., Yersinia enterocolitica, Cryptosporidium parvum, and Norwalk-like virus. A snowball approach was used to identify food safety experts within Canada. Survey respondents provided background information as well as self-assessments of their expertise for each pathogen and the 12 food categories. Depending on the pathogen, food source attribution estimates were based on responses from between 10 and 35 experts. For each pathogen, experts divided their estimates of total foodborne illness across 12 food categories and they provided a best estimate for each category as well as 5th and 95th percentile limits for foods considered to be vehicles. Their responses were treated as triangular probability distributions, and linear aggregation was used to combine the opinions of each group of experts for each pathogen-food source group. Across the 108 pathogen-food groups, a majority of experts agreed on 30 sources and 48 nonsources for illness. The number of food groups considered to be pathogen sources by a majority of experts varied by pathogen from a low of one food source for Vibrio spp. (seafood) and C. parvum (produce) to a high of seven food sources for Salmonella spp. Beta distributions were fitted to the aggregated opinions and were reasonable representations for most of the pathogen-food group attributions. These results will be used to quantitatively assess the burden of foodborne illness in Canada as well as to analyze the uncertainty in our estimates. C1 [Davidson, Valerie J.; Nguyen, To N.] Univ Guelph, Sch Engn, Guelph, ON N1G 2W1, Canada. [Ravel, Andre] Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, St Hyacinthe, PQ, Canada. [Fazil, Aamir] Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, Guelph, ON, Canada. [Ruzante, Juliana M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Davidson, VJ (reprint author), Univ Guelph, Sch Engn, 50 Stone Rd E, Guelph, ON N1G 2W1, Canada. EM vdavidso@uoguelph.ca FU Natural Sciences and Engineering Research Council (NSERC) of Canada FX The authors thank Sandra Hoffmann from Resources for the Future, Washington, DC, and Paul Fishbeck from Carnegie Mellon University, Pittsburgh, PA, for their advice and permission to use their survey tool. The authors also thank all experts who helped build the expert list and those who answered the survey. Financial support from the Strategic Grants program of the Natural Sciences and Engineering Research Council (NSERC) of Canada to undertake this work is gratefully acknowledged. NR 22 TC 18 Z9 18 U1 2 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 SEP PY 2011 VL 8 IS 9 BP 983 EP 995 DI 10.1089/fpd.2010.0786 PG 13 WC Food Science & Technology SC Food Science & Technology GA 812NR UT WOS:000294300700005 PM 21561379 ER PT J AU Ellis, RJ Kaminsky, DA Zhou, EH Fu, PF Chen, WD Brelin, A Faulhaber, PF Bodner, D AF Ellis, Rodney J. Kaminsky, Deborah A. Zhou, Esther H. Fu, Pingfu Chen, Wei-Dong Brelin, Alaina Faulhaber, Peter F. Bodner, Donald TI TEN-YEAR OUTCOMES: THE CLINICAL UTILITY OF SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY/COMPUTED TOMOGRAPHY CAPROMAB PENDETIDE (PROSTASCINT) IN A COHORT DIAGNOSED WITH LOCALIZED PROSTATE CANCER SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Capromab pendetide; Prostascint; Prostate-specific membrane antigen; Staging; Image-guided radiotherapy ID BIOCHEMICAL FAILURE; BRACHYTHERAPY; RADIOTHERAPY; PREDICTS; THERAPY; DISEASE; ANTIGEN; FUSION; SCAN; MEN AB Purpose: To evaluate the clinical utility of capromab pendetide imaging with single photon emission computed tomography coregistration with computed tomography (SPECT/CT) in primary prostate cancer (CaP) for pretreatment prognostic staging and localization of biologic target volumes (WIN) for individualized image-guided radiotherapy close escalation (IGRT-DE). Methods and Materials: Patients consecutively presenting for primary radiotherapy (February 1997 to December 2002), having a clinical diagnosis of localized CaP, were evaluated for tumor stage using conventional staging and SPECT/CT (N = 239). Distant metastatic uptake (mets) were identified by SPECT/CT in 22 (9.2%). None of the suspected mets could be clinically confirmed. Thus, all subjects were followed without alteration in disease management. The SPECT/CT pelvic images defined WIN for IGRT-DE (+150% brachytherapy dose) without (n = 150) or with (n = 89) external radiation of 45 Gy. The National Comprehensive Cancer Network criteria defined risk groups (RC). The median survivor follow-up was 7 years. Biochemical disease-free survival (bDFS) was reported by clinical nadir +2 ng/mL (CN+2) criteria. Statistical analyses included Kaplan-Meier, multivariate analysis, and Concordance-index models. Results: At 10-year analyses, overall survival was 84.8% and bDFS was 84.6%. With stratification by RC, CN+2 bDFS was 93.5% for the low-RG (n = 116), 78.7% for the intermediate-RC (n = 94), and 68.8% for the high-RG (n = 29), p = 0.0002. With stratification by pretreatment SPECT/CT findings, WE'S was 65.5% in patients with suspected mets (n = 22) vs. 86.6% in patients with only localized uptake (n = 217), p = 0.0014. Call disease-specific survival (DSS) was 97.7% for the cohort. With stratification by SPECT/CT findings, DSS was 86.4% (with suspected mets) vs. 99.0% (localized only), p = 0.0001. Using multivariate analysis, the DSS hazard ratio for SPECT/CT findings (mets vs. localized) was 3.58 (p = 0.0026). Concordance-index tests, based on all data, by CN+2 bDFS criteria were 0.710 for RG alone and 0.773 for SPECT/CT + RG. Conclusions: Through long-term outcomes we demonstrate statistically significant bDFS and DSS predictive value for pretreatment capromab pendetide SPECT/CT imaging in primary CaP. Dual clinical utility is demonstrated, using SPECT/CT to define BTV for individualized IGRT-DE. (C) 2011 Elsevier Inc. C1 [Ellis, Rodney J.] Univ Hosp Cleveland, Dept Radiat Oncol, Case Med Ctr, Cleveland, OH 44106 USA. [Fu, Pingfu] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Ellis, Rodney J.] Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Dept Radiol, Rootstown, OH 44272 USA. [Kaminsky, Deborah A.] Aultman Hosp, Div Radiat Therapy, Canton, OH USA. [Zhou, Esther H.] USA Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Chen, Wei-Dong] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Chen, Wei-Dong] Natl Naval Med Ctr, Bethesda, MD USA. [Faulhaber, Peter F.] Univ Hosp Cleveland, Dept Radiol, Case Med Ctr, Cleveland, OH 44106 USA. [Bodner, Donald] Univ Hosp Cleveland, Dept Urol, Case Med Ctr, Cleveland, OH 44106 USA. RP Ellis, RJ (reprint author), Univ Hosp Cleveland, Dept Radiat Oncol, Case Med Ctr, 11000 Euclid Ave, Cleveland, OH 44106 USA. EM rodney.ellis@case.edu RI CHEN, WEI-DONG/F-4521-2014 OI CHEN, WEI-DONG/0000-0003-2264-5515 FU Cytogen Corporation, Princeton, NJ; EUSA Pharma, Longhorne, PA FX Supported by educational grants from the Cytogen Corporation, Princeton, NJ, and EUSA Pharma, Longhorne, PA. NR 29 TC 20 Z9 20 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD SEP 1 PY 2011 VL 81 IS 1 BP 29 EP 34 DI 10.1016/j.ijrobp.2010.05.053 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 809YT UT WOS:000294093300005 PM 20961696 ER PT J AU Kothary, N Diak, IL Brinker, A Bezabeh, S Avigan, M Dal Pan, G AF Kothary, Namita Diak, Ida-Lina Brinker, Allen Bezabeh, Shewit Avigan, Mark Dal Pan, Gerald TI Progressive multifocal leukoencephalopathy associated with efalizumab use in psoriasis patients SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article DE biologics; demyelinating disorders; efalizumab; pharmacoepidemiology; progressive multifocal leukoencephalopathy; psoriasis ID JC VIRUS; NATALIZUMAB; BRAIN AB Background: Progressive multifocal leukoencephalopathy (PML), a rare, potentially fatal demyelinating disease, affects primarily immunocompromised individuals. The Food and Drug Administration (FDA) received reports of PML associated with efalizumab (Raptiva), a biologic agent approved for psoriasis. In. July 2009, efalizumab was voluntarily withdrawn from the US market, because of the risk of PML. Objective: To describe 3 cases of PML in psoriasis patients treated with efalizumab. Methods: The FDA's Adverse Event Reporting System (AERS) database was searched for post-marketing reports of PML associated with biologic agents that are FDA approved for psoriasis (adalimumab, alefacept, efalizumab, etanercept, infliximab) from market approval to January 30, 2009. Results: Twelve cases suggestive of PML were identified: adalimumab (1), efalizumab (4), etanercept (3), and infliximab (4). Efalizumab was the only drug with cases reporting PML in the setting of psoriasis. All cases of PML in efalizumab-treated patients presented 3 years or more after treatment initiation and resulted in death. Cases of PML in patients treated with adalimumab, etanercept, or infliximab occurred in patients treated for conditions other than psoriasis and were confounded by the use of other immunosuppressive therapies or were not confirmed PML cases. Limitations: AERS data are limited because of an underreporting of spontaneous post-marketing adverse events and variable quality and quantity of information provided. Conclusions: These cases suggest that prolonged efalizumab therapy is a risk factor for PML. Although the cases reported treatment for longer than 3 years, a specific treatment duration that does not place patients at risk for PML has not been defined. (J Am Acad Dermatol 2011;65:546-51.) C1 [Kothary, Namita; Diak, Ida-Lina; Brinker, Allen; Bezabeh, Shewit; Avigan, Mark; Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Kothary, N (reprint author), 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM namita.kothary@fda.hhs.gov NR 31 TC 50 Z9 52 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2011 VL 65 IS 3 BP 546 EP 551 DI 10.1016/j.jaad.2010.05.033 PG 6 WC Dermatology SC Dermatology GA 810QK UT WOS:000294142000007 PM 21514689 ER PT J AU Zhang, Q Hitchins, VM Schrand, AM Hussain, SM Goering, PL AF Zhang, Qin Hitchins, Victoria M. Schrand, Amanda M. Hussain, Saber M. Goering, Peter L. TI Uptake of gold nanoparticles in murine macrophage cells without cytotoxicity or production of pro-inflammatory mediators SO NANOTOXICOLOGY LA English DT Article DE Gold nanoparticles; macrophages; cytotoxicity; inflammation; cytokine ID CELLULAR UPTAKE; SILVER NANOPARTICLES; DIFFERENT SIZES; DRUG-DELIVERY; IN-VITRO; TOXICITY; CANCER; BIOCOMPATIBILITY; SCATTERING; NANORODS AB More information characterizing the biological responses to nanoparticles is needed to allow the U. S. Food and Drug Administration to evaluate the safety and effectiveness of products with nano-scale components. The potential cytotoxicity and inflammatory responses of Au NPs (60 nm, NIST standard reference materials) were investigated in murine macrophages. Cytotoxicity was evaluated by MTT and LDH assays. Cytokines (IL-6, TNF-alpha), nitric oxide, and ROS were assayed to assess inflammatory responses. Morphological appearance and localization of particles were examined by high resolution illumination microscopy, transmission electron microscopy (TEM), and scanning TEM coupled with EDX spectroscopy. Results showed no cytotoxicity and no elevated production of proinflammatory mediators; however, imaging analyses demonstrated cellular uptake of Au NPs and localization within intracellular vacuoles. These results suggest that 60 nm Au NPs, under the exposure conditions tested, are not cytotoxic, nor elicit pro-inflammatory responses. The localization of Au NPs in intracellular vacuoles suggests endosomal containment and an uptake mechanism involving endocytosis. C1 [Zhang, Qin; Hitchins, Victoria M.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Schrand, Amanda M.; Hussain, Saber M.] Appl Biotechnol Branch, Dayton, OH USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 64,Rm 4064, Silver Spring, MD 20993 USA. EM peter.goering@fda.hhs.gov FU U.S. Food and Drug Administration; Oak Ridge Research Fellowship Program (ORISE) Associated University through a contract with the U.S. Food and Drug Administration FX This work was supported by U.S. Food and Drug Administration nanotechnology research funds. We would also acknowledge the Research Fellowship Program support administered by the Oak Ridge Research Fellowship Program (ORISE) Associated University through a contract with the U.S. Food and Drug Administration. NR 39 TC 39 Z9 40 U1 2 U2 43 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1743-5390 J9 NANOTOXICOLOGY JI Nanotoxicology PD SEP PY 2011 VL 5 IS 3 BP 284 EP 295 DI 10.3109/17435390.2010.512401 PG 12 WC Nanoscience & Nanotechnology; Toxicology SC Science & Technology - Other Topics; Toxicology GA 811PS UT WOS:000294225600001 PM 20849214 ER PT J AU Wang, CG Daniels, MJ AF Wang, Chenguang Daniels, Michael J. TI A Note on MAR, Identifying Restrictions, Model Comparison, and Sensitivity Analysis in Pattern Mixture Models with and without Covariates for Incomplete Data SO BIOMETRICS LA English DT Article DE Deviance information criterion; Missing at random; Nonfuture dependence ID MISSING DATA; FIT AB Pattern mixture modeling is a popular approach for handling incomplete longitudinal data. Such models are not identifiable by construction. Identifying restrictions is one approach to mixture model identification (Little, 1995, Journal of the American Statistical Association 90, 1112-1121; Little and Wang, 1996, Biometrics 52, 98-111; Thijs et al., 2002, Biostatistics 3, 245-265; Kenward, Molenberghs, and Thijs, 2003, Biometrika 90, 53-71; Daniels and Hogan, 2008, in Missing Data in Longitudinal Studies: Strategies for Bayesian Modeling and Sensitivity Analysis) and is a natural starting point for missing not at random sensitivity analysis (Thijs et al., 2002, Biostatistics 3, 245-265; Daniels and Hogan, 2008, in Missing Data in Longitudinal Studies: Strategies for Bayesian Modeling and Sensitivity Analysis). However, when the pattern specific models are multivariate normal, identifying restrictions corresponding to missing at random (MAR) may not exist. Furthermore, identification strategies can be problematic in models with covariates (e. g., baseline covariates with time-invariant coefficients). In this article, we explore conditions necessary for identifying restrictions that result in MAR to exist under a multivariate normality assumption and strategies for identifying sensitivity parameters for sensitivity analysis or for a fully Bayesian analysis with informative priors. In addition, we propose alternative modeling and sensitivity analysis strategies under a less restrictive assumption for the distribution of the observed response data. We adopt the deviance information criterion for model comparison and perform a simulation study to evaluate the performances of the different modeling approaches. We also apply the methods to a longitudinal clinical trial. Problems caused by baseline covariates with time-invariant coefficients are investigated and an alternative identifying restriction based on residuals is proposed as a solution. C1 [Wang, Chenguang] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Daniels, Michael J.] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. RP Wang, CG (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM chenguang.wang@fda.hhs.gov; mdaniels@stat.ufl.edu FU NIH [CA-85295, HL-079457] FX This research was supported by NIH grants CA-85295 and HL-079457. NR 22 TC 16 Z9 16 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD SEP PY 2011 VL 67 IS 3 BP 810 EP 818 DI 10.1111/j.1541-0420.2011.01565.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 819XE UT WOS:000294866800014 PM 21361893 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Evaluation of a morphine maturation model for the prediction of morphine clearance in children Response SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Letter ID DRUG CLEARANCE; PHARMACOKINETICS; ALLOMETRY; ACCURATE; ADULTS; SIZE C1 US FDA, OBRR, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20852 USA. EM iftekhar.mahmood@fda.hhs.gov NR 12 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD SEP PY 2011 VL 72 IS 3 BP 521 EP 523 DI 10.1111/j.1365-2125.2011.03984.x PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 804LD UT WOS:000293654400019 ER PT J AU Eichelberger, MC Green, MD AF Eichelberger, Maryna C. Green, Martin D. TI Animal models to assess the toxicity, immunogenicity and effectiveness of candidate influenza vaccines SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE attenuated; inactivated; influenza; live; pandemic; seasonal vaccines ID VIRUS-LIKE PARTICLES; PANDEMIC INFLUENZA; H5N1 INFLUENZA; A VIRUSES; IMMUNE-RESPONSE; GUINEA-PIG; COTTON RAT; ANTIBODY-RESPONSES; ADVERSE EVENTS; H1N1 VACCINE AB Introduction: Every year, > 100 million doses of licensed influenza vaccine are administered worldwide, with relatively few serious adverse events reported. Initiatives to manufacture influenza vaccines on different platforms have come about to ensure timely production of strain-specific as well as universal vaccines. To prevent adverse events that may be associated with these new vaccines, it is important to evaluate the toxicity of new formulations in animal models. Areas covered: This review outlines preclinical studies that evaluate safety, immunogenicity and effectiveness of novel products to support further development and clinical trials. This has been done through a review of the latest literature describing vaccines under development. Expert opinion: The objective of preclinical safety tests is to demonstrate the absence of toxic contaminants and adventitious agents. Additional tests that characterize vaccine content more completely, or demonstrate the absence of exacerbated disease following virus challenge in vaccinated animals, may provide additional data to ensure the safety of new vaccine strategies. C1 [Eichelberger, Maryna C.; Green, Martin D.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Eichelberger, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Maryna.Eichelberger@fda.hhs.gov FU Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA) FX Both authors are supported by the Center for Biologics Evaluation and Research (CBER), U.S. Food and Drug Administration (FDA). The opinions and conclusions in this article are those of the authors and do not necessarily reflect those of the FDA. NR 97 TC 4 Z9 4 U1 0 U2 7 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 SEP PY 2011 VL 7 IS 9 BP 1117 EP 1127 DI 10.1517/17425255.2011.602065 PG 11 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 807LY UT WOS:000293901000005 PM 21749266 ER PT J AU Kweon, O Kim, SJ Holland, RD Chen, HY Kim, DW Gao, Y Yu, LR Baek, S Baek, DH Ahn, H Cerniglia, CE AF Kweon, Ohgew Kim, Seong-Jae Holland, Ricky D. Chen, Hongyan Kim, Dae-Wi Gao, Yuan Yu, Li-Rong Baek, Songjoon Baek, Dong-Heon Ahn, Hongsik Cerniglia, Carl E. TI Polycyclic Aromatic Hydrocarbon Metabolic Network in Mycobacterium vanbaalenii PYR-1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SP STRAIN PYR-1; RING-HYDROXYLATING OXYGENASES; DEGRADING MYCOBACTERIUM; SYSTEMS-BIOLOGY; MOLECULAR CHARACTERIZATION; DEGRADATION PATHWAY; PYRENE DEGRADATION; FUNCTIONAL MODULES; GROWTH SUBSTRATE; ORGANIZATION AB This study investigated a metabolic network (MN) from Mycobacterium vanbaalenii PYR-1 for polycyclic aromatic hydrocarbons (PAHs) from the perspective of structure, behavior, and evolution, in which multilayer omics data are integrated. Initially, we utilized a high-throughput proteomic analysis to assess the protein expression response of M. vanbaalenii PYR-1 to seven different aromatic compounds. A total of 3,431 proteins (57.38% of the genome-predicted proteins) were identified, which included 160 proteins that seemed to be involved in the degradation of aromatic hydrocarbons. Based on the proteomic data and the previous metabolic, biochemical, physiological, and genomic information, we reconstructed an experiment-based system-level PAH-MN. The structure of PAH-MN, with 183 metabolic compounds and 224 chemical reactions, has a typical scale-free nature. The behavior and evolution of the PAH-MN reveals a hierarchical modularity with funnel effects in structure/function and intimate association with evolutionary modules of the functional modules, which are the ring cleavage process (RCP), side chain process (SCP), and central aromatic process (CAP). The 189 commonly upregulated proteins in all aromatic hydrocarbon treatments provide insights into the global adaptation to facilitate the PAH metabolism. Taken together, the findings of our study provide the hierarchical viewpoint from genes/proteins/metabolites to the network via functional modules of the PAH-MN equipped with the engineering-driven approaches of modularization and rationalization, which may expand our understanding of the metabolic potential of M. vanbaalenii PYR-1 for bioremediation applications. C1 [Kweon, Ohgew; Kim, Seong-Jae; Kim, Dae-Wi; Cerniglia, Carl E.] Natl Ctr Toxicol Res FDA, Div Microbiol, Jefferson, AR 72079 USA. [Kweon, Ohgew; Kim, Seong-Jae; Kim, Dae-Wi; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Holland, Ricky D.; Gao, Yuan; Yu, Li-Rong] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, Hongyan; Ahn, Hongsik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Baek, Songjoon] USN Hosp, NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20814 USA. [Baek, Dong-Heon] Dankook Univ, Dept Oral Microbiol & Immunol, Sch Dent, Cheonan 330714, South Korea. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM carl.cerniglia@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported in part by an appointment to the Postgraduate Research Fellowship Program (D.K.) at the National Center for Toxicological 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 views presented in this article do not necessarily reflect those of the U.S. FDA. NR 49 TC 32 Z9 34 U1 4 U2 49 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 SEP PY 2011 VL 193 IS 17 BP 4326 EP 4337 DI 10.1128/JB.00215-11 PG 12 WC Microbiology SC Microbiology GA 806EE UT WOS:000293788300003 PM 21725022 ER PT J AU Xie, C Wang, ZJ Chow, MSS Huang, Y Shi, LM Zuo, Z AF Xie, Chen Wang, Zhijun Chow, Moses S. S. Huang, Ying Shi, Leming Zuo, Zhong TI Could Selected Chemical Markers Represent the Bioactivity of Si-Wu-Tang Product? -Evidences from Gene Expression Analysis SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Xie, Chen; Zuo, Zhong] Chinese Univ Hong Kong, Sch Pharm, Fac Med, Hong Kong, Hong Kong, Peoples R China. [Wang, Zhijun; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Ctr Adv Drug Res & Evaluat, Coll Pharm, Pomona, CA USA. [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Zuo, Zhong/B-6884-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 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 SEP PY 2011 VL 51 IS 9 BP 1341 EP 1341 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 806EM UT WOS:000293789100056 ER PT J AU Kaur, P Chaurasia, C Davit, B Conner, D AF Kaur, Paramjeet Chaurasia, Chanrda Davit, Barbara Conner, Dale TI Scientific and Regulatory Considerations for Bioequivalence Study Design of Solid Oral Anticancer Drug Products SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Kaur, Paramjeet; Chaurasia, Chanrda; Davit, Barbara; Conner, Dale] US FDA, Div Bioequivalence, Off Gener Drugs, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 SEP PY 2011 VL 51 IS 9 BP 1363 EP 1363 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 806EM UT WOS:000293789100119 ER PT J AU Sabarinath, S Madabushi, R AF Sabarinath, Sreedharan Madabushi, Rajanikanth TI Physiologically Based Pharmacokinetic (PBPK) Simulations for Quantitatively Predicting Drug Interactions of Simvastatin and Diltiazem SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract C1 [Sabarinath, Sreedharan; Madabushi, Rajanikanth] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 SEP PY 2011 VL 51 IS 9 BP 1365 EP 1365 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 806EM UT WOS:000293789100125 ER PT J AU Novikov, A Cardone, M Thompson, R Shenderov, K Kirschman, KD Mayer-Barber, KD Myers, TG Rabin, RL Trinchieri, G Sher, A Feng, CG AF Novikov, Aleksey Cardone, Marco Thompson, Robert Shenderov, Kevin Kirschman, Kevin D. Mayer-Barber, Katrin D. Myers, Timothy G. Rabin, Ronald L. Trinchieri, Giorgio Sher, Alan Feng, Carl G. TI Mycobacterium tuberculosis Triggers Host Type I IFN Signaling To Regulate IL-1 beta Production in Human Macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PEGYLATED INTERFERON-ALPHA; INFLAMMASOME ACTIVATION; PULMONARY TUBERCULOSIS; INFECTED MACROPHAGES; GENE-EXPRESSION; DENDRITIC CELLS; IMMUNE-SYSTEM; BOVIS BCG; INDUCTION; GAMMA AB Mycobacterium tuberculosis is a virulent intracellular pathogen that survives in macrophages even in the presence of an intact adaptive immune response. Type I IFNs have been shown to exacerbate tuberculosis in mice and to be associated with disease progression in infected humans. Nevertheless, the mechanisms by which type I IFNs regulate the host response to M. tuberculosis infection are poorly understood. In this study, we show that M. tuberculosis induces an IFN-related gene expression signature in infected primary human macrophages, which is dependent on host type I IFN signaling as well as the mycobacterial virulence factor, region of difference-1. We further demonstrate that type I IFNs selectively limit the production of IL-1 beta, a critical mediator of immunity to M. tuberculosis. This regulation occurs at the level of IL1B mRNA expression, rather than caspase-1 activation or autocrine IL-1 amplification and appears to be preferentially used by virulent mycobacteria since avirulent M. bovis bacillus Calmette-Guerin (BCG) fails to trigger significant expression of type I IFNs or release of mature IL-1 beta protein. The latter property is associated with decreased caspase-1-dependent IL-1 beta maturation in the BCG-infected macrophages. Interestingly, human monocytes in contrast to macrophages produce comparable levels of IL-1 beta in response to either M. tuberculosis or BCG. Taken together, these findings demonstrate that virulent and avirulent mycobacteria employ distinct pathways for regulating IL-1 beta production in human macrophages and reveal that in the case of M. tuberculosis infection the induction of type I IFNs is a major mechanism used for this purpose. The Journal of Immunology, 2011, 187:2540-2547. C1 [Novikov, Aleksey; Thompson, Robert; Shenderov, Kevin; Mayer-Barber, Katrin D.; Trinchieri, Giorgio; Sher, Alan; Feng, Carl G.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Novikov, Aleksey] Howard Hughes Med Inst, Howard Hughes Med Inst Natl Inst Hlth Res Scholar, Chevy Chase, MD 20892 USA. [Novikov, Aleksey] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Cardone, Marco; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shenderov, Kevin; Rabin, Ronald L.] US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIAID, Res & Technol Branch, NIH, Bethesda, MD 20892 USA. RP Feng, CG (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Room 6142,Bldg 50,50 South Dr,MSC 8003, Bethesda, MD 20892 USA. EM cfeng@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services FX This research was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services. NR 49 TC 86 Z9 87 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2011 VL 187 IS 5 BP 2540 EP 2547 DI 10.4049/jimmunol.1100926 PG 8 WC Immunology SC Immunology GA 809MD UT WOS:000294059500057 PM 21784976 ER PT J AU Zaitseva, M Kapnick, SM Meseda, CA Shotwell, E King, LR Manischewitz, J Scott, J Kodihalli, S Merchlinsky, M Nielsen, H Lantto, J Weir, JP Golding, H AF Zaitseva, Marina Kapnick, Senta M. Meseda, Clement A. Shotwell, Elisabeth King, Lisa R. Manischewitz, Jody Scott, John Kodihalli, Shantha Merchlinsky, Michael Nielsen, Henriette Lantto, Johan Weir, Jerry P. Golding, Hana TI Passive Immunotherapies Protect WRvFire and IHD-J-Luc Vaccinia Virus-Infected Mice from Lethality by Reducing Viral Loads in the Upper Respiratory Tract and Internal Organs SO JOURNAL OF VIROLOGY LA English DT Article ID EXTRACELLULAR ENVELOPED VIRUS; OUTER-MEMBRANE PROTEINS; SMALLPOX VACCINE; ANTIBODY-RESPONSES; POXVIRUS CHALLENGE; IMMUNE GLOBULIN; IN-VITRO; FORMS; COMPLEMENT; MONKEYPOX AB Whole-body bioimaging was employed to study the effects of passive immunotherapies on lethality and viral dissemination in BALB/c mice challenged with recombinant vaccinia viruses expressing luciferase. WRvFire and IHD-J-Luc vaccinia viruses induced lethality with similar times to death following intranasal infection, but WRvFire replicated at higher levels than IHD-J-Luc in the upper and lower respiratory tracts. Three types of therapies were tested: licensed human anti-vaccinia virus immunoglobulin intravenous (VIGIV); recombinant anti-vaccinia virus immunoglobulin (rVIG; Symphogen, Denmark), an investigational product containing a mixture of 26 human monoclonal antibodies (HuMAbs) against mature virion (MV) and enveloped virion (EV); and HuMAb compositions targeting subsets of MV or EV proteins. Bioluminescence recorded daily showed that pretreatment with VIGIV (30 mg) or with rVIG (100 mu g) on day -2 protected mice from death but did not prevent viral replication at the site of inoculation and dissemination to internal organs. Compositions containing HuMAbs against MV or EV proteins were protective in both infection models at 100 mu g per animal, but at 30 mu g, only anti-EV antibodies conferred protection. Importantly, the t statistic of the mean total fluxes revealed that viral loads in surviving mice were significantly reduced in at least 3 sites for 3 consecutive days (days 3 to 5) postchallenge, while significant reduction for 1 or 2 days in any individual site did not confer protection. Our data suggest that reduction of viral replication at multiple sites, including respiratory tract, spleen, and liver, as monitored by whole-body bioluminescence can be used to predict the effectiveness of passive immunotherapies in mouse models. C1 [Zaitseva, Marina; Kapnick, Senta M.; Meseda, Clement A.; Shotwell, Elisabeth; King, Lisa R.; Manischewitz, Jody; Scott, John; Merchlinsky, Michael; Weir, Jerry P.; Golding, Hana] US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. [Kodihalli, Shantha] Cangene Corp, Dept Clin Res, Winnipeg, MB R3T 5Y3, Canada. [Nielsen, Henriette; Lantto, Johan] Symphogen AS, DK-2800 Lyngby, Denmark. RP Zaitseva, M (reprint author), US FDA, Div Viral Prod, CBER, Bldg 29B,Room 4NN06,8800 Rockville Pike, Bethesda, MD 20892 USA. EM marina.zaitseva@fda.hhs.gov OI Lantto, Johan/0000-0002-8650-7157; 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] 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. NR 39 TC 11 Z9 11 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 SEP PY 2011 VL 85 IS 17 BP 9147 EP 9158 DI 10.1128/JVI.00121-11 PG 12 WC Virology SC Virology GA 804AO UT WOS:000293626100063 PM 21715493 ER PT J AU Lawal, A Jejelowo, O Chopra, AK Rosenzweig, JA AF Lawal, Abidat Jejelowo, Olufisayo Chopra, Ashok K. Rosenzweig, Jason A. TI Ribonucleases and bacterial virulence SO MICROBIAL BIOTECHNOLOGY LA English DT Review ID MESSENGER-RNA DECAY; HUMAN POLYNUCLEOTIDE PHOSPHORYLASE; STAPHYLOCOCCUS-AUREUS RNAIII; TYPE-3 SECRETION SYSTEM; ESCHERICHIA-COLI; LOW-TEMPERATURE; GENE-EXPRESSION; YERSINIA-ENTEROCOLITICA; EXORIBONUCLEASE-R; PSEUDOMONAS-SYRINGAE AB Bacterial stress responses provide them the opportunity to survive hostile environments, proliferate and potentially cause diseases in humans and animals. The way in which pathogenic bacteria interact with host immune cells triggers a complicated series of events that include rapid genetic re-programming in response to the various host conditions encountered. Viewed in this light, the bacterial host-cell induced stress response (HCISR) is similar to any other well-characterized environmental stress to which bacteria must respond by upregulating a group of specific stress-responsive genes. Post stress, bacteria must resume their pre-stress genetic program, and, as a consequence, must degrade unnecessary stress responsive transcripts through RNA decay mechanisms. Further, there is a well-established role for several ribonucleases in the cold shock response whereby they modulate the changing transcript landscape in response to the stress, and during acclimation and subsequent genetic re-programming post stress. Recently, ribonucleases have been implicated as virulence-associated factors in several notable Gram-negative pathogens including, the yersiniae, the salmonellae, Helicobacter pylori, Shigella flexneri and Aeromonas hydrophila. This review will focus on the roles played by ribonucleases in bacterial virulence, other bacterial stress responses, and on their novel therapeutic applications. C1 [Lawal, Abidat; Jejelowo, Olufisayo; Rosenzweig, Jason A.] Texas So Univ, Dept Biol, CBER, Houston, TX 77004 USA. [Chopra, Ashok K.] Univ Texas Med Branch, Dept Microbiol & Immunol, Sealy Ctr Vaccine Dev, Galveston, TX USA. [Chopra, Ashok K.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX USA. RP Rosenzweig, JA (reprint author), Texas So Univ, Dept Biol, CBER, 3100 Cleburne St, Houston, TX 77004 USA. EM rosenzweigja@tsu.edu FU National Aeronautics and Space Administration (NASA) [NNX08B4A47A]; NIH/NIAID [AI064389, N01 AI30065] FX We would like to thank Greg Plano (University of Miami) for his generosity in sharing the Yersinia pestis wild-type and pnp mutant strains. Also, we would like to thank Ambro van Hoof (University of Texas Health Science Center Houston), Kurt Schesser (Univerity of Miami), Chaitanya Jain (University of Miami) and Murray Deutscher (University of Miami) for stimulating conversation. We would also like to thank Shishir Shishodia, Hector Miranda and Ayodotun Sodipe (Texas Southern University) for their insight. We thank Jian Sha, Elena Kozlova, Sheri Foltz and Michelle Kirtley (University of Texas Medical Branch Galveston) for performing murine infections with Y. pestis and its pnp mutant. Work on this manuscript was supported by the National Aeronautics and Space Administration (NASA) cooperative agreement NNX08B4A47A and NIH/NIAID AI064389 and N01 AI30065 grants awarded to AKC. NR 81 TC 9 Z9 12 U1 1 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1751-7907 J9 MICROB BIOTECHNOL JI Microb. Biotechnol. PD SEP PY 2011 VL 4 IS 5 BP 558 EP 571 DI 10.1111/j.1751-7915.2010.00212.x PG 14 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 808XA UT WOS:000294014100003 PM 21375713 ER PT J AU Hamburg, MA AF Hamburg, Margaret A. TI The Growing Role of Epidemiology in Drug Safety Regulation SO EPIDEMIOLOGY LA English DT Editorial Material ID RHABDOMYOLYSIS; THERAPY C1 [Hamburg, Margaret A.] US FDA, Silver Spring, MD USA. RP Hamburg, MA (reprint author), Care of Jeff Ventura, Room 5253,Bldg 32,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 10 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2011 VL 22 IS 5 BP 622 EP 624 DI 10.1097/EDE.0b013e31822837ba PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 801NT UT WOS:000293447500004 PM 21811108 ER PT J AU Anand, O Yu, LX Conner, DP Davit, BM AF Anand, Om Yu, Lawrence X. Conner, Dale P. Davit, Barbara M. TI Dissolution Testing for Generic Drugs: An FDA Perspective SO AAPS JOURNAL LA English DT Article DE bioequivalence; biopharmaceutics; generic drugs; in vitro dissolution; quality by design AB In vitro dissolution testing is an important tool used for development and approval of generic dosage forms. The objective of this article is to summarize how dissolution testing is used for the approval of safe and effective generic drug products in the United States (US). Dissolution testing is routinely used for stability and quality control purposes for both oral and non-oral dosage forms. The dissolution method should be developed using an appropriate validated method depending on the dosage form. There are several ways in which dissolution testing plays a pivotal role in regulatory decision-making. It may be used to waive in vivo bioequivalence (BE) study requirements, as BE documentation for Scale Up and Post Approval Changes (SUPAC), and to predict the potential for a modified-release (MR) drug product to dose-dump if co-administered with alcoholic beverages. Thus, in vitro dissolution testing plays a major role in FDA's efforts to reduce the regulatory burden and unnecessary human studies in generic drug development without sacrificing the quality of the drug products. C1 [Anand, Om; Yu, Lawrence X.; Conner, Dale P.; Davit, Barbara M.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. RP Anand, O (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, 7520 Standish Pl, Rockville, MD 20855 USA. EM om.anand@fda.hhs.gov NR 22 TC 53 Z9 54 U1 6 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD SEP PY 2011 VL 13 IS 3 BP 328 EP 335 DI 10.1208/s12248-011-9272-y PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 798ES UT WOS:000293186000004 PM 21479700 ER PT J AU Bai, JPF Bell, R Buckman, S Burckart, GJ Eichler, HG Fang, KC Goodsaid, FM Jusko, WJ Lesko, LL Meibohm, B Patterson, SD Puig, O Smerage, JB Snider, BJ Wagner, JA Wang, JS Walton, MK Weiner, R AF Bai, Jane P. F. Bell, Robert Buckman, ShaAvhree Burckart, Gilbert J. Eichler, Hans-Georg Fang, Kenneth C. Goodsaid, Federico M. Jusko, William J. Lesko, Lawrence L. Meibohm, Bernd Patterson, Scott D. Puig, Oscar Smerage, Jeffrey B. Snider, Barbara J. Wagner, John A. Wang, Jingsong Walton, Marc K. Weiner, Russell TI Translational Biomarkers: from Preclinical to Clinical a Report of 2009 AAPS/ACCP Biomarker Workshop (vol 13, pg 274, 2011) SO AAPS JOURNAL LA English DT Correction C1 [Bai, Jane P. F.; Burckart, Gilbert J.; Goodsaid, Federico M.; Lesko, Lawrence L.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bell, Robert] Drug & Biotechnol Dev LLC, Clearwater, FL USA. [Eichler, Hans-Georg] EMEA, London, England. [Fang, Kenneth C.] XDx Express Diagnost, Brisbane, Qld, Australia. [Jusko, William J.] SUNY Buffalo, Buffalo, NY 14260 USA. [Meibohm, Bernd] Univ Tennessee, Memphis, TN USA. [Patterson, Scott D.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Puig, Oscar; Wagner, John A.] Merck & Co Inc, Rahway, NJ 07065 USA. [Smerage, Jeffrey B.] Univ Michigan, Ann Arbor, MI 48109 USA. [Snider, Barbara J.] Washington Univ, St Louis, MO USA. [Wang, Jingsong] Hosp Univ Penn, Philadelphia, PA 19104 USA. [Wang, Jingsong; Weiner, Russell] Bristol Myers Squibb Co, Lawrenceville, NJ USA. RP Bai, JPF (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM jbai@fda.hhs.gov RI Jusko, William/G-4885-2015 NR 1 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 SEP PY 2011 VL 13 IS 3 BP 493 EP 493 DI 10.1208/s12248-011-9275-8 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 798ES UT WOS:000293186000018 ER PT J AU Yang, MH Sun, S Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Kostov, Yordan Rasooly, Avraham TI An automated point-of-care system for immunodetection of staphylococcal enterotoxin B SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Point of care; ELISA; Lab-on-a-chip; Open platform; CCD; Microfabrication; Staphylococcal enterotoxins; Food safety ID ENHANCED CHEMILUMINESCENCE IMMUNOASSAY; ON-A-CHIP; ATOPIC-DERMATITIS; RHEUMATOID-ARTHRITIS; CARBON NANOTUBES; SUPERANTIGENS; ANTIBODIES; FOOD; SEB; IMMUNOSENSOR AB An automated point-of-care (POC) immunodetection system for immunological detection of staphylococcal enterotoxin B (SEB) was designed, fabricated, and tested. The system combines several elements: (i) enzyme-linked immunosorbent assay-lab-on-a-chip (ELISA-LOC) with fluidics, (ii) a charge-coupled device (CCD) camera detector, (iii) pumps and valves for fluid delivery to the ELISA-LOC, (iv) a computer interface board, and (v) a computer for controlling the fluidics, logging, and data analysis of the CCD data. The ELISA-LOC integrates a simple microfluidic system into a miniature 96-well sample plate, allowing the user to carry out immunological assays without a laboratory. The analyte is measured in a sandwich ELISA assay format combined with a sensitive electrochemiluminescence (ECL) detection method. Using the POC system, SEB, a major foodborne toxin, was detected at concentrations as low as 0.1 ng/ml. This is similar to the reported sensitivity of conventional ELISA. The open platform with simple modular fluid delivery automation design described here is interchangeable between detection systems, and because of its versatility it can also be used to automate many other LOC systems, simplifying LOC development. This new POC system is useful for carrying out various immunological and other complex medical assays without a laboratory and can easily be adapted for high-throughput biological screening in remote and resource-poor areas. Published by Elsevier Inc. C1 [Yang, Minghui; Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Sun, Steven; Rasooly, Avraham] Food & Drug Adm, Off Sci & Engn, Div Biol, Silver Spring, MD 20993 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), NCI, 6130 Executive Blvd, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 51 TC 25 Z9 25 U1 1 U2 35 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 1 PY 2011 VL 416 IS 1 BP 74 EP 81 DI 10.1016/j.ab.2011.05.014 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 790XG UT WOS:000292623500010 PM 21640067 ER PT J AU Akiyama, T Khan, AA Cheng, CM Stefanova, R AF Akiyama, Tatsuya Khan, Ashraf A. Cheng, Chorng-Ming Stefanova, Rossina TI Molecular characterization of Salmonella enterica serovar Saintpaul isolated from imported seafood, pepper, environmental and clinical samples SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella enterica serovar Saintpaul; Pulsed-field gel electrophoresis; Plasmid; Seafood ID GENOTYPIC CHARACTERIZATION; UNITED-STATES; PLASMIDS; TYPHIMURIUM; PREVALENCE; ANIMALS; PRODUCE; HUMANS; FOODS; SPP. AB A total of 39 Salmonella enterica serovar Saintpaul strains from imported seafood, pepper and from environmental and clinical samples were analyzed for the presence of virulence genes, antibiotic resistance, plasmid and plasmid replicon types. Pulsed-field gel electrophoresis (PFGE) fingerprinting using the Xbal restriction enzyme and plasmid profiling were performed to assess genetic diversity. None of the isolates showed resistance to ampicillin, chloramphenicol, gentamicin, kanamycin, streptomycin, sulfisoxazole, and tetracycline. Seventeen virulence genes were screened for by PCR. All strains were positive for 14 genes (spiA, sifA, invA, spaN, sopE, sipB, iroN, msgA, pagC, orgA, prgH, lpfC, sitC, and tolC)and negative for three genes (spvB, pefA, and cdtB). Twelve strains, including six from clinical samples and six from seafood, carried one or more plasmids. Large plasmids, sized greater than 50 kb were detected in one clinical and three food isolates. One plasmid was able to be typed as Incl1 by PCR-based replicon typing. There were 25 distinct PFGE-Xbal patterns, clustered to two groups. Cluster A, with 68.5% similarity mainly consists of clinical isolates, while Cluster C. with 67.6% similarity, mainly consisted of shrimp isolates from India. Our findings indicated the genetic diversity of S. Saintpaul in clinical samples, imported seafood, and the environment and that this serotype possesses several virulent genes and plasmids which can cause salmonellosis. Published by Elsevier Ltd. C1 [Akiyama, Tatsuya; Khan, Ashraf A.