FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Trucksess, MW Fu, WS Oles, CJ White, KD AF Trucksess, Mary W. Fu, Wu-Sheng Oles, Carolyn J. White, Kevin D. TI Determination of Zearalenone in Botanical Dietary Supplements, Soybeans, Grains, and Grain Products by Immunoaffinity Column Cleanup and Liquid Chromatography: Single-Laboratory Validation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MYCOTOXIN ZEARALENONE; PRECOCIOUS PUBERTY AB The accuracy, repeatability, and reproducibility characteristics of a method for measuring levels of zearalenone (ZON) in botanical root products, soybeans, grains, and grain products were determined by an AOAC single-laboratory validation procedure. Replicates of 10 test portions of each powdered root product (black cohosh, ginger, ginseng), brown rice flour, brown rice grain, oat flour, rice bran, soybeans, and wheat flour at each spiking level (ZON at 0, 50, 100, and 200 mu g/kg) were analyzed on 3 separate days. Test samples were extracted with methanol water (75 + 25, v/v). The extracts were centrifuged or filtered, diluted with phosphate-buffered saline (PBS) containing 0.5% Tween 20, and filtered; the filtrates were applied to an immunoaffinity column containing antibodies specific for ZON. After the column was washed with methanol PBS (15 + 85, v/v) containing 0.5% Tween 20 and then with water, the toxin was eluted from the column with methanol, and the eluate was diluted with water. The eluate containing the toxin was then subjected to RPLC with fluorescence detection. All commodities that were found to contain ZON at < 10 mu g/kg were used for the recovery study. The average within-day and between-days recoveries of ZON added at levels of 50-200 mu g/kg ranged from 82 to 88% and from 