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Cheng, Chorng-Ming] US FDA, Pacific Reg Lab, Jefferson, AR 72079 USA. [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 FU National Center for Toxicological Research; U.S. Department of Energy; U.S. Food and Drug Administration FX We thank Carl E. Cerniglia, John B. Sutherland, and Bruce D. Erickson for critical review of the manuscript. The authors would like to thank Christine Summage West for technical help, Gwendolyn Anderson and Stephanie Horton for Salmonella isolates. The authors would like to acknowledge Alessandra Carattoli, Steven Foley, and Rebecca L Lindsey for replicon typing control strains. This work was supported in part by to the Postgraduate Research Program at the National Center for Toxicological 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 views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration, NR 25 TC 15 Z9 16 U1 1 U2 9 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 SEP PY 2011 VL 28 IS 6 BP 1124 EP 1128 DI 10.1016/j.fm.2011.03.003 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 791NR UT WOS:000292672400003 PM 21645810 ER PT J AU Hitchins, AD AF Hitchins, A. D. TI The determinacy of reproducibility assessments of qualitative microbial food borne pathogen methods detecting a few microbes per analytical portion SO FOOD MICROBIOLOGY LA English DT Article DE Pathogens; Qualitative detection methods; Reproducibility AB A summary of an examination of studies of interlaboratory reproducibility of measurements for detecting the presence of microorganisms in food products is presented. In such studies multiple laboratories, 10 or more, compare the performances of reference and test methods at the limit of detection of the methods that is at spiking levels around 1 cfu per analytical portion. A laboratory's performance is expressed as the number of positive replicates detected per set of six. The data only imply the presence or absence of significant between-laboratory effects with the test method relative to the reference method. It is difficult to parse the observed variability into the contributions of the sample variability and between-laboratory effects. This is because at spiking levels close to 1 cfu per portion it cannot be assured that laboratories are examining portions with equivalent numbers of the target microbe. In this study published data are reformulated to the number of laboratories observing a given number of positive results per replicate set in order to reflect the inhomogeneity of the spike distribution in the replicate portions. A mean spiking level that is less uncertain than the reported 3-tube reference method MPN value is estimated from the pooled proportions of positives that the laboratories obtained with the reference method. The expected distribution of the spike was calculated from its mean value using the binomial equation. The numerical distributions of the laboratories among the 7 possible positive categories (0-6 positives per replicate set) were statistically indistinguishable from the expected binomial distribution thus corroborating this approach. Probable instances of interlaboratory performance differences were detected by further statistical analysis. This analytical approach, as well as transparently reflecting the sampling variability, also suggested ways of improving and simplifying such studies. Published by Elsevier Ltd. C1 FDA, College Pk, MD 20740 USA. RP Hitchins, AD (reprint author), FDA, College Pk, MD 20740 USA. EM anthony.hitchins@fda.hhs.gov NR 7 TC 3 Z9 3 U1 1 U2 7 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 SEP PY 2011 VL 28 IS 6 BP 1140 EP 1144 DI 10.1016/j.fm.2011.03.005 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 791NR UT WOS:000292672400005 PM 21645812 ER PT J AU Sung, KD Khan, SA Nawaz, MS Cerniglia, CE Tamplin, ML Phillips, RW Kelley, LC AF Sung, Kidon Khan, Saeed A. Nawaz, Mohamed S. Cerniglia, Carl E. Tamplin, Mark L. Phillips, Robert W. Kelley, Lynda Collins TI Lysozyme as a barrier to growth of Bacillus anthracis strain Sterne in liquid egg white, milk and beef SO FOOD MICROBIOLOGY LA English DT Article DE Bacillus anthracis; Lysozyme; Spore; Egg white; Inactivation ID SPORES; GERMINATION; PROTEINS; EDTA AB In this study, we investigated the role of lysozyme on the viability of Bacillus cereus, Bacillus subtilis, Bacillus pumilus and Bacillus anthracis (Sterne) in egg white (EW), ground beef and milk. At 35 degrees C in EW, growth rates (GR) for B. cereus, B. subtilis, B. pumilus and B. anthracis were 0.005, -0.018, -0.028 and -0.029 OD(600)/h, respectively. Heat-treating EW at 55 and 60 degrees C reduced the inactivating effect of EW by 3.1 and 10.5-fold, respectively. Addition of lysozyme (2 mg/ml) to 60 degrees C-treated EW increased the inactivation rate 5.76-fold, indicating involvement of lysozyme in B. anthracis inactivation. B. anthracis inactivation was influenced by pH, as shown by a progressive increase in inactivation rate from 0.25 to -4.42 logs CFU/h over a pH range of 6.0-8.5. Adding 2 mg/ml lysozyme to milk and ground beef also suppressed the growth of B. anthracis 3.3 and 6.5-fold, respectively. These data indicate that lysozyme, as a natural component of EW or potential additive in other foods, could reduce biothreat risks presented by bioterror agents. Published by Elsevier Ltd. C1 [Sung, Kidon; Khan, Saeed A.; Nawaz, Mohamed S.; Cerniglia, Carl E.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Tamplin, Mark L.] Univ Tasmania, Food Safety Ctr, Tasmanian Inst Agr Res, Hobart, Tas 7001, Australia. [Phillips, Robert W.; Kelley, Lynda Collins] USDA, Russell Res Ctr, Athens, GA 30605 USA. RP Khan, SA (reprint author), Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM saeed.khan@fda.hhs.gov FU US Department of Homeland Security NBACC; US Department of Agriculture; US Food and Drug Administration FX The authors wish to thank Drs. Rajesh Nayak and Ashraf Khan of the Division of Microbiology. NCTR, for their initial help, and valuable and insightful discussions during the course of this research. The authors also thank Drs. John Sutherland and Huiz-hong Chen of the Division of Microbiology, NCTR, for critical review of the manuscript. The work was supported in part by the US Department of Homeland Security NBACC and the US Department of Agriculture through interagency agreements between the above entities and US Food and Drug Administration. Views presented in this paper do not necessarily reflect those of the FDA or the US Department of Agriculture. NR 21 TC 7 Z9 8 U1 0 U2 13 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 SEP PY 2011 VL 28 IS 6 BP 1231 EP 1234 DI 10.1016/j.fm.2011.03.002 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 791NR UT WOS:000292672400017 PM 21645824 ER PT J AU Luber, P Crerar, S Dufour, C Farber, J Datta, A Todd, ECD AF Luber, Petra Crerar, Scott Dufour, Christophe Farber, Jeff Datta, Atin Todd, Ewen C. D. TI Controlling Listeria monocytogenes in ready-to-eat foods: Working towards global scientific consensus and harmonization - Recommendations for improved prevention and control SO FOOD CONTROL LA English DT Article DE Listeria monocytogenes; Control; RTE foods; Growth potential; Microbiological criteria; Risk communication; Policy; Harmonized regulations; Scientific consensus; Message mapping ID VIRULENCE; STRAINS; SAFETY; RISK AB An international group of experts from the food industry, academia, and governments met in Amsterdam in May 2009 to discuss approaches for controlling Listeria monocytogenes in ready-to-eat (RTE) foods in anticipation of an agreement by Member States on the Codex Guidelines for the pathogen in foods. The workshop was organised by Ewen Todd (Michigan State University) in cooperation with the European Federation of Food Science and Technology and the Global Harmonization Initiative. The group felt there is a need for a risk-based policy with input from all the stakeholders at local and national levels. An important part of the background is to review the critical factors for control, including the unique growth, survival and virulence characteristics of the pathogen; identifying specific populations at risk; and defining what RTE foods are. They also saw the need for L monocytogenes food-source attribution through review of outbreak data, implementation of case-control studies, expert elicitations, microbial source tracking, and development of risk assessment models. They also indicated that surveillance of both listeriosis and the gastrointestinal non-invasive form of illness caused by the pathogen are important for public health agencies to establish or enhance; this would require coordination of laboratories through better communication and reporting for the analysis of clinical cases, foods and environmental sources. These laboratories should be also accredited, with some being reference laboratories at national or regional levels. There was consensus agreement on the microbiological criteria as specified in the Codex Guidelines, but it was recognized there were challenges for industry to meet these and government agencies to assess compliance, requiring a robust testing regime for both food and food-contact surfaces at all stages in the production system, as well as for environmental monitoring. Other issues are the development, validation, and acceptance of quantitative methods sufficient to detect the pathogen in food at levels < 100 CFU g(-1); determining the food's ability to support the growth of the pathogen or not through challenge studies, and risk assessment models, appropriate labelling of RTE foods, and a standardized approach to tracing and tracking of products throughout the food chain. There is also a need for food worker education and training, and consumer awareness and responsibility. Message mapping is one approach to instill the essential food safety messages regarding listeriosis and the safety of RTE foods for both employees and the public. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Todd, Ewen C. D.] Ewen Todd Consulting, Okemos, MI 48864 USA. [Luber, Petra] Fed Off Consumer Protect & Food Safety BVL, D-10117 Berlin, Germany. [Crerar, Scott] Food Stand Australia New Zealand, Risk Assessment Prod Proc, Barton, ACT 2600, Australia. [Dufour, Christophe] Silliker SAS, F-95031 Cergy Pontoise, France. [Farber, Jeff] Hlth Canada, Food Directorate, Bur Microbial Hazards, Ottawa, ON K1A 0K9, Canada. [Datta, Atin] CFSAN FDA, Virulence Mech Branch, Laurel, MD 20708 USA. [Todd, Ewen C. D.] Michigan State Univ, Dept Advertising Publ Relat & Retailing, E Lansing, MI 48823 USA. RP Todd, ECD (reprint author), Ewen Todd Consulting, Okemos, MI 48864 USA. EM todde@msu.edu OI Todd, Ewen/0000-0001-7266-279X FU United States Department of Agriculture National Institutes of Food and Agriculture National Integrated Food Safety Initiative [USDA 2008-51110-04330] FX This paper with its recommendations is part of a Workshop funded by the United States Department of Agriculture National Institutes of Food and Agriculture National Integrated Food Safety Initiative grant no. USDA 2008-51110-04330. NR 53 TC 20 Z9 20 U1 3 U2 40 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 EI 1873-7129 J9 FOOD CONTROL JI Food Control PD SEP PY 2011 VL 22 IS 9 SI SI BP 1535 EP 1549 DI 10.1016/j.foodcont.2011.01.008 PG 15 WC Food Science & Technology SC Food Science & Technology GA 779EW UT WOS:000291761900013 ER PT J AU Anchoori, RK Khan, SR Sueblinvong, T Felthauser, A Iizuka, Y Gavioli, R Destro, F Vogel, RI Peng, SW Roden, RBS Bazzaro, M AF Anchoori, Ravi K. Khan, Saeed R. Sueblinvong, Thanasak Felthauser, Alicia Iizuka, Yoshie Gavioli, Riccardo Destro, Federica Vogel, Rachel Isaksson Peng, Shiwen Roden, Richard B. S. Bazzaro, Martina TI Stressing the Ubiquitin-Proteasome System without 20S Proteolytic Inhibition Selectively Kills Cervical Cancer Cells SO PLOS ONE LA English DT Article ID GREEN TEA POLYPHENOLS; HUMAN-PAPILLOMAVIRUS; OVARIAN-CANCER; ISOPEPTIDASE ACTIVITY; INVASIVE PHENOTYPE; ENZYME-INHIBITORS; PANCREATIC-CANCER; INDUCED APOPTOSIS; IN-VITRO; BORTEZOMIB AB Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their alpha-beta unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation upstream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine. C1 [Anchoori, Ravi K.; Roden, Richard B. S.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. [Anchoori, Ravi K.; Khan, Saeed R.; Peng, Shiwen; Roden, Richard B. S.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. [Gavioli, Riccardo; Destro, Federica] Univ Ferrara, Dept Biochem & Mol Biol, I-44100 Ferrara, Italy. [Khan, Saeed R.] US FDA, CDER, Div Prod Qual Res, Silver Spring, MD USA. [Sueblinvong, Thanasak; Felthauser, Alicia; Iizuka, Yoshie; Vogel, Rachel Isaksson; Bazzaro, Martina] Univ Minnesota Twin Cities, Masonic Canc Ctr, Minneapolis, MN USA. [Sueblinvong, Thanasak; Felthauser, Alicia; Iizuka, Yoshie; Vogel, Rachel Isaksson; Bazzaro, Martina] Univ Minnesota Twin Cities, Dept Obstet Gynecol & Womens Heath, Minneapolis, MN USA. [Roden, Richard B. S.] Johns Hopkins Univ, Dept Gynecol & Obstet, Baltimore, MD USA. RP Anchoori, RK (reprint author), Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. EM mbazzaro@umn.edu RI Destro, Federica/K-5904-2016; Gavioli, Riccardo/K-7594-2016; OI Destro, Federica/0000-0002-3014-0165; Gavioli, Riccardo/0000-0002-7805-4290; Vogel, Rachel/0000-0003-0149-8464 FU National Institutes of Health ATIP; SPORE in Cervical Cancer [P50 CA098252]; HERA foundation (Health, Empowerment, Research, and Awareness); Department of Defense [OC093424] FX This work was supported by the National Institutes of Health ATIP and SPORE in Cervical Cancer P50 CA098252 to SRK, RKA and RBSR and HERA foundation (Health, Empowerment, Research, and Awareness) and Department of Defense Ovarian Cancer Research Program (OCRP) OC093424 to MB. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. NR 41 TC 20 Z9 20 U1 0 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 AUG 31 PY 2011 VL 6 IS 8 AR e23888 DI 10.1371/journal.pone.0023888 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 817NM UT WOS:000294680800036 PM 21909374 ER PT J AU Moore, KL Neugebauer, R Valappil, T van der Laan, MJ AF Moore, Kelly L. Neugebauer, Romain Valappil, Thamban van der Laan, Mark J. TI Robust extraction of covariate information to improve estimation efficiency in randomized trials SO STATISTICS IN MEDICINE LA English DT Article DE clinical trials; efficiency; covariate adjustment; variable selection ID CLINICAL-TRIALS; CAUSAL INFERENCE; LOGISTIC-REGRESSION; SUBGROUP ANALYSIS; ADJUSTMENT; MORTALITY; IMBALANCE; MODELS; TESTS AB In randomized trials, investigators typically rely upon an unadjusted estimate of the mean outcome within each treatment arm to draw causal inferences. Statisticians have underscored the gain in efficiency that can be achieved from covariate adjustment in randomized trials with a focus on problems involving linear models. Despite recent theoretical advances, there has been a reluctance to adjust for covariates based on two primary reasons: (i) covariate-adjusted estimates based on conditional logistic regression models have been shown to be less precise and (ii) concern over the opportunity to manipulate the model selection process for covariate adjustments to obtain favorable results. In this paper, we address these two issues and summarize recent theoretical results on which is based a proposed general methodology for covariate adjustment under the framework of targeted maximum likelihood estimation in trials with two arms where the probability of treatment is 50%. The proposed methodology provides an estimate of the true causal parameter of interest representing the population-level treatment effect. It is compared with the estimates based on conditional logistic modeling, which only provide estimates of subgroup-level treatment effects rather than marginal (unconditional) treatment effects. We provide a clear criterion for determining whether a gain in efficiency can be achieved with covariate adjustment over the unadjusted method. We illustrate our strategy using a resampled clinical trial dataset from a placebo controlled phase 4 study. Results demonstrate that gains in efficiency can be achieved even with binary outcomes through covariate adjustment leading to increased statistical power. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Moore, Kelly L.; van der Laan, Mark J.] Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, Berkeley, CA 94720 USA. [Neugebauer, Romain] Kaiser Permanente, Div Res, Oakland, CA USA. [Valappil, Thamban] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Moore, KL (reprint author), Univ Calif Berkeley, Sch Publ Hlth, Div Biostat, 101 Haviland Hall, Berkeley, CA 94720 USA. EM klmoore@stat.berkeley.edu FU NIAID NIH HHS [R01 AI074345] NR 29 TC 6 Z9 6 U1 2 U2 5 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 AUG 30 PY 2011 VL 30 IS 19 BP 2389 EP 2408 DI 10.1002/sim.4301 PG 20 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 805ON UT WOS:000293738600005 PM 21751231 ER PT J AU Antunes, AMM Godinho, ALA Pereira, SA Surratt, G da Costa, GG Beland, FA Marques, MM AF Antunes, Alexandra M. M. Godinho, Ana L. A. Pereira, Sofia A. Surratt, Gordon da Costa, Goncalo Gamboa Beland, Frederick A. Matilde Marques, M. TI Nevirapine metabolism to 4-formyl-nevirapine: Possible role in nevirapine toxicity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Antunes, Alexandra M. M.; Godinho, Ana L. A.; Matilde Marques, M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1096 Lisbon, Portugal. [Pereira, Sofia A.] Univ Nova Lisboa, Fac Ciencias Med, Dept Farmacol, P-1200 Lisbon, Portugal. [Surratt, Gordon; da Costa, Goncalo Gamboa; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; Faculdade de Ciencias Medicas, Nova Medical School/K-6209-2013 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; NR 0 TC 0 Z9 0 U1 0 U2 7 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 AUG 28 PY 2011 VL 242 MA 67-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378307534 ER PT J AU Bailey, AB Komolprasert, V AF Bailey, Allan B. Komolprasert, Vanee TI Recycled plastics for food contact applications in the US SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Bailey, Allan B.; Komolprasert, Vanee] US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. EM allan.bailey@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 AUG 28 PY 2011 VL 242 MA 3-PMSE PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378306602 ER PT J AU Delclos, BK AF Delclos, Barry K. TI Reproductive and chronic toxicity testing of endocrine-active compounds in rodents SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Delclos, Barry K.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM barry.delclos@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 AUG 28 PY 2011 VL 242 MA 85-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378307553 ER PT J AU Feng, SX Chattopadhaya, C Kijak, P AF Feng, Shixia Chattopadhaya, Chaitali Kijak, Phil TI Development of an LC-MS/MS method for quantitation and confirmation of ceftiofur metabolite desfuroylceftiofur cystine disulfide in bovine kidney SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Feng, Shixia; Chattopadhaya, Chaitali; Kijak, Phil] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM shixia.feng@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 81-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300187 ER PT J AU Fisher, JW AF Fisher, Jeffrey W. TI PBPK modeling of endocrine active chemicals: Linking animal toxicity studies with human exposures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Fisher, Jeffrey W.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jeffrey.fisher@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 AUG 28 PY 2011 VL 242 MA 88-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378307556 ER PT J AU Jackson, LS Jablonski, J Voss, K Ryu, D AF Jackson, Lauren S. Jablonski, Joseph Voss, Kenneth Ryu, Dojin TI Analytical methods for evaluating the effect of thermal processing on fumonisins in corn-based food SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Jackson, Lauren S.; Jablonski, Joseph] US FDA, Inst Food Safety & Hlth, Bedford Pk, IL 60501 USA. [Voss, Kenneth] ARS, Toxicol & Mycotoxin Res Unit, USDA, Athens, GA 30605 USA. [Ryu, Dojin] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. EM Lauren.Jackson@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 U2 7 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 AUG 28 PY 2011 VL 242 MA 18-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300121 ER PT J AU Mendrick, DL AF Mendrick, Donna L. TI Approaches in systems biology to identify and qualify biomarkers of safety and disease SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Mendrick, Donna L.] NCTR FDA, Div Syst Biol, Jefferson, AR 72079 USA. EM donna.mendrick@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 160-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300518 ER PT J AU Nalubola, R AF Nalubola, Ritu TI Regulatory challenges presented by nanotechnology applications: FDA\'s perspective SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Nalubola, Ritu] US FDA, Silver Spring, MD 20993 USA. EM Ritu.Nalubola@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 AUG 28 PY 2011 VL 242 MA 285-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378301700 ER PT J AU Tournas, V Sapp, C Trucksess, MW AF Tournas, Valerie Sapp, Chelsea Trucksess, Mary W. TI Evaluation of a liquid chromatography method for the detection and quantification of aflatoxins in milk thistle supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Tournas, Valerie; Trucksess, Mary W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Sapp, Chelsea] Univ Maryland, JIFSAN, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 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 AUG 28 PY 2011 VL 242 MA 74-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300179 ER PT J AU Tsai, DH DelRio, F Keene, A Tyner, K MacCuspie, R Cho, TJ Zachariah, M Hackley, V AF Tsai, De-Hao DelRio, Frank Keene, Athena Tyner, Katherine MacCuspie, Robert Cho, Tae Joon Zachariah, Michael Hackley, Vincent TI Adsorption and conformation of serum albumin protein on gold nanoparticles investigated using dimensional measurements and in situ spectroscopic methods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Tsai, De-Hao; DelRio, Frank; MacCuspie, Robert; Cho, Tae Joon; Zachariah, Michael; Hackley, Vincent] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena; Tyner, Katherine] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zachariah, Michael] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Zachariah, Michael] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. EM dhtsai@nist.gov RI Tsai, De-Hao/K-6702-2012 OI Tsai, De-Hao/0000-0002-2669-3007 NR 0 TC 0 Z9 0 U1 0 U2 8 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 AUG 28 PY 2011 VL 242 MA 287-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378301702 ER PT J AU Tsai, DH Elzey, S DelRio, F Keene, A Tyner, K Clogston, J Zheng, JW MacCuspie, R Cho, TJ Guha, S Zachariah, M Hackley, V AF Tsai, De-Hao Elzey, Sherrie DelRio, Frank Keene, Athena Tyner, Katherine Clogston, Jeffrey Zheng, Jiwen MacCuspie, Robert Cho, Tae Joon Guha, Suvajyoti Zachariah, Michael Hackley, Vincent TI Characterization of tumor necrosis factor (TNF) protein conjugation on gold nanoparticles SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Tsai, De-Hao; Elzey, Sherrie; DelRio, Frank; MacCuspie, Robert; Cho, Tae Joon; Guha, Suvajyoti; Zachariah, Michael; Hackley, Vincent] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena; Tyner, Katherine] Ctr Drug Evaluat & Res Food & Drug Adm, Silver Spring, MD 20993 USA. [Clogston, Jeffrey; Zheng, Jiwen] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, NCI Frederick, Frederick, MD 21702 USA. [Guha, Suvajyoti; Zachariah, Michael] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Guha, Suvajyoti; Zachariah, Michael] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. EM sherrie.elzey@nist.gov RI Tsai, De-Hao/K-6702-2012 OI Tsai, De-Hao/0000-0002-2669-3007 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 AUG 28 PY 2011 VL 242 MA 249-COLL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378301664 ER PT J AU Tulio, AZ White, KD Jackson, LS AF Tulio, Artemio Z., Jr. White, Kevin D. Jackson, Lauren S. TI Screening of anthocyanins in red and white cranberry extracts and juice concentrates by HR-MS (Exactive Orbitrap) and LC-MS SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Tulio, Artemio Z., Jr.; Jackson, Lauren S.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Safety, Div Food Proc Sci & Technol,Food Chem & Nutr Team, Bedford Pk, IL 60501 USA. [White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem,Spect & Mass Spect Branch, College Pk, MD 20740 USA. EM artemio.tulio@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 86-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300192 ER PT J AU Turnipseed, S Clark, S Storey, J AF Turnipseed, Sherri Clark, Susan Storey, Joseph TI Quadrupole time-of-flight LC-MS analysis of veterinary drug residues in aquaculture samples SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Turnipseed, Sherri] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Clark, Susan; Storey, Joseph] US FDA, Denver Sci Branch, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 197-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378302473 ER PT J AU Twaroski, ML AF Twaroski, Michelle L. TI US safety assessment of food contact substances SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Twaroski, Michelle L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20770 USA. EM michelle.twaroski@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 AUG 28 PY 2011 VL 242 MA 89-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378307557 ER PT J AU Wang, C Wang, Y Juskelis, R Song, Y Koontz, J AF Wang, Chen Wang, Yang Juskelis, Rima Song, Yoonseok Koontz, John TI Flavor, solvent, and photoinitiator migration parameters in polyethylene terephthalate and nylon 6 by the static permeation cell method SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Wang, Chen; Wang, Yang; Juskelis, Rima] IIT, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Song, Yoonseok; Koontz, John] US FDA, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. EM John.Koontz@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 AUG 28 PY 2011 VL 242 MA 80-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300186 ER PT J AU Wang, Y Wang, C Juskelis, R Song, Y Koontz, J AF Wang, Yang Wang, Chen Juskelis, Rima Song, Yoonseok Koontz, John TI Volatile organic compound migration parameters in nylon MXD6 by the dynamic permeation cell method SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Wang, Yang; Wang, Chen; Juskelis, Rima] IIT, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. [Song, Yoonseok; Koontz, John] US FDA, Natl Ctr Food Safety & Technol, Bedford Pk, IL 60501 USA. EM John.Koontz@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 AUG 28 PY 2011 VL 242 MA 79-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300184 ER PT J AU Weisz, A Mai, HT Scher, A AF Weisz, Adrian Mai, Hao T. Scher, Alan TI Determination of synthetic by-products in the color additive D&C Yellow No. 10 (quinoline yellow) using high-performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Weisz, Adrian; Mai, Hao T.; Scher, Alan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Adrian.Weisz@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 AUG 28 PY 2011 VL 242 MA 72-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300177 ER PT J AU Weisz, A Mazzola, EP Ito, Y AF Weisz, Adrian Mazzola, Eugene P. Ito, Yoichiro TI Preparative separation of 1,3,6-pyrenetrisulfonic acid from the color additive D&C Green No. 8 using pH-zone-refining counter-current chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Weisz, Adrian; Mazzola, Eugene P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ito, Yoichiro] NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA. EM adrian.weisz@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 73-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300178 ER PT J AU Wyzgoski, FJ Reese, RN Paudel, L Rinaldi, PL Giusti, MM Johnson, J Scheerens, JC Bomser, J Chanon, AM Hardy, JK Wesdemiotis, C Miller, AR Tulio, AZ AF Wyzgoski, Faith J. Reese, R. Neil Paudel, Liladhar Rinaldi, Peter L. Giusti, M. Monica Johnson, Jodee Scheerens, Joseph C. Bomser, Joshua Chanon, Ann M. Hardy, James K. Wesdemiotis, Chrys Miller, A. Raymond Tulio, Artemio Z., Jr. TI Metabolomic models of fruit extracts and chemoprevention SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Wyzgoski, Faith J.] Ohio State Univ, Dept Chem, Mansfield, OH 44906 USA. [Reese, R. Neil] S Dakota State Univ, Dept Biol & Microbiol, Brookings, SD 57007 USA. [Paudel, Liladhar; Rinaldi, Peter L.; Hardy, James K.; Wesdemiotis, Chrys] Univ Akron, Dept Chem, Akron, OH 44325 USA. [Giusti, M. Monica; Johnson, Jodee] Ohio State Univ, Dept Food Sci & Technol, Columbus, OH 43210 USA. [Bomser, Joshua] Ohio State Univ, Dept Human Nutr, Columbus, OH 43210 USA. [Scheerens, Joseph C.; Chanon, Ann M.; Miller, A. Raymond] Ohio State Univ, Dept Hort & Crop Sci, Ohio Agr Res & Dev Ctr, Wooster, OH 44691 USA. [Tulio, Artemio Z., Jr.] US FDA, Summit Argo, IL 60501 USA. EM wyzgoski.1@osu.edu RI Giusti, Maria/B-3367-2012; Miller, Ray Miller/E-2999-2017 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 AUG 28 PY 2011 VL 242 MA 47-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300152 ER PT J AU Yang, HHW Scher, A AF Yang, Huei Hsuan Wendy Scher, Alan TI Determination of components of the color additive FD&C Green No. 3 (Food Green 3) using high performance liquid chromatography SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Yang, Huei Hsuan Wendy; Scher, Alan] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM hueihsuan.yang@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 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 AUG 28 PY 2011 VL 242 MA 84-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378300190 ER PT J AU Zahner, HM Eirkson, CE Silberhorn, E AF Zahner, Holly M. Eirkson, Charles E. Silberhorn, Eric TI Risk assessment of steroid hormones in veterinary drugs at the US Food and Drug Administration Center for Veterinary Medicine SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Zahner, Holly M.; Eirkson, Charles E.; Silberhorn, Eric] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM holly.zahner@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 AUG 28 PY 2011 VL 242 MA 236-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378302517 ER PT J AU Zahner, HM Hunter, W Silberhorn, E Eirkson, C AF Zahner, Holly M. Hunter, Wesley Silberhorn, Eric Eirkson, Charles TI Overview of the US Food and Drug Administration Center for Veterinary Medicine environmental risk assessment process for veterinary pharmaceuticals SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 242nd National Meeting of the American-Chemical-Society (ACS) CY AUG 28-SEP 01, 2011 CL Denver, CO SP Amer Chem Soc (ACS) C1 [Zahner, Holly M.; Hunter, Wesley; Silberhorn, Eric; Eirkson, Charles] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM holly.zahner@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 28 PY 2011 VL 242 MA 167-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 880BE UT WOS:000299378302441 ER PT J AU Ali, S Sharma, HS AF Ali, S. Sharma, H. S. TI Substituted amphetamine-induces neurotoxicity and alterations in blood-brain-barrier function SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 47th Congress of the European-Societies-of-Toxicology CY AUG 28-31, 2011 CL Paris, FRANCE SP European Soc Toxicol C1 [Ali, S.] US FDA, Neurochem Lab, Div Neurotox, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Sharma, Hari/G-4508-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 28 PY 2011 VL 205 SU 1 BP S26 EP S26 DI 10.1016/j.toxlet.2011.05.106 PG 1 WC Toxicology SC Toxicology GA 806NI UT WOS:000293814500087 ER PT J AU Chen, T Fuscoe, JC Li, Z AF Chen, T. Fuscoe, J. C. Li, Z. TI MicroRNAs and their predicted target messenger RNAs are deregulated by exposure to a carcinogenic dose of comfrey in rat live SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 47th Congress of the European-Societies-of-Toxicology CY AUG 28-31, 2011 CL Paris, FRANCE SP European Soc Toxicol C1 [Chen, T.; Li, Z.] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Fuscoe, J. C.] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 28 PY 2011 VL 205 SU 1 BP S62 EP S62 DI 10.1016/j.toxlet.2011.05.243 PG 1 WC Toxicology SC Toxicology GA 806NI UT WOS:000293814500198 ER PT J AU Dorne, JL Doerge, D Boobis, A AF Dorne, J. L. Doerge, D. Boobis, A. TI Mechanistic basis for the harmonisation of ecological and human risk assessment SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 47th Congress of the European-Societies-of-Toxicology CY AUG 28-31, 2011 CL Paris, FRANCE SP European Soc Toxicol C1 [Dorne, J. L.] EFSA, Parma, Italy. [Doerge, D.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Boobis, A.] Univ London Imperial Coll Sci Technol & Med, London, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 28 PY 2011 VL 205 SU 1 BP S9 EP S9 DI 10.1016/j.toxlet.2011.05.1020 PG 1 WC Toxicology SC Toxicology GA 806NI UT WOS:000293814500027 ER PT J AU Slikker, W Zhang, X Newport, GD Paule, MG Liu, F Berridge, MS Kabalka, G Wang, C AF Slikker, W. Zhang, X. Newport, G. D. Paule, M. G. Liu, F. Berridge, M. S. Kabalka, G. Wang, C. TI Minimally invasive quantitative assessment of inhalation anesthetic-induced brain cell death using microPET imaging SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 47th Congress of the European-Societies-of-Toxicology CY AUG 28-31, 2011 CL Paris, FRANCE SP European Soc Toxicol C1 [Slikker, W.] US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. [Berridge, M. S.] 3D Imaging, Little Rock, AR USA. [Kabalka, G.] Univ Tennessee, Knoxville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 28 PY 2011 VL 205 SU 1 BP S237 EP S238 DI 10.1016/j.toxlet.2011.05.812 PG 2 WC Toxicology SC Toxicology GA 806NI UT WOS:000293814500760 ER PT J AU Tong, W AF Tong, W. TI Development of a benchmark drug list for study of drug-induced liver injury SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 47th Congress of the European-Societies-of-Toxicology CY AUG 28-31, 2011 CL Paris, FRANCE SP European Soc Toxicol C1 [Tong, W.] NCTR, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD AUG 28 PY 2011 VL 205 SU 1 BP S56 EP S57 DI 10.1016/j.toxlet.2011.05.217 PG 2 WC Toxicology SC Toxicology GA 806NI UT WOS:000293814500182 ER PT J AU Chan, D Tarbin, J Sharman, M Carson, M Smith, M Smith, S AF Chan, D. Tarbin, J. Sharman, M. Carson, M. Smith, M. Smith, S. TI Screening method for the analysis of antiviral drugs in poultry tissues using zwitterionic hydrophilic interaction liquid chromatography/tandem mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 6th International Symposium on Hormone and Veterinary Drug Residue Analysis (VRDA) CY JUN 01-04, 2010 CL Ghent Univ, Ghent, BELGIUM HO Ghent Univ DE Antiviral; Amantadine; Acyclovir; Ganciclovir; Imiquimod; Oseltamivir; Oseltamivir carboxylate; Rimantadine; Poultry; Zanamivir ID PLASMA; OSELTAMIVIR; AMANTADINE; RAT AB A screening method for the analysis of seven anti-viral drugs in poultry tissue has been developed. These include anti-influenza drugs (amantadine, rimantadine, zanamivir and oseltamivir and its carboxylate metabolite), anti-herpes drugs (acyclovir and ganciclovir) and an immunomodulator (imiquimod). Poultry tissue was extracted in acetonitrile:water:acetic acid. After sample purification, using a strong cation exchange column, the eluate was split into two fractions. The first portion was dissolved in methanol:water and the second in acetonitrile:methanol:water. Both fractions were analysed on a zwitterionic hydrophilic interaction liquid chromatography column coupled to a triple quadrupole mass spectrometer. The screening method was successfully validated according to Commission Decision 2002/657/EC in three different laboratories with CC beta concentrations of <= 10 mu g kg(-1). Crown Copyright (C) 2010 Published by Elsevier B.V. All rights reserved. C1 [Chan, D.; Tarbin, J.; Sharman, M.] Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. [Carson, M.; Smith, M.; Smith, S.] US FDA, Div Residue Chem, Off Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Chan, D (reprint author), Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. EM danny.chan@fera.gsi.gov.uk OI Chan, Danny/0000-0003-1456-7844 NR 8 TC 22 Z9 27 U1 0 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD AUG 26 PY 2011 VL 700 IS 1-2 SI SI BP 194 EP 200 DI 10.1016/j.aca.2010.11.015 PG 7 WC Chemistry, Analytical SC Chemistry GA 801HJ UT WOS:000293428900025 PM 21742133 ER PT J AU Yu, HW Fischer, G Jia, GF Reiser, J Park, F Hogan, QH AF Yu, Hongwei Fischer, Greg Jia, Guangfu Reiser, Jakob Park, Frank Hogan, Quinn H. TI Lentiviral gene transfer into the dorsal root ganglion of adult rats SO MOLECULAR PAIN LA English DT Article ID VECTOR INTEGRATION SITES; IN-VIVO TRANSDUCTION; NEUROPATHIC PAIN; NERVOUS-SYSTEM; ADENOASSOCIATED VIRUS; VIRAL VECTORS; TRANSGENE EXPRESSION; NOCICEPTIVE NEURONS; THERAPEUTIC LEVELS; PERIPHERAL-NERVE AB Background: Lentivector-mediated gene delivery into the dorsal root ganglion (DRG) is a promising method for exploring pain pathophysiology and for genetic treatment of chronic neuropathic pain. In this study, a series of modified lentivector particles with different cellular promoters, envelope glycoproteins, and viral accessory proteins were generated to evaluate the requirements for efficient transduction into neuronal cells in vitro and adult rat DRG in vivo. Results: In vitro, lentivectors expressing enhanced green fluorescent protein (EGFP) under control of the human elongation factor 1 alpha (EF1 alpha) promoter and pseudotyped with the conventional vesicular stomatitis virus G protein (VSV-G) envelope exhibited the best performance in the transfer of EGFP into an immortalized DRG sensory neuron cell line at low multiplicities of infection (MOIs), and into primary cultured DRG neurons at higher MOIs. In vivo, injection of either first or second-generation EF1 alpha-EGFP lentivectors directly into adult rat DRGs led to transduction rates of 19 +/- 9% and 20 +/- 8% EGFP-positive DRG neurons, respectively, detected at 4 weeks post injection. Transduced cells included a full range of neuronal phenotypes, including myelinated neurons as well as both non-peptidergic and peptidergic nociceptive unmyelinated neurons. Conclusion: VSV-G pseudotyped lentivectors containing the human elongation factor 1 alpha (EF1 alpha)-EGFP expression cassette demonstrated relatively efficient transduction to sensory neurons following direct injection into the DRG. These results clearly show the potential of lentivectors as a viable system for delivering target genes into DRGs to explore basic mechanisms of neuropathic pain, with the potential for future clinical use in treating chronic pain. C1 [Jia, Guangfu; Park, Frank] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA. [Yu, Hongwei; Fischer, Greg; Hogan, Quinn H.] Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. [Reiser, Jakob] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. [Park, Frank] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Hogan, Quinn H.] Milwaukee VA Med Ctr, Milwaukee, WI 53226 USA. RP Park, F (reprint author), Med Coll Wisconsin, Dept Med, 8100 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM fpark@mcw.eu; qhogan@mcw.edu FU VA Rehabilitation Research and Development grant [3690-03] FX The authors would like to thank Luigi Naldini (University of Torino, Italy) for the lentivector packaging plasmids, Dr. D. von Laer (Goethe-University, Frankfurt, Germany) for providing the pLCMV-GP plasmid, and Dr. Ahmet Hoke (Department of Neurology, Johns Hopkins University) for providing the 50B11 cells. This study was funded in part by the VA Rehabilitation Research and Development grant 3690-03. NR 75 TC 19 Z9 19 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1744-8069 J9 MOL PAIN JI Mol. Pain PD AUG 23 PY 2011 VL 7 AR 63 DI 10.1186/1744-8069-7-63 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 829OR UT WOS:000295593900002 PM 21861915 ER PT J AU Whittle, JRR Zhang, RJ Khurana, S King, LR Manischewitz, J Golding, H Dormitzer, PR Haynes, BF Walter, EB Moody, MA Kepler, TB Liao, HX Harrison, SC AF Whittle, James R. R. Zhang, Ruijun Khurana, Surender King, Lisa R. Manischewitz, Jody Golding, Hana Dormitzer, Philip R. Haynes, Barton F. Walter, Emmanuel B. Moody, M. Anthony Kepler, Thomas B. Liao, Hua-Xin Harrison, Stephen C. TI Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE B-cell lineage; affinity maturation; X-ray crystallography ID MEMBRANE GLYCOPROTEIN; STRUCTURAL BASIS; SOFTWARE; TRACES; HIV-1 AB Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor. C1 [Whittle, James R. R.; Harrison, Stephen C.] Harvard Univ, Childrens Hosp, Sch Med, Mol Med Lab, Boston, MA 02115 USA. [Whittle, James R. R.; Harrison, Stephen C.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Zhang, Ruijun; Haynes, Barton F.; Walter, Emmanuel B.; Moody, M. Anthony; Kepler, Thomas B.; Liao, Hua-Xin] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC 27710 USA. [Haynes, Barton F.; Liao, Hua-Xin] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Haynes, Barton F.] Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA. [Kepler, Thomas B.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Walter, Emmanuel B.; Moody, M. Anthony] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Khurana, Surender; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Dormitzer, Philip R.] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA. RP Harrison, SC (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Mol Med Lab, Boston, MA 02115 USA. EM harrison@crystal.harvard.edu OI Kepler, Thomas/0000-0002-1383-6865; Moody, Tony/0000-0002-3890-5855 FU National Center for Research Resources at the National Institutes of Health (NIH) [RR-15301]; DOE [DE-AC02-06CH11357]; Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), NIH with the Center for HIV/AIDS Vaccine Immunology NIAID [U19 AI067854] FX We thank Andrew Foulger, Robert Parks, Robert Meyerhoff, and Krissey LIoyd for antibody expression and binding assays; Ethan Settembre, Andrea Carfi, Yingxia Wen, and Kyoko Uehara for advice and assistance; and Vladimir Lugovtsev for maintaining the archived influenza type A strains used in the current study. This work is based upon research conducted at the Advanced Photon Source on the Northeastern Collaborative Access Team beamlines, which are supported by Award RR-15301 from the National Center for Research Resources at the National Institutes of Health (NIH). Use of the Advanced Photon Source, an Office of Science User Facility operated for the Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the DOE under Contract no. DE-AC02-06CH11357. The work was supported in part by the Division of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), NIH with the Center for HIV/AIDS Vaccine Immunology NIAID Grant U19 AI067854. S.C.H. is an Investigator in the Howard Hughes Medical Institute. NR 28 TC 160 Z9 164 U1 0 U2 21 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 AUG 23 PY 2011 VL 108 IS 34 BP 14216 EP 14221 DI 10.1073/pnas.1111497108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 810XO UT WOS:000294163500070 PM 21825125 ER PT J AU Badano, A AF Badano, Aldo TI In silico imaging: Definition, possibilities and challenges SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION A-ACCELERATORS SPECTROMETERS DETECTORS AND ASSOCIATED EQUIPMENT LA English DT Article DE Medical imaging simulation; Monte Carlo; In silico imaging ID MONTE-CARLO SIMULATIONS; X-RAY; BREAST TOMOSYNTHESIS; PERFORMANCE; SYSTEMS; VALIDATION; RESOLUTION; DETECTORS; ELECTRON; SCREENS AB The capability to simulate the imaging performance of new detector concepts is crucial to develop the next generation of medical imaging systems. Proper modeling tools allow for optimal designs that maximize image quality while minimizing patient and occupational radiation doses. In this context, in silico imaging has become an emerging field of imaging research. This paper reviews current progress and challenges in the simulation of imaging systems with a focus on Monte Carlo approaches to X-ray detector modeling, acceleration approaches, and validation strategies. Published by Elsevier B.V. C1 US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 30 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-9002 J9 NUCL INSTRUM METH A JI Nucl. Instrum. Methods Phys. Res. Sect. A-Accel. Spectrom. Dect. Assoc. Equip. PD AUG 21 PY 2011 VL 648 SU S1 BP S276 EP S280 DI 10.1016/j.nima.2010.11.054 PG 5 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Nuclear; Physics, Particles & Fields SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 960GV UT WOS:000305376900068 ER PT J AU Throckmorton, DC Temple, R Rappaport, BA Roca, R Winchell, CJ AF Throckmorton, Douglas C. Temple, Robert Rappaport, Bob A. Roca, Rigoberto Winchell, Celia J. TI Injectable extended-release naltrexone for opioid dependence SO LANCET LA English DT Letter C1 [Throckmorton, Douglas C.; Temple, Robert; Rappaport, Bob A.; Roca, Rigoberto; Winchell, Celia J.] US FDA, Div Anesthesia Analgesia & Addict Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rappaport, BA (reprint author), US FDA, Div Anesthesia Analgesia & Addict Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Bob.Rappaport@fda.hhs.gov 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 0140-6736 J9 LANCET JI Lancet PD AUG 20 PY 2011 VL 378 IS 9792 BP 665 EP 666 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 815EW UT WOS:000294509900024 PM 21856478 ER PT J AU Li, HL Baldwin, BR Zahnow, CA AF Li, Huili Baldwin, Brenda R. Zahnow, Cynthia A. TI LIP expression is regulated by IGF-1R signaling and participates in suppression of anoikis SO MOLECULAR CANCER LA English DT Article DE C/EBP beta; LIP/LAP; IGF-1R; EGFR; Breast Cancer; MCF10A; Anoikis ID GROWTH-FACTOR-I; BINDING-PROTEIN-BETA; MAMMARY EPITHELIAL-CELLS; ENRICHED INHIBITORY PROTEIN; HUMAN BREAST-CANCER; C/EBP-BETA; FACTOR RECEPTOR; TRANSCRIPTION FACTOR; DUCTAL MORPHOGENESIS; ISOFORM EXPRESSION AB Background: The transcription factor, CCAAT enhancer binding protein-beta (C/EBP beta), is expressed as several distinct protein isoforms (LAP1, LAP2 and LIP) that have opposing actions in cellular proliferation and differentiation. Increases in the ratio of LIP/LAP are associated with aggressive, metastatic breast cancer; however, little is known regarding the molecular mechanisms that regulate LIP expression or the biological actions of an increase in the LIP/LAP ratio. Metastasis is highly dependent upon the suppression of anoikis and the role of C/EBP beta and LIP in this anchorage-independent, survival process is currently not known in mammary epithelial cells. IGF-1R signaling is important for the survival of breast cancer cells and crosstalk between IGF-1R and EGFR signaling pathways have been implicated in the development of more aggressive disease. We therefore evaluated in mammary epithelial cells whether IGF-1R signaling regulates the LIP/LAP ratio, analyzed the potential interplay between EGFR and IGF-1R signaling and addressed the biological significance of increased LIP expression in cellular survival and suppression of anoikis. Results: Our data provide the first evidence that IGF-1R signaling regulates LIP expression in an EGFR independent manner to increase the LIP/LAP ratio in mammary epithelial cells. Although crosstalk between IGF-1R signaling and EGFR signaling is detectable in MCF10A cells, this crosstalk is not required for the IGF-1 mediated regulation of LIP expression. Rather, the critical regulator of IGF-1 induced LIP expression appears to be EGFR-independent, Akt activity. Our data also demonstrate that increases in LIP expression promote cell survival via suppression of anoikis. Likewise, knockdown of total C/EBP beta leads to increased cell death and suggest that C/EBP beta expression is important for survival and resistance to anoikis. IGF-1 treatment can partially rescue vector control cells from anoikis; however, cells with reduced C/EBP beta expression do not survive anoikis. Conclusions: Taken together, our data demonstrate that IGF-1R signaling regulates LIP expression in an EGFR independent manner to increase the LIP/LAP ratio in mammary epithelial cells. C/EBP beta expression and elevations in LIP play an important role in regulating cellular survival via suppression of anoikis, in an IGF-1R mediated context or in a manner independent of IGF-1R signaling. C1 [Li, Huili; Zahnow, Cynthia A.] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD 21231 USA. [Baldwin, Brenda R.] FDA CBER, Rockville, MD 20852 USA. RP Zahnow, CA (reprint author), Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Dept Oncol, Baltimore, MD 21231 USA. EM zahnoci@jhmi.edu FU Flight Attendants Medical Research Institute; NIH [R01 CA113795]; Breast Spore at Johns Hopkins; [KG 080509] FX We thank Dr. Barry Nelkin for his helpful discussions and critical review of this manuscript and V. Lynn Flowers for cell culture and technical support. This study was supported in part by the Flight Attendants Medical Research Institute to (BRB) and (CAZ), by NIH grant R01 CA113795 to (CAZ), by KG 080509 to (CAZ and HLL) and by support from the Breast Spore at Johns Hopkins. NR 63 TC 9 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD AUG 19 PY 2011 VL 10 AR 100 DI 10.1186/1476-4598-10-100 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 823AC UT WOS:000295092100001 PM 21854628 ER PT J AU Cavallaro, E Date, K Medus, C Meyer, S Miller, B Kim, C Nowicki, S Cosgrove, S Sweat, D Phan, Q Flint, J Daly, ER Adams, J Hyytia-Trees, E Gerner-Smidt, P Hoekstra, RM Schwensohn, C Langer, A Sodha, SV Rogers, MC Angulo, FJ Tauxe, RV Williams, IT Behravesh, CB AF Cavallaro, Elizabeth Date, Kashmira Medus, Carlota Meyer, Stephanie Miller, Benjamin Kim, Clara Nowicki, Scott Cosgrove, Shaun Sweat, David Phan, Quyen Flint, James Daly, Elizabeth R. Adams, Jennifer Hyytia-Trees, Eija Gerner-Smidt, Peter Hoekstra, Robert M. Schwensohn, Colin Langer, Adam Sodha, Samir V. Rogers, Michael C. Angulo, Frederick J. Tauxe, Robert V. Williams, Ian T. Behravesh, Casey Barton CA Salmonella Typhimurium Outbreak TI Salmonella Typhimurium Infections Associated with Peanut Products SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID UNITED-STATES; BUTTER; OUTBREAK AB BACKGROUND Contaminated food ingredients can affect multiple products, each distributed through various channels and consumed in multiple settings. Beginning in November 2008, we investigated a nationwide outbreak of salmonella infections. METHODS A case was defined as laboratory-confirmed infection with the outbreak strain of Salmonella Typhimurium occurring between September 1, 2008, and April 20, 2009. We conducted two case-control studies, product "trace-back," and environmental investigations. RESULTS Among 714 case patients identified in 46 states, 166 (23%) were hospitalized and 9 (1%) died. In study 1, illness was associated with eating any peanut butter (matched odds ratio, 2.5; 95% confidence interval [CI], 1.3 to 5.3), peanut butter-containing products (matched odds ratio, 2.2; 95% CI, 1.1 to 4.7), and frozen chicken products (matched odds ratio, 4.6; 95% CI, 1.7 to 14.7). Investigations of focal clusters and single cases associated with nine institutions identified a single institutional brand of peanut butter (here called brand X) distributed to all facilities. In study 2, illness was associated with eating peanut butter outside the home (matched odds ratio, 3.9; 95% CI, 1.6 to 10.0) and two brands of peanut butter crackers (brand A: matched odds ratio, 17.2; 95% CI, 6.9 to 51.5; brand B: matched odds ratio, 3.6; 95% CI, 1.3 to 9.8). Both cracker brands were made from brand X peanut paste. The outbreak strain was isolated from brand X peanut butter, brand A crackers, and 15 other products. A total of 3918 peanut butter-containing products were recalled between January 10 and April 29, 2009. CONCLUSIONS Contaminated peanut butter and peanut products caused a nationwide salmonellosis outbreak. Ingredient-driven outbreaks are challenging to detect and may lead to widespread contamination of numerous food products. C1 [Cavallaro, Elizabeth; Date, Kashmira; Adams, Jennifer; Hyytia-Trees, Eija; Gerner-Smidt, Peter; Hoekstra, Robert M.; Schwensohn, Colin; Langer, Adam; Sodha, Samir V.; Angulo, Frederick J.; Tauxe, Robert V.; Williams, Ian T.; Behravesh, Casey Barton] Ctr Dis Control & Prevent, Program Off Sci Educ & Profess Dev, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. [Cavallaro, Elizabeth; Date, Kashmira; Kim, Clara] Ctr Dis Control & Prevent, Program Off Sci Educ & Profess Dev, Epidem Intelligence Serv, Atlanta, GA USA. [Medus, Carlota; Meyer, Stephanie] Minnesota Dept Hlth, St Paul, MN USA. [Miller, Benjamin] Minnesota Dept Agr, St Paul, MN USA. [Kim, Clara; Nowicki, Scott] Ohio Dept Hlth, Columbus, OH USA. [Cosgrove, Shaun] Colorado Dept Publ Hlth & Environm, Denver, CO USA. [Sweat, David] N Carolina Div Publ Hlth, Raleigh, NC USA. [Phan, Quyen] Connecticut Dept Publ Hlth, Hartford, CT USA. [Flint, James] Publ Hlth Agcy Canada, Ottawa, ON, Canada. [Daly, Elizabeth R.] New Hampshire Dept Hlth & Human Serv, Concord, NH USA. [Rogers, Michael C.] US FDA, Silver Spring, MD USA. RP Cavallaro, E (reprint author), Ctr Dis Control & Prevent, Program Off Sci Educ & Profess Dev, Natl Ctr Emerging & Zoonot Infect Dis, Div Foodborne Waterborne & Environm Dis, Atlanta, GA 30333 USA. EM ecavallaro@cdc.gov OI Miller, Benjamin/0000-0003-1647-0122 NR 28 TC 38 Z9 39 U1 4 U2 29 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 AUG 18 PY 2011 VL 365 IS 7 BP 601 EP 610 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 808ER UT WOS:000293960500007 PM 21848461 ER PT J AU Kirkland, DJ Hayashi, M Jacobson-Kram, D Kasper, P Gollapudi, B Muller, L Uno, Y AF Kirkland, D. J. Hayashi, M. Jacobson-Kram, D. Kasper, P. Gollapudi, B. Mueller, L. Uno, Y. TI Summary of major conclusions from the 5th IWGT, Basel, Switzerland, 17-19 August 2009 SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Editorial Material DE Genotoxicity; IWGT workshop; Conclusions ID GENOTOXICITY TEST PROCEDURES; INTERNATIONAL WORKSHOP; IN-VITRO; RODENT CARCINOGENS; MUTATION ASSAY; MOUSE; IDENTIFICATION; STRATEGY C1 [Kirkland, D. J.] Kirkland Consulting, Tadcaster LS24 0AS, England. [Hayashi, M.] Biosafety Res Ctr, Iwata, Japan. [Jacobson-Kram, D.] US FDA, Off New Drugs, Ctr Drugs Evaluat & Res, Silver Spring, MD 20993 USA. [Kasper, P.] Fed Inst Drugs & Med Devices BfArM, Bonn, Germany. [Gollapudi, B.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Mueller, L.] F Hoffmann La Roche & Cie AG, Nonclin Safety, CH-4070 Basel, Switzerland. [Uno, Y.] Mitsubishi Tanabe Pharma Co, Safety Res Labs, Chiba 2920818, Japan. RP Kirkland, DJ (reprint author), Kirkland Consulting, POB 79, Tadcaster LS24 0AS, England. EM dkirkland@genetoxconsulting.co.uk NR 10 TC 8 Z9 8 U1 2 U2 4 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 AUG 16 PY 2011 VL 723 IS 2 BP 73 EP 76 DI 10.1016/j.mrgentox.2011.03.003 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400001 PM 21419235 ER PT J AU Galloway, S Lorge, E Aardema, MJ Eastmond, D Fellows, M Heflich, R Kirkland, D Levy, DD Lynch, AM Marzin, D Morita, T Schuler, M Speit, G AF Galloway, Sheila Lorge, Elisabeth Aardema, Marilyn J. Eastmond, David Fellows, Mick Heflich, Robert Kirkland, David Levy, Dan D. Lynch, Anthony M. Marzin, Daniel Morita, Takeshi Schuler, Maik Speit, Guenter TI Workshop summary: Top concentration for in vitro mammalian cell genotoxicity assays; and report from working group on toxicity measures and top concentration for in vitro cytogenetics assays (chromosome aberrations and micronucleus) SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE In vitro tests; Chromosome aberrations; Micronucleus; Cytotoxicity; Upper concentration limit ID DEVELOPMENTAL TOXICITY; CARCINOGENICITY DATA; COLLABORATIVE TRIAL; CYTOSTATIC MEASURES; ACCURATE ASSESSMENT; RODENT CARCINOGENS; GENETIC TOXICITY; CYTOTOXICITY; TESTS; IDENTIFICATION AB The selection of maximum concentrations for in vitro mammalian cell genotoxicity assays was reviewed at the 5th International Workshop on Genotoxicity Testing (IWGT), 2009. Currently, the top concentration recommended when toxicity is not limiting is 10 mM or 5 mg/ml, whichever is lower. The discussion was whether to reduce the limit, and if so whether the 1 mM limit proposed for human pharmaceuticals was appropriate for testing other chemicals. The consensus was that there was reason to consider reducing the 10 mM limit, and many, but not all, attendees favored a reduction to 1 mM. Several proposals are described here for the concentration limit. The in vitro cytogenetics expert working group also discussed appropriate measures and level of cytotoxicity. Data were reviewed from a multi-laboratory trial of the in vitro micronucleus (MN) assay with multiple cell types and several types of toxicity measurements. The group agreed on a preference for toxicity measures that take cell proliferation after the beginning of treatment into account (relative increase in cell counts, relative population doubling, cytokinesis block proliferation index or replicative index), and that this applies both to in vitro MN assays and to in vitro chromosome aberration assays. Since relative cell counts (RCC) underestimate toxicity, many group members favored making a recommendation against the use of RCC as a toxicity measure for concentration selection. All 14 chemicals assayed for MN induction in the multi-laboratory trial were detected without exceed, ing 50% toxicity by any measure, but some were positive only at concentrations with toxicity quite close to 50%. The expert working group agreed to accept the cytotoxicity range recommended by OECD guideline 487 (55 +/- 5% toxicity at the top concentration scored). This also reinforces the original intent of the guidance for the in vitro chromosome aberration assay. where "> 50%" was intended to target the range close to 50% toxicity. (C) 2011 Elsevier B.V. All rights reserved. C1 [Galloway, Sheila] Merck Res Labs, West Point, PA 19486 USA. [Lorge, Elisabeth] Servier Grp, F-45403 Fleury Les Aubrais, France. [Aardema, Marilyn J.] Procter & Gamble Co, Cincinnati, OH 45253 USA. [Eastmond, David] Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. [Fellows, Mick] AstraZeneca, Safety Assessment, Macclesfield SK10 4TG, Cheshire, England. [Heflich, Robert] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kirkland, David] Kirkland Consulting, Tadcaster LS2 0AS, England. [Levy, Dan D.] US FDA, Div Dietary Supplement Programs, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lynch, Anthony M.] GlaxoSmithKline R&D 3F02, Ware SG12 0DP, Herts, England. [Marzin, Daniel] Inst Pasteur Lille 1, Toxicol Lab, F-59019 Lille, France. [Morita, Takeshi] Natl Inst Hlth Sci, Div Safety Informat Drug Food & Chem, Setagaya Ku, Tokyo 1588501, Japan. [Schuler, Maik] PGRD Pfizer Inc, Groton, CT 06340 USA. [Speit, Guenter] Univ Ulm, Inst Humangenet, D-89069 Ulm, Germany. RP Galloway, S (reprint author), Merck Res Labs, W 45-316, West Point, PA 19486 USA. EM sheila_galloway@merck.com NR 25 TC 20 Z9 21 U1 2 U2 9 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 AUG 16 PY 2011 VL 723 IS 2 BP 77 EP 83 DI 10.1016/j.mrgentox.2011.01.003 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400002 PM 21255675 ER PT J AU Moore, MM Honma, M Clements, J Awogi, T Douglas, GR van Goethem, F Gollapudi, B Kimura, A Muster, W O'Donovan, M Schoeny, R Wakuri, S AF Moore, Martha M. Honma, Masamitsu Clements, Julie Awogi, Takumi Douglas, George R. van Goethem, Freddy Gollapudi, Bhaskar Kimura, Aoi Muster, Wolfgang O'Donovan, Mike Schoeny, Rita Wakuri, Shinobu TI Suitable top concentration for tests with mammalian cells: Mouse lymphoma assay workgroup SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Review DE Mouse lymphoma assay; Top concentration; Thymidine kinase mutation ID GENE MUTATION ASSAY; GENOTOXICITY TEST PROCEDURES; INTERNATIONAL WORKSHOP; CRITERIA AB The Mouse Lymphoma Expert Workgroup of the International Workshop for Genotoxicity Tests (IWGT) met in Basel. Switzerland in August of 2009. The Workgroup (WG) was tasked with discussing the appropriate top concentration for non-pharmaceuticals that would be required for the conduct of the mouse lymphoma assay (MLA) when sufficient cytotoxicity [to between 10 and 20% relative total growth (RIG)] has not been attained. The WG approached this task by (1) enumerating the various regulatory decisions/use for MLA data, (2) discussing the appropriate assays to which MLA data and assay performance should be compared and (3) discussing all the proposals put forth concerning the top concentration for non-pharmaceuticals. In addition, one of the members presented a summary of a re-evaluation of the National Toxicology Program MLA data using the IWGT harmonized guidance that was underway as a separate (non IWGT) activity, being conducted by two members of the Expert WG. The WG was asked to vote on each of the various proposals for top concentration for when cytotoxicity is not concentration limiting. While there was general agreement that the top concentration for non-pharmaceuticals should be re-evaluated and likely lowered from the current recommended levels, there was no agreement on a specific new recommendation. Published by Elsevier B.V. C1 [Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Honma, Masamitsu] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo, Japan. [Clements, Julie] Covance Labs Ltd, Harrogate, N Yorkshire, England. [Awogi, Takumi] Otsuka Pharmaceut Co Ltd, Tokushima, Japan. [Douglas, George R.] Hlth Canada, Healthy Environm & Consumer Safety Branch, Mechanist Studies Div, Ottawa, ON K1A 0L2, Canada. [van Goethem, Freddy] Janssen, Res & Dev, Pharmaceut Co Johnson & Johnson, Beerse, Belgium. [Gollapudi, Bhaskar] Dow Chem Co USA, Midland, MI 48674 USA. [Kimura, Aoi] Shin Nippon Biomed Labs Ltd, Drug Safety Res Labs, Kagoshima, Japan. [Muster, Wolfgang] F Hoffmann La Roche Ltd, Basel, Switzerland. [O'Donovan, Mike] AstraZeneca R&D, Macclesfield, Cheshire, England. [Schoeny, Rita] US EPA, Off Water, Washington, DC 20460 USA. [Wakuri, Shinobu] Food & Drug Safety Ctr, Hatano Res Inst, Kanagawa, Japan. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Martha.Moore@fda.hhs.gov NR 7 TC 7 Z9 7 U1 0 U2 2 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 AUG 16 PY 2011 VL 723 IS 2 BP 84 EP 86 DI 10.1016/j.mrgentox.2011.04.001 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400003 PM 21514400 ER PT J AU Lynch, AM Guzzie, PJ Bauer, D Gocke, E Itoh, S Jacobs, A Krul, CAM Schepky, A Tanaka, N Kasper, P AF Lynch, Anthony M. Guzzie, Peggy J. Bauer, Daniel Gocke, Elmar Itoh, Satoru Jacobs, Abby Krul, Cyrille A. M. Schepky, Andreas Tanaka, Noriho Kasper, Peter TI Considerations on photochemical genotoxicity. II: Report of the 2009 International Workshop on Genotoxicity Testing Working Group SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Photosafety; Photogenotoxicity; Photoclastogenicity; Phototoxicity; Risk assessment ID HUMAN SKIN MODEL; IN-VIVO; COMET ASSAY; MICRONUCLEUS INDUCTION; PHOTOTOXICITY TEST; HAIRLESS MICE; PHASE-II; DRUG; 8-METHOXYPSORALEN; PHOTOSENSITIVITY AB A workshop to reappraise the previous IWGT recommendations for photogenotoxicity testing [E. Gocke, L Muller, P.J. Guzzie, S. Brendler-Schwaab, S. Bulera, CF. Chignell, LM. Henderson, A. Jacobs, H. Murli, R.D. Snyder, N. Tanaka, Considerations on photochemical genotoxicity: report of the International Workshop on Genotoxicity Test Procedures working group, Environ. Mol. Mutagen., 35 (2000) 173-184] was recently held as part of the 5th International Workshop on Genotoxicity Testing (IWGT) meeting in Basel, Switzerland (August 17-19, 2009). An Expert Panel was convened from regulatory, academic and industrial scientists (with several members serving on the original panel) and chaired by Dr Peter Kasper (BfArM, Germany). The aim of the workshop was to review progress made in photo(geno)toxicity testing over the past decade: a period which saw the introduction of several regulatory photosafety guidances in particular in Europe and the USA. Based on current regulatory guidelines a substantial proportion of compounds trigger the requirements for photosafety testing. Moreover, there has been growing concern within industry about the performance of the in vitro photosafety tests in the "real world" of compound development. Therefore, the expert group reviewed the status of the current regulatory guidance's and the impact these have had on compound development in the context of the various triggers for photosafety testing. In addition, the performance of photogenotoxicity assays (old and new) was discussed, particularly in view of reports of pseudophotoclastogencity. The Expert Panel finished with an assessment of the positioning of photogenotoxicity testing within a photosafety testing strategy. The most significant conclusion made by the Expert Panel was that photogenotoxicity testing should no longer be recommended as part of the standard photosafety testing strategy. In addition, progress was made on the refinement of triggers for photosafety testing. For example, there was support for harmonisation of methods to determine the Molar Extinction Coefficient (MEC) and a consensus agreement that there should be no requirement for testing of compounds with a MEC < 1000 L mol(-1) cm(-1). (C) 2011 Elsevier B.V. All rights reserved. C1 [Lynch, Anthony M.] GlaxoSmithKline Inc, Ware, Herts, England. [Guzzie, Peggy J.] Johnson & Johnson, Newark, NY USA. [Bauer, Daniel] Novartis Pharma AG, Basel, Switzerland. [Gocke, Elmar] F Hoffmann La Roche Ltd, Basel, Switzerland. [Itoh, Satoru] Daiichi Sankyo Co Ltd, Tokyo, Japan. [Jacobs, Abby] US FDA, Silver Spring, MD USA. [Krul, Cyrille A. M.] TNO, NL-3700 AJ Zeist, Netherlands. [Schepky, Andreas] Beiersdorf AG, Hamburg, Germany. [Tanaka, Noriho] Hatano Res Inst, Kanagawa, Japan. [Kasper, Peter] Fed Inst Drugs & Med Devices BfArM, Bonn, Germany. RP Lynch, AM (reprint author), GlaxoSmithKline Inc, Ware, Herts, England. EM Anthony.m.lynch@gsk.com NR 43 TC 3 Z9 3 U1 1 U2 4 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 AUG 16 PY 2011 VL 723 IS 2 BP 91 EP 100 DI 10.1016/j.mrgentox.2010.10.010 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400005 PM 21296679 ER PT J AU Rothfuss, A Honma, M Czich, A Aardema, MJ Burlinson, B Galloway, S Hamada, S Kirkland, D Heflich, RH Howe, J Nakajima, M O'Donovan, M Plappert-Helbig, U Priestley, C Recio, L Schuler, M Uno, Y Martus, HJ AF Rothfuss, Andreas Honma, Masamitu Czich, Andreas Aardema, Marilyn J. Burlinson, Brian Galloway, Sheila Hamada, Shuichi Kirkland, David Heflich, Robert H. Howe, Jonathan Nakajima, Madoka O'Donovan, Mike Plappert-Helbig, Ulla Priestley, Catherine Recio, Leslie Schuler, Maik Uno, Yoshifumi Martus, Hans-Joerg TI Improvement of in vivo genotoxicity assessment: Combination of acute tests and integration into standard toxicity testing SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE IWGT; In vivo genotoxicity testing; Combination; Integration ID PERIPHERAL-BLOOD RETICULOCYTES; ERYTHROCYTE MICRONUCLEUS ASSAY; FLOW-CYTOMETRIC ANALYSIS; RECOMBINANT-HUMAN-ERYTHROPOIETIN; MONITORING CHROMOSOMAL DAMAGE; IWGT WORKING GROUP; COMET ASSAY; BONE-MARROW; EFFICIENT METHOD; RAT AB A working group convened at the 2009 5th IWGT to discuss possibilities for improving in vivo genotoxicity assessment by investigating possible links to standard toxicity testing. The working group considered: (1) combination of acute micronucleus (MN) and Comet assays into a single study, (2) integration of MN assays into repeated-dose toxicity (RDT) studies, (3) integration of Comet assays into RDT studies, and (4) requirements for the top dose when integrating genotoxicity measurements into RDT studies. The working group reviewed current requirements for in vivo genotoxicity testing of different chemical product classes and identified opportunities for combination and integration of genotoxicity endpoints for each class. The combination of the acute in vivo MN and Comet assays was considered by the working group to represent a technically feasible and scientifically acceptable alternative to conducting independent assays. Two combination protocols, consisting of either a 3- or a 4-treament protocol, were considered equally acceptable. As the integration of MN assays into RDT studies had already been discussed in detail in previous IWGT meetings, the working group focussed on factors that could affect the results of the integrated MN assay, such as the possible effects of repeated bleeding and the need for early harvests. The working group reached the consensus that repeated bleeding at reasonable volumes is not a critical confounding factor for the MN assay in rats older than 9 weeks of age and that rats bled for toxicokinetic investigations or for other routine toxicological purposes can be used for MN analysis. The working group considered the available data as insufficient to conclude that there is a need for an early sampling point for MN analysis in RDT studies, in addition to the routine determination at terminal sacrifice. Specific scenarios were identified where an additional early sampling can have advantages, e.g., for compounds that exert toxic effects on hematopoiesis. including some aneugens. For the integration of Comet assays into RDT studies, the working group reached the consensus that, based upon the limited amount of data available, integration is scientifically acceptable and that the liver Comet assay can complement the MN assay in blood or bone marrow in detecting in vivo genotoxins. Practical issues need to be considered when conducting an integrated Comet assay study. Freezing of tissue samples for later Comet assay analysis could alleviate logistical problems. However, the working group concluded that freezing of tissue samples can presently not be recommended for routine use, although it was noted that results from some laboratories look promising. Another discussion topic centred around the question as to whether tissue toxicity, which is more likely observed in RDT than in acute toxicity studies, would affect the results of the Comet assay. Based on the available data from in vivo studies, the working group concluded that there are no clear examples where cytotoxicity, by itself, generates increases or decreases in DNA migration. The working group identified the need for a refined guidance on the use and interpretation of cytotoxicity methods used in the Comet assay, as the different methods used generally lead to inconsistent conclusions. Since top doses in ROT studies often are limited by toxicity that occurs only after several doses, the working group discussed whether the sensitivity of integrated genotoxicity studies is reduced under these circumstances. For compounds for which in vitro genotoxicity tudies yielded negative results, the working group reached the consensus that integration of in vivo genotoxicity endpoints (typically the MN assay) into RDT studies is generally acceptable. If in vitro genotoxicity results are unavailable or positive, consensus was reached that the maximum tolerated dose (MTD) is acceptable as the top dose in ROT studies in many cases, such as when the RDT study MTD or exposure is close (50% or greater) to an acute study MTD or exposure. Finally, the group agreed that exceptions to this general rule might be acceptable, for example when human exposure is lower than the preclinical exposure by a large margin. (C) 2010 Elsevier B.V. All rights reserved. C1 [Rothfuss, Andreas] Bayer Schering Pharma AG, Nonclin Drug Safety, Genet Toxicol, D-13342 Berlin, Germany. [Honma, Masamitu] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo, Japan. [Czich, Andreas] Sanofi Aventis Deutschland GmbH, Preclin Safety, Hattersheim, Germany. [Aardema, Marilyn J.] Procter & Gamble Co, Cincinnati, OH 45253 USA. [Burlinson, Brian] Huntington Life Sci, Alconbury, Cambridge, England. [Galloway, Sheila] Merck Res Labs, West Point, PA 19486 USA. [Hamada, Shuichi] Mitsubishi Chem Medience Corp, Ibaraki, Japan. [Kirkland, David] Kirkland Consulting, Tadcaster LS24 0AS, England. [Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Howe, Jonathan] GlaxoSmithKline R&D, Ware SG12 0DP, Herts, England. [Nakajima, Madoka] Foods Drugs & Pesticides BSRC, Biosafety Res Ctr, Iwata, Japan. [O'Donovan, Mike; Priestley, Catherine] AstraZeneca R&D, Genet Toxicol, Safety Assessment, Macclesfield SK10 4TG, Cheshire, England. [Plappert-Helbig, Ulla; Martus, Hans-Joerg] Novartis Inst BioMed Res, Basel, Switzerland. [Recio, Leslie] Integrated Lab Syst Inc, Genet & Mol Toxicol Div, Res Triangle Pk, NC 27709 USA. [Schuler, Maik] Pfizer Global Res & Dev, Groton, CT USA. [Uno, Yoshifumi] Mitsubishi Tanabe Pharma Co, Safety Res Labs, Chiba, Japan. RP Rothfuss, A (reprint author), Bayer Schering Pharma AG, Nonclin Drug Safety, Genet Toxicol, D-13342 Berlin, Germany. EM andreas.rothfuss@bayerhealthcare.com NR 61 TC 40 Z9 41 U1 0 U2 10 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 AUG 16 PY 2011 VL 723 IS 2 BP 108 EP 120 DI 10.1016/j.mrgentox.2010.12.005 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400007 PM 21182982 ER PT J AU Thybaud, V MacGregor, JT Muller, L Crebelli, R Dearfield, K Douglas, G Farmer, PB Gocke, E Hayashi, M Lovell, DP Lutz, WK Marzin, D Moore, M Nohmi, T Phillips, DH Van Benthem, J AF Thybaud, Veronique MacGregor, James T. Mueller, Lutz Crebelli, Riccardo Dearfield, Kerry Douglas, George Farmer, Peter B. Gocke, Elmar Hayashi, Makoto Lovell, David P. Lutz, Werner K. Marzin, Daniel Moore, Martha Nohmi, Takehiko Phillips, David H. Van Benthem, Jan TI Strategies in case of positive in vivo results in genotoxicity testing SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Risk assessment; Genotoxicity; In vivo assays; Mode of action; Dose-response ID PERIPHERAL-BLOOD RETICULOCYTES; FLOW-CYTOMETRIC ANALYSIS; DOSE-RESPONSE RELATIONSHIPS; MONITORING CHROMOSOMAL DAMAGE; CONGENITAL HEART-DISEASE; SPLEEN T-CELLS; RISK-ASSESSMENT; ETHYL METHANESULFONATE; MICRONUCLEUS ASSAY; EFFICIENT METHOD AB At the 2009 International Workshop on Genotoxicity Testing in Basel, an expert group gathered to provide guidance on suitable follow-up tests to describe risk when basic in vivo genotoxicity tests have yielded positive results. The working group agreed that non-linear dose-response curves occur in vivo with at least some DNA-reactive agents. Quantitative risk assessment in such cases requires the use of (1) adequate data, i.e., the use of all available data for the selection of reliable in vivo models to be used for quantitative risk assessment, (2) appropriate mathematical models and statistical analysis for characterizing the dose-response relationships and allowing the use of quantitative and dose-response information in the interpretation of results, (3) mode of action (MOA) information for the evaluation and analysis of risk, and (4) reliable assessments of the internal dose across species for deriving acceptable margins of exposure and risk levels. Hence, the elucidation of MOA and understanding of the mechanism underlying the dose-response curve are important components of risk assessment. The group agreed on the need for (i) the development of in vivo assays, especially multi-endpoint, multi-species assays, with emphasis on those applicable to humans, and (ii) consensus about the most appropriate mathematical models and statistical analyses for defining non-linear dose-responses and exposure levels associated with acceptable risk. (C) 2010 Elsevier B.V. All rights reserved. C1 [Thybaud, Veronique] Sanofi Aventis, Vitry Alfortville Res Ctr, Disposit Safety & Anim Res, F-94400 Vitry Sur Seine, France. [MacGregor, James T.] Toxicol Consulting Serv, Arnold, MD USA. [Mueller, Lutz; Gocke, Elmar] F Hoffmann La Roche & Cie AG, Basel, Switzerland. [Crebelli, Riccardo] Ist Super Sanita, I-00161 Rome, Italy. [Dearfield, Kerry] US Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. [Douglas, George] Hlth Canada, Ottawa, ON K1A 0K9, Canada. [Farmer, Peter B.] Univ Leicester, Leicester, Leics, England. [Hayashi, Makoto] Biosafety Res Ctr, Iwata, Japan. [Lovell, David P.] St Georges Univ London, Div Basic Med Sci, London, England. [Lutz, Werner K.] Univ Wurzburg, Wurzburg, Germany. [Marzin, Daniel] Inst Pasteur, Lab Toxicol Genet, F-59019 Lille, France. [Moore, Martha] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Nohmi, Takehiko] Natl Inst Hlth Sci, Tokyo, Japan. [Phillips, David H.] Inst Canc Res, Sutton, Surrey, England. [Van Benthem, Jan] Natl Inst Publ Hlth & Environm, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands. RP Thybaud, V (reprint author), Sanofi Aventis, Vitry Alfortville Res Ctr, Disposit Safety & Anim Res, 13 Quai Jules Guesde, F-94400 Vitry Sur Seine, France. EM Veronique.thybaud@sanofi-aventis.com OI Phillips, David/0000-0001-8509-3485 NR 84 TC 9 Z9 10 U1 3 U2 9 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 AUG 16 PY 2011 VL 723 IS 2 BP 121 EP 128 DI 10.1016/j.mrgentox.2010.09.002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 799VY UT WOS:000293315400008 PM 20854927 ER PT J AU Feigelstock, DA Mihalik, KB Feinstone, SM AF Feigelstock, Dino A. Mihalik, Kathleen B. Feinstone, Stephen M. TI Selection of hepatitis C virus resistant to ribavirin SO VIROLOGY JOURNAL LA English DT Article ID DEPENDENT RNA-POLYMERASE; CRYSTAL-STRUCTURE; GENOTYPE 2A; REPLICATION; MUTATIONS; SYSTEM; NS5B; SUSCEPTIBILITY; IDENTIFICATION; MONOTHERAPY AB Background: Given the side effects associated with intravenous injections of interferon, an interferon-free regimen for the treatment of HCV infections is highly desirable. Recently published clinical studies show that interferon-free combination therapies containing ribavirin are efficacious, suggesting that an interferon-free therapy could be adopted in the near future. Therefore, understanding HCV resistance to ribavirin could be of major importance. In an approach to understand the effect of ribavirin on HCV replication and HCV resistance, we have selected a ribavirin resistant mutant of HCV in vitro. Methods: We serially passed the J6/JFH1 strain of HCV in Huh7D cells (a Huh7 cell derivative more permissive to HCV replication) in the presence of different concentrations of ribavirin. Virus replication was assessed by detection of HCV antigens by immunfluorscence of infected cells and titration of recovered virus present in the supernatant. cDNAs from virus RNA grown in 0 or 250 uM concentrations of ribavirin were synthesized by RT-PCR, and sequenced. Results: A concentration of 125 uM of ribavirin did not have a dramatic effect on HCV replication, while 500 uM of ribavirin lead to viral extinction. Concentrations of 250 uM of ribavirin dramatically reduced virus replication which was sustained over six passages. At passage seven viral resurgence began and over two passages the level of virus reached that of the wild type virus grown without ribavirin. Virus recovered from these cultures were more resistant to 250 uM ribavirin than wild type virus, and showed no difference in replication relative to wild type virus when grown in the absence of ribavirin. The ribavirin resistant virus accumulated multiple synonymous and non-synonymous mutations that are presently being analyzed for their relationship to ribavirin resistance. Conclusions: It is possible to select a ribavirin resistant mutant of HCV that can replicate to levels similar to wild type virus grown without ribavirin. Analysis of the mutations responsible for the ribavirin resistance may aid in understanding the mechanism of action of ribavirin. C1 [Feigelstock, Dino A.; Mihalik, Kathleen B.; Feinstone, Stephen M.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Feigelstock, DA (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM dino.feigelstock@fda.hhs.gov FU Food and Drug Administration FX This work was supported by internal funding from the Food and Drug Administration. NR 30 TC 13 Z9 14 U1 0 U2 1 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 AUG 15 PY 2011 VL 8 AR 402 DI 10.1186/1743-422X-8-402 PG 8 WC Virology SC Virology GA 815UK UT WOS:000294555100001 PM 21843317 ER PT J AU Sheth, AN Hoekstra, M Patel, N Ewald, G Lord, C Clarke, C Villamil, E Niksich, K Bopp, C Nguyen, TA Zink, D Lynch, M AF Sheth, Anandi N. Hoekstra, Mike Patel, Nehal Ewald, Gwen Lord, Cathy Clarke, Carmen Villamil, Elizabeth Niksich, Katherine Bopp, Cheryl Thai-An Nguyen Zink, Donald Lynch, Michael TI A National Outbreak of Salmonella Serotype Tennessee Infections From Contaminated Peanut Butter: A New Food Vehicle for Salmonellosis in the United States SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EAT SAVOURY SNACK; AGONA INFECTION; HEAT TOLERANCE; TYPHIMURIUM AB Background. Salmonella serotype Tennessee is a rare cause of the estimated 1 million cases of salmonellosis occurring annually in the United States. In January 2007, we began investigating a nationwide increase in Salmonella Tennessee infections. Methods. We defined a case as Salmonella Tennessee infection in a patient whose isolate demonstrated 1 of 3 closely related pulsed-field gel electrophoresis patterns and whose illness began during the period 1 August 2006 through 31 July 2007. We conducted a case-control study in 22 states and performed laboratory testing of foods and environmental samples. Results. We identified 715 cases in 48 states; 37% of isolates were from urine specimens. Illness was associated with consuming peanut butter more than once a week (matched odds ratio [mOR], 3.5 [95% confidence interval {95% CI}, 1.4-9.9]), consuming Brand X peanut butter (mOR, 12.1 [95% CI, 3.6-66.3]), and consuming Brand Y peanut butter (mOR, 9.1 [95% CI, 1.0-433]). Brands X and Y were produced in 1 plant, which ceased production and recalled products on 14 February 2007. Laboratories isolated outbreak strains of Salmonella Tennessee from 34 Brands X and Y peanut butter jars and 2 plant environmental samples. Conclusions. This large, widespread outbreak of salmonellosis is the first linked to peanut butter in the United States; a nationwide recall resulted in outbreak control. Environmental contamination in the peanut butter plant likely caused this outbreak. This outbreak highlights the risk of salmonellosis from heat-processed foods of nonanimal origin previously felt to be low risk for Salmonella contamination. C1 [Sheth, Anandi N.; Hoekstra, Mike; Patel, Nehal; Ewald, Gwen; Bopp, Cheryl; Thai-An Nguyen; Lynch, Michael] Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, Atlanta, GA 30333 USA. [Sheth, Anandi N.; Niksich, Katherine] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Sheth, Anandi N.; Niksich, Katherine] Ctr Dis Control & Prevent, Epidemiol Elect Program, Off Workforce & Career Dev, Atlanta, GA 30333 USA. [Lord, Cathy] Iowa State Hyg Lab, Iowa City, IA USA. [Clarke, Carmen] Oklahoma Dept Hlth, Oklahoma City, OK USA. [Villamil, Elizabeth] New York State Dept Hlth, Albany, NY USA. [Zink, Donald] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Sheth, AN (reprint author), Ctr Dis Control & Prevent, Div Foodborne Bacterial & Mycot Dis, 1600 Clifton Rd NE,Mailstop A-38, Atlanta, GA 30333 USA. EM asheth@cdc.gov NR 31 TC 32 Z9 33 U1 0 U2 25 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 AUG 15 PY 2011 VL 53 IS 4 BP 356 EP 362 DI 10.1093/cid/cir407 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 804DW UT WOS:000293635500007 PM 21810748 ER PT J AU Reddy, MK Mills, G Nixon, C Wyatt, SA Croley, TR AF Reddy, Muntha K. Mills, Grier Nixon, Christopher Wyatt, Shane A. Croley, Timothy R. TI High-throughput sample preparation and simultaneous column regeneration liquid chromatography-tandem mass spectrometry method for determination of nitrogen mustard metabolites in human urine SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE HTP-LC-MS/MS; LC-column switching; High-throughput extraction; N-ethyldiethanolamine; N-methyldiethanolamine ID CHEMICAL WARFARE AGENTS; DEGRADATION-PRODUCTS; DNA; WATER; EXCHANGE AB Nitrogen mustards (NMs) are known to have DNA alkylation and strong vesicant properties. Their availability to terrorist organizations makes them a potential choice for chemical attacks on civilian populations. After an exposure, it is difficult to measure NMs directly because of their rapid metabolism in the human body. Therefore to determine an individual's level of exposure to NMs, it is necessary to analyze for NM metabolites being excreted by the body. The metabolites of NMs are generated by a hydrolysis reaction, and are easily detectable by liquid chromatography tandem mass spectrometry (LC-MS/MS). This work is focused on the development of a high-throughput assay for the quantitation of N-ethyldiethanolamine (EDEA) and N-methyldiethanolamine (MDEA) metabolites of bis (2-chloroethyl) ethylethanamine (HN1) and bis (2-chloroethyl) methylethanamine (HN2), respectively. The method uses automated 96-well plate sample preparation of human urine samples and a 2-position 10-port switching valve to allow for simultaneous regeneration of the liquid chromatography (LC) columns. Using this method, over 18 h was saved through the reduction of sample preparation and analysis time when compared to a conventional method for 96 samples. The validated method provided excellent accuracy for both EDEA (100.9%) and MDEA (100.6%) with precision better than 5.27% for each analyte. (C) 2011 Elsevier B.V. All rights reserved. C1 [Reddy, Muntha K.; Mills, Grier; Nixon, Christopher; Wyatt, Shane A.] 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), 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 20 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 15 PY 2011 VL 879 IS 24 BP 2383 EP 2388 DI 10.1016/j.jchromb.2011.06.029 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 811TU UT WOS:000294239800004 PM 21764395 ER PT J AU Howard, TB Tassinari, MS Feibus, KB Mathis, LL AF Howard, Tammie B. Tassinari, Melissa S. Feibus, Karen B. Mathis, Lisa L. TI Monitoring for Teratogenic Signals: Pregnancy Registries and Surveillance Methods SO AMERICAN JOURNAL OF MEDICAL GENETICS PART C-SEMINARS IN MEDICAL GENETICS LA English DT Article DE pregnancy exposure registry; pregnancy surveillance programs; teratogenic signal detection; medication and pregnancy; fetal risk and medication ID EXPOSURE REGISTRIES; DRUGS; SAFETY; COHORT; RISK; FDA AB Pregnant women should have access to medications that have been adequately studied for use to facilitate evidence-based risk-benefit discussions with their health care providers. Pregnant women experience acute medical emergencies, have existing conditions that require continued medical treatment or may develop pregnancy-induced conditions, making drug use during pregnancy unavoidable. Drug labeling is the primary source of information about a drug's use. The safety and efficacy data found in the label is derived from well-controlled clinical trials conducted prior to a drug's approval. However, pregnant women are rarely enrolled in clinical trials unless a product is specifically indicated for a pregnancy-related condition. Consequently, information regarding a product's use during pregnancy is usually collected postapproval. Current data collection tools include pregnancy exposure registries, retrospective cohort studies, pregnancy surveillance programs, case-control studies, spontaneous reports of adverse events and case reports. Each tool has strengths and limitations in its ability to detect teratogenic signals. Combinations of different sources of data are necessary to acquire the most complete picture of potential teratogenic risk, as no single method can capture all desired data to help pregnant patients and women of child bearing potential make appropriate risk benefits decisions along with their health care providers. Published 2011 Wiley-Liss, Inc.(dagger) C1 [Howard, Tammie B.; Tassinari, Melissa S.] US FDA, Pediat & Maternal Hlth Staff, Maternal Hlth Team, CDER Off New Drugs, Silver Spring, MD 20993 USA. [Mathis, Lisa L.] US FDA, Off New Drugs, Pediat & Maternal Hlth Staff, CDER, Silver Spring, MD 20993 USA. [Mathis, Lisa L.] US PHS, Washington, DC 20201 USA. RP Tassinari, MS (reprint author), US FDA, Pediat & Maternal Hlth Staff, Maternal Hlth Team, CDER Off New Drugs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melissa.tassinari@fda.hhs.gov NR 25 TC 7 Z9 7 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4868 J9 AM J MED GENET C JI Am. J. Med. Genet. C PD AUG 15 PY 2011 VL 157C IS 3 SI SI BP 209 EP 214 DI 10.1002/ajmg.c.30304 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 802VM UT WOS:000293539100009 PM 21766431 ER PT J AU McGuire, V Van den Eeden, SK Tanner, CM Kamel, F Umbach, DM Marder, K Mayeux, R Ritz, B Ross, GW Petrovitch, H Topol, B Popat, RA Costello, S Manthripragada, AD Southwick, A Myers, RM Nelson, LM AF McGuire, V. Van den Eeden, S. K. Tanner, C. M. Kamel, F. Umbach, D. M. Marder, K. Mayeux, R. Ritz, B. Ross, G. W. Petrovitch, H. Topol, B. Popat, R. A. Costello, S. Manthripragada, A. D. Southwick, A. Myers, R. M. Nelson, L. M. TI Association of DRD2 and DRD3 polymorphisms with Parkinson's disease in a multiethnic consortium SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Parkinson's disease; Dopamine receptor genes; Case-control studies; Epidemiology ID DOPAMINE-RECEPTOR; GENE; SUSCEPTIBILITY; SMOKING; ANKK1; DEPENDENCE; AMERICAN; BEHAVIOR; TTC12; NCAM1 AB Objective: To examine genetic associations of polymorphisms in the dopamine receptor D2 (DRD2) and D3 (DRD3) genes with risk of Parkinson's disease (PD). Methods: The study included 1325 newly diagnosed patients with PD and 1735 controls from a consortium of five North American case-control studies. We collected risk factor information by in-person or telephone interview. Six DRD2 and two DRD3 polymorphisms were genotyped using a common laboratory. Odds ratios were estimated using logistic regression. Results: Among non-Hispanic whites, homozygous carriers of Taq1A DRD2 (rs1800497) polymorphism had an increased risk of PD compared to homozygous wildtype carriers (OR = 1.5, 95% CI 1.0-2.3). In contrast, the direction of association for Taq1A polymorphism was opposite for African-Americans, showing an inverse association with PD risk (OR = 0.10, 95% CI 0.2-0.7). Among white Hispanics who carried two alleles, the Ser9Gly DRD3 (rs6280) polymorphism was associated with a decreased risk of PD (OR = 0.4, 95% CI 0.2-0.8). The inverse association of smoking with PD risk was not modified by any of the DRD2 or DRD3 polymorphisms. Conclusions: DRD2 polymorphisms are unlikely to be true disease-causing variants; however, three DRD2 polymorphisms (including Taq1A) may be in linkage disequilibrium with possible disease associated variants in the DRD2-ANKK1-NCAM1-TTC12 gene cluster. (C) 2011 Elsevier B.V. All rights reserved. C1 [McGuire, V.; Topol, B.; Popat, R. A.; Nelson, L. M.] Stanford Univ, Dept Hlth Res & Policy, Sch Med, Div Epidemiol, Stanford, CA 94305 USA. [Van den Eeden, S. K.] Kaiser Fdn Res Inst, Div Res, Oakland, CA USA. [Tanner, C. M.] Parkinsons Inst, Sunnyvale, CA USA. [Kamel, F.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. [Umbach, D. M.] Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. [Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. [Marder, K.; Mayeux, R.] Columbia Univ, Gertrude H Sergievsky Ctr, Coll Phys & Surg, New York, NY 10027 USA. [Marder, K.; Mayeux, R.] Columbia Univ, Coll Phys & Surg, Taub Inst, New York, NY USA. [Ritz, B.; Costello, S.; Manthripragada, A. D.] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. [Ross, G. W.; Petrovitch, H.] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA. [Ross, G. W.; Petrovitch, H.] Pacific Hlth Res Inst, Honolulu, HI USA. [Costello, S.] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Manthripragada, A. D.] US FDA, Rockville, MD 20857 USA. [Southwick, A.; Myers, R. M.] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. RP McGuire, V (reprint author), Stanford Univ, Dept Hlth Res & Policy, Sch Med, Div Epidemiol, HRP Redwood Bldg,Room T213C, Stanford, CA 94305 USA. EM vmcguire@stanford.edu RI Ritz, Beate/E-3043-2015; OI Kamel, Freya/0000-0001-5052-6615 FU Michael J. Fox Foundation for Parkinson's Research; NIH [NS R01-31964, ES R03-13970, R01-NS32527, ES10544]; Tobacco-Related Disease Research Fund [8RT-0131, 11RT-0237]; SCEHSC [5P30 ES07048]; Parkinson's Disease Association; United States Department of the Army [DAMD17-98-1-8621, NIA NO1-AG-4-2149, NINDSR01-NS41265, NHLBINO1-HC-05102]; Office of Research and Development, Medical Research Service, Veterans Affairs; NIH; NCI (Division of Cancer Epidemiology and Genetics) [U54-ES12077]; [NIAPO1 AG07232]; [U54-ES12078]; [NIEHS01-ES10803] FX Funding was provided to the PEGASUS genetic consortium by the Michael J. Fox Foundation for Parkinson's Research. Additional funding to individual investigators for the original studies was provided by: NIH NS R01-31964, NIH ES R03-13970, and Tobacco-Related Disease Research Fund Grants 8RT-0131 and 11RT-0237 (Dr. Lorene Nelson,); NIH R01-NS32527 (Drs. Richard Mayeux and Karen Marder), NIAPO1 AG07232 (Dr. Richard Mayeux); NIH ES10544 and U54-ES12078, pilot funding from SCEHSC # 5P30 ES07048, the Parkinson's Disease Association (Dr. Beate Ritz); United States Department of the Army-DAMD17-98-1-8621, NIA NO1-AG-4-2149, NINDSR01-NS41265, NHLBINO1-HC-05102, and Office of Research and Development, Medical Research Service, Veterans Affairs (Dr. G. Webster Ross); NIEHS01-ES10803 and NIH intramural funding to NIEHS (Epidemiology Branch) and NCI (Division of Cancer Epidemiology and Genetics) U54-ES12077 (Drs. Caroline Tanner and Freya Kamel). The information in this paper does not necessarily reflect the position or the policy of the government and no official endorsement should be inferred. NR 29 TC 15 Z9 16 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD AUG 15 PY 2011 VL 307 IS 1-2 BP 22 EP 29 DI 10.1016/j.jns.2011.05.031 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 796KF UT WOS:000293049500005 PM 21663922 ER PT J AU Kleemann, R Bureeva, S Perlina, A Kaput, J Verschuren, L Wielinga, PY Hurt-Camejo, E Nikolsky, Y van Ommen, B Kooistra, T AF Kleemann, Robert Bureeva, Svetlana Perlina, Ally Kaput, Jim Verschuren, Lars Wielinga, Peter Y. Hurt-Camejo, Eva Nikolsky, Yuri van Ommen, Ben Kooistra, Teake TI A Systems Biology Strategy for Predicting Similarities and Differences of Drug Effects: Evidence for Drug-specific Modulation of Inflammation in Atherosclerosis SO BMC SYSTEMS BIOLOGY LA English DT Article ID PPAR-ALPHA ACTIVATORS; GENE-EXPRESSION; TRANSGENIC MICE; RECEPTOR-ALPHA; CARDIOVASCULAR-DISEASES; PLASMA-CHOLESTEROL; IN-VIVO; FENOFIBRATE; BETA; STATINS AB Background: Successful drug development has been hampered by a limited understanding of how to translate laboratory-based biological discoveries into safe and effective medicines. We have developed a generic method for predicting the effects of drugs on biological processes. Information derived from the chemical structure and experimental omics affected by drugs. Results: Validation of the method with anti-atherosclerotic compounds (fenofibrate, rosuvastatin, LXR activator T0901317) demonstrated a great conformity between the computationally predicted effects and the wet-lab biochemical effects. Comparative genome-wide pathway mapping revealed that the biological drug effects were realized largely via different pathways and mechanisms. In line with the predictions, the drugs showed differential effects on inflammatory pathways (downstream of PDGF, VEGF, IFN gamma, TGF beta, IL1 beta, TNF alpha, LPS), transcriptional regulators (NF kappa B, C/EBP, STAT3, AP-1) and enzymes (PKC delta, AKT, PLA2), and they quenched different aspects of the inflammatory signaling cascade. Fenofibrate, the compound predicted to be most efficacious in inhibiting early processes of atherosclerosis, had the strongest effect on early lesion development. Conclusion: Our approach provides mechanistic rationales for the differential and common effects of drugs and may help to better understand the origins of drug actions and the design of combination therapies. C1 [Kleemann, Robert; Verschuren, Lars; Wielinga, Peter Y.; Kooistra, Teake] TNO, NL-2333 CK Leiden, Netherlands. [Verschuren, Lars; van Ommen, Ben] TNO, NL-3704 HE Zeist, Netherlands. [Bureeva, Svetlana; Perlina, Ally; Nikolsky, Yuri] GeneGo Inc, Carlsbad, CA 92008 USA. [Kaput, Jim] Natl Ctr Toxicol Res, Div Personalized Nutr & Med FDA, Jefferson, AR 72079 USA. [Kaput, Jim] Nestle Inst Hlth Sci, CH-1015 Lausanne, Switzerland. [Hurt-Camejo, Eva] AstraZeneca, Cardiovasc & Gastrointestinal Innovat Med Unit, S-43183 Molndal, Sweden. RP Kleemann, R (reprint author), TNO, Zernikedreef 9, NL-2333 CK Leiden, Netherlands. EM robert.kleemann@tno.nl FU TNO; Centre for Medical Systems Biology within the framework of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research [050-060-409] FX This study was supported by the TNO research program VP Personalized Health (to R.K., B.v.O, T.K.). L.V. received grant support (050-060-409) from the Centre for Medical Systems Biology within the framework of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research. We are grateful to Maren White and Graham Smith for helpful discussions and critical reading of the manuscript. We thank Annie Jie, Wim van Duyvenvoorde and Karin Toet for excellent bioinformatical and analytical help. NR 38 TC 13 Z9 13 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1752-0509 J9 BMC SYST BIOL JI BMC Syst. Biol. PD AUG 12 PY 2011 VL 5 AR 125 DI 10.1186/1752-0509-5-125 PG 16 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA 814HY UT WOS:000294440400001 PM 21838869 ER PT J AU Green, JO Nagaraja, S Diab, T Vidakovic, B Guldberg, RE AF Green, Jessica O. Nagaraja, Srinidhi Diab, Tamim Vidakovic, Brani Guldberg, Robert E. TI Age-related changes in human trabecular bone: Relationship between microstructural stress and strain and damage morphology SO JOURNAL OF BIOMECHANICS LA English DT Article DE Trabecular bone; Microdamage; Microcomputed tomography; Finite element analysis; Aging; Biomechanics ID VERTEBRAL CANCELLOUS BONE; FINITE-ELEMENT MODELS; MICRODAMAGE ACCUMULATION; COMPACT-BONE; OSTEOPOROSIS; COMPRESSION; FRACTURES; FRAGILITY; DENSITY; VOLUME AB Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32-37 years, n=3 donors) and post-menopausal (71-80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% Cl for von Mises stress on undamaged regions ranged from 50.7-67.9 MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7-50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Green, Jessica O.; Nagaraja, Srinidhi; Diab, Tamim; Guldberg, Robert E.] Georgia Inst Technol, Woodruff Sch Mech Engn, Atlanta, GA 30332 USA. [Green, Jessica O.] Med Coll Georgia, Sch Med, Augusta, GA 30912 USA. [Nagaraja, Srinidhi] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Vidakovic, Brani; Guldberg, Robert E.] Georgia Inst Technol, Wallace H Coulter Dept Biomed Engn, Atlanta, GA 30332 USA. RP Guldberg, RE (reprint author), Inst Bioengn & Biosci, 315 Ferst Dr, Atlanta, GA 30332 USA. EM robert.guldberg@me.gatech.edu FU NIH [R01 AG027249]; NSF [9977551] FX This research study was supported by NIH, Grant R01 AG027249. The micro-CT system was provided by NSF Major Research Instrumentation Award 9977551. The authors would like to thank Karl Jepsen for assistance with this study. 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 32 TC 18 Z9 21 U1 0 U2 14 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 EI 1873-2380 J9 J BIOMECH JI J. Biomech. PD AUG 11 PY 2011 VL 44 IS 12 BP 2279 EP 2285 DI 10.1016/j.jbiomech.2011.05.034 PG 7 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 809DY UT WOS:000294033200015 PM 21724189 ER PT J AU Levis, S Strickman-Stein, N Ganjei-Azar, P Xu, P Doerge, DR Krischer, J AF Levis, Silvina Strickman-Stein, Nancy Ganjei-Azar, Parvin Xu, Ping Doerge, Daniel R. Krischer, Jeffrey TI Soy Isoflavones in the Prevention of Menopausal Bone Loss and Menopausal Symptoms A Randomized, Double-blind Trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MINERAL DENSITY CHANGES; POSTMENOPAUSAL WOMEN; HEALTH; OSTEOPOROSIS; METAANALYSIS; PHYTOESTROGENS; COMPLEMENTARY; METABOLISM; TRANSITION; GENISTEIN AB Background: Concerns regarding the risk of estrogen replacement have resulted in a significant increase in the use of soy products by menopausal women who, despite the lack of evidence of the efficacy of such products, seek alternatives to menopausal hormone therapy. Our goal was to determine the efficacy of soy isoflavone tablets in preventing bone loss and menopausal symptoms. Methods: The study design was a single-center, randomized, placebo-controlled, double-blind clinical trial conducted from July 1, 2004, through March 31, 2009. Women aged 45 to 60 years within 5 years of menopause and with a bone mineral density T score of -2.0 or higher in the lumbar spine or total hip were randomly assigned, in equal proportions, to receive daily soy isoflavone tablets, 200 mg, or placebo. The primary outcome was changes in bone mineral density in the lumbar spine, total hip, and femoral neck at the 2-year follow-up. Secondary outcomes included changes in menopausal symptoms, vaginal cytologic characteristics, N-telopeptide of type I bone collagen, lipids, and thyroid function. Results: After 2 years, no significant differences were found between the participants receiving soy tablets (n= 122) and those receiving placebo (n= 126) regarding changes in bone mineral density in the spine (-2.0% and -2.3%, respectively), the total hip (-1.2% and -1.4%, respectively), or the femoral neck (-2.2% and -2.1%, respectively). A significantly larger proportion of participants in the soy group experienced hot flashes and constipation compared with the control group. No significant differences were found between groups in other outcomes. Conclusions: In this population, the daily administration of tablets containing 200 mg of soy isoflavones for 2 years did not prevent bone loss or menopausal symptoms. C1 [Levis, Silvina] Univ Miami, Miller Sch Med, Dept Med, Miami, FL 33101 USA. [Strickman-Stein, Nancy] Univ Miami, Miller Sch Med, Dept Epidemiol, Miami, FL 33101 USA. [Ganjei-Azar, Parvin] Univ Miami, Miller Sch Med, Dept Pathol, Miami, FL 33101 USA. Miami Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Miami, FL USA. [Xu, Ping; Krischer, Jeffrey] Univ S Florida, Dept Pediat, Tampa, FL 33620 USA. [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Levis, S (reprint author), Univ Miami, Miller Sch Med, Dept Med, POB 016960,D-503, Miami, FL 33101 USA. EM slevis@med.miami.edu FU National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health [RO1AR048932-01A1] FX National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, grant RO1AR048932-01A1 (Dr Levis). NR 29 TC 67 Z9 72 U1 5 U2 23 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 8 PY 2011 VL 171 IS 15 BP 1363 EP 1369 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 804GR UT WOS:000293642800011 PM 21824950 ER PT J AU Khurana, S Larkin, C Verma, S Joshi, MB Fontana, J Steven, AC King, LR Manischewitz, J McCormick, W Gupta, RK Golding, H AF Khurana, Surender Larkin, Christopher Verma, Swati Joshi, Manju B. Fontana, Juan Steven, Alasdair C. King, Lisa R. Manischewitz, Jody McCormick, William Gupta, Rajesh K. Golding, Hana TI Recombinant HA1 produced in E. coli forms functional oligomers and generates strain-specific SRID potency antibodies for pandemic influenza vaccines SO VACCINE LA English DT Article DE Pandemic influenza; Vaccine potency; Single-radial immunodiffusion assay; H5N1; H1N1; Vaccine ID SINGLE-RADIAL-IMMUNODIFFUSION; UNIVERSAL ANTIBODIES; ELECTRON-MICROSCOPY; VIRUS PROTEINS; UNITED-STATES; A VIRUS; HEMAGGLUTININ; HUMANS; QUANTIFICATION; RESOLUTION AB Vaccine production and initiation of mass vaccination is a key factor in rapid response to new influenza pandemic. During the 2009-2010 H1N1 pandemic, several bottlenecks were identified, including the delayed availability of vaccine potency reagents. Currently, antisera for the single-radial immunodiffusion (SRID) potency assay are generated in sheep immunized repeatedly with HA released and purified after bromelain-treatment of influenza virus grown in eggs. This approach was a major bottleneck for pandemic H1N1 (H1N1pdm09) potency reagent development in 2009. Alternative approaches are needed to make HA immunogens for generation of SRID reagents in the shortest possible time. In this study, we found that properly folded recombinant HA1 globular domain (rHA1) from several type A viruses including H1N1pdm09 and two H5N1 viruses could be produced efficiently using a bacterial expression system and subsequent purification. The rHA1 proteins were shown to form functional oligomers of trimers, similar to virus derived HA, and elicited high titer of neutralizing antibodies in rabbits and sheep. Importantly, the immune sera formed precipitation rings with reference antigens in the SRID assay in a dose-dependent manner. The HA contents in multiple H1N1 vaccine products from different manufacturers (and in several lots) as determined with the rHA1-generated sheep sera were similar to the values obtained with a traditionally generated sheep serum from NIBSC. We conclude that bacterially expressed recombinant HA1 proteins can be produced rapidly and used to generate SRID potency reagents shortly after new influenza strains with pandemic potential are identified. Published by Elsevier Ltd. C1 [Khurana, Surender; Verma, Swati; King, Lisa R.; Manischewitz, Jody; Golding, Hana] US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. [Larkin, Christopher; Joshi, Manju B.; McCormick, William; Gupta, Rajesh K.] US FDA, Div Prod Qual, CBER, Bethesda, MD 20892 USA. [Fontana, Juan; Steven, Alasdair C.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, CBER, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov RI Fontana, Juan/A-9138-2009 OI Fontana, Juan/0000-0002-9084-2927 FU BARDA/HHS; DMID IAA [224-10-1006]; National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health FX We thank Vladimir Lugovtsev, and Falko Schmeisser for a thorough review of the manuscript. This work was partly supported funds from BARDA/HHS, by DMID IAA 224-10-1006, and by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. The funders had no role in study design, data collection and analysis, or preparation of the manuscript. NR 30 TC 21 Z9 24 U1 1 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 AUG 5 PY 2011 VL 29 IS 34 BP 5657 EP 5665 DI 10.1016/j.vaccine.2011.06.014 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 810RW UT WOS:000294145800012 PM 21704111 ER PT J AU Brewer, MT Xiong, NL Dier, JD Anderson, KL Rasmussen, MA Franklin, SK Carlson, SA AF Brewer, Matt T. Xiong, Nalee Dier, Jeffery D. Anderson, Kristi L. Rasmussen, Mark A. Franklin, Sharon K. Carlson, Steve A. TI Comparisons of Salmonella conjugation and virulence gene hyperexpression mediated by rumen protozoa from domestic and exotic ruminants SO VETERINARY MICROBIOLOGY LA English DT Article DE Salmonella; Invasion; Pathogenicity; Protozoa; Antibiotic resistance; Integron ID TYPHIMURIUM DT104; ANTIBIOTIC-RESISTANCE; INVASION; EXPOSURE; DIET AB Recent studies have identified a phenomenon in which ciliated protozoa engulf Salmonella and the intra-protozoal environment hyperactivates virulence gene expression and provides a venue for conjugal transfer of antibiotic resistance plasmids. The former observation is relegated to Salmonella bearing the SGI1 multiresistance integron while the latter phenomenon appears to be a more generalized event for recipient Salmonella. Our previous studies have assessed virulence gene hyperexpression only with protozoa from the bovine rumen while conjugal transfer has been demonstrated in rumen protozoa from cattle and goats. The present study examined virulence gene hyperexpression for Salmonella exposed to rumen protozoa obtained from cattle, sheep, goats, or two African ruminants (giraffe and bongo). Conjugal transfer was also assessed in these protozoa using Salmonella as the recipient. Virulence gene hyperexpression was only observed following exposure to the rumen protozoa from cattle and sheep while elevated virulence was also observed in these animals. Conjugal transfer events were, however, observed in all protozoa evaluated. It therefore appears that the protozoa-based hypervirulence is not universal to all ruminants while conjugal transfer is more ubiquitous. (C) 2011 Elsevier B.V. All rights reserved. C1 [Brewer, Matt T.; Xiong, Nalee; Anderson, Kristi L.; Carlson, Steve A.] Iowa State Univ, Coll Vet Med, Dept Biomed Sci, Ames, IA 50011 USA. [Dier, Jeffery D.] Blank Pk Zoo, Des Moines, IA USA. [Rasmussen, Mark A.; Franklin, Sharon K.] FDA CVM, Laurel, MD USA. RP Carlson, SA (reprint author), Iowa State Univ, Coll Vet Med, Dept Biomed Sci, 2028 VetMed, Ames, IA 50011 USA. EM stevec@iastate.edu RI Rasmussen, Mark/N-9509-2014 NR 16 TC 4 Z9 4 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD AUG 5 PY 2011 VL 151 IS 3-4 BP 301 EP 306 DI 10.1016/j.vetmic.2011.03.011 PG 6 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 801HE UT WOS:000293428400011 PM 21481550 ER PT J AU Chae, MH Chen, JJ AF Chae, Minho Chen, James J. TI Reordering Hierarchical Tree Based on Bilateral Symmetric Distance SO PLOS ONE LA English DT Article ID GENE-EXPRESSION; PATTERNS AB Background: In microarray data analysis, hierarchical clustering (HC) is often used to group samples or genes according to their gene expression profiles to study their associations. In a typical HC, nested clustering structures can be quickly identified in a tree. The relationship between objects is lost, however, because clusters rather than individual objects are compared. This results in a tree that is hard to interpret. Methodology/Principal Findings: This study proposes an ordering method, HC-SYM, which minimizes bilateral symmetric distance of two adjacent clusters in a tree so that similar objects in the clusters are located in the cluster boundaries. The performance of HC-SYM was evaluated by both supervised and unsupervised approaches and compared favourably with other ordering methods. Conclusions/Significance: The intuitive relationship between objects and flexibility of the HC-SYM method can be very helpful in the exploratory analysis of not only microarray data but also similar high-dimensional data. C1 [Chae, Minho; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Chae, Minho] Univ Texas SW Med Ctr Dallas, Cecil H & Ida Green Ctr Reprod Biol Sci, Dallas, TX 75390 USA. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chae, MH (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. EM jamesj.chen@fda.hhs.gov FU FDA at the NCTR FX Dr. Minho Chae was supported by the FDA Research Participation Program at the NCTR administered by the Oak Ridge Associated Universities. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 16 TC 2 Z9 2 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD AUG 4 PY 2011 VL 6 IS 8 AR e22546 DI 10.1371/journal.pone.0022546 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 803DK UT WOS:000293561200021 PM 21829631 ER PT J AU Kozlowski, S Woodcock, J Midthun, K Sherman, RB AF Kozlowski, Steven Woodcock, Janet Midthun, Karen Sherman, Rachel Behrman TI Developing the Nation's Biosimilars Program SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Kozlowski, Steven; Woodcock, Janet; Sherman, Rachel Behrman] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Midthun, Karen] Ctr Biol Evaluat & Res, Silver Spring, MD USA. RP Kozlowski, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 99 Z9 102 U1 4 U2 18 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 AUG 4 PY 2011 VL 365 IS 5 BP 385 EP 388 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 801NW UT WOS:000293447800001 PM 21812668 ER PT J AU Fedio, WM Jinneman, KC Yoshitomi, KJ Zapata, R Wendakoon, CN Browning, P Weagant, SD AF Fedio, Willis M. Jinneman, Karen C. Yoshitomi, Ken J. Zapata, Ruben Wendakoon, Chitra N. Browning, Paul Weagant, Stephen D. TI Detection of E. coli O157:H7 in raw ground beef by Pathatrix (TM) immunomagnetic-separation, real-time PCR and cultural methods SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Pathogen detection; Real-time PCR; Immunomagnetic separation ID ESCHERICHIA-COLI; HEMORRHAGIC COLITIS; SEROTYPE O157-H7; RAPID ISOLATION; ENRICHMENT; FOODS; IDENTIFICATION; EPIDEMIOLOGY; SPROUTS; PRODUCE AB Detection of Escherichia coli O157:H7 by conventional cultural methods can be difficult in food matrices with a high background flora such as raw ground beef. Raw ground beef samples, artificially contaminated separately with five strains of E. coli O157:H7 at low (similar to 0.2 cfu/g) and high (similar to 2 cfu/g) levels, were enriched by two enrichment protocols; buffered peptone water (BPW) at 37 C for 5 h and 24 h and modified buffered peptone water with pyruvate (mBPWp) for 5 h at 37 degrees C followed by adding selective agents and incubating at 42 degrees C to 24 h. Detection of added E. coli O157:H7 by real-time PCR (RTiPCR) and recovery on isolation agars was performed before and after PATHATRIX (TM) immunomagnetic separation (IMS). RTiPCR detection and cultural recovery of inoculated E. coli O157:H7 after 5 h enrichment were poor at 0.21-0.24 cfu/g. The addition of IMS after 5 h enrichment did not improve RTiPCR detection but markedly improved recovery by culturing. By extending enrichment to 24 h, RTiPCR detection improved to 76% for either enrichment protocol without IMS. When 24 h enrichment was followed by IMS, RTiPCR detection was also further improved. Cultural recovery after 24 h enrichment was 56% and 84% without IMS and 100% and 92% after IMS for BPW and mBPWp respectively. Extended enrichment to 24 h followed by IMS was found to be sensitive and reliable for detection and cultural recovery from raw ground beef using either enrichment method. (C) 2011 Elsevier B.V. All rights reserved. C1 [Fedio, Willis M.] New Mexico State Univ, Food Safety Lab, Ctr Anim Hlth Food Safety & Biosecur, Las Cruces, NM 88003 USA. [Jinneman, Karen C.; Yoshitomi, Ken J.; Weagant, Stephen D.] US FDA, Bothell, WA USA. RP Fedio, WM (reprint author), New Mexico State Univ, Food Safety Lab, Ctr Anim Hlth Food Safety & Biosecur, 2990 Knox St, Las Cruces, NM 88003 USA. EM wfedio@nmsu.edu FU US FDA [WL5QKN-05-D-0022] FX This study was supported in part by US FDA Contract No. WL5QKN-05-D-0022. NR 34 TC 29 Z9 33 U1 4 U2 30 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 AUG 2 PY 2011 VL 148 IS 2 BP 87 EP 92 DI 10.1016/j.ijfoodmicro.2011.05.005 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 797EX UT WOS:000293108400003 PM 21641670 ER PT J AU Koti, KM AF Koti, Kallappa M. TI Exponential Failure-Time Mixture Model Approach for Validating KRAS as a Predictive Biomarker for Panitumumab Monotherapy in the Treatment of Metastatic Colorectal Cancer SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Accelerated failure-time model; Identifiability; Intent-to-treat analysis; Interaction; Likelihood ratio test ID EFFICACY; TRIALS AB Progression-free survival (PFS) results from the Amgen Study 20020408 were presented and discussed in the December 2008 Oncologic Drugs Advisory Committee. Using the retrospective "sorted" subgroup analyses it was claimed that Kirsten rat Sarcoma (KRAS) status should be considered when selecting metastatic colorectal cancer (mCRC) patients as candidates for panitumumab monotherapy. A similar conclusion was reached by Amado et al. (2008). Results based on sorted subgroup analyses may not be conclusive. We propose an exponential failure-time mixture model that helps to both validate a marker and demonstrate drug efficacy. This analysis includes all randomized KRAS-evaluable subjects and considers the KRAS status as a random outcome. The model also facilitates a comparison of PFS between the wild-type and mutant KRAS subgroups of subjects on the panitumumab arm. We conclude that KRAS is a predictive biomarker for the panitumumab therapy as measured by PFS in the treatment of mCRC patients. The objective of this article is to provide details and to discuss the scope and limitation of the proposed methodology. C1 US FDA, Silver Spring, MD 20993 USA. RP Koti, KM (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kallappa.koti@fda.hhs.gov NR 18 TC 0 Z9 0 U1 1 U2 1 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD AUG PY 2011 VL 3 IS 3 BP 425 EP 433 DI 10.1198/sbr.2011.09034 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 834EH UT WOS:000295941700001 ER PT J AU Tseng, SC Kimchi-Sarfaty, C AF Tseng, Sandra Chang Kimchi-Sarfaty, Chava TI SNPs in ADAMTS13 SO PHARMACOGENOMICS LA English DT Review DE ADAMTS13; genetic variation; polymorphism; thrombocytopenic thrombotic purpura; von Willebrand factor-cleaving protease ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; FACTOR-CLEAVING PROTEASE; UPSHAW-SCHULMAN-SYNDROME; SPACER DOMAIN; METALLOPROTEASE ADAMTS13; PRO475SER POLYMORPHISM; SUBSTRATE-SPECIFICITY; MYOCARDIAL-INFARCTION; P475S POLYMORPHISM AB The multidomain metalloprotease ADAMTS13 limits thrombus formation via the cleavage of large multimeric forms of von Willebrand factor. Deficiency of functional ADAMTS13 is associated with a number of disease pathologies including thrombotic thrombocytopenic purpura, cardiovascular disease and inflammation. To date, deficiency is known to result from mutations in the ADAMTS13 gene or from inhibitory and non-neutralizing antibodies. The exact contributory effect of genetic variation in ADAMTS13 on observable pathology is unclear, and specifically, polymorphisms of ADAMTS13 have not been the focus of much systematic study. Here we have amassed an up-to-date collection of ADAMTS13 polymorphisms described in the literature and from the National Center for Biotechnology Information's SNP database. This article considers the effect that these polymorphisms may have on the expression and function of ADAMTS13 and speculates on their relevance in future therapies based on pharmacogenomics. C1 [Tseng, Sandra Chang; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kimchi-Sarfaty, C (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM chava.kimchi-sarfaty@fda.hhs.gov NR 76 TC 3 Z9 3 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 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD AUG PY 2011 VL 12 IS 8 BP 1147 EP 1160 DI 10.2217/PGS.11.66 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 826CX UT WOS:000295330100013 PM 21843064 ER PT J AU Abou-Ali, A Kang, EM Pinheiro, S Hammad, TA AF Abou-Ali, Adel Kang, Elizabeth M. Pinheiro, Simone Hammad, Tarek A. TI Association between Antidepressant Drugs and Cataracts in the UK-Based General Practice Research Database: A Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Abou-Ali, Adel; Kang, Elizabeth M.; Pinheiro, Simone; Hammad, Tarek A.] US FDA, CDER, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 677 BP S294 EP S294 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600650 ER PT J AU Abou-Ali, A Kang, EM Pinheiro, S Hammad, TA AF Abou-Ali, Adel Kang, Elizabeth M. Pinheiro, Simone Hammad, Tarek A. TI Association between Antidepressant Drugs and Cancer in the UK-Based General Practice Research Database: A Cohort Study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Abou-Ali, Adel; Kang, Elizabeth M.; Pinheiro, Simone; Hammad, Tarek A.] US FDA, CDER, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 441 BP S192 EP S193 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600426 ER PT J AU Abou-Ali, A Callaham, M Kuyateh, F Hammad, TA AF Abou-Ali, Adel Callaham, Marian Kuyateh, Fatmatta Hammad, Tarek A. TI SSRIs Use during Pregnancy and the Risk of Cardiac Congenital Malformations using the General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Abou-Ali, Adel; Callaham, Marian; Kuyateh, Fatmatta; Hammad, Tarek A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 99 BP S43 EP S43 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600097 ER PT J AU Ahmad, SR Zhou, E AF Ahmad, Syed Rizwanuddin Zhou, Esther TI Acetaminophen-Associated Poisonings/Exposure Calls in Children SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ahmad, Syed Rizwanuddin; Zhou, Esther] US FDA, Div Epidemiol, OSE, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 733 BP S318 EP S318 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600704 ER PT J AU Ahmad, SR Elixhauser, A Sutton, JP AF Ahmad, Syed Rizwanuddin Elixhauser, Anne Sutton, Janet P. TI Hepatotoxicity in Association with Acetaminophen Poisonings in the US SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ahmad, Syed Rizwanuddin] DEPI OSE FDA CDER, Silver Spring, MD USA. [Elixhauser, Anne] AHRQ, Rockville, MD USA. [Sutton, Janet P.] Social & Sci Syst, Silver Spring, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 588 BP S256 EP S256 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600567 ER PT J AU Bird, S Liu, XY Pepe, S Brophy, J Etminan, M Delaney, J AF Bird, Steven Liu, Xinyue Pepe, Salvatore Brophy, James Etminan, Mahyar Delaney, Joseph TI The Association between Drospirenone and Hyperkalemia among Women Taking Oral Contraceptives SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Bird, Steven; Liu, Xinyue; Pepe, Salvatore; Delaney, Joseph] Univ Florida, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA. [Bird, Steven; Pepe, Salvatore] US FDA, Ctr Drug Evalut & Res, Silver Spring, MD USA. [Etminan, Mahyar] Univ British Columbia, Ctr Clin Epidemiol & Evaluat, Vancouver, BC V5Z 1M9, Canada. [Brophy, James] McGill Univ, Royal Victoria Hosp, MUHC Technol Assessment Unit, Div Cardiol, Montreal, PQ H3A 1A1, Canada. [Brophy, James] McGill Univ, Royal Victoria Hosp, MUHC Technol Assessment Unit, Div Clin Epidemiol, Montreal, PQ H3A 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 167 BP S72 EP S73 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600162 ER PT J AU Boggon, R Moller, H Gallagher, A Leufkens, H Hammad, T Zhang, H van Staa, T AF Boggon, R. Moller, H. Gallagher, A. Leufkens, H. Hammad, T. Zhang, H. van Staa, T. TI Cancer Recording and Mortality in the General Practice Research Database and Linked Cancer Registry, Hospital and Death Certificate Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Boggon, R.; Gallagher, A.; van Staa, T.] Gen Practice Res Database Med & Healthcare Prod R, London, England. [Moller, H.] Kings Coll London, Thames Canc Registry, London WC2R 2LS, England. [Leufkens, H.] Univ Utrecht, Utecht Inst Pharmaceut Sci, Utrecht, Netherlands. [Hammad, T.; Zhang, H.] US FDA, Off Surveillance & Epidemiol, Washington, DC 20204 USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 373 BP S162 EP S162 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600359 ER PT J AU Brookhart, MA Li, J Paeglow, C Puenpatom, T Polakowski, L Lu, Y Walker, AM Izurieta, H Daniel, GW AF Brookhart, M. A. Li, J. Paeglow, C. Puenpatom, T. Polakowski, L. Lu, Y. Walker, A. M. Izurieta, H. Daniel, G. W. TI Characterizing Vaccine-Associated Risk Using Natural Smoothing Splines SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Brookhart, M. A.] Univ N Carolina, Chapel Hill, NC USA. [Li, J.; Paeglow, C.; Puenpatom, T.; Daniel, G. W.] HealthCore, Wilmington, DE USA. [Polakowski, L.; Lu, Y.; Izurieta, H.] US FDA, CBER, Rockville, MD 20857 USA. [Walker, A. M.] WHISCON, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 597 BP S260 EP S261 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600576 ER PT J AU Chang, SH Shih, DC Pham, T AF Chang, Stephen H. Shih, David C. Tracy Pham TI Pediatric Antiretroviral Outpatient Drug Utilization in the US: Y2002-Y2010 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Chang, Stephen H.; Shih, David C.; Tracy Pham] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 211 BP S91 EP S92 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600204 ER PT J AU Daniel, GW Menis, M Wallace, AE Sridhar, G Izurieta, H AF Daniel, Gregory W. Menis, Mikhail Wallace, Anna E. Sridhar, Gayathri Izurieta, Hector TI Identification of Adverse Events after Immunoglobulin Exposure: Exploratory Analysis of Administrative Claims Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Daniel, Gregory W.; Wallace, Anna E.; Sridhar, Gayathri] HealthCore Inc, Govt & Acad Res, Alexandria, VA USA. [Menis, Mikhail; Izurieta, Hector] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 768 BP S333 EP S333 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600738 ER PT J AU DeMarco, A Pinnow, E Farb, A Brown, S Zuckerman, B AF DeMarco, Angela Pinnow, Ellen Farb, Andrew Brown, Sheila Zuckerman, Bram TI The Safety of Live Case Demonstrations at Cardiovascular Meetings SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [DeMarco, Angela; Pinnow, Ellen] US FDA, Div Epidemiol, Silver Spring, MD USA. [Farb, Andrew; Zuckerman, Bram] US FDA, Div Cardiovasc Devices, Silver Spring, MD USA. [Brown, Sheila] US FDA, Invest Device Exempt Sect, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 81 BP S35 EP S36 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600079 ER PT J AU Edlavitch, SA Dal Pan, GJ Raine, JM Avorn, J Leufkens, HG Park, BJ AF Edlavitch, Stanley A. Dal Pan, Gerald J. Raine, June M. Avorn, Jerry Leufkens, Hubert G. Park, Byong-Ju TI Challenges to Improving the Science of Regulatory Decision-Making SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Edlavitch, Stanley A.] Univ Missouri, Sch Med, Kansas City, MO 64108 USA. [Dal Pan, Gerald J.] US FDA, Off Drug Safety, Silver Spring, MD USA. [Raine, June M.] MHRA UK, London, England. [Avorn, Jerry] Harvard Univ, Sch Med, Div Pharmacoepidemiol & Pharmacoecon, Boston, MA USA. [Leufkens, Hubert G.] Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands. [Park, Byong-Ju] Seoul Natl Univ, Coll Med, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 341 BP S148 EP S148 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600329 ER PT J AU Freedman, AN van der Zee, AHM Zineh, I Pacanowski, M Papaluca-Amati, M Carl, K Leufkens, B AF Freedman, Andrew N. van der Zee, Anke-Hilse Maitland Zineh, Issam Pacanowski, Michael Papaluca-Amati, Marissa Carl, Kevin Leufkens, Burt TI Regulatory Trends in Pharmacogenomic Biomarker Evaluation (Molecular Epi/Biomarkers/Pharmacogenetics SIG Symposium) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Freedman, Andrew N.] NCI, Bethesda, MD 20892 USA. [van der Zee, Anke-Hilse Maitland; Leufkens, Burt] Univ Utrecht, Utrecht, Netherlands. [Zineh, Issam; Pacanowski, Michael] US FDA, Silver Spring, MD USA. EMA, London, England. Novartis, Suffern, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 42 BP S19 EP S19 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600043 ER PT J AU Grijalva, CG Chen, L Delzell, E Baddley, JW Beukelman, T Griffin, MR Herrinton, L Liu, LY Nourjah, P Ouellet-Hellstrom, R Patkar, NM Solomon, DH Winthrop, KL Xie, FL Saag, KG Curtis, JR AF Grijalva, Carlos G. Chen, Lang Delzell, Elizabeth Baddley, John W. Beukelman, Timothy Griffin, Marie R. Herrinton, Lisa Liu, Liyan Nourjah, Parivash Ouellet-Hellstrom, Rita Patkar, Nivedita M. Solomon, Daniel H. Winthrop, Kevin L. Xie, Fenglong Saag, Kenneth G. Curtis, Jeffrey R. TI Initiation of Biologic DMARDs and the Risk of Hospitalized Bacterial Infections in Patients with Rheumatoid Arthritis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Grijalva, Carlos G.; Griffin, Marie R.] Vanderbilt Univ, Nashville, TN USA. [Chen, Lang; Delzell, Elizabeth; Baddley, John W.; Beukelman, Timothy; Patkar, Nivedita M.; Xie, Fenglong; Saag, Kenneth G.; Curtis, Jeffrey R.] Univ Alabama, Birmingham, AL USA. [Herrinton, Lisa; Liu, Liyan] Kaiser Permanente No Calif, Oakland, CA USA. [Solomon, Daniel H.] Harvard Univ, Brigham & Women Hospital, Boston, MA 02115 USA. [Nourjah, Parivash; Ouellet-Hellstrom, Rita] US FDA, Silver Spring, MD USA. [Winthrop, Kevin L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 419 BP S182 EP S183 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600404 ER PT J AU Guo, T Jones, C Zhao, EX Gelperin, K Swartz, L Du, T Rothstein, A Swann, J Hammad, TA AF Guo, Ted Jones, Chris Zhao, Enxu Gelperin, Kate Swartz, Lynette Du, Tony Rothstein, Adrienne Swann, Joslyn Hammad, Tarek A. TI AERscope: A Streamlined Method To Describe FDA Adverse Event Reporting System (AERS) Data Using a Novel SAS/IntrNet Application SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Guo, Ted; Jones, Chris; Zhao, Enxu; Gelperin, Kate; Swartz, Lynette; Du, Tony; Rothstein, Adrienne; Swann, Joslyn; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 772 BP S335 EP S335 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600742 ER PT J AU Hartzema, AG Racoosin, JA Ryan, PB Stang, PE AF Hartzema, Abraham G. Racoosin, Judith A. Ryan, Patrick B. Stang, Paul E. TI Methods Development in Active Drug Safety Surveillance Highlighting the Observational Medical Outcomes Partnership's Findings SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Hartzema, Abraham G.] Univ Florida, Coll Publ Hlth & Hlth Profess, Gainesville, FL USA. [Racoosin, Judith A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Ryan, Patrick B.] Johnson & Johnson, Johnson & Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA. [Stang, Paul E.] Johnson & Johnson, Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 345 BP S150 EP S150 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600333 ER PT J AU Herz, ND Duggirala, HJ Canos, DA Sullivan, R Schaaf, R Pinnow, E Marinac-Dabic, D AF Herz, Naomi D. Duggirala, Hesha J. Canos, Daniel A. Sullivan, Roberta Schaaf, Richard Pinnow, Ellen Marinac-Dabic, Danica TI Disproportionality Analysis for Signal Detection of Implantable Cardioverter-Defibrillator Lead Related Adverse Events SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Herz, Naomi D.; Duggirala, Hesha J.; Canos, Daniel A.; Sullivan, Roberta; Pinnow, Ellen; Marinac-Dabic, Danica] US FDA, Div Epidemiol, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Schaaf, Richard] Oracle Hlth Sci Global Business Unit, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 571 BP S249 EP S249 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600552 ER PT J AU Kaplan, S Zhou, E AF Kaplan, Sigal Zhou, Esther TI Characterization of Long-Acting Beta-Adrenergic Agonists Use for Asthma Treatment SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Zhou, Esther] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 577 BP S251 EP S252 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600557 ER PT J AU Kaplan, S Callaham, M Ding, Y Keeton, S Levenson, M Lowy, N Hammad, T AF Kaplan, Sigal Callaham, Marian Ding, Yulan Keeton, Stephine Levenson, Mark Lowy, Naomi Hammad, Tarek TI Association between Minocycline and Thyroid Cancer in the GPRD: Preliminary Findings SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Kaplan, Sigal; Callaham, Marian; Ding, Yulan; Keeton, Stephine; Levenson, Mark; Lowy, Naomi; Hammad, Tarek] US FDA, Silver Spring, MD USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 83 BP S36 EP S37 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600081 ER PT J AU Krulewitch, CJ Ritchey, MBE Cheng, H Marinac-Dabic, D Gross, T Gibbs, J Worrall, C Kelman, JA AF Krulewitch, Cara J. Ritchey, Mary Beth E. Cheng, Hong Marinac-Dabic, Danica Gross, Tom Gibbs, Jonathan Worrall, Christopher Kelman, Jeffery A. TI Medical Device Safety Surveillance: The Safety of Urogynecologic Surgical Mesh for Repair of Pelvic Organ Prolapse SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Krulewitch, Cara J.; Ritchey, Mary Beth E.; Cheng, Hong; Marinac-Dabic, Danica; Gross, Tom] US FDA, Ctr Devices & Radiologial Hlth, Silver Spring, MD USA. [Gibbs, Jonathan] Acumen LLC, Burlingame, CA USA. [Worrall, Christopher; Kelman, Jeffery A.] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 318 BP S138 EP S138 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600307 ER PT J AU Li, J Daniel, GW Paeglow, C Puenpatom, T Polakowski, L Lu, Y Walker, AM Brookhart, MA Izurieta, H AF Li, Jie Daniel, Gregory W. Paeglow, Corrie Puenpatom, Tom Polakowski, Laura Lu, Yun Walker, Alec M. Brookhart, M. Alan Izurieta, Hector TI Use of Self-Controlled Risk-Interval Design in Childhood Vaccine Safety SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Li, Jie; Daniel, Gregory W.; Paeglow, Corrie; Puenpatom, Tom] HealthCore Inc, Alexandria, VA USA. [Polakowski, Laura; Lu, Yun; Izurieta, Hector] US FDA, CBER OBE DE AEB, Rockville, MD 20857 USA. [Walker, Alec M.] WHISCON, Newton, MA USA. [Brookhart, M. Alan] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 555 BP S242 EP S243 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600537 ER PT J AU Liu, W Munoz, MA Delaney, JAC Brown, E Mugavero, MJ Matthews, C Napravnik, S Willig, JH Saag, MS Kitahata, MM Crane, HM AF Liu, Wei Munoz, Monica A. Delaney, Joseph A. C. Brown, Elizabeth Mugavero, Michael J. Matthews, Chris Napravnik, Sonia Willig, James H. Saag, Michael S. Kitahata, Mari M. Crane, Heidi M. TI Comparative Effectiveness of Fish Oil, Atorvastatin and Fibrates for Lowering Triglyceride Levels among HIV-Infected Patients SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Liu, Wei; Munoz, Monica A.; Delaney, Joseph A. C.] Univ Florida, Gainesville, FL USA. [Munoz, Monica A.] US FDA, Washington, DC 20204 USA. [Brown, Elizabeth; Kitahata, Mari M.; Crane, Heidi M.] Univ Washington, Seattle, WA 98195 USA. [Mugavero, Michael J.; Willig, James H.; Saag, Michael S.] Uinvers Alabama, Birmingham, AL USA. [Matthews, Chris] Univ Calif San Diego, San Diego, CA 92103 USA. [Napravnik, Sonia] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 431 BP S187 EP S188 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600416 ER PT J AU Manthripragada, AD Pinheiro, SP MaCurdy, TE Saneinejad, S Graham, DJ AF Manthripragada, Angelika D. Pinheiro, Simone P. MaCurdy, Thomas E. Saneinejad, Shahin Graham, David J. TI Characteristics and Patterns of Topical Calcineurin Inhibitor Use in Children SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Manthripragada, Angelika D.; Pinheiro, Simone P.; Graham, David J.] US FDA, Off Surveillance & Epidemiol, Silver Spgs, MD USA. [MaCurdy, Thomas E.; Saneinejad, Shahin] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 176 BP S76 EP S77 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600171 ER PT J AU Marinac-Dabic, D Matheny, M West, S Steinbuch, M Sedrakyan, A AF Marinac-Dabic, Danica Matheny, Michael West, Suzanne Steinbuch, Michael Sedrakyan, Art TI Applying Rigorous Methods To Advance the Evidence for Safety and Effectiveness of Implantable Medical Devices SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Marinac-Dabic, Danica] US FDA, Silver Spring, MD USA. [Matheny, Michael] Vanderbilt Univ, Nashville, TN USA. [West, Suzanne] RTI Int, Res Triangle Pk, NC USA. [Steinbuch, Michael] Johnson&Johnson, Princeton, NJ USA. [Sedrakyan, Art] Cornell Univ, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 38 BP S17 EP S18 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600039 ER PT J AU Menschik, D Martin, D AF Menschik, David Martin, David TI Empirical Bayesian Data Mining as an FDA Tool for Prospective Early Detection of Novel Safety Signals in the Vaccine Adverse Events Reporting System (VAERS): A Case Study of Febrile Seizures after an Influenza Virus Vaccine SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Menschik, David; Martin, David] US FDA, Div Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 552 BP S241 EP S241 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600534 ER PT J AU Meyer, TE Taylor, LG Xie, S Graham, DJ Mosholder, AD RWilliams, J Moeny, D Ouellet-Hellestrom, R Coster, TS AF Meyer, Tamra E. Taylor, Lockwood G. Xie, Suji Graham, David J. Mosholder, Andrew D. RWilliams, James Moeny, David Ouellet-Hellestrom, Rita Coster, Trinka S. TI Neuropsychiatric Events in Varenicline Compared to Nicotine Replacement Therapy (NRT) Patch Users, Military Health System (MHS) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Meyer, Tamra E.; Taylor, Lockwood G.; Xie, Suji; Coster, Trinka S.] Pharmacovigilance Ctr, Dept Army Hlth Policy & Serv, Silver Spring, MD USA. [Graham, David J.; Mosholder, Andrew D.; RWilliams, James; Moeny, David; Ouellet-Hellestrom, Rita] US FDA, Off Surveillance & Epidemiol, White Oak, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 562 BP S245 EP S246 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600544 ER PT J AU Moeny, D Taylor, L Coster, T AF Moeny, David Taylor, Lockwood Coster, Trinka TI Fluoroquinolone Use and Risk of Achilles Tendon Rupture SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Moeny, David] US FDA, Silver Spring, MD USA. [Taylor, Lockwood; Coster, Trinka] PVC, Dept Army, OTSG, HP&S, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 434 BP S189 EP S189 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600419 ER PT J AU Moro, PL Arana, J Cano, M Lewis, P Haber, P Menschik, D Martin, D Broder, K AF Moro, Pedro L. Arana, Jorge Cano, Maria Lewis, Paige Haber, Penina Menschik, David Martin, David Broder, Karen TI Clinical Patterns of Adverse Events after High-Dose Influenza Vaccine Reported to the Vaccine Adverse Event Reporting System SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Moro, Pedro L.; Arana, Jorge; Cano, Maria; Lewis, Paige; Haber, Penina; Broder, Karen] Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. [Menschik, David; Martin, David] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 840 BP S362 EP S362 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600804 ER PT J AU Neyarapally, GA Hammad, TA Pinheiro, SP Iyasu, S Murray, MD Stang, P AF Neyarapally, George A. Hammad, Tarek A. Pinheiro, Simone P. Iyasu, Solomon Murray, Michael D. Stang, Paul TI Application of Quality of Evidence Assessment Tools to the Evaluation of Pharmacoepidemiologic Safety Studies SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Neyarapally, George A.; Hammad, Tarek A.; Pinheiro, Simone P.; Iyasu, Solomon] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Murray, Michael D.] Purdue Univ, Coll Pharm, Regenstrief Ctr Healthcare Improvement & Res, Indianapolis, IN USA. [Stang, Paul] J&J Pharmaceut Res & Dev, Titusville, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 37 BP S17 EP S17 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600038 ER PT J AU Paeglow, CE Daniel, GW Polakowski, L Brookhart, MA Lu, Y Li, J Puenpatom, T Izurieta, H Walker, AM AF Paeglow, Corrie E. Daniel, Gregory W. Polakowski, Laura Brookhart, M. A. Lu, Yun Li, Jie Puenpatom, Tom Izurieta, Hector Walker, Alexander M. TI Hypothesis Generating Self-Controlled Analysis: Example in Childhood Vaccine Safety SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Paeglow, Corrie E.; Daniel, Gregory W.; Li, Jie; Puenpatom, Tom] HealthCore Inc, Govt & Acad Res, Alexandria, VA 20857 USA. [Polakowski, Laura; Lu, Yun; Izurieta, Hector] US FDA, Ctr Biol Evaulat & Res, Rockville, MD USA. [Brookhart, M. A.] Univ N Carolina, Chapel Hill, NC USA. [Walker, Alexander M.] WHISCON, Newton, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY PERIODICALS, INC PI SAN FRANCISCO PA ONE MONTGOMERY ST, SUITE 1200, SAN FRANCISCO, CA 94104 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 730 BP S316 EP S317 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600701 ER PT J AU Pinheiro, SP Kang, EM Governale, LA Zhou, EH Kim, CY Hammad, TA AF Pinheiro, Simone P. Kang, Elizabeth M. Governale, Laura A. Zhou, Esther H. Kim, Clara Y. Hammad, Tarek A. TI Use Patterns and Concomittant Use of Isotretinoin and Contraceptive Agents before and after iPLEDGE Implementation SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Pinheiro, Simone P.; Kang, Elizabeth M.; Governale, Laura A.; Zhou, Esther H.; Hammad, Tarek A.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Kim, Clara Y.] US FDA, Off Biostat, Div Biometr 7, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 505 BP S220 EP S221 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600488 ER PT J AU Platt, R Racoosin, J Curtis, L Hennessy, S Schneeweiss, S Toh, D AF Platt, Richard Racoosin, Judith Curtis, Lesley Hennessy, Sean Schneeweiss, Sebastian Toh, Darren TI FDA's Mini-Sentinel Program To Evaluate the Safety of Marketed Medical Products: Progress and Prospects SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Platt, Richard; Toh, Darren] Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Racoosin, Judith] US FDA, Silver Spring, MD USA. [Curtis, Lesley] Duke Univ, Sch Med, Durham, NC USA. [Hennessy, Sean] Univ Penn, Philadelphia, PA 19104 USA. [Schneeweiss, Sebastian] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Schneeweiss, Sebastian/C-2125-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 616 BP S268 EP S269 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600594 ER PT J AU Polakowski, L Li, J Daniel, GW Paeglow, C Puenpatom, T Lu, Y Walker, A Brookhart, MA Izurieta, H AF Polakowski, Laura Li, Jie Daniel, Greg W. Paeglow, Corrie Puenpatom, Tom Lu, Yun Walker, Alec Brookhart, M. A. Izurieta, Hector TI Temporal Trends in Health Care Utilization among 1-Year Old Vaccinees: Study Design Refinement for Vaccine Safety SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Polakowski, Laura; Lu, Yun; Izurieta, Hector] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Li, Jie; Daniel, Greg W.; Paeglow, Corrie; Puenpatom, Tom] HealthCore Inc, Wilmington, DE USA. [Walker, Alec] WHISCON, Newton, MA USA. [Brookhart, M. A.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 179 BP S78 EP S78 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600174 ER PT J AU Racoosin, JA Mosholder, AE Young, S Wernecke, M MaCurdy, T Worrall, C Kelman, J AF Racoosin, Judith A. Mosholder, Andrew E. Young, Stephanie Wernecke, Michael MaCurdy, Thomas Worrall, Chris Kelman, Jeffrey TI Hemorrhage Following Concurrent Use of Warfarin and Oseltamivir by Medicare Beneficiaries SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Racoosin, Judith A.; Mosholder, Andrew E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Young, Stephanie; Wernecke, Michael; MaCurdy, Thomas] Acumen LLC, Burlingame, CA USA. [MaCurdy, Thomas] Stanford Univ, Stanford, CA 94305 USA. [Worrall, Chris; Kelman, Jeffrey] Ctr Medicare Serv, Baltimore, MD USA. [Worrall, Chris; Kelman, Jeffrey] Ctr Medicaid Serv, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 339 BP S147 EP S148 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600327 ER PT J AU Raebel, MA Kuldorff, M Dal Pan, G Lindquist, M Fireman, B AF Raebel, Marsha A. Kuldorff, Martin Dal Pan, Gerald Lindquist, Marie Fireman, Bruce TI Structured Approaches to Evaluating Statistical Signals from Drug and Vaccine Safety Surveillance Systems SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Kuldorff, Martin] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA. [Kuldorff, Martin] Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Dal Pan, Gerald] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Lindquist, Marie] WHO Collaborating Ctr Int Drug Monitoring, Uppsala Monitoring Ctr, Uppsala, Sweden. [Fireman, Bruce] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 346 BP S150 EP S151 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600334 ER PT J AU Ritchey, ME Sansing, VV Domurat, R MaCurdy, T AF Ritchey, Mary E. Sansing, Veronica V. Domurat, Richard MaCurdy, Thomas TI Comparison of Negative Pressure Wound Therapy Utilizaton between Inpatient and Non-Inpatient Settings as Seen in Medicare Data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ritchey, Mary E.; Sansing, Veronica V.] US FDA, Div Epidemiol, Off Surveillance & Biometr, Ctr Devices & Radiol, Silver Spring, MD USA. [Domurat, Richard; MaCurdy, Thomas] Acumen LLC, Burlingame, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 536 BP S233 EP S234 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600518 ER PT J AU Ritchey, ME Sansing, VV Domurat, R MaCurdy, T AF Ritchey, Mary E. Sansing, Veronica V. Domurat, Richard MaCurdy, Thomas TI Pain and Hemorrhage with Negative Pressure Wound Therapy: Inpatient and Non-Inpatient Experience SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Ritchey, Mary E.; Sansing, Veronica V.] US FDA, Div Epidemiol, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Domurat, Richard; MaCurdy, Thomas] Acumen LLC, Burlingame, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 91 BP S40 EP S40 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600089 ER PT J AU Rubino, A Wallander, MA Callreus, T Saddier, P Ritchey, MB Perez-Gutthann, S AF Rubino, Annalisa Wallander, Mari-Ann Callreus, Torbjorn Saddier, Patricia Ritchey, Mary B. Perez-Gutthann, Susana TI Drug Utilization Studies and Risk Management Plans: A Missing Link SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Rubino, Annalisa] European Med Agcy, London, England. [Wallander, Mari-Ann] BayerSheringPharma, Global Epidemiol, Berlin, Germany. [Callreus, Torbjorn] Danish Med Agcy, Copenhagen, Denmark. [Saddier, Patricia] Merck Res Labs, N Wales, PA USA. [Ritchey, Mary B.] CDRH FDA, Div Epidemiol, Off Surveillance & Biometr, Silver Spring, MD USA. [Perez-Gutthann, Susana] RTI Hlth Solut, Global Epidemiol, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 617 BP S269 EP S269 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600595 ER PT J AU Smith, DJ Winterstein, AG Willy, M Karwoski, C AF Smith, Danielle J. Winterstein, Almut G. Willy, Mary Karwoski, Claudia TI Generalizability of Risk Evaluation and Mitigation Strategies (REMS) Effectiveness Evaluations SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Smith, Danielle J.; Winterstein, Almut G.] Univ Florida, Gainesville, FL USA. [Smith, Danielle J.; Winterstein, Almut G.; Willy, Mary; Karwoski, Claudia] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 512 BP S223 EP S224 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600495 ER PT J AU Sridhar, G Menis, M Wallace, AE Daniel, GW Izurieta, H AF Sridhar, G. Menis, M. Wallace, A. E. Daniel, G. W. Izurieta, H. TI Immunoglobulin Use and Thromboembolic Events SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Sridhar, G.; Wallace, A. E.; Daniel, G. W.] Hlth Core Inc, Govt & Acad Res, Alexandria, VA USA. [Menis, M.; Izurieta, H.] Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 189 BP S82 EP S83 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600184 ER PT J AU Tilson, H Roberts, SS Watts, DH Beckerman, K Dominguez, K Pikis, A Scaglia, F Baugh, B Haddad, W Peng, M Trylesinski, A AF Tilson, Hugh Roberts, Susan S. Watts, D. Heather Beckerman, Karen Dominguez, Kenneth Pikis, Andreas Scaglia, Fernando Baugh, Bryan Haddad, William Peng, Michael Trylesinski, Aldo TI The Antiretroviral Pregnancy Registry: A 20(th) Anniversary Celebration SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Tilson, Hugh] Univ N Carolina, UNC Gillings Sch Global Publ Hlth, Chapel Hill, NC USA. [Roberts, Susan S.] Univ N Carolina, Clin Res Program, Wilmington, NC 28401 USA. [Roberts, Susan S.] Kendle Int Inc, Registries & Hlth Outcomes, Wilmington, NC USA. [Watts, D. Heather] NICHD, PAMA, CRMC, NIH, Bethesda, MD USA. [Beckerman, Karen] Albert Einstein Coll Med, New Rochelle, NY USA. [Dominguez, Kenneth] Ctr Dis Control & Prevent, Atlanta, GA USA. [Pikis, Andreas] US FDA, Div Antiviral Drugs & Prod, Silver Spring, MD USA. [Scaglia, Fernando] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. [Baugh, Bryan] Tibotec Therapeut, Clin Affairs, Titusville, NJ USA. [Haddad, William] Biogenerics Inc, Poughquag, NY USA. [Peng, Michael] Roche, Roche Biometr EpiPRO, Nutley, NJ USA. [Trylesinski, Aldo] Novartis Pharma AG, Immunol & Infect Dis, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY PERIODICALS, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN, MA 02148-529 USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 437 BP S190 EP S191 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600422 ER PT J AU Walker, AM Puenpatom, T Li, J Daniel, GW Brookhart, MA Polakowski, L Lu, Y Izurieta, H AF Walker, A. M. Puenpatom, T. Li, J. Daniel, G. W. Brookhart, M. A. Polakowski, L. Lu, Y. Izurieta, H. TI Search for New Safety Signals in the Patterns of Care Following MMR Vaccine SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Walker, A. M.] WHISCON, Newton, MA USA. [Puenpatom, T.; Li, J.; Daniel, G. W.] HealthCore, Wilmington, DE USA. [Polakowski, L.; Lu, Y.; Izurieta, H.] US FDA, CBER, Rockville, MD 20857 USA. [Brookhart, M. A.] Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 805 BP S347 EP S348 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600770 ER PT J AU Wang, CL Chu, HT Tavris, D Xi, J Nie, L AF Wang, Cunlin Chu, Haitao Tavris, Dale Xi, Jing Nie, Lei TI Assessing Publication Bias from Clinical Studies of Coronary Artery Stents SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Wang, Cunlin; Tavris, Dale; Xi, Jing] US FDA, Ctr Device & Radiol Hlth, Silver Spring, MD USA. [Chu, Haitao] Univ Minnesota, Dept Biostat, Twin City, MN USA. [Nie, Lei] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RI Chu, Haitao /J-7576-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 752 BP S326 EP S327 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600723 ER PT J AU Wang, CL Tavris, D Lu, N AF Wang, Cunlin Tavris, Dale Lu, Nelson TI Trends in Pre-Market Application (PMA) Approval of Medical Devices in the USA SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Wang, Cunlin; Tavris, Dale; Lu, Nelson] US FDA, Ctr Device & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 539 BP S235 EP S235 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600521 ER PT J AU Williams, JR Crentsil, V Duncan, L Goldstein, S Graham, D Hammer, M Kavanagh, J Kornegay, C Levin, R Weintraub, D Wilkinson, J Kales, H AF Williams, James R. Crentsil, Victor Duncan, Laurie Goldstein, Susanne Graham, David Hammer, Marlene Kavanagh, Janet Kornegay, Cynthia Levin, Robert Weintraub, Daniel Wilkinson, Jayne Kales, Helen TI Retrospective Method To Identify Tardive Dyskinesia in Electronic Medical Records SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Williams, James R.; Kornegay, Cynthia] US FDA, Div Epidemiol, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Crentsil, Victor; Duncan, Laurie; Levin, Robert] US FDA, Div Psychiat Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Drug Evaluat 1, Silver Spring, MD USA. [Goldstein, Susanne] US FDA, Div Neurol Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Drug Evaluat 1, Silver Spring, MD USA. [Graham, David; Hammer, Marlene] US FDA, Immediate Off, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Kavanagh, Janet; Kales, Helen] Ann Arbor Ctr Excellence, Serious Mental Illness Treatment Res & Evaluat Ct, Dept Vet Affairs, Ann Arbor, MI USA. [Kavanagh, Janet; Kales, Helen] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. [Weintraub, Daniel; Wilkinson, Jayne] Philadelphia Vet Affairs Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Dept Vet Affairs, Philadelphia, PA USA. [Weintraub, Daniel] Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. [Wilkinson, Jayne] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 807 BP S348 EP S349 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600772 ER PT J AU Willy, M Nevarapally, G Kroetsch, A Karwoski, C AF Willy, Mary Nevarapally, George Kroetsch, Adam Karwoski, Claudia TI Update on REMS Evaluations: What Have We Learned? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Willy, Mary; Nevarapally, George; Karwoski, Claudia] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kroetsch, Adam] US FDA, Off Policy & Informat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 520 BP S227 EP S227 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600503 ER PT J AU Winterstein, AG Hampp, C Kubilis, P Saidi, A AF Winterstein, Almut G. Hampp, Christian Kubilis, Paul Saidi, Arwa TI Age-Dependent Effectiveness of RSV Immunoprophylaxis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Winterstein, Almut G.; Kubilis, Paul; Saidi, Arwa] Univ Florida, Gainesville, FL USA. [Hampp, Christian] US FDA, Off Surveillance & Epidemiol, CDER, Silver Spring, MD USA. RI winterstein, Almut/A-3017-2014 OI winterstein, Almut/0000-0002-6518-5961 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 743 BP S322 EP S323 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600714 ER PT J AU Zhou, EH Kaplan, S Mosholder, A Moeny, D Ding, YL Hammad, TA AF Zhou, Esther H. Kaplan, Sigal Mosholder, Andrew Moeny, David Ding, Yulan Hammad, Tarek A. TI Antidepressant and Antipsychotic Dispensing among Montelukast Initiators SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zhou, Esther H.; Kaplan, Sigal; Mosholder, Andrew; Moeny, David; Ding, Yulan; Hammad, Tarek A.] US FDA, OSE, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 154 BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600149 ER PT J AU Zornberg, GL Hsu, L Dong, D Wernecke, M Kim, C Southworth, MR Houstoun, M MaCurdy, T Reichman, M Tracy, L Cunningham, F Coster, TS Moreschi, G Chen, A Karkowsky, AM Worrall, C Kelman, J AF Zornberg, Gwen L. Hsu, Lucy Dong, Diane Wernecke, Michael Kim, Clara Southworth, Mary Ross Houstoun, Monika MaCurdy, Thomas Reichman, Marsha Tracy, LaRee Cunningham, Francesca Coster, Trinka S. Moreschi, Gail Chen, Amy Karkowsky, Abraham M. Worrall, Chris Kelman, Jeffrey TI Dronedarone or Amiodarone and Risk of Heart Failure (HF): A Federal Partners Collaboration (FPC) SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 [Zornberg, Gwen L.; Kim, Clara; Southworth, Mary Ross; Houstoun, Monika; Reichman, Marsha; Tracy, LaRee; Moreschi, Gail; Chen, Amy; Karkowsky, Abraham M.] US FDA, Dept Hlth & Human Serv, Silver Spring, MD USA. [Hsu, Lucy; Coster, Trinka S.] USA, Ctr Hlth Promot, Dept Def, Silver Spring, MD USA. [Dong, Diane; Cunningham, Francesca] Dept Vet Affairs, Ctr Medicat Safety, Hines, IL USA. [Wernecke, Michael; MaCurdy, Thomas] Acumen, Burlingame, CA USA. [MaCurdy, Thomas] Stanford Univ, Stanford, CA 94305 USA. [Worrall, Chris; Kelman, Jeffrey] Dept Hlth & Human Serv, Ctr Medicare & Medicaid Serv, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 SU 1 MA 59 BP S26 EP S26 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 821AG UT WOS:000294946600059 ER PT J AU Chen, MJ Vijay, V Shi, Q Liu, ZC Fang, H Tong, WD AF Chen, Minjun Vijay, Vikrant Shi, Qiang Liu, Zhichao Fang, Hong Tong, Weida TI FDA-approved drug labeling for the study of drug-induced liver injury SO DRUG DISCOVERY TODAY LA English DT Review ID BLACK-BOX WARNINGS; TABULAR COMPILATION; HEPATOTOXICITY; INFORMATION; FREQUENCY; EVENTS; SAFETY; RISK AB Drug-induced liver injury (DILI) is a leading cause of drugs failing during clinical trials and being withdrawn from the market. Comparative analysis of drugs based on their DILI potential is an effective approach to discover key DILI mechanisms and risk factors. However, assessing the DILI potential of a drug is a challenge with no existing consensus methods. We proposed a systematic classification scheme using FDA-approved drug labeling to assess the DILI potential of drugs, which yielded a benchmark dataset with 287 drugs representing a wide range of therapeutic categories and daily dosage amounts. The method is transparent and reproducible with a potential to serve as a common practice to study the DILI of marketed drugs for supporting drug discovery and biomarker development. C1 [Chen, Minjun; Vijay, Vikrant; Shi, Qiang; Liu, Zhichao; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Fang, Hong] Z Tech Corp, Jefferson, AR USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Vijay, Vikrant/E-7651-2010; Qiang, Shi/E-6266-2012; Liu, Zhichao/C-4035-2011 OI Vijay, Vikrant/0000-0001-8425-1285; FU FDA's Critical Path Initiative; Office of Women's Health; Chief Scientist Challenge Grant FX The report study is a part of FDA's Liver Toxicity Knowledge Base (LTKB) project that is supported by the FDA's Critical Path Initiative, the Office of Women's Health and the Chief Scientist Challenge Grant. Vikrant Vijay, Qiang Shi and Zhichao Liu greatly appreciate the opportunity to work at NCTR through the ORISE program. The authors have no conflicts of interest related to this study. NR 44 TC 97 Z9 104 U1 0 U2 17 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG PY 2011 VL 16 IS 15-16 BP 697 EP 703 DI 10.1016/j.drudis.2011.05.007 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 812SO UT WOS:000294313400008 PM 21624500 ER PT J AU Distefano, P AF Distefano, Paul TI VIBRIO VULNIFICUS CONTROL PLANS: ASSESSMENT OF FIRST SEASON OF IMPLEMENTATION IN GULF STATES SO JOURNAL OF SHELLFISH RESEARCH LA English DT Meeting Abstract C1 [Distefano, Paul] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2011 VL 30 IS 2 BP 500 EP 500 PG 1 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 812SC UT WOS:000294312200098 ER PT J AU Parveen, S Dasilva, L DePaola, A Bowers, J Brohawn, K Tamplin, M AF Parveen, Salina Dasilva, Ligia DePaola, Angelo Bowers, John Brohawn, Kathy Tamplin, Mark TI DEVELOPMENT AND VALIDATION OF PREDICTIVE MODEL FOR THE GROWTH AND SURVIVAL OF VIBRIO VULNIFICUS IN POST-HARVEST SHELLSTOCK OYSTERS FROM TWO ESTUARIES AND TWO OYSTER SPECIES SO JOURNAL OF SHELLFISH RESEARCH LA English DT Meeting Abstract C1 [Parveen, Salina; Dasilva, Ligia] Univ Maryland Eastern Shore, Ctr Food Sci & Tech 2116, Princess Anne, MD 21853 USA. [DePaola, Angelo; Bowers, John] US FDA, Dauphin Isl, AL 36528 USA. [Brohawn, Kathy] Maryland Dept Environm, Baltimore, MD 21230 USA. [Tamplin, Mark] Univ Tasmania, Hobart, Tas 7001, Australia. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2011 VL 30 IS 2 BP 541 EP 542 PG 2 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 812SC UT WOS:000294312200238 ER PT J AU Solomotis, M Fanaselle, W AF Solomotis, Marianne Fanaselle, Wendy TI FDA'S RISK PROFILE ON TRANSMISSION OF NOROVIRUS VIA READY-TO-EAT FOOD SO JOURNAL OF SHELLFISH RESEARCH LA English DT Meeting Abstract C1 [Solomotis, Marianne; Fanaselle, Wendy] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2011 VL 30 IS 2 BP 553 EP 554 PG 2 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 812SC UT WOS:000294312200278 ER PT J AU Woods, J AF Woods, Jacquelina TI ENTERIC VIRUSES IN SHELLFISH: RESEARCH PROSPECTIVE AND OUTBREAK ANALYSIS SO JOURNAL OF SHELLFISH RESEARCH LA English DT Meeting Abstract C1 [Woods, Jacquelina] USFDA CFSAN OFS, Dauphin Isl, AL 36528 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL SHELLFISHERIES ASSOC PI GROTON PA C/O DR. SANDRA E. SHUMWAY, UNIV CONNECTICUT, 1080 SHENNECOSSETT RD, GROTON, CT 06340 USA SN 0730-8000 J9 J SHELLFISH RES JI J. Shellfish Res. PD AUG PY 2011 VL 30 IS 2 BP 564 EP 564 PG 1 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 812SC UT WOS:000294312200315 ER PT J AU Fink, DL Kamgno, J Nutman, TB AF Fink, Doran L. Kamgno, Joseph Nutman, Thomas B. TI Rapid Molecular Assays for Specific Detection and Quantitation of Loa loa Microfilaremia SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID POLYMERASE-CHAIN-REACTION; REVERSE-TRANSCRIPTASE-PCR; REAL-TIME PCR; HUMAN OCCULT LOIASIS; WUCHERERIA-BANCROFTI; DNA; INFECTION; MOSQUITOS; SEQUENCE; LARVAE AB Background: Accurate diagnosis of Loa loa infection is essential to the success of mass drug administration efforts to eliminate onchocerciasis and lymphatic filariasis, due to the risk of fatal encephalopathic reactions to ivermectin occurring among highly microfilaremic Loa-infected individuals living in areas co-endemic for multiple filarial species. Methodology/Principal Findings: From a pool of over 1,800 L. loa microfilaria (mf) expressed sequence tags, 18 candidate L. loa mf-specific PCR targets were identified. Real-time PCR (qPCR) assays were developed for two targets (LLMF72 and LLMF269). The qPCR assays were highly specific for L. loa compared with related filariae and also highly sensitive, with detection limits of 0.1 pg genomic DNA, or 1% of DNA extracted from normal blood spiked with a single L. loa microfilaria. Using various DNA extraction methods with dried blood spots obtained from Cameroonian subjects with parasitologically proven loiasis, the LLMF72 qPCR assay successfully estimated mf burden in 65 of 68 samples (50-96,000 mf/mL by microscopy), including all 12 samples subjected to a simple 10-minute boiling extraction. Additionally, the assay detected low-level microfilaremia among 5 of 16 samples from patients thought to be amicrofilaremic by microscopy. Conclusions/Significance: This novel, rapid, highly sensitive and specific qPCR assay is an important step forward in the laboratory diagnosis of L. loa infection. C1 [Fink, Doran L.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Kamgno, Joseph] Univ Yaounde 1, Filariasis Res Ctr, Yaounde, Cameroon. [Kamgno, Joseph] Univ Yaounde 1, Fac Med & Biomed Sci, Yaounde, Cameroon. RP Fink, DL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM tnutman@niaid.nih.gov FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Mectizan Donation Program FX This work was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Fieldwork in Cameroon was funded by the Mectizan Donation Program as part of their support to the Filariasis Research Center in Cameroon. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 29 TC 26 Z9 26 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2011 VL 5 IS 8 AR e1299 DI 10.1371/journal.pntd.0001299 PG 8 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 814TJ UT WOS:000294479800045 PM 21912716 ER PT J AU Stamper, LW Patrick, RL Fay, MP Lawyer, PG Elnaiem, DEA Secundino, N Debrabant, A Sacks, DL Peters, NC AF Stamper, Lisa W. Patrick, Rachel L. Fay, Michael P. Lawyer, Phillip G. Elnaiem, Dia-Eldin A. Secundino, Nagila Debrabant, Alain Sacks, David L. Peters, Nathan C. TI Infection Parameters in the Sand Fly Vector That Predict Transmission of Leishmania major SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Article ID LUTZOMYIA-LONGIPALPIS; CUTANEOUS LEISHMANIASIS; FLIES; BITE; SKIN AB To identify parameters of Leishmania infection within a population of infected sand flies that reliably predict subsequent transmission to the mammalian host, we sampled groups of infected flies and compared infection intensity and degree of metacyclogenesis with the frequency of transmission. The percentage of parasites within the midgut that were metacyclic promastigotes had the highest correlation with the frequency of transmission. Meta-analysis of multiple transmission experiments allowed us to establish a percent-metacyclic "cutoff" value that predicted transmission competence. Sand fly infections initiated with variable doses of parasites resulted in correspondingly altered percentages of metacyclic promastigotes, resulting in altered transmission frequency and disease severity. Lastly, alteration of sand fly oviposition status and environmental conditions at the time of transmission also influenced transmission frequency. These observations have implications for transmission of Leishmania by the sand fly vector in both the laboratory and in nature, including how the number of organisms acquired by the sand fly from an infection reservoir may influence the clinical outcome of infection following transmission by bite. C1 [Stamper, Lisa W.; Patrick, Rachel L.; Lawyer, Phillip G.; Elnaiem, Dia-Eldin A.; Secundino, Nagila; Sacks, David L.; Peters, Nathan C.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. [Elnaiem, Dia-Eldin A.] Univ Maryland Eastern Shore, Princess Anne, MD USA. [Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA. RP Stamper, LW (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM NPeters@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 FU National Institutes of Health, National Institute of Allergy and Infectious Disease FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Disease. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 21 TC 11 Z9 11 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD AUG PY 2011 VL 5 IS 8 AR e1288 DI 10.1371/journal.pntd.0001288 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 814TJ UT WOS:000294479800038 PM 21886852 ER PT J AU Sapsford, KE Spindel, S Jennings, T Tao, GL Triulzi, RC Algar, WR Medintz, IL AF Sapsford, Kim E. Spindel, Samantha Jennings, Travis Tao, Guoliang Triulzi, Robert C. Algar, W. Russ Medintz, Igor L. TI Optimizing Two-Color Semiconductor Nanocrystal Immunoassays in Single Well Microtiter Plate Formats SO SENSORS LA English DT Article DE quantum dot (QD); nanocrystal (NC); semiconductor; bioconjugation; sensor; multiplex; immunoassay; sulfhydryl chemistry ID STAPHYLOCOCCAL-ENTEROTOXIN-B; QUANTUM DOTS; MULTIPLEXED DETECTION; CDSE; PROTEINS; ASSAYS; MILK AB The simultaneous detection of two analytes, chicken IgY (IgG) and Staphylococcal enterotoxin B (SEB), in the single well of a 96-well plate is demonstrated using luminescent semiconductor quantum dot nanocrystal (NC) tracers. The NC-labeled antibodies were prepared via sulfhydryl-reactive chemistry using a facile protocol that took <3 h. Dose response curves for each target were evaluated in a single immunoassay format and compared to Cy5, a fluorophore commonly used in fluorescent immunoassays, and found to be equivalent. Immunoassays were then performed in a duplex format, demonstrating multiplex detection in a single well with limits of detection equivalent to the single assay format: 9.8 ng/mL chicken IgG and 7.8 ng/mL SEB. C1 [Sapsford, Kim E.; Spindel, Samantha] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Spindel, Samantha] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20993 USA. [Jennings, Travis; Tao, Guoliang; Triulzi, Robert C.] eBioscience Inc, San Diego, CA 92121 USA. [Algar, W. Russ; Medintz, Igor L.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Algar, W. Russ] George Mason Univ, Coll Sci, Fairfax, VA 22030 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kim.sapsford@fda.hhs.go; samantha.spindel@fda.hhs.gov; travis.jennings@ebioscience.com; guoliang.tao@ebioscience.com; robert.triulzi@ebioscience.com; russ.algar.ctr.ca@nrl.navy.mil; igor.medintz@nrl.navy.mil FU CB Directorate/Physical S&T Division (DTRA); DARPA; ONR; NRL; NRL-NSI; Critical Path Initiative FX The authors would like to thank Edward Gordon (FDA/CDRH/OSEL/DB) for his assistance taking the digital images of the illuminated NCs in Figure 1. The authors acknowledge the CB Directorate/Physical S&T Division (DTRA), DARPA, ONR, NRL and the NRL-NSI for financial support. K. S. and S. S. acknowledges the Critical Path Initiative for financial support. NR 33 TC 13 Z9 13 U1 0 U2 21 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD AUG PY 2011 VL 11 IS 8 BP 7879 EP 7891 DI 10.3390/s110807879 PG 13 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 811YE UT WOS:000294253900034 PM 22164051 ER PT J AU Oh, E Delehanty, JB Sapsford, KE Susumu, K Goswami, R Blanco-Canosa, JB Dawson, PE Granek, J Shoff, M Zhang, Q Goering, PL Huston, A Medintz, IL AF Oh, Eunkeu Delehanty, James B. Sapsford, Kim E. Susumu, Kimihiro Goswami, Ramasis Blanco-Canosa, Juan B. Dawson, Philip E. Granek, Jessica Shoff, Megan Zhang, Qin Goering, Peter L. Huston, Alan Medintz, Igor L. TI Cellular Uptake and Fate of PEGylated Gold Nanoparticles Is Dependent on Both Cell-Penetration Peptides and Particle Size SO ACS NANO LA English DT Article DE gold nanoparticle; cell-penetrating peptide; cellular uptake; cytotoxicity; PEG; surface charge; endotoxin; dual mode fluorescence; silver staining ID NUCLEAR-LOCALIZATION SIGNALS; QUANTUM DOTS; MAMMALIAN-CELLS; MULTIFUNCTIONAL LIGANDS; GENE DELIVERY; PORE COMPLEX; TAT PEPTIDE; STABILITY; FUNCTIONALITIES; ENDOTOXIN AB Numerous studies have examined how the cellular delivery of gold nanoparticles (AuNPs) is influenced by different physical and chemical characteristics; however, the complex relationship. between AuNP size, uptake efficiency, and intracellular localization remains only partially understood. Here we examine the cellular uptake of a series of AuNPs ranging in diameter from 2.4 to 89 nm that are synthesized and made soluble with poly(ethylene glycol)-functionalized dithiolane ligands terminating in either carboxyl or methoxy groups and covalently conjugated to cell penetrating peptides. Following synthesis, extensive physical characterization of the AuNPs was performed with UV-vis absorption, gel electrophoresis, zeta potential, dynamic light scattering, and high resolution transmission electron microscopy. Uptake efficiency and intracellular localization of the AuNP-peptide conjugates In a model COS-1 cell line were probed with a combination of silver staining, fluorescent counterstaining, and dual mode fluorescence coupled to nonfluorescent scattering. Our findings show that AuNP cellular uptake Is directly dependent on the surface display of the cell-penetrating peptide and that the ultimate intracellular destination is further determined by AuNP diameter. The smallest 2.4 nm AuNPs were found to localize in the nucleus, while intermediate 5.5 and 8.2 nm particles were partially delivered into the cytoplasm, showing a. primarily perinuclear fate along with a portion of the nanoparticles appearing to remain at the membrane. The 16 nm and larger AuNPs did not enter the cells and were located at the cellular periphery. A preliminary assessment of cytotoxicity demonstrated minimal effects on cellular viability following peptide-mediated uptake. C1 [Oh, Eunkeu; Susumu, Kimihiro; Huston, Alan] USN, Res Lab, Opt Sci Div, Washington, DC 20375 USA. [Delehanty, James B.; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. [Goswami, Ramasis] USN, Res Lab, Nanosci Inst, Washington, DC 20375 USA. [Sapsford, Kim E.; Granek, Jessica; Shoff, Megan; Zhang, Qin; Goering, Peter L.] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Blanco-Canosa, Juan B.; Dawson, Philip E.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Blanco-Canosa, Juan B.; Dawson, Philip E.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Oh, E (reprint author), USN, Res Lab, Opt Sci Div, Washington, DC 20375 USA. EM Eunkeuoh@ccs.nrl.navy.mil; Igor.Medintz@nrl.navy.mil FU NRL; NRL NSI; ONR; DTRA/ARO; DARPA; FDA [HHSF223200610765P] FX The authors acknowledge NRL, the NRL NSI, ONR, DTRA/ARO, DARPA, and FDA Contract HHSF223200610765P for financial support. J.B.B.-C. acknowledges a Marie Curie IOF. NR 70 TC 154 Z9 160 U1 17 U2 239 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD AUG PY 2011 VL 5 IS 8 BP 6434 EP 6448 DI 10.1021/nn201624c PG 15 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 809VS UT WOS:000294085400043 PM 21774456 ER PT J AU Tassinari, MS Benson, K Elayan, I Espandiari, P Davis-Bruno, K AF Tassinari, Melissa S. Benson, Kimberly Elayan, Ikram Espandiari, Parvaneh Davis-Bruno, Karen TI Juvenile Animal Studies and Pediatric Drug Development Retrospective Review: Use in Regulatory Decisions and Labeling SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article; Proceedings Paper CT ILSI/HESI Workshop on the Value of Juvenile Animal Studies CY MAY 05-06, 2010 CL Washington, DC AB Juvenile animal toxicity studies are conducted to support applications for drugs intended for use in children. They are designed to address specific questions of potential toxicity in the growing animal or provide data about long-term safety effects of drugs that cannot be obtained from clinical trials. Decisions to conduct a juvenile animal study are based on existing data, such as a safety signal already identified in adult studies, or previous knowledge of the drug or chemical class for its potential to impair growth or developmental milestones. In 2006, the FDA issued an industry guidance in which considerations for determining when a juvenile animal study is warranted were outlined. A retrospective study was conducted covering years both before and after the issued guideline to examine the contribution of juvenile animal toxicity studies to the risk/benefit assessment of pediatric drugs at the FDA. The initial findings were presented as part of the May 2010 HESI workshop on the value of juvenile animal studies. The objective of the review was to better understand the value that the juvenile animal study contributes to regulatory decision making for pediatric drug development by looking at when the studies have been included in the product assessment; what, if any, impact the studies had on the regulatory decisions made; and whether the data were incorporated into the label. The data described below represent a first look at impact of the juvenile animal study since the pediatric legislation and the juvenile animal guidance were issued in the US. Birth Defects Res (Part B) 92:261-265, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Tassinari, Melissa S.] US FDA, Pediat & Maternal Hlth Staff, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Benson, Kimberly] US FDA, Off Sci, Ctr Tobacco Prod, Rockville, MD 20857 USA. [Elayan, Ikram] US FDA, Div Psychiat Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Espandiari, Parvaneh; Davis-Bruno, Karen] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Tassinari, MS (reprint author), 10903 New Hampshire Ave,WO22 Rm 6423, Silver Spring, MD 20993 USA. EM melissa.tassinari@fda.hhs.gov NR 4 TC 13 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2011 VL 92 IS 4 BP 261 EP 265 DI 10.1002/bdrb.20304 PG 5 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 810UG UT WOS:000294152400004 PM 21594977 ER PT J AU Leconte, I Bailey, G Davis-Bruno, K Hew, KW Kim, J Lima, BS Liminga, U Moffit, J De Schaepdrijver, L Schmitt, G Tassinari, M Thompson, K Hurtt, M AF Leconte, Isabelle Bailey, Graham Davis-Bruno, Karen Hew, Kok Wah Kim, James Lima, Beatriz Silva Liminga, Ulla Moffit, Jeffrey De Schaepdrijver, Luc Schmitt, Georg Tassinari, Melissa Thompson, Kary Hurtt, Mark TI Value of Juvenile Animal Studies SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE pharmaceuticals; safety assessment; postnatal evaluation AB The Developmental and Reproductive Toxicology Technical Committee of the ILSI Health and Environmental Sciences Institute has undertaken a project to address the impact of juvenile animal studies on pediatric drug development. A workshop, sponsored and organized by the Health and Environmental Sciences Institute Developmental and Reproductive Toxicity Technical Committee, was held on May 5-6, 2010, in Washington, DC, to discuss the outcome of a global survey and the value of juvenile animal studies in the development of drugs intended for use in pediatric patients. During this workshop, summary data from the 2009-2010 survey were presented, and breakout sessions were used to discuss specific case studies to try to assess the impact of juvenile animal studies performed to support specific pediatric drug development. The objectives of the Workshop on The Value of Juvenile Animal Studies were to (1) provide a forum for scientists representing industry, academia, and regulatory agencies to discuss the impact of juvenile animal studies on pediatric drug development, (2) evaluate summary data from the survey to understand how the juvenile study data are being used and their impact in labeling and risk assessment, (3) discuss selected case studies from the survey to highlight key findings, and (4) identify the areas of improvement for the designs of juvenile animal studies. The take home message that resonated from the workshop discussions was that well-designed juvenile animal studies have demonstrated value in support of certain pediatric drug development programs. However, it was also clear that a juvenile animal study is not always warranted. Birth Defects Res (Part B) 92:292-303, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Leconte, Isabelle] Sanofi Aventis Res & Dev, Porcheville, France. [Bailey, Graham; De Schaepdrijver, Luc] Janssen Pharmaceut NV, Beerse, Belgium. [Davis-Bruno, Karen; Tassinari, Melissa] US FDA, Silver Spring, MD USA. [Hew, Kok Wah] Takeda Global Res & Dev Ctr Inc, Deerfield, IL USA. [Kim, James] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Lima, Beatriz Silva] Univ Lisbon, iMED UL, P-1699 Lisbon, Portugal. [Lima, Beatriz Silva] Inst Nacl Farm & Medicamento, Lisbon, Portugal. [Liminga, Ulla] Med Prod Agcy, Uppsala, Sweden. [Moffit, Jeffrey] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Schmitt, Georg] F Hoffmann La Roche, Basel, Switzerland. [Thompson, Kary] Bristol Myers Squibb, New Brunswick, NJ USA. [Hurtt, Mark] Pfizer Global Res & Dev, Groton, CT USA. RP Hurtt, M (reprint author), Pfizer Inc, Drug Safety Res & Dev, Eastern Point Rd MS 8274-1306, Groton, CT 06340 USA. EM mark.e.hurtt@pfizer.com RI Silva Lima, Beatriz/A-4284-2014; iMed.ULisboa, PharmRegSci /B-5723-2014; iMed.ULisboa, iMed.ULisboa/C-6292-2014 OI Silva Lima, Beatriz/0000-0003-0910-7245; iMed.ULisboa, PharmRegSci /0000-0003-0910-7245; NR 18 TC 10 Z9 12 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2011 VL 92 IS 4 BP 292 EP 303 DI 10.1002/bdrb.20331 PG 12 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 810UG UT WOS:000294152400008 PM 22623020 ER PT J AU Wang, MS Lin, L Chen, J Jackson, D Kainz, W Qi, YH Jarmuszewski, P AF Wang, Minshen Lin, Li Chen, Ji Jackson, David Kainz, Wolfgang Qi, Yihong Jarmuszewski, Perry TI Evaluation and Optimization of the Specific Absorption Rate for Multiantenna Systems SO IEEE TRANSACTIONS ON ELECTROMAGNETIC COMPATIBILITY LA English DT Article DE Antenna radiation efficiency; finite-difference time domain (FDTD) calculation; multiantenna system; optimization; specific absorption rate ID HUMAN HEAD; TEMPERATURE INCREASE; SAR DISTRIBUTIONS; CELLULAR PHONES; 65 MHZ; 2 GHZ; ANTENNAS; MODELS; EXPOSURE; FIELDS AB This paper proposes an effective and efficient technique for the evaluation and optimization of the specific absorption rate for multiantenna wireless systems. This technique is based on a decomposition/superposition procedure with two different measurement scenarios. Using this proposed approach, we can estimate the lower and upper bounds of specific absorption rate within anatomically correct human head models as well as minimize the specific absorption rate within selected tissues in the head models. Furthermore, this technique can be combined with a beamforming technique to maximize the overall system reception and minimize peak spatial specific absorption rate. Numerical examples are used to demonstrate the effectiveness of this proposed approach. C1 [Wang, Minshen; Chen, Ji; Jackson, David] Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. [Kainz, Wolfgang] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Qi, Yihong; Jarmuszewski, Perry] Res Mot Ltd, Waterloo, ON N2L 3W8, Canada. RP Wang, MS (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. EM minshen.wang@gmail.com; jchen18@uh.edu; djackson@uh.edu; wolfgang.kainz@fda.hhs.gov; yqi@rim.com; pjarmuszewski@rim.com FU National Science Foundation [IIP 0856085] FX This work was supported by the National Science Foundation under Grant IIP 0856085. NR 36 TC 12 Z9 12 U1 1 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9375 EI 1558-187X J9 IEEE T ELECTROMAGN C JI IEEE Trans. Electromagn. Compat. PD AUG PY 2011 VL 53 IS 3 BP 628 EP 637 DI 10.1109/TEMC.2011.2109005 PG 10 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA 810NJ UT WOS:000294131700009 ER PT J AU Banda, NK Hyatt, S Glogowska, M Takahashi, K Merkel, TJ Stahl, GL Lu, B Gerard, C Wetsel, RA Arend, WP Holers, VM AF Banda, N. K. Hyatt, S. Glogowska, M. Takahashi, K. Merkel, T. J. Stahl, G. L. Lu, B. Gerard, C. Wetsel, R. A. Arend, W. P. Holers, V. M. TI Independent roles for complement C3a and C5a receptors and the membrane attack complex in the pathogenesis of collagen antibody-induced arthritis in mice: Potential therapeutic implications SO MOLECULAR IMMUNOLOGY LA English DT Meeting Abstract CT 13th European Meeting on Complement in Human Disease CY AUG 21-24, 2011 CL Leiden, NETHERLANDS C1 [Banda, N. K.; Hyatt, S.; Glogowska, M.; Arend, W. P.; Holers, V. M.] Univ Colorado Denver, Aurora, CO USA. [Takahashi, K.] Massachusetts Gen Hosp Children, Boston, MA USA. [Merkel, T. J.] US FDA, CBER, Bethesda, MD 20014 USA. [Stahl, G. L.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Lu, B.; Gerard, C.] Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. [Wetsel, R. A.] Univ Texas Houston, Sch Med, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD AUG PY 2011 VL 48 IS 14 SI SI BP 1670 EP 1670 DI 10.1016/j.molimm.2011.06.234 PG 1 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 809ZV UT WOS:000294096100023 ER PT J AU Cantu-Medellin, N Vitturi, DA Rodriguez, C Murphy, S Dorman, S Shiva, S Zhou, YP Jia, YP Palmer, AF Patel, RP AF Cantu-Medellin, Nadiezhda Vitturi, Dario A. Rodriguez, Cilina Murphy, Serena Dorman, Scott Shiva, Sruti Zhou, Yipin Jia, Yiping Palmer, Andre F. Patel, Rakesh P. TI Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE Hypoxia; Blood flow; Oxygen sensing; Blood substitute; Nitrite reduction ID TANGENTIAL FLOW FILTRATION; RED-BLOOD-CELLS; REDUCTASE-ACTIVITY; DEPENDENT VASODILATION; HYPOXIC CONDITIONS; BOVINE HEMOGLOBIN; NO; OXYGEN; SUBSTITUTES; CIRCULATION AB Recent data suggest that transitions between the relaxed (R) and tense (T) state of hemoglobin control the reduction of nitrite to nitric oxide (NO) by deoxyhemoglobin. This reaction may play a role in physiologic NO homeostasis and be a novel consideration for the development of the next generation of hemoglobin-based blood oxygen carriers (HBOCs, i.e. artificial blood substitutes). Herein we tested the effects of chemical stabilization of bovine hemoglobin in either the T- (THb) or R-state (RHb) on nitrite-reduction kinetics, NO-gas formation and ability to stimulate NO-dependent signaling. These studies were performed over a range of fractional saturations that is expected to mimic biological conditions. The initial rate for nitrite-reduction decreased in the following order RHb > bHb > THb, consistent with the hypothesis that the rate constant for nitrite reduction is faster with R-state Hb and slower with T-state Hb. Moreover, RHb produced more NO-gas and inhibited mitochondrial respiration more potently than both bHb and THb. Interestingly, at low oxygen fractional saturations, THb produced more NO and stimulated nitrite-dependent vasodilation more potently than bHb despite both derivatives having similar initial rates for nitrite reduction and a more negative reduction potential in THb versus bHb. These data suggest that cross-linking of bovine hemoglobin in the T-state conformation leads to a more effective coupling of nitrite reduction to NO-formation. Our results support the model of allosteric regulation of nitrite reduction by deoxyhemoglobin and show that cross-linking hemoglobins in distinct quaternary states can generate products with increased NO yields from nitrite reduction that could be harnessed to promote NO-signaling in vivo. (C) 2011 Elsevier Inc. All rights reserved. C1 [Cantu-Medellin, Nadiezhda; Vitturi, Dario A.; Patel, Rakesh P.] Univ Alabama, Dept Pathol, Ctr Free Rad Biol, Birmingham, AL 35294 USA. [Rodriguez, Cilina] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. [Murphy, Serena; Dorman, Scott] Birmingham So Coll, Dept Chem, Birmingham, AL USA. [Shiva, Sruti] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Vasc Biol & Med Inst, Pittsburgh, PA USA. [Zhou, Yipin; Palmer, Andre F.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Jia, Yiping] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20892 USA. RP Patel, RP (reprint author), Univ Alabama, Dept Pathol, Ctr Free Rad Biol, 901,19th St S,BMR-2,Room 434, Birmingham, AL 35294 USA. EM rakeshp@uab.edu OI Patel, Rakesh/0000-0002-1526-4303; Vitturi, Dario/0000-0003-0354-4567 FU NIH [HL92624, HL078840, DK070862]; American Heart Association [AHA 0815248E] FX This study was supported by Grants NIH HL92624 to RPP, NIH HL078840 and DK070862 to AFP, and an American Heart Association pre-doctoral fellowship to DAV (AHA 0815248E). NR 59 TC 19 Z9 20 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD AUG 1 PY 2011 VL 25 IS 2 SI SI BP 59 EP 69 DI 10.1016/j.niox.2011.01.006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 812FE UT WOS:000294275700002 PM 21277987 ER PT J AU Ostroff, C Lee, CE McMeekin, J AF Ostroff, Craig Lee, Charles E. McMeekin, Judith TI Unapproved Prescription Cough, Cold, and Allergy Drug Products Recent US Food and Drug Administration Regulatory Action on Unapproved Cough, Cold, and Allergy Medications SO CHEST LA English DT Editorial Material AB The US Food and Drug Administration (FDA) drug approval and over-the-counter drug monograph processes play an essential role in ensuring that all drugs are both safe and effective for their intended uses. Manufacturers of drugs that lack required approval have not provided the FDA with evidence demonstrating that their products are safe and effective. Some of these prescription drugs have been marketed for many years and have remained on the market despite changes to the Federal Food, Drug, and Cosmetic Act, which requires approval for safety and efficacy purposes. Many health-care providers may be unaware that unapproved drugs exist because the product labels of these drugs do not disclose that they lack FDA approval. The FDA recently took action against unapproved prescription oral cough, cold, and allergy drug products because of concerns about the potential risks of these products, particularly some extended-release formulations that have not been reviewed for quality. There is a potential for medication errors because product names and labeling have not been reviewed for potential confusion, with some products inappropriately labeled for use in children aged <= 2 years. FDA-approved prescription drugs or drugs appropriately marketed as over the counter remain available for treatment of cough, cold, and allergy symptoms. Such products are of known efficacy, safety, identity, quality, and purity. Removing unapproved drugs from the marketplace and encouraging manufacturers of unapproved products to seek FDA review and approval is a top priority for the FDA. Since the initiation of the Unapproved Drugs Initiative in 2006, the FDA hasremoved similar to 1,500 unapproved products from the market and has worked with firms to bring other unapproved drugs into the approval process. The FDA remains committed to its mission of ensuring that safe and effective drugs are available to American consumers. CHEST 2011; 140(2):295-300 C1 [Lee, Charles E.; McMeekin, Judith] US FDA, Off Unapproved Drugs & Labeling Compliance, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ostroff, Craig] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Ostroff, Craig] US FDA, Res Participat Program, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Lee, CE (reprint author), US FDA, Off Unapproved Drugs & Labeling Compliance, Off Compliance, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Room 5184, Silver Spring, MD 20993 USA. EM charles.lee@fda.hhs.gov NR 14 TC 5 Z9 5 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD AUG PY 2011 VL 140 IS 2 BP 295 EP 300 DI 10.1378/chest.11-0981 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 808QS UT WOS:000293994100011 PM 21813527 ER PT J AU Trucksess, MW Abbas, HK Weaver, CM Shier, WT AF Trucksess, M. W. Abbas, H. K. Weaver, C. M. Shier, W. T. TI Distribution of aflatoxins in shelling and milling fractions of naturally contaminated rice SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE HPLC; aflatoxins; mycotoxins; natural toxicants; rice; cereals ID MYCOTOXINS; PRODUCTS AB The objective of this study was to determine the distribution of an economically important class of mycotoxins, the aflatoxins, in rice milling fractions. Rice plants grown under field production conditions are frequently infected with types of pathogenic fungi that produce toxic metabolites (mycotoxins). Paddy (seeds) rice from healthy plants in the field was collected and stored on a farm under humid, poorly ventilated conditions. Samples were milled into four fractions (hulls, brown rice, bran and white rice) and analysed for aflatoxins (B-1, B-2, G(1) and G(2)) using a validated method. Rice fractions from healthy plants, which contained low levels of aflatoxins (less than 1 mu g kg(-1)), were used to determine the efficiency of the extraction method. Seeds stored under poor conditions were found to be contaminated with aflatoxins B-1 and B-2 as were the fractions. The sums of AFB(1) and AFB(2) in stored paddy rice, hulls, brown rice, bran and white rice were 141, 39, 158, 367 and 56 mu g kg(-1), respectively. The ratio of aflatoxin B-1 and B-2 was about 10:1. AFG(1) and AFG(2) were less than 1 mu g kg(-1). Thus, brown rice contained 92.9% of the aflatoxins in paddy rice, whereas white rice contained only 27.9%. C1 [Trucksess, M. W.; Weaver, C. M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Abbas, H. K.] ARS, Dept Agr, BCPRU, Stoneville, MS USA. [Shier, W. T.] Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM mary.trucksess@fda.hhs.gov NR 18 TC 6 Z9 6 U1 0 U2 13 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 AUG PY 2011 VL 28 IS 8 BP 1076 EP 1082 DI 10.1080/19440049.2011.576441 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 809QR UT WOS:000294072300010 PM 21598135 ER PT J AU Shin, EJ Duong, CX Nguyen, XKT Bing, G Bach, JH Park, DH Nakayama, K Ali, SF Kanthasamy, AG Cadet, JL Nabeshima, T Kim, HC AF Shin, Eun-Joo Duong, Chu Xuan Xuan-Khanh Thi Nguyen Bing, Guoying Bach, Jae-Hyung Park, Dae Hun Nakayama, Keiichi Ali, Syed F. Kanthasamy, Anumantha G. Cadet, Jean L. Nabeshima, Toshitaka Kim, Hyoung-Chun TI PKC delta inhibition enhances tyrosine hydroxylase phosphorylation in mice after methamphetamine treatment SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE Methamphetamine; Dopaminergic toxicity; Hyperthermia; PKC delta gene; Phospho-TH at ser-40; Striatum ID PROTEIN-KINASE-C; DOPAMINERGIC NEURONAL CELLS; PANCREATIC ACINAR-CELLS; OXIDATIVE STRESS; PROTEOLYTIC ACTIVATION; PARKINSONS-DISEASE; INDUCED APOPTOSIS; SH-SY5Y CELLS; ANIMAL-MODELS; PC12 CELLS AB The present study was designed to evaluate the specific role of protein kinase C (PKC) delta in methamphetamine (MA)-induced dopaminergic toxicity. A multiple-dose administration regimen of MA significantly increases PKC delta expression, while rottlerin, a PKC delta inhibitor, significantly attenuates MA-induced hyperthermia and behavioral deficits. These behavioral effects were not significantly observed in PKC delta antisense oligonucleotide (ASO)-treated- or PKC delta knockout (-/-)-mice. There were no MA-induced significant decreases of dopamine (DA) content or tyrosine hydroxylase (TH) expression in the striatum in rottlerin-treated-, ASO-treated- or PKC delta (-/-)-mice. The administration of MA also results in a significant decrease of TH phosphorylation at set 40, but not ser 31, while the inhibition of PKC delta consistently and significantly attenuates MA-induced reduction in the phosphorylation of TH at ser 40. Therefore, these results suggest that the MA-induced enhancement of PKC delta expression is a critical factor in the impairment of TH phosphorylation at ser 40 and that pharmacological or genetic inhibition of PKC delta may be protective against MA-induced dopaminergic neurotoxicity in vivo. (C) 2011 Elsevier B.V. All rights reserved. C1 [Shin, Eun-Joo; Duong, Chu Xuan; Xuan-Khanh Thi Nguyen; Bach, Jae-Hyung; Park, Dae Hun; Kim, Hyoung-Chun] Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. [Bing, Guoying] Univ Kentucky, Dept Anat & Neurobiol, Coll Med, Lexington, KY 40536 USA. [Nakayama, Keiichi] Kyushu Univ, Med Inst Bioregulat, Dept Mol & Cellular Biol, Fukuoka 8128582, Japan. [Ali, Syed F.] Natl Ctr Toxicol Res, FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. [Kanthasamy, Anumantha G.] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA. [Cadet, Jean L.] NIDA, Mol Neuropsychiat Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA. [Nabeshima, Toshitaka] Meijo Univ, Grad Sch Pharmaceut Sci, Dept Chem Pharmacol, Nagoya, Aichi 4688503, Japan. RP Kim, HC (reprint author), Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr FU Ministry of Science and Technology, Republic of Korea [2011K000271]; National Research Foundation of Korea, Republic of Korea [E00025]; Ministry of Health Labour and Welfare (MHLW); Ministry of Education, Culture, Sports, Science and Technology (MEXT); BK 21 Program FX This study was supported by a Grant (#2011K000271) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, and by a Grant (#E00025) of the Korea-Japan Joint Research Program, National Research Foundation of Korea, Republic of Korea. This work was, in part, supported by grants from Ministry of Health Labour and Welfare (MHLW): Research on Risk of Chemical Substances, and Ministry of Education, Culture, Sports, Science and Technology (MEXT): Academic Frontier Project. Xuan-Khanh Thi Nguyen and Jae-Hyung Bach were supported by BK 21 Program. NR 78 TC 13 Z9 13 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD AUG PY 2011 VL 59 IS 1 BP 39 EP 50 DI 10.1016/j.neuint.2011.03.022 PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 802FA UT WOS:000293493500006 PM 21672585 ER PT J AU Koturbash, I Scherhag, A Sorrentino, J Sexton, K Bodnar, W Swenberg, JA Beland, FA de Villena, FPM Rusyn, I Pogribny, IP AF Koturbash, Igor Scherhag, Anne Sorrentino, Jessica Sexton, Kenneth Bodnar, Wanda Swenberg, James A. Beland, Frederick A. de villena, Fernando Pardo-Manuel Rusyn, Ivan Pogribny, Igor P. TI Epigenetic Mechanisms of Mouse Interstrain Variability in Genotoxicity of the Environmental Toxicant 1,3-Butadiene SO TOXICOLOGICAL SCIENCES LA English DT Article DE liver; systems toxicology; 1; 3-butadiene; mouse; epigenetics ID HISTONE LYSINE METHYLATION; HEALTH-RISK ASSESSMENT; CPG ISLANDS; DNA; MICE; BUTADIENE; EXPOSURE; RATS; METABOLISM; LIVER AB 1,3-Butadiene (BD) is a common environmental contaminant classified as "carcinogenic to humans." Formation of BD-induced DNA adducts plays a major role in its carcinogenicity. BD is also an epigenotoxic agent (i.e., it affects DNA and histone methylation in the liver). We used a panel of genetically diverse inbred mice (NOD/LtJ, CAST/EiJ, A/J, WSB/EiJ, PWK/PhJ, C57BL/6J, and 129S1/SvImJ) to assess whether BD-induced genotoxic and epigenotoxic events may be subject to interstrain differences. Mice (male, 7 weeks) were exposed via inhalation to 0 or 625 ppm BD for 6 h/day and 5 days/week for 2 weeks and liver BD-DNA adducts, epigenetic alterations, and liver toxicity were assessed. N-7-(2,3,4-trihydroxybut-1-yl)-guanine adducts were detected in all strains after exposure, yet BD-induced DNA damage in CAST/EiJ mice was two to three times lower. Epigenetic effects of BD were most prominent in C57BL/6J mice where loss of global DNA methylation and loss of trimethylation of histone H3 lysine 9, histone H3 lysine 27, and histone H4 lysine 20, accompanied by dysregulation of liver gene expression indicative of hepatotoxicity, were found. Interestingly, we observed an increase in histone methylation in the absence of changes in gene expression and DNA methylation in CAST/EiJ strain. We hypothesized that mitigated genotoxicity of BD in CAST/EiJ mice may be due to chromatin condensation. Indeed, we show that in response to BD exposure, chromatin condensation occurs in CAST/EiJ, whereas the opposite effect is observed in C57BL/6J mice. These findings demonstrate that interstrain susceptibility to genotoxicity by a well-known environmental carcinogen may be due to strain-specific epigenetic events in response to the exposure. C1 [Sorrentino, Jessica; Swenberg, James A.; Rusyn, Ivan] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. [Koturbash, Igor; Scherhag, Anne; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Scherhag, Anne] Tech Univ Kaiserslautern, D-67663 Kaiserslautern, Rheinland Pfalz, Germany. [Sexton, Kenneth; Bodnar, Wanda; Swenberg, James A.; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [de villena, Fernando Pardo-Manuel] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. RP Rusyn, I (reprint author), Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [R01 ES012689, R01 ES015241, P30 ES010126] FX National Institutes of Health (R01 ES012689, R01 ES015241, and P30 ES010126). NR 49 TC 14 Z9 14 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2011 VL 122 IS 2 BP 448 EP 456 DI 10.1093/toxsci/kfr133 PG 9 WC Toxicology SC Toxicology GA 807QJ UT WOS:000293914500020 PM 21602187 ER PT J AU Cervenakova, L Akimov, S Vasilyeva, I Yakovleva, O McKenzie, C Cervenak, J Piccardo, P Asher, DM AF Cervenakova, Larisa Akimov, Sergey Vasilyeva, Irina Yakovleva, Oksana McKenzie, Carroll Cervenak, Juraj Piccardo, Pedro Asher, David M. TI Fukuoka-1 strain of transmissible spongiform encephalopathy agent infects murine bone marrow-derived cells with features of mesenchymal stem cells SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; THERAPY POSITION STATEMENT; SCRAPIE VIRUS-INFECTION; PRION PROTEIN; BLOOD-TRANSFUSION; PROGENITOR CELLS; INTERNATIONAL-SOCIETY; NATURAL SCRAPIE; VARIANT CJD; MICE AB BACKGROUND: The possible risk of iatrogenic transmissible spongiform encephalopathies (TSEs, prion diseases) from transplantation of marrow-derived mesenchymal stem cells (MSCs) is uncertain. While most cell lines resist infection, a few propagate TSE agents. STUDY DESIGN AND METHODS: We generated MSC-like (MSC-L) cell cultures from bone marrow (BM) of mice inoculated with the human-derived Fukuoka-1 (Fu) strain of TSE agent. Cultured cells were characterized for various markers and cellular prion protein (PrP(C)) by fluorescence-activated cell sorting and for PrP(C) and its pathologic TSE-associated form (PrP(TSE)) by Western blotting (WB). Cell cultures were tested for their susceptibility to infection with Fu in vitro. The infectivity of one Fu-infected cell culture was assayed in mice. RESULTS: BM cells from Fu-infected mice expressed neither PrP(C) nor PrP(TSE) after 3 days in culture as demonstrated by WB. Cells adherent to plastic and maintained under two different culture conditions became spontaneously immortalized and began to express PrPC at about the same time. One culture became transformed shortly after exposure to Fu in vitro and remained persistently infected, continuously generating PrPTSE through multiple passages; the infectivity of cultured cells was confirmed by intracerebral inoculation of lysates into mice. Both persistently TSE-infected and uninfected cells expressed a number of typical MSC markers. CONCLUSION: BM-derived MSC-L cells of mice became persistently infected with the Fu agent under certain conditions in culture-conditions that differ substantially from those currently used to develop investigational human stem cell therapies. C1 [Cervenakova, Larisa] Amer Red Cross, Transmissible Dis Dept, Holland Lab, Rockville, MD 20855 USA. US FDA, Lab Bacterial & Transmissible Spongiform Encephal, DETTD, OBRR,CBER, Kensington, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. RP Cervenakova, L (reprint author), Amer Red Cross, Transmissible Dis Dept, Holland Lab, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM cervenakl@usa.redcross.org FU National Institute of Allergy and Infectious Diseases (NIAID), NIH [Y1-AI-4893-02, 224-05-1307] FX Research in this report was supported in part by the National Institute of Allergy and Infectious Diseases (NIAID), NIH, under NIH Agreement No. Y1-AI-4893-02 (Assessing Safety of Cell Substrates and Vaccine Components) with the FDA (FDA Agreement No. 224-05-1307). NR 74 TC 9 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2011 VL 51 IS 8 BP 1755 EP 1768 DI 10.1111/j.1537-2995.2010.03041.x PG 14 WC Hematology SC Hematology GA 805QF UT WOS:000293743400016 PM 21303371 ER PT J AU Temple, R AF Temple, Robert TI Translating study results to labeling SO CLINICAL TRIALS LA English DT Editorial Material C1 FDA Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Temple, R (reprint author), FDA Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM robert.temple@fda.hhs.gov NR 0 TC 1 Z9 1 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 AUG PY 2011 VL 8 IS 4 BP 427 EP 429 DI 10.1177/1740774511411322 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 806HN UT WOS:000293797000010 PM 21835860 ER PT J AU Fleming, TR Odem-Davis, K Rothmann, MD Shen, YL AF Fleming, Thomas R. Odem-Davis, Katherine Rothmann, Mark D. Shen, Yuan Li TI Some essential considerations in the design and conduct of non-inferiority trials SO CLINICAL TRIALS LA English DT Article ID ORAL ANTICOAGULANT-THERAPY; ACTIVE-CONTROLLED TRIAL; TEAM WHITE PAPER; VENOUS THROMBOEMBOLISM; CLINICAL-TRIALS; NONINFERIORITY TRIALS; CONSISTENT STANDARD; EPISODE; ISSUES; EFFICACY AB Background Suppose a standard therapy (Standard) has been established to provide a clinically important reduction in risk of irreversible morbidity or mortality. In that setting, the safety and efficacy of an experimental intervention likely would be assessed in a clinical trial providing a comparison with Standard rather than a placebo arm. Such a trial often is designed to assess whether the efficacy of the experimental intervention is not unacceptably worse than that of Standard, and is called a non-inferiority trial. Formally, the non-inferiority trial usually is designed to rule out a non-inferiority margin, defined as the minimum threshold for what would constitute an unacceptable loss of efficacy. Purpose Even though the literature has many important articles identifying various approaches to the design and conduct of non-inferiority trials, confusion remains especially regarding key considerations for selecting the non-inferiority margin. The purpose of this article is to provide improved clarity regarding these considerations. Methods We present scientific insights into many factors that should be addressed in the design and conduct of non-inferiority trials to enhance their integrity and reliability, and provide motivation for key considerations that guide the selection of non-inferiority margins. We also provide illustrations and insights from recent experiences. Results Two considerations are essential, and should be addressed in separate steps, in the formulation of the non-inferiority margin. First, the margin should be formulated using adjustments to account for bias or lack of reliability in the estimate of the effect of Standard in the non-inferiority trial setting. Second, the non-inferiority margin should be formulated to achieve preservation of an appropriate percentage of the effect of Standard. Limitations The considerations, in particular regarding the importance of preservation of effect, might not apply to settings where it would be ethical as well as clinically relevant to include both Standard and placebo arms in the trial for direct comparisons with the experimental intervention arm. Conclusions Non-inferiority trials with non-rigorous margins allow substantial risk for accepting inadequately effective experimental regimens, leading to the risk of erosion in quality of health care. The design and conduct of non-inferiority trials, including selection of non-inferiority margins, should account for many factors that can induce bias in the estimated effect of Standard in the non-inferiority trial and thus lead to bias in the estimated effect of the experimental treatment, for the need to ensure the experimental treatment preserves a clinically acceptable fraction of Standard's effect, and for the particular vulnerability of the integrity of a non-inferiority trial to the irregularities in trial conduct. Due to the inherent uncertainties in non-inferiority trials, alternative designs should be pursued whenever possible. Clinical Trials 2011; 8: 432-439. http://ctj.sagepub.com C1 [Fleming, Thomas R.; Odem-Davis, Katherine] Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Fleming, Thomas R.; Odem-Davis, Katherine] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Rothmann, Mark D.; Shen, Yuan Li] US FDA, Div Biometr 5, Silver Spring, MD USA. RP Fleming, TR (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM tfleming@u.washington.edu FU NIH/NIAID [R37 AI 29168, T32 AI07450] FX For TR Fleming and K Odem-Davis, the sources of financial support for research described in this article are NIH/NIAID grants entitled 'Statistical Issues in AIDS Research' (R37 AI 29168) and 'Clinical Research on AIDS Training Grant' (T32 AI07450). NR 38 TC 24 Z9 24 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 AUG PY 2011 VL 8 IS 4 BP 432 EP 439 DI 10.1177/1740774511410994 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 806HN UT WOS:000293797000012 PM 21835862 ER PT J AU Shin, EC Park, SH Demino, M Nascimbeni, M Mihalik, K Major, M Veerapu, NS Heller, T Feinstone, SM Rice, CM Rehermann, B AF Shin, Eui-Cheol Park, Su-Hyung Demino, Mary Nascimbeni, Michelina Mihalik, Kathleen Major, Marian Veerapu, Naga S. Heller, Theo Feinstone, Stephen M. Rice, Charles M. Rehermann, Barbara TI Delayed Induction, Not Impaired Recruitment, of Specific CD8(+) T Cells Causes the Late Onset of Acute Hepatitis C SO GASTROENTEROLOGY LA English DT Article DE Liver Disease; Virology; Immune Response; Monkey ID VIRUS-INFECTION; GENOMIC ANALYSIS; HOST RESPONSE; B-VIRUS; LIVER; CHEMOKINE; LYMPHOCYTES; KINETICS; IMMUNITY; DISEASE AB BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is characterized by lack of immune-mediated liver injury despite a high level of HCV replication during the incubation phase, which lasts about 8 weeks. We investigated whether this results from delayed recruitment of HCV-specific T cells and whether it facilitates HCV persistence. METHODS: Six chimpanzees were infected with HCV; blood and liver samples were collected for 28 weeks and analyzed for immune cells and chemokines. RESULTS: Two chimpanzees developed self-limited infections, whereas the remaining 4 developed chronic infections. Levels of the chemokines CXCL10, CXCL11, CCL4, and CCL5 increased in blood and liver samples from all chimpanzees within 1 month of HCV infection. Chemokine induction correlated with intrahepatic type I interferon (IFN) responses in vivo and was blocked by neutralizing antibodies against IFN-beta in vitro. Despite the early-stage induction of chemokines, the intrahepatic lymphocytic infiltrate started to increase no earlier than 8 weeks after HCV infection, when HCV-specific, tetramer-positive CD8(+) T cells appeared in the circulation. The HCV-specific CD8(+) T cells expressed chemokine receptors when they were initially detected in blood samples, so they could be recruited to the liver as soon as they entered the circulation. CONCLUSIONS: Chemokines are induced during early stages of HCV infection, which requires a type I IFN-mediated response. The delayed onset of acute hepatitis does not result from delayed recruitment of HCV-specific T cells, but could instead be related to a primary delay in the induction of HCV-specific T cells. Divergent outcomes occur without evident differences in chemokine induction and T-cell recruitment. C1 [Shin, Eui-Cheol; Park, Su-Hyung; Nascimbeni, Michelina; Veerapu, Naga S.; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Mihalik, Kathleen; Major, Marian; Feinstone, Stephen M.] US FDA, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [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,Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA. EM rehermann@nih.gov RI Veerapu, Naga Suresh/F-4338-2011; Park, Su-Hyung/N-3514-2014 FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health; Center for Biologics Evaluation and Research, Food and Drug Administration; US Public Health Service [CA85883-01] FX Supported by the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health intramural research program; the Center for Biologics Evaluation and Research, Food and Drug Administration intramural research program; and the US Public Health Service grant CA85883-01 (to C.M.R.). NR 29 TC 27 Z9 30 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2011 VL 141 IS 2 BP 686 EP U804 DI 10.1053/j.gastro.2011.05.006 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 802PK UT WOS:000293523300047 PM 21699897 ER PT J AU Anderson, NM Walker, PN AF Anderson, N. M. Walker, P. N. TI Quality Comparison of Continuous Steam Sterilization Segmented-Flow Aseptic Processing versus Conventional Canning of Whole and Sliced Mushrooms SO JOURNAL OF FOOD SCIENCE LA English DT Article DE Agaricus bisporus; aseptic; food preservation; mushroom; thermal processing ID CANNED MUSHROOMS; YIELD AB This study was carried out to investigate segmented-flow aseptic processing of particle foods. A pilot-scale continuous steam sterilization unit capable of producing shelf stable aseptically processed whole and sliced mushrooms was developed. The system utilized pressurized steam as the heating medium to achieve high temperature-short time processing conditions with high and uniform heat transfer that will enable static temperature penetration studies for process development. Segmented-flow technology produced a narrower residence time distribution than pipe-flow aseptic processing; thus, whole and sliced mushrooms were processed only as long as needed to achieve the target F-o = 7.0 min and were not overcooked. Continuous steam sterilization segmented-flow aseptic processing produced shelf stable aseptically processed mushrooms of superior quality to conventionally canned mushrooms. When compared to conventionally canned mushrooms, aseptically processed yield (weight basis) increased 6.1% (SD = 2.9%) and 6.6% (SD = 2.2%), whiteness (L) improved 3.1% (SD = 1.9%) and 4.7% (SD = 0.7%), color difference (Delta E) improved 6.0% (SD = 1.3%) and 8.5% (SD = 1.5%), and texture improved 3.9% (SD = 1.7%) and 4.6% (SD = 4.2%), for whole and sliced mushrooms, respectively. Segmented-flow aseptic processing eliminated a separate blanching step, eliminated the unnecessary packaging of water and promoted the use of bag-in-box and other versatile aseptic packaging methods. C1 [Walker, P. N.] Penn State Univ, Dept Agr & Biol Engn, University Pk, PA 16802 USA. [Anderson, N. M.] US FDA, Summit Argo, IL 60501 USA. RP Walker, PN (reprint author), Penn State Univ, Dept Agr & Biol Engn, University Pk, PA 16802 USA. EM pnw@psu.edu FU Pennsylvania Dept. of Agriculture FX This work was supported by a grant from the Pennsylvania Dept. of Agriculture. NR 26 TC 2 Z9 2 U1 4 U2 16 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 AUG PY 2011 VL 76 IS 6 BP E429 EP E437 DI 10.1111/j.1750-3841.2011.02221.x PG 9 WC Food Science & Technology SC Food Science & Technology GA 804DA UT WOS:000293633100025 PM 22417494 ER PT J AU Day, JB Sharma, D Siddique, N Hao, YYD Strain, EA Blodgett, RJ Al-Khaldi, SF AF Day, James B. Sharma, Devang Siddique, Nusrat Hao, Yun-Yun D. Strain, Errol A. Blodgett, Robert J. Al-Khaldi, Sufian F. TI Survival of Salmonella Typhi and Shigella dysenteriae in Dehydrated Infant Formula SO JOURNAL OF FOOD SCIENCE LA English DT Article DE infant formula; Salmonella Typhi; Shigella dysenteriae; survival ID ENTEROBACTER-SAKAZAKII; ESCHERICHIA-COLI; FEVER; OUTBREAK; FLEXNERI; GROWTH; INFECTIONS; RESTAURANT; SONNEI; MILK AB Powdered infant formula has previously been linked to the transmission of various bacterial pathogens in infants resulting in life-threatening disease and death. Survival studies of 2 common foodborne pathogens, Salmonella enterica serovar Typhi and Shigella dysenteriae, in powdered infant formula have not been previously studied despite the potentially devastating consequences from ingestion of these organisms, particularly by newborns, in case of a natural or deliberate contamination event. Therefore, to better predict the risk of S. Typhi and S. dysenteriae infection from consumption of infant formula, the present study was undertaken to determine survival of these microorganisms in dry infant formula under varying atmospheric conditions. A 2-strain cocktail of S. Typhi and a 3-strain cocktail of S. dysenteriae were stored for up to 12 wk in dehydrated infant formula in an ambient air or nitrogen atmosphere. Viable counts of S. Typhi at 12 wk in infant formula revealed a 2.9- and 1.69-log decrease in ambient air and nitrogen atmosphere, respectively. Viable counts of S. dysenteriae at 12 wk in infant formula revealed a 0.81- and 0.42-log decrease in ambient air and nitrogen atmosphere, respectively. These results show that S. Typhi and S. dysenteriae can remain viable for prolonged periods of time in powdered infant formula, and the presence of nitrogen enhances survival. C1 [Day, James B.; Sharma, Devang; Siddique, Nusrat; Hao, Yun-Yun D.; Al-Khaldi, Sufian F.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Sharma, Devang] Univ Maryland, Fischell Dept Bioengn, A James Clark Sch Engn, Sch Life Sci, College Pk, MD 20740 USA. [Siddique, Nusrat] Univ Maryland, Dept Cell Biol & Mol Genet, Sch Life Sci, College Pk, MD 20740 USA. [Strain, Errol A.; Blodgett, Robert J.] US FDA, Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Al-Khaldi, SF (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Sufian.alkhaldi@fda.hhs.gov NR 54 TC 6 Z9 6 U1 1 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2011 VL 76 IS 6 BP M324 EP M328 DI 10.1111/j.1750-3841.2011.02268.x PG 5 WC Food Science & Technology SC Food Science & Technology GA 804DA UT WOS:000293633100041 PM 22417504 ER PT J AU Murugesan, L Williams-Hill, D Prakash, A AF Murugesan, Latha Williams-Hill, Donna Prakash, Anuradha TI Effect of Irradiation on Salmonella Survival and Quality of 2 Varieties of Whole Green Onions SO JOURNAL OF FOOD SCIENCE LA English DT Article DE green onion; irradiation; quality; Salmonella ID ESCHERICHIA-COLI O157-H7; CILANTRO CORIANDRUM-SATIVUM; DOSE GAMMA-IRRADIATION; LISTERIA-MONOCYTOGENES; RADIATION SENSITIVITY; MODIFIED ATMOSPHERE; IONIZING-RADIATION; ICEBERG LETTUCE; SHELF-LIFE; TOMATOES AB Two varieties of green onions, Banner and Baja Verde, were inoculated with a cocktail of 3 Salmonella strains using dip and spot inoculation and irradiated at 0, 0.3, 0.6, 0.9, and 1.2 kGy using electron beam. Salmonella survivors were enumerated using a XLD underlay/TSAYE overlay plating method. The D values were in the range of 0.26 to 0.32 kGy depending on variety but not on the method of inoculation. This indicated that a 5-log reduction of Salmonella can be achieved at a dose of 1.6 kGy. For the quality study, both varieties of green onions were irradiated at 0, 1.5, 2.0, and 2.5 kGy and evaluated for changes in microbial counts, color, texture, and visual quality during storage at 4 degrees C. Irradiation reduced total plate counts and psychrotrophs by 3 logs. Although the counts increased during storage, they did not exceed the initial counts of control. No significant difference was observed in color and texture between irradiated samples and control. The control maintained good visual quality for about 13 d as compared to 15 d for 1.5 and 2.5 kGy samples. The 2.0 kGy samples maintained good visual quality for 17 d suggesting that irradiation can increase shelf life by reducing spoilage microorganisms but higher doses can be detrimental to quality. At the dose levels required to achieve a 5-log reduction in Salmonella, the shelf life of whole green onion can be extended. This study shows that irradiation can be used to enhance safety without adverse effects on quality. C1 [Murugesan, Latha; Prakash, Anuradha] Chapman Univ, Food Sci Program, Orange, CA 92866 USA. [Williams-Hill, Donna] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. RP Prakash, A (reprint author), Chapman Univ, Food Sci Program, 1 Univ Dr, Orange, CA 92866 USA. EM prakash@chapman.edu NR 33 TC 4 Z9 4 U1 3 U2 16 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2011 VL 76 IS 6 BP M439 EP M444 DI 10.1111/j.1750-3841.2011.02216.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 804DA UT WOS:000293633100058 PM 21623790 ER PT J AU Jackson, LS Jablonski, J Bullerman, LB Bianchini, A Hanna, MA Voss, KA Hollub, AD Ryu, D AF Jackson, Lauren S. Jablonski, Joseph Bullerman, Lloyd B. Bianchini, Andreia Hanna, Milford A. Voss, Kenneth A. Hollub, April D. Ryu, Dojin TI Reduction of Fumonisin B-1 in Corn Grits by Twin-Screw Extrusion SO JOURNAL OF FOOD SCIENCE LA English DT Article DE fumonisin; N-(deoxy-D-fructos-1-yl) fumonisin; reduction; twin-screw extrusion ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; ESOPHAGEAL CANCER; REACTION-PRODUCT; TOXICITY; MYCOTOXINS; SINGLE; FOODS; CYTOTOXICITY; TEMPERATURE AB This study was designed to investigate the fate of fumonisins in flaking corn grits during twin-screw extrusion by measuring fumonisin B-1 (FB1) and its analogs with a mass balance approach. Food grade corn grits and 2 batches of grits contaminated with FB1 at 10 and 50 mu g/g by Fusarium verticillioides M-2552 were processed with or without glucose supplementation (10%, w/w) with a twin-screw extruder. Extrusion reduced FB1 in contaminated grits by 64% to 72% without glucose and 89% to 94% with added glucose. In addition, extrusion alone resulted in 26% to 73% reduction in the levels of fumonisin B-2 and fumonisin B-3, while levels of both mycotoxins were reduced by > 89% in extruded corn grits containing 10% glucose. Mass balance analysis showed that 38% to 46% of the FB1 species detected in corn extruded with glucose was N-(deoxy-D-fructos-1-yl)-FB1, while 23% to 37% of FB1 species detected in extruded corn grits with and without added glucose was bound to the matrix. It was also found that the hydrolyzed form of FB1 was a minor species in extruded corn grits with or without added glucose, representing < 15% of the total FB1 species present. Less than 46% of FB1 originally present in corn grits could be detected in the fumonisin analogues measured in this study. Research is needed to identify the reaction products resulting from extrusion processing of fumonisin-contaminated corn products. C1 [Hollub, April D.; Ryu, Dojin] Texas Womans Univ, Dept Nutr & Food Sci, Denton, TX 76204 USA. [Jackson, Lauren S.; Jablonski, Joseph] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Bullerman, Lloyd B.; Bianchini, Andreia; Hanna, Milford A.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. [Voss, Kenneth A.] USDA, Russell Res Ctr, Athens, GA 30605 USA. RP Ryu, D (reprint author), Texas Womans Univ, Dept Nutr & Food Sci, POB 425888, Denton, TX 76204 USA. EM dryu@twu.edu FU Natl. Research Initiative of the USDA Cooperative State Research, Education and Extension Service [2005-35201-16329] FX This study was supported by a grant from the Natl. Research Initiative of the USDA Cooperative State Research, Education and Extension Service, grant nr. 2005-35201-16329. NR 37 TC 7 Z9 7 U1 3 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD AUG PY 2011 VL 76 IS 6 BP T150 EP T155 DI 10.1111/j.1750-3841.2011.02231.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 804DA UT WOS:000293633100075 PM 22417527 ER PT J AU Moore, HM Kelly, AB Jewell, SD McShane, LM Clark, DP Greenspan, R Hayes, DF Hainaut, P Kim, P Mansfield, E Potapova, O Riegman, P Rubinstein, Y Seijo, E Somiari, S Watson, P Weier, HU Zhu, C Vaught, J AF Moore, Helen M. Kelly, Andrea B. Jewell, Scott D. McShane, Lisa M. Clark, Douglas P. Greenspan, Renata Hayes, Daniel F. Hainaut, Pierre Kim, Paula Mansfield, Elizabeth Potapova, Olga Riegman, Peter Rubinstein, Yaffa Seijo, Edward Somiari, Stella Watson, Peter Weier, Heinz-Ulrich Zhu, Claire Vaught, Jim TI Biospecimen Reporting for Improved Study Quality (BRISQ) SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE biospecimen; specimen; sample; collection; processing; handling; storage; preanalytical; reporting; BRISQ ID FLIGHT-MASS-SPECTROMETRY; PATHOLOGISTS GUIDELINE RECOMMENDATIONS; APPROACHING CLINICAL PROTEOMICS; GENE-EXPRESSION PROFILES; NEEDLE-ASPIRATION BIOPSY; PARAFFIN-EMBEDDED TISSUE; HUMAN POSTMORTEM TISSUES; MICROARRAY ANALYSIS; BREAST-CANCER; HUMAN BRAIN AB Human biospecimens are subjected to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is crucial that information the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and help reassure patient contributors and the advocacy community that their contributions are valued and respected. Copyright (C) 2011 American Cancer Society. C1 [Moore, Helen M.; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, Bethesda, MD 20892 USA. [McShane, Lisa M.] NCI, Biometr Res Branch, Bethesda, MD 20892 USA. [Zhu, Claire] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Kelly, Andrea B.] Rose Li & Associates Inc, Bethesda, MD USA. [Jewell, Scott D.] Program Biospecimen Sci, Grand Rapids, MI USA. [Jewell, Scott D.] Van Andel Res Inst, Grand Rapids, MI USA. [Clark, Douglas P.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. [Greenspan, Renata] US Mil Canc Inst, Washington, DC USA. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hainaut, Pierre] WHO, Int Agcy Res Canc, Lyon, France. [Mansfield, Elizabeth] US FDA, Silver Spring, MD USA. [Potapova, Olga] Cureline Inc, San Francisco, CA USA. [Riegman, Peter] Erasmus MC Tissue Bank, Rotterdam, Netherlands. [Rubinstein, Yaffa] NIH, Off Rare Dis Res, Rockville, MD USA. [Seijo, Edward] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Somiari, Stella] Windber Res Inst, Windber, PA USA. [Watson, Peter] British Columbia Canc Agcy, Vancouver Isl Ctr, Victoria, BC, Canada. [Weier, Heinz-Ulrich] Lawrence Berkeley Natl Lab, Berkeley, CA USA. RP Vaught, J (reprint author), NCI, Off Biorepositories & Biospecimen Res, 11400 Rockville Pike,Rm 700,MSC 9160, Bethesda, MD 20892 USA. EM kellya2@mail.nih.gov RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH [CA 136685, DE-AC02-05CH11231] FX This project has been funded in whole or in part with Federal Funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This work was supported in part by NIH grant CA 136685 (HUW) carried out at the Lawrence Berkeley National Laboratory under contract DE-AC02-05CH11231. NR 85 TC 61 Z9 62 U1 1 U2 12 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 AUG PY 2011 VL 10 IS 8 BP 3429 EP 3438 DI 10.1021/pr200021n PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 802CW UT WOS:000293487900011 PM 21574648 ER PT J AU Zineh, I Pacanowski, MA AF Zineh, Issam Pacanowski, Michael A. TI Pharmacogenomics in the Assessment of Therapeutic Risks versus Benefits: Inside the United States Food and Drug Administration SO PHARMACOTHERAPY LA English DT Article DE drug development; United States Food and Drug Administration; FDA; pharmacogenetics; pharmacogenomics ID INFORMATION; FDA AB Pharmacogenomics is the study of how genetic variations influence responses to drugs, diagnostics, or biologic agents. The field of pharmacogenomics has significant potential to enhance drug development and aid in making regulatory decisions. The United States Food and Drug Administration (FDA) has supported pharmacogenomics for nearly a decade by providing regulatory advice and reviewing applications, with the intent of discovering and applying genetic determinants of treatment effects. The FDA will continue to develop policies and processes centered on genomics and individualized therapeutics to guide rational drug development. It will also continue to inform the public of clinically relevant pharmacogenomic issues through various mechanisms of communication, such as drug labeling. In this review, we provide a perspective on several pharmacogenomic activities at the FDA. In addition, we attempt to clarify what we believe are several misperceptions regarding the FDA's pharmacogenomic initiatives. We hope this perspective provides a window into some ways in which the FDA is enabling individualized therapeutics through its mission-critical activities. C1 [Zineh, Issam; Pacanowski, Michael A.] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Zineh, I (reprint author), US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 51,Room 31, Silver Spring, MD 20993 USA. EM Issam.Zineh@fda.hhs.gov NR 16 TC 18 Z9 18 U1 0 U2 4 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD AUG PY 2011 VL 31 IS 8 BP 729 EP 735 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 801KN UT WOS:000293437700002 PM 21923598 ER PT J AU Kouiavskaia, D Collett, MS Dragunsky, EM Sarafanov, A Chumakov, KM AF Kouiavskaia, Diana Collett, Marc S. Dragunsky, Eugenia M. Sarafanov, Andrey Chumakov, Konstantin M. TI Immunogenicity of Inactivated Polio Vaccine with Concurrent Antiviral V-073 Administration in Mice SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID POLIOMYELITIS AB Immunization of mice with inactivated polio vaccine (IPV) with concurrent dosing of poliovirus antiviral V-073 showed no detrimental impact on the elicitation of serum-neutralizing antibodies. A strategy involving coadministration of antiviral V-073 and IPV can be considered for the management of poliovirus incidents. C1 [Chumakov, Konstantin M.] US FDA, CBER, HFM 470, NLRC, Rockville, MD 20852 USA. [Collett, Marc S.] ViroDefense Inc, Rockville, MD USA. RP Chumakov, KM (reprint author), US FDA, CBER, HFM 470, NLRC, Room 122,1401 Rockville Pike, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU CBER/FDA [224-06-1322/Y1-AI-6153-01]; NIAID/NIH [224-06-1322/Y1-AI-6153-01]; Task Force for Global Health, Inc., through WHO; Task Force for Global Health, Inc., through Rotary International FX The work was supported by Interagency Agreement number 224-06-1322/Y1-AI-6153-01 between CBER/FDA and NIAID/NIH. Viro-Defense, Inc., received financial support from The Task Force for Global Health, Inc., through grants from the WHO and Rotary International. NR 8 TC 5 Z9 5 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2011 VL 18 IS 8 BP 1387 EP 1390 DI 10.1128/CVI.05147-11 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800ID UT WOS:000293352100025 PM 21715577 ER PT J AU Banugaria, SG Prater, SN Ng, YK Kobori, JA Finkel, RS Ladda, RL Chen, YT Rosenberg, AS Kishnani, PS AF Banugaria, Suhrad G. Prater, Sean N. Ng, Yiu-Ki Kobori, Joyce A. Finkel, Richard S. Ladda, Roger L. Chen, Yuan-Tsong Rosenberg, Amy S. Kishnani, Priya S. TI The impact of antibodies on clinical outcomes in diseases treated with therapeutic protein: Lessons learned from infantile Pompe disease SO GENETICS IN MEDICINE LA English DT Article DE Pompe disease; enzyme replacement therapy; crossreactive immunologic material; CRIM negative; high sustained antibody titers; high-titer CRIM-positive; low-titer CRIM-positive; therapeutic proteins ID ENZYME-REPLACEMENT THERAPY; ACID ALPHA-GLUCOSIDASE; MUCOPOLYSACCHARIDOSIS-I; ALGLUCOSIDASE ALPHA; IMMUNE TOLERANCE; RECOMBINANT; CHILDREN; TETRASACCHARIDE; HEMOPHILIA; INDUCTION AB Purpose: Enzyme replacement therapy with rhGAA (Myozyme (R)) has lead to improved survival, which is largely attributable to improvements in cardiomyopathy and skeletal muscle function. However, crossreactive immunologic material-negative patients have a poor clinical response to enzyme replacement therapy secondary to high sustained antibody titers. Furthermore, although the majority of crossreactive immunologic material-positive patients tolerize or experience a downtrend in anti-rhGAA antibody titers, antibody response is variable with some crossreactive immunologic material-positive infants also mounting high sustained antibody titers. Methods: We retrospectively analyzed 34 infants with Pompe disease: 11 crossreactive immunologic material-negative patients, nine high-titer crossreactive immunologic material-positive patients, and 14 low-titer crossreactive immunologic material-positive patients. Clinical outcome measures were overall survival, ventilator-free survival, left ventricular mass index, Alberta Infant Motor Scale score, and urine Glc(4) levels. Results: Clinical outcomes in the high-titer crossreactive immunologic material-positive group were poor across all areas evaluated relative to the low-titer crossreactive immunologic material-positive group. For the crossreactive immunologic material-negative and high-titer crossreactive immunologic material-positive groups, no statistically significant differences were observed for any outcome measures, and both patient groups did poorly. Conclusions: Our data indicate that, irrespective of crossreactive immunologic material status, patients with infantile Pompe disease with high sustained antibody titer have an attenuated therapeutic response to enzyme replacement therapy. With the advent of immunomodulation therapies, identification of patients at risk for developing high sustained antibody titer is critical. Genet Med 2011: 13(8): 729-736. C1 [Banugaria, Suhrad G.; Prater, Sean N.; Kishnani, Priya S.] Duke Univ, Med Ctr, Dept Pediat, Div Med Genet, Durham, NC 27710 USA. [Ng, Yiu-Ki] Univ Hong Kong, Dept Pediat & Adolescent Med, Hong Kong, Hong Kong, Peoples R China. [Kobori, Joyce A.] Permanente Med Grp Inc, Dept Genet, San Jose, CA USA. [Finkel, Richard S.] Childrens Hosp Philadelphia, Div Neurol, Philadelphia, PA 19104 USA. [Ladda, Roger L.] Penn State Univ, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA 17033 USA. [Chen, Yuan-Tsong] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. [Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kishnani, PS (reprint author), DUMC 103856,GSRB 1,4th Floor,595 LaSalle St, Durham, NC 27710 USA. EM kishn001@mc.duke.edu FU Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN); NINDS [1U54NS065768-01]; NIH Office of Rare Diseases Research (ORDR); Synpac, Inc. (Durham, NC); Genzyme Corporation (Cambridge, MA); Genzyme Corporation; Duke Clinical Research Unit, National Center for Research Resources [1UL1RR024128]; National Institutes of Health FX The authors thank the patients, their families and the health care providers who participated in different clinical studies of rhGAA whose outcomes are summarized here. This project was funded in part by the Lysosomal Disease Network, a part of NIH Rare Diseases Clinical Research Network (RDCRN). Funding and/or programmatic support for this project has been provided by (1U54NS065768-01) from the NINDS and the NIH Office of Rare Diseases Research (ORDR). The views expressed in written materials or publications do not necessarily reflect the official policies of the Department of Health and Human Services; nor does mention by trade names, commercial practices, or organizations imply endorsement by the U. S. Government. The clinical studies from which patients were culled for this analysis were sponsored by Synpac, Inc. (Durham, NC) and Genzyme Corporation (Cambridge, MA). The clinical trials were supported by Genzyme Corporation and Grant 1UL1RR024128 from the Duke Clinical Research Unit Program, National Center for Research Resources and the National Institutes of Health. All data included in this paper NR 37 TC 86 Z9 86 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD AUG PY 2011 VL 13 IS 8 BP 729 EP 736 DI 10.1097/GIM.0b013e3182174703 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 802HV UT WOS:000293501000007 PM 21637107 ER PT J AU Manthripragada, AD Zhou, EH Budnitz, DS Lovegrove, MC Willy, ME AF Manthripragada, Angelika D. Zhou, Esther H. Budnitz, Daniel S. Lovegrove, Maribeth C. Willy, Mary E. TI Characterization of acetaminophen overdose-related emergency department visits and hospitalizations in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE acetaminophen overdose; liver toxicity; hospitalizations; emergency department visits ID ACUTE LIVER-FAILURE; ADULT-POPULATION; NONPRESCRIPTION; PRESCRIPTION; SURVEILLANCE; PARACETAMOL; ANALGESICS; ENGLAND AB Purpose To estimate the number of acetaminophen overdose-related emergency department (ED) visits and hospitalizations in the United States, characterize these by intentionality, age, and gender, and compare the strengths and limitations of the utilized databases. Methods We used data from the National Hospital Ambulatory Medical Care Survey (NHAMCS) and the National Electronic Injury Surveillance System (NEISS) to estimate the number of relevant ED visits in the United States between 2000 and 2007, and the National Hospital Discharge Survey (NHDS) to estimate the number of relevant hospitalizations in the United States between 1991 and 2006. National estimates and their standard errors were calculated using information provided in each database. We used the standard United States population in 2000 to calculate age-adjusted rates. Results We estimate an annual average of 44 348 (NHAMCS, 2000-2007) or 78 414 (NEISS, 2006-2007) acetaminophen overdose-related ED visits and 33 520 (NHDS, 2000-2006) hospitalizations. For 2000-2006 we calculated an age-adjusted rate of 13.9 acetaminophen overdose-related hospitalizations per 100 000 US population, with the highest rate (15.7) occurring from 2005 to 2006. Between 1991 and 2006, there was no decrease noted in hospitalizations for intentional or unintentional overdoses. The majority of overdoses reported in NEISS (69.8%) and NHDS (74.2%) were classified as intentional (suicides or suicidal gestures), whereas in NHAMCS, intentionality was evenly distributed. Conclusions Our results suggest that acetaminophen overdose, both intentional and unintentional, remains a significant public health concern. With an understanding of their methodological characteristics and limitations, these national databases can be useful tools to characterize acetaminophen overdose-related ED visits and hospitalizations. Published in 2011 by John Wiley & Sons, Ltd. C1 [Manthripragada, Angelika D.] US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Budnitz, Daniel S.; Lovegrove, Maribeth C.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. RP Manthripragada, AD (reprint author), US FDA, Div Epidemiol, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2415, Silver Spring, MD 20993 USA. EM angelika.manthripragada@fda.hhs.gov NR 29 TC 25 Z9 26 U1 2 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2011 VL 20 IS 8 BP 819 EP 826 DI 10.1002/pds.2090 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 800PK UT WOS:000293375200006 PM 21294217 ER PT J AU Lanzarotta, A Lakes, K Marcott, CA Witkowski, MR Sommer, AJ AF Lanzarotta, Adam Lakes, Kendra Marcott, Curtis A. Witkowski, Mark R. Sommer, Andre J. TI Analysis of Counterfeit Pharmaceutical Tablet Cores Utilizing Macroscopic Infrared Spectroscopy and Infrared Spectroscopic Imaging SO ANALYTICAL CHEMISTRY LA English DT Article ID RAMAN-SPECTROSCOPY; SOLID-STATE; ANTIMALARIAL TABLETS; CHEMICAL-STABILITY; EXCIPIENTS; DISSOLUTION; SODIUM; DRUGS; MICROSPECTROSCOPY; MICROCAPSULES AB Advantages and limitations of analyzing authentic and counterfeit pharmaceutical tablets with both macro (nonimaging) attenuated total internal reflection Fourier transform infrared (ATR-FT-IR) spectroscopy and micro ATR-FT-IR spectroscopic imaging have been evaluated. The results of this study demonstrated that micro ATR imaging was more effective for extracting formulation information (sourcing), whereas a macro ATR approach was better suited for counterfeit detection (screening). More importantly, this study demonstrated that a thorough analysis of the counterfeit core can be achieved by combining the results of both techniques. C1 [Lanzarotta, Adam; Witkowski, Mark R.] US FDA, Trace Examinat Sect, Forens Chem Ctr, Cincinnati, OH 45237 USA. [Lakes, Kendra; Sommer, Andre J.] Miami Univ, Dept Chem & Biochem, Mol Microspect Lab, Oxford, OH 45056 USA. [Marcott, Curtis A.] Light Light Solut, Athens, GA 30608 USA. RP Lanzarotta, A (reprint author), US FDA, Trace Examinat Sect, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM adam.lanzarotta@fda.hhs.gov NR 52 TC 16 Z9 16 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 AUG 1 PY 2011 VL 83 IS 15 BP 5972 EP 5978 DI 10.1021/ac200957d PG 7 WC Chemistry, Analytical SC Chemistry GA 798ZV UT WOS:000293252500025 PM 21651233 ER PT J AU Slater, JE Rabin, RL Martin, D AF Slater, Jay E. Rabin, Ronald L. Martin, David TI Comments on cow's milk allergy and diphtheria, tetanus, and pertussis vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID ADOLESCENTS; ANAPHYLAXIS; CHILDREN C1 [Slater, Jay E.; Rabin, Ronald L.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. [Martin, David] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD USA. RP Slater, JE (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA. EM Jay.slater@fda.hhs.gov NR 6 TC 8 Z9 8 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD AUG PY 2011 VL 128 IS 2 BP 434 EP 434 DI 10.1016/j.jaci.2011.06.028 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 799IQ UT WOS:000293280800039 PM 21807255 ER PT J AU Galvin, TA Ahmed, IA Williams, DK Bryan, T Khan, AS AF Galvin, Teresa A. Ahmed, Imran A. Williams, Dhanya K. Bryan, Theodore Khan, Arifa S. TI GENETIC ANALYSIS OF THE RELATIONSHIP OF TWO SFV SEROTYPES ISOLATED FROM MACACA CYCLOPIS: SFVMAC(MCY-1) AND SFVMAC(MCY-2) (ORIGINALLY DESIGNATED AS SFV-1 AND SFV-2, RESPECTIVELY) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 [Galvin, Teresa A.; Ahmed, Imran A.; Williams, Dhanya K.; Bryan, Theodore; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2011 VL 40 IS 4 MA 91 BP 277 EP 277 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 795YL UT WOS:000293015700098 ER PT J AU Corbett, K Kremzner, M Stifano, T AF Corbett, Kristine Kremzner, Mary Stifano, Toni TI Providing adequate directions for medication use in pregnant women and nursing mothers: An overview of pregnancy labeling SO JOURNAL OF THE AMERICAN ACADEMY OF NURSE PRACTITIONERS LA English DT Editorial Material C1 [Kremzner, Mary] US FDA, Div Drug Informat, Off Commun, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Stifano, Toni] US FDA, Promot & Advertising Policy Staff, Off Compliance, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Corbett, K (reprint author), Food & Drug Adm Silver Spring, Div Nonprescript Drug Labeling & Compliance, Off Compliance, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1041-2972 J9 J AM ACAD NURSE PRAC JI J. Am. Acad. Nurse Pract. PD AUG PY 2011 VL 23 IS 8 BP 389 EP 391 DI 10.1111/j.1745-7599.2011.00641.x PG 3 WC Health Care Sciences & Services; Nursing SC Health Care Sciences & Services; Nursing GA 796ZW UT WOS:000293093000001 PM 21790831 ER PT J AU Zang, QD Keire, DA Buhse, LF Wood, RD Mital, DP Haque, S Srinivasan, S Moore, CMV Nasr, M Al-Hakim, A Trehy, ML Welsh, WJ AF Zang, Qingda Keire, David A. Buhse, Lucinda F. Wood, Richard D. Mital, Dinesh P. Haque, Syed Srinivasan, Shankar Moore, Christine M. V. Nasr, Moheb Al-Hakim, Ali Trehy, Michael L. Welsh, William J. TI Identification of heparin samples that contain impurities or contaminants by chemometric pattern recognition analysis of proton NMR spectral data SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Heparin; Proton nuclear magnetic resonance (H-1 NMR); Pattern recognition; Classification and regression tree (CART); Artificial neural network (ANN); Support vector machine (SVM) ID ARTIFICIAL NEURAL-NETWORKS; SUPPORT VECTOR MACHINES; OVERSULFATED CHONDROITIN SULFATE; NUCLEAR-MAGNETIC-RESONANCE; ADVERSE CLINICAL EVENTS; REGRESSION TREES; CLASSIFICATION; SPECTROSCOPY; CART AB Chemometric analysis of a set of one-dimensional (1D) H-1 nuclear magnetic resonance (NMR) spectral data for heparin sodium active pharmaceutical ingredient (API) samples was employed to distinguish USP-grade heparin samples from those containing oversulfated chondroitin sulfate (OSCS) contaminant and/or unacceptable levels of dermatan sulfate (DS) impurity. Three chemometric pattern recognition approaches were implemented: classification and regression tree (CART), artificial neural network (ANN), and support vector machine (SVM). Heparin sodium samples from various manufacturers were analyzed in 2008 and 2009 by 1D H-1 NMR, strong anion-exchange high-performance liquid chromatography, and percent galactosamine in total hexosamine tests. Based on these data, the samples were divided into three groups: Heparin, DS a parts per thousand currency signaEuro parts per thousand 1.0% and OSCS = 0%; DS, DS > 1.0% and OSCS = 0%; and OSCS, OSCS > 0% with any content of DS. Three data sets corresponding to different chemical shift regions (1.95-2.20, 3.10-5.70, and 1.95-5.70 ppm) were evaluated. While all three chemometric approaches were able to effectively model the data in the 1.95-2.20 ppm region, SVM was found to substantially outperform CART and ANN for data in the 3.10-5.70 ppm region in terms of classification success rate. A 100% prediction rate was frequently achieved for discrimination between heparin and OSCS samples. The majority of classification errors between heparin and DS involved cases where the DS content was close to the 1.0% DS borderline between the two classes. When these borderline samples were removed, nearly perfect classification results were attained. Satisfactory results were achieved when the resulting models were challenged by test samples containing blends of heparin APIs spiked with non-, partially, or fully oversulfated chondroitin sulfate A, heparan sulfate, or DS at the 1.0%, 5.0%, and 10.0% (w/w) levels. This study demonstrated that the combination of 1D H-1 NMR spectroscopy with multivariate chemometric methods is a nonsubjective, statistics-based approach for heparin quality control and purity assessment that, once standardized, minimizes the need for expert analysts. C1 [Zang, Qingda; Welsh, William J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. [Zang, Qingda; Wood, Richard D.] Snowdon Inc, Monmouth Jct, NJ 08852 USA. [Zang, Qingda; Mital, Dinesh P.; Haque, Syed; Srinivasan, Shankar] Univ Med & Dent New Jersey, Dept Hlth Informat, Sch Hlth Related Profess, Newark, NJ 07107 USA. [Keire, David A.; Buhse, Lucinda F.; Trehy, Michael L.] US FDA, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. [Moore, Christine M. V.; Nasr, Moheb; Al-Hakim, Ali] US FDA, Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA. RP Welsh, WJ (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. EM welshwj@umdnj.edu NR 48 TC 14 Z9 14 U1 0 U2 16 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD AUG PY 2011 VL 401 IS 3 BP 939 EP 955 DI 10.1007/s00216-011-5155-4 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 795JJ UT WOS:000292970200019 PM 21678118 ER PT J AU Reynolds, KS AF Reynolds, K. S. TI Transplantation Pharmacology: Putting the Puzzle Together SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Reynolds, KS (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM kellie.reynolds@fda.hhs.gov NR 14 TC 1 Z9 1 U1 0 U2 3 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 AUG PY 2011 VL 90 IS 2 BP 193 EP 196 DI 10.1038/clpt.2011.143 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 795LE UT WOS:000292974900001 PM 21772291 ER PT J AU Gieser, G Harigaya, H Colangelo, PM Burckart, G AF Gieser, G. Harigaya, H. Colangelo, P. M. Burckart, G. TI Biomarkers in Solid-Organ Transplantation SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT FDA Workshop on Pharmacodynamic and Pharmacogenomic Biomarkers in Solid Organ Transplantation CY SEP 28, 2010 CL Silver Spring, MD ID INDEPENDENT PREDICTOR; CYCLOSPORINE; RECIPIENTS; IMMUNOSUPPRESSION; INJURY AB This workshop was organized by the US Food and Drug Administration (FDA) Office of Clinical Pharmacology Review Team supporting the Division of Special Pathogen and Transplant Products in the Center for Drug Evaluation and Research. The main goal of the workshop was to enhance the knowledge base regarding biomarkers in solid-organ transplantation via presentation and discussion of scientific findings. C1 [Gieser, G.; Harigaya, H.; Colangelo, P. M.; Burckart, G.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat, Silver Spring, MD USA. RP Gieser, G (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat, Silver Spring, MD USA. EM gerlie.gieser@fda.hhs.gov NR 10 TC 5 Z9 5 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 AUG PY 2011 VL 90 IS 2 BP 217 EP 220 DI 10.1038/clpt.2011.75 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 795LE UT WOS:000292974900013 PM 21772300 ER PT J AU Ball, R Botsis, T AF Ball, R. Botsis, T. TI Can Network Analysis Improve Pattern Recognition Among Adverse Events Following Immunization Reported to VAERS? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID QUANTITATIVE SIGNAL-DETECTION; SYSTEM VAERS; INTUSSUSCEPTION; VACCINATION AB Current methods of statistical data mining are limited in their ability to facilitate the identification of patterns of potential clinical interest from spontaneous reporting systems of medical product adverse events (AEs). Network analysis (NA) allows for simultaneous representation of complex connections among the key elements of such a system. The Vaccine Adverse Event Reporting System (VAERS) can be represented as a network of 6,428 nodes (74 vaccines and 6,354 AEs) with more than 1.4 million interlinkages. VAERS has the characteristics of a "scale-free" network, with certain vaccines and AEs acting as "hubs" in the network. Known safety signals were visualized using NA methods, including hub identification. NA offers a complementary approach to current statistical data-mining techniques for visualizing multidimensional patterns, providing a structural framework for evaluating AE data. C1 [Ball, R.; Botsis, T.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Botsis, T (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Taxiarchis.Botsis@fda.hhs.gov FU Center for Biologics Evaluation and Research FX This project was supported in part by an appointment of T. B. 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 US Department of Energy and the US Food and Drug Administration. We thank Michael Nguyen, Jane Woo, Estelle Russek-Cohen, Rich Forshee, David Martin, and Rick Wilson for helpful discussions and reviews of early drafts of the manuscript. NR 19 TC 15 Z9 15 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 AUG PY 2011 VL 90 IS 2 BP 271 EP 278 DI 10.1038/clpt.2011.119 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 795LE UT WOS:000292974900020 PM 21677640 ER PT J AU Florian, JA Tornoe, CW Brundage, R Parekh, A Garnett, CE AF Florian, Jeffry A. Tornoe, Christoffer W. Brundage, Richard Parekh, Ameeta Garnett, Christine E. TI Population Pharmacokinetic and Concentration-QTc Models for Moxifloxacin: Pooled Analysis of 20 Thorough QT Studies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Population pharmacokinetics; exposure-response modeling; QT prolongation; moxifloxacin; ICH E14; thorough QT studies ID INTERVAL PROLONGATION; TRAFFICKING; QUINIDINE; QT/QTC; WOMEN AB To increase our understanding of important subject characteristics and design variables affecting the performance of oral moxifloxacin in thorough QT studies, population pharmacokinetic and concentration-QTc models were developed by pooling data from 20 studies. A 1-compartment model with first-order elimination described the pharmacokinetics. Absorption delay was modeled using 8 transit compartments. Mean (95% confidence interval) values for oral clearance, apparent volume of distribution, the first-order absorption rate constant, and mean transit time were 11.7 (11.5-11.9) L/h, 147 (144-150) L, 1.9 (1.7-2.1) 1/h, and 0.3 (0.28-0.34) hours, respectively. Overencapsulating the moxifloxacin tablet increased mean transit time by 138% and delayed time to maximum concentration by 0.5 hours but had a minimal effect on overall exposure. Administration with food decreased absorption rate constant by 27%. Women had higher moxifloxacin exposure compared with men, which was explained by lower body weights. A linear model described the concentration-QTc relationship with a mean slope of 3.1 (2.8-3.3) milliseconds per mu g/mL moxifloxacin. Mean slopes for individual studies ranged from 1.6 to 4.8 milliseconds per mu g/mL. Hysteresis between moxifloxacin plasma concentrations and QTc was modest, and incorporating this delay did not result in a different slope (3.3 milliseconds per mu g/mL). There were no differences in slope estimates between men and women or among race categories. C1 [Florian, Jeffry A.; Tornoe, Christoffer W.; Garnett, Christine E.] US FDA, Div Pharmacometr, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Brundage, Richard] Univ Minnesota, Coll Pharm, Dept Expt & Clin Pharmacol, Minneapolis, MN 55455 USA. [Parekh, Ameeta] US FDA, Off Womens Hlth, Off Commissioner, Rockville, MD 20857 USA. RP Garnett, CE (reprint author), 10903 New Hampshire Ave,Room 1260,Bldg 51, Silver Spring, MD 20993 USA. EM christine.garnett@fda.hhs.gov NR 26 TC 71 Z9 71 U1 0 U2 2 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 AUG PY 2011 VL 51 IS 8 BP 1152 EP 1162 DI 10.1177/0091270010381498 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 794BF UT WOS:000292868600002 PM 21228407 ER PT J AU Honchel, R Carraway, J Gopee, N Callicott, R Chen, J Patton, R Xu, Q Zalkkar, J Laniyonu, A Krefting, I Cato, M Robie-Suh, K Rieves, R AF Honchel, R. Carraway, J. Gopee, N. Callicott, R. Chen, J. Patton, R. Xu, Q. Zalkkar, J. Laniyonu, A. Krefting, I. Cato, M. Robie-Suh, K. Rieves, R. TI A dose-response study in animals to evaluate the anticoagulant effect of the stage 2 unfractionated heparin USP monograph change SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Heparin; Dose-response; In-vivo; aPTT; ACT ID PLATELET-AGGREGATION; INHIBITION AB The United States Pharmacopeia (USP) monograph for unfractionated heparin (UFH) was revised in October 2009. This revision was anticipated, based upon in vitro tests, to reduce UFH potency by approximately 10%. To study the potential in vivo consequences of the monograph change, we evaluated activated partial thromboplastin time (aPTT) and activated clotting time (ACT) responses in animals. Female mini-pigs and monkeys (n = 8/species) were administered intravenously 60, 54, 48, or 42 U/kg and 50, 45, 40, or 35 U/kg "old" (pre-USP revision) UFH, respectively, in a Williams 4 x 4 crossover design. Blood samples for aPTT and ACT were collected at 15 min after dosing. The same study design was then repeated using "new" (post-USP revision) UFH. Mean "new" UFH aPTT and ACT values were generally lower than those for "old" UFH although individual animal responses varied considerably. The aPTT and ACT response was generally dose-proportional for both "old" and "new" UFH. These studies indicate that the USP monograph alteration for UFH may result in a modest reduction in the anticoagulant response across a population, but the variability in animal responses underscores the importance of individualization of clinical UFH dosing and the importance of anticoagulant test monitoring. Published by Elsevier Inc. C1 [Honchel, R.; Laniyonu, A.; Krefting, I.; Rieves, R.] US FDA, Div Med Imaging Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Carraway, J.; Gopee, N.; Callicott, R.; Chen, J.; Patton, R.] Natl Ctr Toxicol Res, Jefferson, AR 72029 USA. [Xu, Q.; Zalkkar, J.] US FDA, Div Biometr 5, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Cato, M.; Robie-Suh, K.] US FDA, Div Hematol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Honchel, R (reprint author), US FDA, Div Med Imaging Prod, Off New Drugs, Ctr Drug Evaluat & Res, White Oak Bldg 22,Room 2389,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM ronald.honchel@fda.hhs.gov; jeff.carraway@fda.hhs.gov; neera.gopee@fda.hhs.gov; ralph.callicott@fda.hhs.gov; jamesJ.chen@fda.hhs.gov; ralph.patton@fda.hhs.-gov; qing.xu@fda.hhs.gov; jyoti.zalkkar@fda.hhs.gov; adebayo.laniyonu@fda.hhs.gov; ira.krefting@fda.hhs.gov; marcus.cato@fda.hhs.gov; kathy.robiesuh@fda.hhs.gov; rafel.rieves@fda.hhs.gov FU United States Food and Drug Administration FX This study was funded by the United States Food and Drug Administration. NR 9 TC 3 Z9 3 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2011 VL 60 IS 3 BP 318 EP 322 DI 10.1016/j.yrtph.2011.04.008 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 795AM UT WOS:000292943900006 PM 21549797 ER PT J AU Lo Piparo, E Worth, A Manibusan, M Yang, C Schilter, B Mazzatorta, P Jacobs, MN Steinkellner, H Mohimont, L AF Lo Piparo, Elena Worth, Andrew Manibusan, Mary Yang, Chihae Schilter, Benoit Mazzatorta, Paolo Jacobs, Miriam N. Steinkellner, Hans Mohimont, Luc TI Use of computational tools in the field of food safety SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Alternative method; Risk assessment; Quantitative Structure Activity Relationship (QSAR); Structure Activity Relationship (SAR); Toxicity; Mode of Action (MOA); Threshold of Toxicological Concern (ITC); Margin of Exposure (MoE); Lowest Observed Adverse Effect Level (LOAEL); Maximum Recommended Therapeutic Dose (MRTD) ID TOXICITY HAZARD IDENTIFICATION; COMPREHENSIVE MODEL; EFFECT LEVEL; QSAR MODELS; MDL-QSAR; PREDICTION; TOXICOLOGY; CARCINOGENICITY; MUTAGENICITY; PERFORMANCE AB In this article we give an overview of how computational methods are currently used in the field of food safety by national regulatory bodies, international advisory organisations and the food industry. Our results show that currently the majority of stakeholders in the field of food safety do not apply computational methods on a routine basis, mainly because of a lack of in-house expertise. Some organisations, however, are very experienced in their use and have developed specialised in-house approaches. Despite this variable situation, computational tools are widely perceived to be a useful tool to support regulatory assessments and decision making in the field of food safety. Recognized, however, is a widespread need to develop guidance documents and software tools that will promote and harmonise the use of computational methods, together with appropriate training. (C) 2011 Elsevier Inc. All rights reserved. C1 [Lo Piparo, Elena; Worth, Andrew] European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, I-21027 Ispra, VA, Italy. [Yang, Chihae] US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. [Schilter, Benoit; Mazzatorta, Paolo] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. [Jacobs, Miriam N.; Steinkellner, Hans; Mohimont, Luc] European Food Safety Author, I-43121 Parma, Italy. RP Lo Piparo, E (reprint author), European Commiss Joint Res Ctr, Inst Hlth & Consumer Protect, Via Enrico Fermi 2749, I-21027 Ispra, VA, Italy. EM lopiparo@live.com FU EFSA [SLA/EFSA-JRC/2009-01] FX This work was carried out under the terms of a Grant awarded by EFSA to the European Commission Joint Research Centre, Institute for Health & Consumer Protection, Ispra, Italy (Contract No.: SLA/EFSA-JRC/2009-01). Chihae Yang thanks the US FDA CFSAN CERES team for allowing description of the CERES system. NR 34 TC 3 Z9 3 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2011 VL 60 IS 3 BP 354 EP 362 DI 10.1016/j.yrtph.2011.05.003 PG 9 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 795AM UT WOS:000292943900010 PM 21600952 ER PT J AU Stine, CB Reimschuessel, R Gieseker, CM Evans, ER Mayer, TD Hasbrouck, NR Tall, E Boehmer, J da Costa, GG Ward, JL AF Stine, Cynthia B. Reimschuessel, Renate Gieseker, Charles M. Evans, Eric R. Mayer, Tamara D. Hasbrouck, Nicholas R. Tall, Elizabeth Boehmer, Jamie da Costa, Goncalo Gamboa Ward, Jeffrey L. TI A No Observable Adverse Effects Level (NOAEL) for pigs fed melamine and cyanuric acid SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Melamine; Cyanuric acid; Pig; NOAEL; Crystals; Kidney; Triazine; Feed ID ACUTE-RENAL-FAILURE; YOUNG-CHILDREN; KIDNEY; CATS; FOOD; CARCINOGENICITY; TOXICITY; RATS; DOGS; UROLITHIASIS AB Ingesting melamine adulterated milk products led to kidney stones in many infants in 2008. This differs from the renal failure caused by intratubular crystal formation after co-ingestion of melamine (MEL) and cyanuric acid (CYA) in adulterated pet foods in 2007. To better understand the potential risk of developing crystal nephropathy following co-ingestion of MEL and CYA, we fed 16 weanling pigs 0, 1, 3.3, 10, 33, or 100 mg/kg bw/day of each MEL and CYA, or 200 mg/kg bw/day of either compound individually for 7 days. Crystals were found in the renal medulla and cortex and urine sediments of all pigs fed both MEL and CYA each at 10 mg/kg bw/day (or greater). Crystals were also found in one of the two pigs fed 200 mg/kg bw/day MEL-only. In a 28 day study, 36 weanling pigs were fed 0,1, or 3.3 mg/kg bw/day of MEL and CYA or 200 mg/kg bw/day MEL-only. Only one of the 3.3 mg/kg MEL and CYA pig kidneys contained crystals. The no-observed-adverse-effect level (NOAEL) for pigs fed MEL and CYA for 28 days was concluded to be 1.0 mg/kg bw/day corresponding to 25 mg/kg (ppm) MEL and 25 mg/kg (ppm) CYA in dry feed. Published by Elsevier Inc. C1 [Stine, Cynthia B.; Reimschuessel, Renate; Gieseker, Charles M.; Evans, Eric R.; Mayer, Tamara D.; Hasbrouck, Nicholas R.; Tall, Elizabeth; Boehmer, Jamie; Ward, Jeffrey L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Stine, CB (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM cynthia.stine@fda.hhs.gov; renate.reimschuessel@fda.hhs.gov; charles.gieseker@fda.hhs.gov; eric.evans@fda.hhs.gov; nicholas.hasbrouck@fda.hhs.gov; elizabeth.tall@fda.hhs.gov; jamie.boehmer@fda.hhs.gov; goncalo.gamboa@fda.hhs.gov; jeffrey.ward@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 FU NIEHS [FDA IAG:224-07-0007, NIH Y1ES1027] FX The authors gratefully acknowledge the animal care assistance by Steven Rill, Steven Matthews, Mark McDonald and Virginia Mills, animal care assistance and laboratory support of Meredith Myers, the chemistry support of Cristina Nochetto, and the critical review of the manuscript by Dave Hattan. This study was supported in part through an interagency agreement between the FDA and the National Toxicology Program at NIEHS (FDA IAG:224-07-0007; NIH Y1ES1027). The opinions expressed in this paper do not necessarily represent those of the US Food and Drug Administration. NR 64 TC 19 Z9 22 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD AUG PY 2011 VL 60 IS 3 BP 363 EP 372 DI 10.1016/j.yrtph.2011.05.004 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 795AM UT WOS:000292943900011 PM 21620919 ER PT J AU Shi, Q Yang, X Greenhaw, J Salminen, WF AF Shi, Qiang Yang, Xi Greenhaw, James Salminen, William F. TI Hepatic Cytochrome P450s Attenuate the Cytotoxicity Induced by Leflunomide and Its Active Metabolite A77 1726 in Primary Cultured Rat Hepatocytes SO TOXICOLOGICAL SCIENCES LA English DT Article DE rat; hepatocytes; hepatotoxicity; leflunomide; A77 1726; cytochrome P450s ID RHEUMATOID-ARTHRITIS; INHIBITION; TOXICITY; DRUG; HEPATOTOXICITY; INDUCTION; A77-1726; INJURY; LIVER; TRANSPORTER AB The Black Box Warning section of the U.S. drug label for leflunomide was recently updated to include stronger warnings about potential hepatotoxicity from this novel anti-arthritis drug. Because metabolic activation is a key mechanism for drug-induced hepatotoxicity, we examined whether leflunomide and its major metabolite, A77 1726, are cytotoxic to primary rat hepatocytes and whether their toxicity is modulated by hepatic cytochrome P450s (CYPs). As measured by lactate dehydrogenase leakage, time-dependent cytotoxicity was observed at 250-500 mu M for leflunomide and 330-500 mu M for A77 1726 within 20 h. Unexpectedly, three nonisoenzyme-specific CYP inhibitors, including SKF-525A, metyrapone, and 1-aminobenzotriazole, did not reduce but remarkably enhanced the cytotoxicity of leflunomide or A77 1726. SKF-525A pretreatment notably rendered hepatocytes susceptible to as low as 15 mu M leflunomide or A77 1726. Three isoenzyme-specific CYP inhibitors including alpha-naphthoflavone, ticlopidine, and ketoconazole that mainly target CYP1A, CYP2B/2C, and CYP3A, respectively, also enhanced the cytotoxicity. A strong synergistic effect, similar to SKF-525A alone, was noted using a combination of all three of the isoenzyme-specific inhibitors. Hepatocytes pretreated with the CYP inducer dexamethasone for 24 h exhibited decreased cytotoxicity to leflunomide and A77 1726. At the concentrations tested, the CYP inhibitors and inducer showed no cytotoxicity. These data demonstrate that the parent forms of leflunomide and A77 1726 are more toxic to hepatocytes than their poorly characterized metabolites, indicating that the metabolic process of leflunomide is a detoxification step rather than an initiating event leading to toxicity. C1 [Shi, Qiang; Yang, Xi; Greenhaw, James; Salminen, William F.] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. RP Salminen, WF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. EM william.salminen@fda.hhs.gov RI Qiang, Shi/E-6266-2012 FU NCTR; U.S. Department of Energy; U.S. FDA FX Dr Xi Yang is supported by the Research Participation Program at the NCTR 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. FDA. NR 35 TC 15 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD AUG PY 2011 VL 122 IS 2 BP 579 EP 586 DI 10.1093/toxsci/kfr106 PG 8 WC Toxicology SC Toxicology GA 807QJ UT WOS:000293914500032 PM 21546349 ER PT J AU He, GX Zhang, C Crow, RR Thorpe, C Chen, HZ Kumar, S Tsuchiya, T Varela, MF AF He, Gui-Xin Zhang, Chu Crow, Robert R. Thorpe, Conner Chen, Huizhong Kumar, Sanath Tsuchiya, Tomofusa Varela, Manuel F. TI SugE, a New Member of the SMR Family of Transporters, Contributes to Antimicrobial Resistance in Enterobacter cloacae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MULTIDRUG EFFLUX PUMP; PSEUDOMONAS-AERUGINOSA; SUSCEPTIBILITY; CLONING; SYSTEM; STRAIN; ACRAB AB We cloned a gene, sugE, from the chromosome of Enterobacter cloacae ATCC 13047. Analysis of the susceptibilities of the sugE-containing strain (Escherichia coli KAM32/pSUGE28) and sugE-deficient E. cloacae (Ec Delta sugE) showed that SugE confers resistance to cetyltrimethylammonium bromide, cetylpyridinium chloride, tetraphenylphosphonium, benzalkonium chloride, ethidium bromide, and sodium dodecyl sulfate. We also investigated expression of sugE. We confirm here that SugE from E. cloacae is an SMR family transporter as determined by observing its energy-dependent drug efflux activity. C1 [He, Gui-Xin; Zhang, Chu; Thorpe, Conner] Univ Massachusetts Lowell, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. [Crow, Robert R.; Kumar, Sanath; Varela, Manuel F.] Eastern New Mexico Univ, Dept Biol, Portales, NM 88130 USA. [Chen, Huizhong] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Tsuchiya, Tomofusa] Okayma Univ, Dept Mol Microbiol, Okayama 7008530, Japan. RP He, GX (reprint author), Univ Massachusetts Lowell, Dept Clin Lab & Nutr Sci, Lowell, MA 01854 USA. EM Guixin_He@uml.edu RI Varela, Manuel/A-7782-2009 OI Varela, Manuel/0000-0001-8667-7853 FU National Center for Research Resources [P20 RR016480]; University of Massachusetts Lowell FX This work was supported by NIH grant P20 RR016480 (M.F.V.), which is from the NM-INBRE program of the National Center for Research Resources, and by an Internal Research grant from the University of Massachusetts Lowell (G.-X.H.). NR 21 TC 11 Z9 15 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2011 VL 55 IS 8 BP 3954 EP 3957 DI 10.1128/AAC.00094-11 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 792HV UT WOS:000292733800043 PM 21576447 ER PT J AU Lienau, EK DeSalle, R Allard, M Brown, EW Swofford, D Rosenfeld, JA Sarkar, IN Planet, PJ AF Lienau, E. Kurt DeSalle, Rob Allard, Marc Brown, Eric W. Swofford, David Rosenfeld, Jeffrey A. Sarkar, Indra N. Planet, Paul J. TI The mega-matrix tree of life: using genome-scale horizontal gene transfer and sequence evolution data as information about the vertical history of life SO CLADISTICS LA English DT Article ID PHYLOGENETIC ANALYSIS; BACTERIAL PHYLOGENY; UNIVERSAL ANCESTOR; RNA-POLYMERASE; DATA SETS; ORIGIN; CORE; PROKARYOTES; ORGANISMS; RECONSTRUCTION AB Because horizontal gene transfer can confound the recovery of the largely prokaryotic tree of life (ToL), most genome-based techniques seek to eliminate horizontal signal from ToL analyses, commonly by sieving out incongruent genes and data. This approach greatly limits the number of gene families analysed to a subset thought to be representative of vertical evolutionary history. However, formalized tests have not been performed to determine whether combining the massive amounts of information available in fully sequenced genomes can recover a reasonable ToL. Consequently, we used empirically defined gene homology definitions from a previous study that delineate xenologous gene families (gene families derived from a common transfer event) to generate a massively concatenated, combined-data ToL matrix derived from 323 404 translated open reading frames arranged into 12 381 gene homologue groups coded as amino acid data and 63 336, 64 105, 65 153, 66 922 and 67 109 gene homologue groups coded as gene presence/absence data for 166 fully sequenced genomes. This whole-genome gene presence/absence and amino acid sequence ToL data matrix is composed of 4867 184 characters (a combined data-type mega-matrix). Phylogenetic analysis of this mega-matrix yielded a fully resolved ToL that classifies all three commonly accepted domains of life as monophyletic and groups most taxa in traditionally recognized locations with high support. Most importantly, these results corroborate the existence of a common evolutionary history for these taxa present in both data types that is evident only when these data are analysed in combination. (C) The Willi Hennig Society 2010. C1 [Lienau, E. Kurt; DeSalle, Rob; Planet, Paul J.] Amer Museum Nat Hist, Sackler Inst Comparat Genom, New York, NY 10024 USA. [Lienau, E. Kurt; Rosenfeld, Jeffrey A.] NYU, Grad Sch Arts & Sci, Dept Biol, New York, NY 10003 USA. [Lienau, E. Kurt; Allard, Marc; Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. [Swofford, David] Duke Univ, Duke Inst Genomes & Sci Policy, Durham, NC 27708 USA. [Sarkar, Indra N.] Marine Biol Lab, Woods Hole, MA 02543 USA. [Planet, Paul J.] Columbia Univ, Coll Phys & Surg, Childrens Hosp New York, Dept Pediat, New York, NY 10032 USA. RP Lienau, EK (reprint author), Amer Museum Nat Hist, Sackler Inst Comparat Genom, Cent Pk W & 79th St, New York, NY 10024 USA. EM kurt.lienau@FDA.HHS.gov FU US National Institutes of Health; NYU; Sackler Institute for Comparative Genomics; American Museum of Natural History; Oak Ridge Institute for Science Education to the Food and Drug Administration of the USA FX We thank Al Phillips Mark Siddall and Rich Baker for insightful discussion; Francisca Almeida, George Amato, Angelica Cibiran Jaramillio, Sergios-Orestis Kolokotronis, Matt Leslie, Cristina Pomilla and Ilya Temkin for reviewing an earlier version of this paper. We further thank three anonymous reviewers for their valuable criticism. This work was funded by grants from the US National Institutes of Health (to David Figurski, R.D. and P.J.P.). E.K.L. and J.A.R. were partially supported by a training grant from the US National Institutes of Health to New York University and E.K.L. and J.A.R. were further supported by a McKracken Fellowship of NYU. Our group also acknowledges the support of the Sackler Institute for Comparative Genomics and the Lewis and Dorothy Cullman Program in Molecular Systematics at the American Museum of Natural History. E.K.L. is now supported by a fellowship from the Oak Ridge Institute for Science Education to the Food and Drug Administration of the USA. NR 63 TC 3 Z9 3 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0748-3007 J9 CLADISTICS JI Cladistics PD AUG PY 2011 VL 27 IS 4 BP 417 EP 427 DI 10.1111/j.1096-0031.2010.00337.x PG 11 WC Evolutionary Biology SC Evolutionary Biology GA 790AY UT WOS:000292562100008 ER PT J AU Liu, YT Flynn, TJ Ferguson, MS Hoagland, EM Yu, LL AF Liu, Yitong Flynn, Thomas J. Ferguson, Martine S. Hoagland, Erica M. Yu, Liangli (Lucy) TI Effects of dietary phenolics and botanical extracts on hepatotoxicity-related endpoints in human and rat hepatoma cells and statistical models for prediction of hepatotoxicity SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Hepatotoxicity; Dietary phenolics; Botanical extracts; Cluster analysis ID GREEN TEA EXTRACTS; IN-VITRO; ANTICANCER PROPERTIES; POTENTIAL TOXICITY; HEPATOCYTES; ACID; ANTIOXIDANT; METABOLISM; FLAVONOIDS; CULTURE AB Toxicity assessment of botanical materials is difficult because they are typically complex mixtures of phytochemicals. In the present study, 16 phenolics were tested in both human (HepG2/C3A) and rat (MH1C1) hepatoma cells using a battery of eight toxicity endpoints. Cluster analysis was used to group the phenolics into four clusters for each cell type. Comparison of overall and individual liver activity of phenolics on both human and rat hepatoma cell lines showed significant differences for some endpoints. However, the cluster membership was similar across both cell types with the majority of phenolics clustering with the solvent control group (cluster 1). Each cell type produced a cluster of compounds with reported in vivo liver toxicity (cluster 2). Five herbal extracts were prepared and then tested as above. Using the cluster model developed with the phenolics, in the HepG2/C3A cells green tea was assigned to cluster 2 and the remaining four extracts to cluster 1. In the MH1C1 cells, green tea and thyme were assigned to cluster 2, cinnamon to cluster 4, and juniper berry and peppermint to cluster 1. The data suggest that this in vitro model may be useful for identifying hepatotoxic phenolics and botanical preparations rich in phenolics. Published by Elsevier Ltd. C1 [Flynn, Thomas J.] US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, FDA MOD Labs 1, Laurel, MD 20708 USA. [Liu, Yitong; Yu, Liangli (Lucy)] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Ferguson, Martine S.] US FDA, Div Publ Hlth & Biostat, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Flynn, TJ (reprint author), US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, 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 FU Joint Institute for Food Safety and Nutrition at the University of Maryland [U032] FX This work was supported by the Joint Institute for Food Safety and Nutrition at the University of Maryland (Grant No. U032 to L.Y. and T.J.F.). NR 41 TC 11 Z9 13 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD AUG PY 2011 VL 49 IS 8 BP 1820 EP 1827 DI 10.1016/j.fct.2011.04.034 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 792ZK UT WOS:000292788700023 PM 21569817 ER PT J AU Wong-Chew, RM Garcia-Leon, ML Torrija, BET Hernandez-Perez, B Cardiel-Marmolejo, LE Beeler, JA Audet, S Santos-Preciado, JI AF Maria Wong-Chew, Rosa Leonardo Garcia-Leon, Miguel Espinosa-Torres Torrija, Bogart Hernandez-Perez, Brenda Cardiel-Marmolejo, Lino E. Beeler, Judy A. Audet, Susette Ignacio Santos-Preciado, Jose TI Increasing the Time of Exposure to Aerosol Measles Vaccine Elicits an Immune Response Equivalent to That Seen in 9-Month-Old Mexican Children Given the Same Dose Subcutaneously SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SUCCESSFUL IMMUNIZATION; ADDITIONAL EVIDENCE; MATERNAL ANTIBODY; RANDOMIZED-TRIAL; DIPLOID-CELL; INFANTS; AGE; ROUTES; MEMORY AB Background. A 30-second aerosol measles vaccination successfully primes children 12 months of age and older but is poorly immunogenic when given to 9-month-old children. We examined the immune responses when increasing the duration to aerosol exposure in 9-month-olds. Methods. One hundred and thirteen healthy 9-month-old children from Mexico City were enrolled; 58 received aerosol EZ measles vaccine for 2.5 minutes and 55 subcutaneously. Measles-specific neutralizing antibodies and cellular responses were measured before and at 3 and 6 months postimmunization. Results. Adaptive immunity was induced in 97% after aerosol and 98% after subcutaneous administration. Seroconversion rates and GMCs were 95% and 373 mIU/mL (95% confidence interval [CI], 441-843) following aerosol vaccination and 91% and 306 mIU/mL (95% CI, 367-597) after subcutaneous administration at 3 months. The percentage of children with a measles-specific stimulation index >= 3 was 45% and 60% in the aerosol versus 55% and 59% in the subcutaneous group at 3 and 6 months, respectively. CD8 memory cell frequencies were higher in the aerosol group at 3 months compared with the subcutaneous group. Adverse reactions were comparable in both groups. Conclusions. Increasing exposure time to aerosol measles vaccine elicits immune responses that are comparable to those seen when an equivalent dose is administered by the subcutaneous route in 9-month-old infants. C1 [Maria Wong-Chew, Rosa; Leonardo Garcia-Leon, Miguel; Ignacio Santos-Preciado, Jose] Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Mexico City 06726, DF, Mexico. [Espinosa-Torres Torrija, Bogart; Hernandez-Perez, Brenda; Cardiel-Marmolejo, Lino E.] Hosp Gen Mexico City, Serv Pediat, Mexico City, DF, Mexico. [Beeler, Judy A.; Audet, Susette] US FDA, Div Viral Prod, Rockville, MD 20857 USA. RP Wong-Chew, RM (reprint author), Univ Nacl Autonoma Mexico, Fac Med, Dept Expt Med, Dr Balmis 148, Mexico City 06726, DF, Mexico. EM rmwong@unam.mx FU Fogarty International Center; Office of Research on Women's Health [TW006193] FX This work was supported by a grant from the Fogarty International Center and the Office of Research on Women's Health (TW006193). NR 31 TC 12 Z9 12 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2011 VL 204 IS 3 BP 426 EP 432 DI 10.1093/infdis/jir278 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 790BA UT WOS:000292562300017 PM 21742842 ER PT J AU Keene, AM Tyner, KM AF Keene, Athena M. Tyner, Katherine M. TI Analytical characterization of gold nanoparticle primary particles, aggregates, agglomerates, and agglomerated aggregates SO JOURNAL OF NANOPARTICLE RESEARCH LA English DT Article DE Gold nanoparticle; Aggregate; Agglomerate; Analytical characterization; Transmission electron microscopy; Biocompatibility ID DIFFERENT SIZES; ONE-PHASE; SURFACE; BIODISTRIBUTION; NANOTECHNOLOGY; NANOCRYSTALS; FLUORESCENCE; SEPARATION AB Gold nanoparticles have been studied for many biomedical applications. However, alterations in the gold nanoparticles' environment frequently lead to the formation of aggregates and agglomerates, which have not been well characterized. These new structures could significantly change the biological impact of the nanoparticles, so the appropriate characterization of these structures prior to biological administration is vital for the correct interpretation of toxicology results. By varying the solvent or heating under pressure, four reproducible gold nanoparticles structures were created: 10 nm primary particles, aggregates of the primary particles that contain non-reversible bonds between the individual nanoparticles, agglomerates of primary particles that contain reversible interactions between the individual nanoparticles, and agglomerated aggregates that have reversible bonds linking individual aggregates. Ultraviolet-visible (UV-Vis) spectroscopy, thermal gravitational analysis, and neutron activation analysis were each found to accurately measure the concentration of the primary particles. The primary particles measured 10 nm by dynamic light scattering (DLS) and had a spherical morphology by transmission electron microscopy (TEM) while the aggregates measured 110 nm by DLS and had a distorted morphology by TEM. The agglomerate and aggregated agglomerate samples both measured > 1,000 nm by DLS, but the individual particles had significantly different morphologies by TEM. Multiple other analytical techniques, including ultracentrifugation, gel electrophoresis, and X-ray diffraction, also showed unique traits for each structure. The structural differences did not change in the presence of cell culture media or rat serum. In addition, the primary particles, aggregates, and agglomerates each had a unique UV-Vis spectrum, allowing for an inexpensive, rapid method to differentiate between the structures. C1 [Keene, Athena M.; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tyner, KM (reprint author), US FDA, Ctr Drug Evaluat & Res, Bldg 64,Rm 2086,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Katherine.Tyner@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration FX The authors acknowledge Dr. Rodney Rouse, FDA, for providing the rat serum samples, Dr. Beni Dair, FDA, for TEM assistance, Jeff Davis, National Institutes of Standards and Technology, for the use of his XRD and standards, and the Office of Science and Engineering Laboratories, FDA, for the use of their TEM and TGA. 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. 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. 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 35 TC 14 Z9 14 U1 6 U2 33 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1388-0764 EI 1572-896X J9 J NANOPART RES JI J. Nanopart. Res. PD AUG PY 2011 VL 13 IS 8 BP 3465 EP 3481 DI 10.1007/s11051-011-0268-4 PG 17 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 792MG UT WOS:000292749100038 ER PT J AU Prince, JL Pham, DL Myers, KJ AF Prince, Jerry L. Pham, Dzung L. Myers, Kyle J. TI Untitled SO MEDICAL IMAGE ANALYSIS LA English DT Editorial Material C1 [Prince, Jerry L.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Pham, Dzung L.] Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Bethesda, MD 20892 USA. [Myers, Kyle J.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, CDRH, Silver Spring, MD 20993 USA. RP Prince, JL (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM prince@jhu.edu; dzung.pham@nih.gov; kyle.myers@fda.hhs.gov RI Prince, Jerry/A-3281-2010 OI Prince, Jerry/0000-0002-6553-0876 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1361-8415 J9 MED IMAGE ANAL JI Med. Image Anal. PD AUG PY 2011 VL 15 IS 4 BP 601 EP 602 DI 10.1016/j.media.2011.05.011 PG 2 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 791QC UT WOS:000292678700017 PM 21669390 ER PT J AU Kundoor, V Dalby, RN AF Kundoor, Vipra Dalby, Richard N. TI Effect of Formulation- and Administration-Related Variables on Deposition Pattern of Nasal Spray Pumps Evaluated Using a Nasal Cast SO PHARMACEUTICAL RESEARCH LA English DT Article DE deposition pattern; droplet size; formulation; nasal spray; spray pump design; viscosity ID CLEARANCE; VISCOSITY; DELIVERY; MODEL; SIZE AB To systematically evaluate the effect of formulation- and administration-related variables on nasal spray deposition using a nasal cast. Deposition pattern was assessed by uniformly coating a transparent nose model with Sar-GelA (R), which changes from white to purple on contact with water. Sprays were subsequently discharged into the cast, which was then digitally photographed. Images were quantified using AdobeA (R) Photoshop. The effects of formulation viscosity (which influences droplet size), simulated administration techniques (head orientation, spray administration angle, spray nozzle insertion depth), spray pump design and metering volume on nasal deposition pattern were investigated. There was a significant decrease in the deposition area associated with sprays of increasing viscosity. This appeared to be mediated by an increase in droplet size and a narrowing of the spray plume. Administration techniques and nasal spray pump design also had a significant effect on the deposition pattern. This simple color-based method provides quantitative estimates of the effects that different formulation and administration variables may have on the nasal deposition area, and provides a rational basis on which manufacturers of nasal sprays can base their patient instructions or post approval changes when it is impractical to optimize these using a clinical study. C1 [Kundoor, Vipra; Dalby, Richard N.] Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Kundoor, V (reprint author), US FDA, 7520 Standish Pl, Rockville, MD 20857 USA. EM vipra.kundoor@fda.hhs.gov; rdalby@rx.umaryland.edu NR 16 TC 16 Z9 17 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD AUG PY 2011 VL 28 IS 8 BP 1895 EP 1904 DI 10.1007/s11095-011-0417-6 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 789ME UT WOS:000292518800009 PM 21499839 ER PT J AU Chen, ML Davit, B Lionberger, R Wahba, Z Ahn, HY Yu, LX AF Chen, Mei-Ling Davit, Barbara Lionberger, Robert Wahba, Zakaria Ahn, Hae-Young Yu, Lawrence X. TI Using Partial Area for Evaluation of Bioavailability and Bioequivalence SO PHARMACEUTICAL RESEARCH LA English DT Review DE bioavailability/bioequivalence; early exposure; partial area; partial AUC; truncated area ID HIGHLY VARIABLE DRUGS; ABSORPTION RATE; METRICS; EXPOSURE; PRODUCTS; EXTENT AB Assessment of bioavailability/bioequivalence generally relies on the comparison of rate and extent of drug absorption between products. Rate of absorption is commonly expressed by peak concentration (C-max) and time to peak concentration (T-max), although these parameters are indirect measures of absorption rate. Recognizing the importance of systemic exposure to drug efficacy and safety, FDA recommended that systemic exposure be better used for bioavailability/bioequivalence assessment. Apart from peak exposure and total exposure, FDA also recommended a new metric for early exposure that is considered necessary when a control of input rate is critical to ascertain drug efficacy and/or safety profile. The early exposure can be measured by truncating the area under the curve at T-max of the reference product (PAUC(r,tmax)) or some designated early time after dosing. The choice of truncation is most appropriately based on PK/PD relationship or efficacy/safety data for the drug under examination. Compared with C-max, PAUC(r,tmax) has higher sensitivity in detecting formulation differences and may be more variable. If the metric is highly variable, the reference-scaling approach can be employed for bioequivalence evaluation. The partial area metric is useful in PK/PD characterization as well as in the evaluation of bioavailability, bioequivalence and/or comparability. C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Davit, Barbara; Lionberger, Robert; Wahba, Zakaria; Yu, Lawrence X.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Ahn, Hae-Young] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 4108, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 24 TC 16 Z9 16 U1 1 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD AUG PY 2011 VL 28 IS 8 BP 1939 EP 1947 DI 10.1007/s11095-011-0421-x PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 789ME UT WOS:000292518800013 PM 21487930 ER PT J AU Yakes, BJ Prezioso, S Haughey, SA Campbell, K Elliott, CT DeGrasse, SL AF Yakes, Betsy Jean Prezioso, Samantha Haughey, Simon A. Campbell, Katrina Elliott, Christopher T. DeGrasse, Stacey L. TI An improved immunoassay for detection of saxitoxin by surface plasmon resonance biosensors SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE Surface plasmon resonance; Paralytic shellfish poisoning; Saxitoxin; Biosensor; Inhibition immunoassay ID SHELLFISH POISONING TOXINS; RECEPTOR-BINDING ASSAY; SINGLE-LABORATORY VALIDATION; PARALYTIC SHELLFISH; LIQUID-CHROMATOGRAPHY; CELL BIOASSAY; SPECTROMETRY; OXIDATION; SEAFOOD AB Saxitoxin and its analogs, the causative agents of paralytic shellfish poisoning (PSP), are a worldwide threat to seafood safety. Effective monitoring of potentially contaminated fishing areas as well as screening of seafood samples is necessary to adequately protect the public. While many analytical methods exist for detecting paralytic shellfish toxins (PSTs), each technique has challenges associated with routine use. One recently developed method [1] that overcomes ethical or performance-related issues of other techniques is the surface plasmon resonance (SPR) bioassay. Notwithstanding the advantages of this method, much research remains in optimizing the sensor substrate and assay conditions to create a robust technique for rapid and sensitive measurement of PSTs. This manuscript describes a more rigorous and stable SPR inhibition immunoassay through optimization of the surface chemistry as well as determination of optimum mixture ratios and mixing times. The final system provides rapid substrate formation (18 h saxitoxin conjugation with low reagent consumption), contains a reference channel for each assay, and is capable of triplicate measurements in a single run with detection limits well below the regulatory action level. Published by Elsevier B.V. C1 [Yakes, Betsy Jean; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Prezioso, Samantha] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. [Haughey, Simon A.; Campbell, Katrina; Elliott, Christopher T.] Queens Univ Belfast, Sch Biol Sci, IAFLU, Belfast BT9 5AG, Antrim, North Ireland. RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov; smprezioso@gmail.com; s.a.haughey@qub.ac.uk; katrina.campbell@qub.ac.uk; chris.elliott@qub.ac.uk; stacey.degrasse@fda.hhs.gov RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 NR 38 TC 17 Z9 17 U1 3 U2 41 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD AUG PY 2011 VL 156 IS 2 BP 805 EP 811 DI 10.1016/j.snb.2011.02.043 PG 7 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 787CQ UT WOS:000292354600044 ER PT J AU Kelly, EP Polo, S Sun, W Falgout, B AF Kelly, Eileen P. Polo, Stephanie Sun, Wellington Falgout, Barry TI Evolution of attenuating mutations in dengue-2 strain S16803 PDK50 vaccine and comparison of growth kinetics with parent virus SO VIRUS GENES LA English DT Article DE Dengue virus; Vaccine mutation analysis; Infectious clone ID TICK-BORNE ENCEPHALITIS; AMINO-ACID SUBSTITUTION; DOUBLE-STRANDED-RNA; DOG KIDNEY-CELLS; WEST-NILE-VIRUS; ENVELOPE GLYCOPROTEIN; NS1 PROTEIN; VIRAL-RNA; NONSTRUCTURAL PROTEINS; HEMORRHAGIC-FEVER AB A live-attenuated dengue-2 virus strain S16803 vaccine candidate that is immunogenic and safe in humans was derived by 50 passages in primary dog kidney (PDK) cells. To identify mutations associated with attenuation of the dengue-2 PDK50 vaccine strain, we determined the nucleotide changes that arose during PDK passage of the dengue-2 virus. Thirteen mutations distinguished the PDK50 virus from low-passage parent resulting in amino acid substitutions in the premembrane (E89G), envelope (E202K, N203D), nonstructural proteins NS1 (A43T), NS2A (L181F), NS2B (I26V), and NS4B (I/T108T, L112F). In addition, the PDK50 virus contained a C to T change of nucleotide 57 in the 5' non-coding region and four silent mutations of nucleotides 591, 987, 6471, and 8907. An infectious PDK50 cDNA clone virus was produced and characterized for growth kinetics in monkey (LLC-MK(2), Vero) and mosquito (C6/36) cells. Identification of mutations in the vaccine strain and availability of an infectious clone will permit systematic analysis of the importance of individual or collective mutations on attenuation of dengue virus. C1 [Kelly, Eileen P.] Walter Reed Army Inst Res, Div Virus Dis, Silver Spring, MD 20910 USA. [Polo, Stephanie; Sun, Wellington; Falgout, Barry] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Kelly, EP (reprint author), Walter Reed Army Inst Res, Div Virus Dis, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. EM eileen.kelly@amedd.army.mil FU United States Army Medical Research and Materiel Command FX The authors would like to thank Dr. Ken Eckels, Walter Reed Army Institute of Research, for providing the lyophilized low-passage parent and PDK10, PDK30, PDK40 and PDK50 vaccine candidate viruses. The studies were supported by the United States Army Medical Research and Materiel Command. NR 53 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD AUG PY 2011 VL 43 IS 1 BP 18 EP 26 DI 10.1007/s11262-011-0602-z PG 9 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 784LN UT WOS:000292158900004 PM 21461924 ER PT J AU An, YM Cipollo, JF AF An, Yanming Cipollo, John F. TI An unbiased approach for analysis of protein glycosylation and application to influenza vaccine hemagglutinin SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Glycoprotein; Permethylation profiling; Mass spectrometry; Hemagglutinin; Hydrophilic interaction chromatography; NetNGlyc; GlycoMod; Cn3D ID PERFORMANCE LIQUID-CHROMATOGRAPHY; N-LINKED GLYCOSYLATION; LECTIN AFFINITY-CHROMATOGRAPHY; MASS-SPECTROMETRY; MONOCLONAL-ANTIBODY; STRUCTURAL-ANALYSIS; GLYCOPROTEIN ENRICHMENT; H-1-NMR SPECTROSCOPY; THERAPEUTIC PROTEINS; COLON-CANCER AB Here a mass spectrometry-based platform for the analysis of glycoproteins is presented. Glycopeptides and released glycans are analyzed, the former by quadrupole orthogonal time-of-flight liquid chromatography/mass spectrometry (QoTOF LC/MS) and the latter by permethylation analysis using matrix-assisted laser desorption/ionization (MALDI)-TOF MS. QoTOF LC/MS analysis reveals the stochastic distribution of glycoforms at occupied sequons, and the latter provides a semiquantitative assessment of overall protein glycosylation. Hydrophilic interaction chromatography (HILIC) was used for unbiased enrichment of glycopeptides and was validated using five model N-glycoproteins bearing a wide array of glycans, including high-mannose, complex, and hybrid subtypes such as sulfo and sialyl forms. Sialyl and especially sulfated glycans are difficult to analyze because these substitutions are labile. The conditions used here allow detection of these compounds quantitatively, intact, and in the context of overall glycosylation. As a test case, we analyzed influenza B/Malaysia/2506/2004 hemagglutinin, a component of the 2006-2007 influenza vaccine. It bears 11 glycosylation sites. Approximately 90% of its glycans are high mannose, and 10% are present as complex and hybrid types, including those with sulfate. The stochastic distribution of glycoforms at glycosylation sites is revealed. This platform should have wide applications to glycoproteins in basic sciences and industry because no apparent bias for any glycoforms is observed. Published by Elsevier Inc. C1 [An, Yanming; Cipollo, John F.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cipollo, JF (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM john.cipollo@fda.hhs.gov NR 69 TC 19 Z9 19 U1 1 U2 22 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD AUG 1 PY 2011 VL 415 IS 1 BP 67 EP 80 DI 10.1016/j.ab.2011.04.018 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 774SX UT WOS:000291407900010 PM 21545787 ER PT J AU Laird, DT Sun, Y Reineke, KF Shieh, YC AF Laird, David T. Sun, Yan Reineke, Karl F. Shieh, Y. Carol TI Effective hepatitis A virus inactivation during low-heat dehydration of contaminated green onions SO FOOD MICROBIOLOGY LA English DT Article DE Hepatitis A virus; Thermal inactivation; Low heat dehydration; Green onion ID ENTERIC VIRUSES; RELATIVE-HUMIDITY; UNITED-STATES; SURVIVAL; OUTBREAK; TEMPERATURE; BERRIES; MUSSELS; STORAGE; HERBS AB Preserving fruits and vegetables by dehydration is common; however, information is limited concerning viral survival on the produce during the process. This work demonstrated the effects of low heat dehydration on inactivating hepatitis A virus (HAV) on contaminated green onions. Inoculated and uninoculated onion samples were dehydrated at target temperatures of 45-65 degrees C for 20 h. HAV from artificially contaminated onions (fresh or dehydrated) was eluted by shaking at 145 rpm at 20 degrees C for 20 min with 3% beef extract, pH 8, and followed by 0.2 mu M-membrane filtration before plaque assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Dilutions of the filtrates were made for obtaining countable plaques on FRhK-4 cell monolayers in 6-well plates, and also for eliminating inhibitors in qRT-PCR. Average water activity of the onions after 20 h-dehydration was 0.227, regardless of temperature used (47.9 degrees C or 651 degrees C). Eight dehydration trials resulted in a linear relationship between HAV inactivation and dehydration temperature, with HAV log reduction = 0.1372x(degrees C) -5.5572, r(2) = 0.88. Therefore, the 20 h-heating at 47.8, 55.1, and 62.4 degrees C reduced infectious HAV in onions by 1, 2, and 3 logs respectively, the Z value being 7.3 degrees C. It was concluded that low heat dehydration using 62.5 degrees C or above could effectively inactivate HAV on contaminated onions by >3 logs. Published by Elsevier Ltd. C1 [Laird, David T.; Sun, Yan; Reineke, Karl F.; Shieh, Y. Carol] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Shieh, YC (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM carol.shieh@fda.hhs.gov FU FDA; National Center for Food Safety and Technology (NCFST), Summit [IL 60501] FX The authors appreciate the critiques provided by D. Stewart and Dr. M. L Tortorello. This research was support by FDA as well as National Center for Food Safety and Technology (NCFST), Summit, IL 60501. NR 20 TC 9 Z9 9 U1 1 U2 8 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 AUG PY 2011 VL 28 IS 5 BP 998 EP 1002 DI 10.1016/j.fm.2011.01.011 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 771DO UT WOS:000291137600020 PM 21569944 ER PT J AU Ackerman, LK Noonan, GO Begley, TH Mazzola, EP AF Ackerman, Luke K. Noonan, Gregory O. Begley, Timothy H. Mazzola, Eugene P. TI Accurate mass and nuclear magnetic resonance identification of bisphenolic can coating migrants and their interference with liquid chromatography/tandem mass spectrometric analysis of bisphenol A (vol 25, pg 1336, 2011) SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Correction C1 [Ackerman, Luke K.; Noonan, Gregory O.; Begley, Timothy H.; Mazzola, Eugene P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ackerman, LK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 1 TC 1 Z9 1 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JUL 30 PY 2011 VL 25 IS 14 BP 2113 EP 2113 DI 10.1002/rcm.5085 PG 1 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 789XD UT WOS:000292551600024 ER PT J AU Umberger, K Bassen, HI AF Umberger, Ken Bassen, Howard I. TI Radiated radiofrequency immunity testing of automated external defibrillators - modifications of applicable standards are needed SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article AB Background: We studied the worst-case radiated radiofrequency (RF) susceptibility of automated external defibrillators (AEDs) based on the electromagnetic compatibility (EMC) requirements of a current standard for cardiac defibrillators, IEC 60601 2 4. Square wave modulation was used to mimic cardiac physiological frequencies of 1 - 3 Hz. Deviations from the IEC standard were a lower frequency limit of 30 MHz to explore frequencies where the patient-connected leads could resonate. Also testing up to 20 V/m was performed. We tested AEDs with ventricular fibrillation (V-Fib) and normal sinus rhythm signals on the patient leads to enable testing for false negatives (inappropriate "no shock advised" by the AED). Methods: We performed radiated exposures in a 10 meter anechoic chamber using two broadband antennas to generate E fields in the 30 - 2500 MHz frequency range at 1% frequency steps. An AED patient simulator was housed in a shielded box and delivered normal and fibrillation waveforms to the AED's patient leads. We developed a technique to screen ECG waveforms stored in each AED for electromagnetic interference at all frequencies without waiting for the long cycle times between analyses (normally 20 to over 200 s). Results: Five of the seven AEDs tested were susceptible to RF interference, primarily at frequencies below 80 MHz. Some induced errors could cause AEDs to malfunction and effectively inhibit operator prompts to deliver a shock to a patient experiencing lethal fibrillation. Failures occurred in some AEDs exposed to E fields between 3 V/m and 20 V/m, in the 38 - 50 MHz range. These occurred when the patient simulator was delivering a V-Fib waveform to the AED. Also, we found it is not possible to test modern battery-only-operated AEDs for EMI using a patient simulator if the IEC 60601-2-4 defibrillator standard's simulated patient load is used. Conclusions: AEDs experienced potentially life-threatening false-negative failures from radiated RF, primarily below the lower frequency limit of present AED standards. Field strengths causing failures were at levels as low as 3 V/m at frequencies below 80 MHz where resonance of the patient leads and the AED input circuitry occurred. This plus problems with the standard's' prescribed patient load make changes to the standard necessary. C1 [Bassen, Howard I.] US FDA, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. RP Bassen, HI (reprint author), US FDA, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM howard.bassen@fda.hhs.gov NR 10 TC 0 Z9 0 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-925X J9 BIOMED ENG ONLINE JI Biomed. Eng. Online PD JUL 29 PY 2011 VL 10 AR 66 DI 10.1186/1475-925X-10-66 PG 16 WC Engineering, Biomedical SC Engineering GA 812GV UT WOS:000294280000001 PM 21801368 ER PT J AU Chattopadhyay, R de la Vega, P Paik, SH Murata, Y Ferguson, EW Richie, TL Ooi, GT AF Chattopadhyay, Rana de la Vega, Patricia Paik, Sun H. Murata, Yoko Ferguson, Earl W. Richie, Thomas L. Ooi, Guck T. TI Early Transcriptional Responses of HepG2-A16 Liver Cells to Infection by Plasmodium falciparum Sporozoites SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN HEPATOCELLULAR-CARCINOMA; CIRCUMSPOROZOITE PROTEIN; PROTECTIVE ANTIBODIES; GLYPICAN-3 EXPRESSION; INVITRO CULTURE; GENE-EXPRESSION; T-CELLS; MALARIA; STAGE; VIVAX AB Invasion of hepatocytes by Plasmodium sporozoites deposited by Anopheles mosquitoes, and their subsequent transformation into infective merozoites is an obligatory step in the initiation of malaria. Interactions between the sporozoites and hepatocytes lead to a distinct, complex and coordinated cellular and systemic host response. Little is known about host liver cell response to sporozoite invasion, or whether it is primarily adaptive for the parasite, for the host, or for both. Our present study used gene expression profiling of human HepG2-A16 liver cells infected with Plasmodium falciparum sporozoites to understand the host early cellular events and factors influencing parasite infectivity and sporozoite development. Our results show that as early as 30 min following wild-type, non-irradiated sporozoite exposure, the expressions of at least 742 genes was selectively altered. These genes regulate diverse biological functions, such as immune processes, cell adhesion and communications, metabolism pathways, cell cycle regulation, and signal transduction. These functions reflect cellular events consistent with initial host cell defense responses, as well as alterations in host cells to sustain sporozoites growth and survival. Irradiated sporozoites gave very similar gene expression pattern changes, but direct comparative analysis between liver gene expression profiles caused by irradiated and non-irradiated sporozoites identified 29 genes, including glypican-3, that were specifically up-regulated only in irradiated sporozoites. Elucidating the role of this subset of genes may help identify the molecular basis for the irradiated sporozoites inability to develop intrahepatically, and their usefulness as an immunogen for developing protective immunity against pre-erythrocytic stage malaria. C1 [Chattopadhyay, Rana; de la Vega, Patricia; Richie, Thomas L.] US Mil Malaria Vaccine Program, Malaria Program, Silver Spring, MD 20910 USA. [de la Vega, Patricia] Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. [Richie, Thomas L.] USN, Med Res Ctr, Silver Spring, MD 20910 USA. [Paik, Sun H.; Murata, Yoko; Ferguson, Earl W.; Ooi, Guck T.] Sun BioMed Technol Inc, Ridgecrest, CA 93555 USA. RP Chattopadhyay, R (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM rana.chattopadhyay@fda.hhs.gov; guckooi@sunbmt.com OI Richie, Thomas/0000-0002-2946-5456 FU Department of Defense [W81XWH-05-C-0030]; CRADA [LP-CRADA-NMRC-05-2107, 6000.RAD1.F.A0309] FX This work was supported by Department of Defense Small Business Innovative Research Grant W81XWH-05-C-0030 (to S. H. P., Y. M., E. W. F., and G. T. O.) and the work between Sun BioMedical Technologies and the Malaria Program, Naval Medical Research Center was conducted through a CRADA collaboration Grant LP-CRADA-NMRC-05-2107 and was supported by Grant 6000.RAD1.F.A0309 (to R. C., P. V., and T. L. R.). NR 64 TC 8 Z9 8 U1 0 U2 3 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 JUL 29 PY 2011 VL 286 IS 30 BP 26396 EP 26405 DI 10.1074/jbc.M111.240879 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 796UK UT WOS:000293078200017 PM 21652718 ER PT J AU Egan, A Colman, E AF Egan, Amy Colman, Eric TI Weighing the Benefits of High-Dose Simvastatin against the Risk of Myopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHOLESTEROL C1 [Egan, Amy; Colman, Eric] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Metab & Endocrinol Prod, Silver Spring, MD USA. RP Egan, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Div Metab & Endocrinol Prod, Silver Spring, MD USA. NR 6 TC 51 Z9 53 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 28 PY 2011 VL 365 IS 4 BP 285 EP 287 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 798AJ UT WOS:000293172200001 PM 21675881 ER PT J AU Turnipseed, SB Storey, JM Clark, SB Miller, KE AF Turnipseed, Sherri B. Storey, Joseph M. Clark, Susan B. Miller, Keith E. TI Analysis of Veterinary Drugs and Metabolites in Milk Using Quadrupole Time-of-Flight Liquid Chromatography-Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Milk; quadrupole time-of-flight LC-MS; veterinary drug residues; metabolites ID BETA-LACTAM ANTIBIOTICS; BOVINE-MILK; ELECTROSPRAY-IONIZATION; MULTIRESIDUE ANALYSIS; ION-TRAP; TOF-MS; RESIDUES; CONFIRMATION; FOOD; PHARMACOKINETICS AB A quadrupole time-of-flight (Q-TOF) liquid chromatography mass-spectrometry (LC-MS) method was developed to analyze veterinary drug residues in milk. Milk samples were extracted with acetonitrile. A molecular weight cutoff filter was the only cleanup step in the procedure. Initially, a set of target compounds (including representative sulfonamides, tetracyclines, beta-lactams, and macrolides) was used for validation. Screening of residues was accomplished by collecting TOF (MS(1)) data and comparing the accurate mass and retention times of found compounds to a database containing information for veterinary drugs. The residues included in the study could be detected in samples fortified at the levels of concern with this procedure 97% of the time. Although the method was intended to be qualitative, an evaluation of the MS data indicated a linear response and acceptable recoveries for a majority of target compounds. In addition, MS/MS data were also generated for the [M + H](+) ions. Product ions for each compound were identified, and their mass accuracy was compared to theoretical values. Finally, incurred milk samples from cows dosed with veterinary drugs, including sulfamethazine, flunixin, cephapirin, or enrofloxacin, were analyzed with Q-TOF LC-MS. In addition to monitoring for the parent residues, several metabolites were detected in these samples by TOF. Proposed identification of these residues could be made by evaluating the MS and MS/MS data. For example, several plausible metabolites of enrofloxacin, some not previously observed in milk, are reported in this study. C1 [Turnipseed, Sherri B.] US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Storey, Joseph M.; Clark, Susan B.] US FDA, Denver Sci Branch, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Dept Chem & Biochem, Denver, CO 80208 USA. RP Turnipseed, SB (reprint author), US FDA, Denver Fed Ctr, Anim Drugs Res Ctr, Bldg 20,POB 25087, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 43 TC 30 Z9 31 U1 6 U2 52 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 JUL 27 PY 2011 VL 59 IS 14 SI SI BP 7569 EP 7581 DI 10.1021/jf103808t PG 13 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 794JS UT WOS:000292892900005 PM 21284383 ER PT J AU Zhang, K Wong, JW Yang, P Tech, K DiBenedetto, AL Lee, NS Hayward, DG Makovi, CM Krynitsky, AJ Banerjee, K Jao, L Dasgupta, S Smoker, MS Simonds, R Schreiber, A AF Zhang, Kai Wong, Jon W. Yang, Paul Tech, Katherine DiBenedetto, Alex L. Lee, Nathaniel S. Hayward, Douglas G. Makovi, Carolyn M. Krynitsky, Alexander J. Banerjee, Kaushik Jao, Lillian Dasgupta, Soma Smoker, Michael S. Simonds, Roger Schreiber, Andre TI Multiresidue Pesticide Analysis of Agricultural Commodities Using Acetonitrile Salt-Out Extraction, Dispersive Solid-Phase Sample Clean-Up, and High-Performance Liquid Chromatography-Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE QuEChERS; LC-MS/MS; matrix effects; identification criteria; multiresidue pesticide analysis ID MULTI-RESIDUE METHOD; GAS-CHROMATOGRAPHY; LC-MS/MS; VEGETABLES; FRUITS; CROPS; CONFIRMATION AB A multiresidue method analyzing 209 pesticides in 24 agricultural commodities has been developed and validated using the original Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure and high performance liquid chromatography-positive electrospray ionization-tandem mass, spectrometry (LC-MS/MS) analysis. Using solvent-only calibration standards (SOCSs) and matrix-matched calibration standards (MMCSs), it was demonstrated that a minimal concentration of 5-10 mu g/kg (part per billion, ppb) of analytes in matrix is required for the consistent identification of targeted pesticides with two MRM transitions. Method performance was validated by the precision and accuracy results obtained from fortification studies at 10, 25, 100, and 500 ppb and MMCSs. The method was demonstrated to achieve an average recovery of 100 +/- 20% (n = 4) for >75% of evaluated pesticides at the low fortification level (10 ppb) and improved to >84% at the higher fortification concentrations in all 24 matrices. Matrix effects in LC-MS/MS analysis were studied by evaluating the slope ratios of calibration curves (1.0-100 ng/mL) obtained from the SOCSs and MMCSs. Principal component analysis (PCA) of LC-MS/MS and method validation data confirmed that each matrix exerts its specific effect during the sample preparation and LC-MS/MS analysis. The matrix effect is primarily dependent on the matrix type, pesticide type and concentration. Some caution is warranted when using matrix matched calibration curves for the quantitation of pesticides to alleviate concerns on matrix effects. The QuECKERS method with LC-MS/MS was used to identify and quantitate pesticides residues, with concentrations ranging from 2.5 to >1000 ppb in a variety of agricultural samples, demonstrating fitness for screening and surveillance applications. C1 [Zhang, Kai; Wong, Jon W.; Hayward, Douglas G.; Makovi, Carolyn M.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, HFS 706, College Pk, MD 20740 USA. [Yang, Paul; Jao, Lillian] Ontario Minist Environm, Etobicoke, ON M9P 3V6, Canada. [Tech, Katherine; DiBenedetto, Alex L.; Lee, Nathaniel S.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Banerjee, Kaushik; Dasgupta, Soma] Natl Res Ctr Grapes, Pune 412307, Maharashtra, India. [Smoker, Michael S.] US FDA, Off Regulatory Affairs, Kansas City Dist Lab, HFR SW360, Lenexa, KS 66214 USA. [Simonds, Roger] Agr Mkt Serv, USDA, Natl Sci Lab, Gastonia, NC 28054 USA. [Schreiber, Andre] AB Sciex, Concord, ON L4K4 V8, Canada. RP Wong, JW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, HFS 706, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM jon.wong@fda.hhs.gov NR 26 TC 47 Z9 53 U1 7 U2 46 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 JUL 27 PY 2011 VL 59 IS 14 SI SI BP 7636 EP 7646 DI 10.1021/jf2010723 PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 794JS UT WOS:000292892900012 PM 21671617 ER PT J AU Ferron, SR Charalambous, M Radford, E McEwen, K Wildner, H Hind, E Morante-Redolat, JM Laborda, J Guillemot, F Bauer, SR Farinas, I Ferguson-Smith, AC AF Ferron, Sacri R. Charalambous, Marika Radford, Elizabeth McEwen, Kirsten Wildner, Hendrik Hind, Eleanor Manuel Morante-Redolat, Jose Laborda, Jorge Guillemot, Francois Bauer, Steven R. Farinas, Isabel Ferguson-Smith, Anne C. TI Postnatal loss of Dlk1 imprinting in stem cells and niche astrocytes regulates neurogenesis SO NATURE LA English DT Article ID DIFFERENTIATION; EXPRESSION; GENES; ZONE; MOUSE-CHROMOSOME-12; PROLIFERATION; GTL2; GLIA AB The gene for the atypical NOTCH ligand delta-like homologue 1 (Dlk1) encodes membrane-bound and secreted isoforms that function in several developmental processes in vitro and in vivo. Dlk1, a member of a cluster of imprinted genes, is expressed from the paternally inherited chromosome(1,2). Here we show that mice that are deficient in Dlk1 have defects in postnatal neurogenesis in the subventricular zone: a developmental continuum that results in depletion of mature neurons in the olfactory bulb. We show that DLK1 is secreted by niche astrocytes, whereas its membrane-bound isoform is present in neural stem cells (NSCs) and is required for the inductive effect of secreted DLK1 on self-renewal. Notably, we find that there is a requirement for Dlk1 to be expressed from both maternally and paternally inherited chromosomes. Selective absence of Dlk1 imprinting in both NSCs and niche astrocytes is associated with postnatal acquisition of DNA methylation at the germ-line-derived imprinting control region. The results emphasize molecular relationships between NSCs and the niche astrocyte cells of the microenvironment, identifying a signalling system encoded by a single gene that functions coordinately in both cell types. The modulation of genomic imprinting in a stem-cell environment adds a new level of epigenetic regulation to the establishment and maintenance of the niche, raising wider questions about the adaptability, function and evolution of imprinting in specific developmental contexts. C1 [Ferron, Sacri R.; Charalambous, Marika; Radford, Elizabeth; McEwen, Kirsten; Hind, Eleanor; Ferguson-Smith, Anne C.] Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. [Wildner, Hendrik; Guillemot, Francois] Natl Inst Med Res, MRC, Dept Mol Neurobiol, London NW7 1AA, England. [Manuel Morante-Redolat, Jose; Farinas, Isabel] Univ Valencia, Ctr Invest Biomed Red Enfermedades Neurodegenerat, Dept Biol Celular, E-46100 Burjassot, Spain. [Laborda, Jorge] Univ Castilla La Mancha, Reg Ctr Biomed Res, Sch Med, Dept Inorgan & Organ Chem & Biochem, Albacete 02006, Spain. [Bauer, Steven R.] US FDA, Cellular & Tissue Therapies Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ferguson-Smith, AC (reprint author), Univ Cambridge, Dept Physiol Dev & Neurosci, Cambridge CB2 3EG, England. EM afsmith@mole.bio.cam.ac.uk RI Ferguson-Smith, Anne/G-7534-2011; Bauer, Steven/G-5559-2012; Laborda, Jorge/L-5726-2014; Farinas, Isabel/L-7118-2014; Ferron, Sacri/I-2958-2015; OI Laborda, Jorge/0000-0002-9210-838X; Farinas, Isabel/0000-0003-2903-4960; Ferron, Sacri/0000-0003-0854-8575; Bauer, Steven/0000-0003-2831-846X; Charalambous, Marika/0000-0002-1684-5783 FU Medical Research Council; Wellcome Trust; Ministerio de Ciencia e Innovacion [SAF2008-01006, CB06/05/0086, RD06/0010/0010]; Generalitat Valenciana (Prometeo); University of Cambridge FX We are grateful to J. Herbert and E. B. Keverne for sharing expertise during the course of this work. We thank members of the Ferguson-Smith laboratory for discussions and B. Sun, D. Gray, S. Curran, I. Gutteridge, R. Rancourt and X. d'Anglemont de Tassigny for technical assistance. The work was funded by grants from the Medical Research Council and Wellcome Trust to A.C.F.-S. and by grants from Ministerio de Ciencia e Innovacion (SAF2008-01006, CB06/05/0086, RD06/0010/0010) and Generalitat Valenciana (Prometeo) to I. F. S. R. F. is a recipient of a University of Cambridge Herchel-Smith Fellowship. NR 30 TC 107 Z9 112 U1 3 U2 22 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 21 PY 2011 VL 475 IS 7356 BP 381 EP U136 DI 10.1038/nature10229 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 794PA UT WOS:000292911200043 PM 21776083 ER PT J AU Dayton, AI AF Dayton, Andrew I. TI Matrin 3 and HIV Rev Regulation of mRNA SO RETROVIROLOGY LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; NUCLEAR; PROTEINS; COMPLEX; ELEMENTS; PSF AB The nuclear matrix protein, MATR3, is a newly-described Rev cofactor whose mechanism of action is only starting to be revealed. C1 US FDA, CBER, OBRR, DETTD,LMV, Rockville, MD 20852 USA. RP Dayton, AI (reprint author), US FDA, CBER, OBRR, DETTD,LMV, HFM 315 1401 Rockville Pike, Rockville, MD 20852 USA. EM andrew.dayton@fda.hhs.gov NR 18 TC 7 Z9 7 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUL 20 PY 2011 VL 8 AR 62 DI 10.1186/1742-4690-8-62 PG 3 WC Virology SC Virology GA 813FY UT WOS:000294353400003 PM 21771348 ER PT J AU Zheng, J Tian, F Cui, SH Song, JZ Zhao, SH Brown, EW Meng, JH AF Zheng, Jie Tian, Fei Cui, Shenghui Song, Jiuzhou Zhao, Shaohua Brown, Eric W. Meng, Jianghong TI Differential Gene Expression by RamA in Ciprofloxacin-Resistant Salmonella Typhimurium SO PLOS ONE LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; MULTIPLE-ANTIBIOTIC-RESISTANCE; MEDIATED MULTIDRUG-RESISTANCE; OXIDATIVE STRESS GENES; TOLC EFFLUX PUMP; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; FLUOROQUINOLONE RESISTANCE; TRANSCRIPTIONAL REGULATOR; ENTEROBACTER-CLOACAE AB Overexpression of ramA has been implicated in resistance to multiple drugs in several enterobacterial pathogens. In the present study, Salmonella Typhimurium strain LTL with constitutive expression of ramA was compared to its ramA-deletion mutant by employing both DNA microarrays and phenotype microarrays (PM). The mutant strain with the disruption of ramA showed differential expression of at least 33 genes involved in 11 functional groups. The study confirmed at the transcriptional level that the constitutive expression of ramA was directly associated with increased expression of multidrug efflux pump AcrAB-TolC and decreased expression of porin protein OmpF, thereby conferring multiple drug resistance phenotype. Compared to the parent strain constitutively expressing ramA, the ramA mutant had increased susceptibility to over 70 antimicrobials and toxic compounds. The PM analysis also uncovered that the ramA mutant was better in utilization of 10 carbon sources and 5 phosphorus sources. This study suggested that the constitutive expression of ramA locus regulate not only multidrug efflux pump and accessory genes but also genes involved in carbon metabolic pathways. C1 [Zheng, Jie; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Zheng, Jie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Tian, Fei; Song, Jiuzhou] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Cui, Shenghui] State Food & Drug Adm, Beijing, Peoples R China. [Zhao, Shaohua] Univ Maryland, US FDA, Ctr Vet Med, College Pk, MD 20742 USA. [Zheng, Jie; Brown, Eric W.] Univ Maryland, Ctr Food Safety & Appl Nutr, US FDA, College Pk, MD 20742 USA. RP Zheng, J (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety & Applied Nutrition (JIFSAN), University of Maryland FX This study was supported in part by the Joint Institute for Food Safety & Applied Nutrition (JIFSAN), University of Maryland. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional external funding was received for this study. NR 58 TC 9 Z9 10 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 JUL 19 PY 2011 VL 6 IS 7 AR e22161 DI 10.1371/journal.pone.0022161 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 794VN UT WOS:000292929500043 PM 21811569 ER PT J AU Baur, C Ostrove, N AF Baur, Cynthia Ostrove, Nancy TI Testing Rules of Thumb and the Science of Health Literacy SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 [Baur, Cynthia] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Ostrove, Nancy] US FDA, Silver Spring, MD 20993 USA. RP Baur, C (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MS E21, Atlanta, GA 30333 USA. EM cynthia.baur@cdc.hhs.gov NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 19 PY 2011 VL 155 IS 2 BP 129 EP + DI 10.7326/0003-4819-155-2-201107190-00010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 793KW UT WOS:000292822000021 PM 21768587 ER PT J AU De Leon, JT Iwai, A Feau, C Garcia, Y Balsiger, HA Storer, CL Suro, RM Garza, KM Lee, S Kim, YS Chen, Y Ning, YM Riggs, DL Fletterick, RJ Guy, RK Trepel, JB Neckers, LM Cox, MB AF De Leon, Johanny Tonos Iwai, Aki Feau, Clementine Garcia, Yenni Balsiger, Heather A. Storer, Cheryl L. Suro, Raquel M. Garza, Kristine M. Lee, Sunmin Kim, Yeong Sang Chen, Yu Ning, Yang-Min Riggs, Daniel L. Fletterick, Robert J. Guy, R. Kiplin Trepel, Jane B. Neckers, Leonard M. Cox, Marc B. TI Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immunophilin; FKBP4; steroid hormone receptor ID HSP90; COMPENDIUM; EXPRESSION; REPORTER; BINDING; LINES; OLD AB Drugs that target novel surfaces on the androgen receptor (AR) and/or novel AR regulatory mechanisms are promising alternatives for the treatment of castrate-resistant prostate cancer. The 52 kDa FK506 binding protein (FKBP52) is an important positive regulator of AR in cellular and whole animal models and represents an attractive target for the treatment of prostate cancer. We used a modified receptor-mediated reporter assay in yeast to screen a diversified natural compound library for inhibitors of FKBP52-enhanced AR function. The lead compound, termed MJC13, inhibits AR function by preventing hormone-dependent dissociation of the Hsp90-FKBP52-AR complex, which results in less hormone-bound receptor in the nucleus. Assays in early and late stage human prostate cancer cells demonstrated that MJC13 inhibits AR-dependent gene expression and androgen-stimulated prostate cancer cell proliferation. C1 [De Leon, Johanny Tonos; Garcia, Yenni; Balsiger, Heather A.; Storer, Cheryl L.; Suro, Raquel M.; Garza, Kristine M.; Cox, Marc B.] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA. [De Leon, Johanny Tonos; Garcia, Yenni; Balsiger, Heather A.; Storer, Cheryl L.; Suro, Raquel M.; Garza, Kristine M.; Cox, Marc B.] Univ Texas El Paso, Border Biomed Res Ctr, El Paso, TX 79968 USA. [Iwai, Aki; Neckers, Leonard M.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. [Feau, Clementine; Guy, R. Kiplin] St Jude Childrens Hosp, Dept Chem Biol & Therapeut, Memphis, TN 38105 USA. [Lee, Sunmin; Kim, Yeong Sang; Trepel, Jane B.] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Chen, Yu] Univ S Florida, Dept Mol Med, Tampa, FL 33612 USA. [Ning, Yang-Min] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Riggs, Daniel L.] Mayo Clin Arizona, Scottsdale, AZ 85259 USA. [Fletterick, Robert J.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94158 USA. RP Cox, MB (reprint author), Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA. EM mbcox@utep.edu RI Guy, Rodney/J-7107-2013 OI Guy, Rodney/0000-0002-9638-2060 FU Border Biomedical Research Center's [National Center for Research Resources/National Institutes of Health (NIH)] [5G12RR008124]; National Institute of General Medical Sciences, NIH [SC1GM084863]; Research Initiative for Scientific Enhancement [R25GM069621]; National Science Foundation [HRD-0832951]; American Lebanese Syrian Associated Charities; St. Jude Children's Research Hospital; NIH [DK58080]; Department of Defense [PC060344-W81XWH-07-1-0073]; National Cancer Institute FX We thank Brian Freeman, Charles Sawyers, Robert Reiter, David Toft, and Donald Tindall for providing reagents. The authors are grateful to David Smith and Charles Miller for critically reading the manuscript. We thank the Border Biomedical Research Center's [Grant 5G12RR008124, National Center for Research Resources/National Institutes of Health (NIH)] Biomolecule Analysis Core Facility, Tissue Culture Core Facility, and the DNA Analysis Core Facility for the use of the instruments. This project was also supported in part by American Recovery and Reinvestment Act funds through Grant SC1GM084863 to M. B. C. from the National Institute of General Medical Sciences, NIH. J.T.D.L. was supported by Research Initiative for Scientific Enhancement (R25GM069621) and National Science Foundation Louis Stokes Alliances for Minority Participation (HRD-0832951) fellowships. R. K. G. and C. F. were supported by the American Lebanese Syrian Associated Charities, St. Jude Children's Research Hospital, the NIH (DK58080), and the Department of Defense Prostate Cancer Research Program (PC060344-W81XWH-07-1-0073). A. I., S. L., Y.S.K., Y.N., J.B.T., and L.M.N. were supported by funds from the Intramural Research Program of the National Cancer Institute. NR 20 TC 54 Z9 54 U1 0 U2 9 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 JUL 19 PY 2011 VL 108 IS 29 BP 11878 EP 11883 DI 10.1073/pnas.1105160108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 794DY UT WOS:000292876900038 PM 21730179 ER EF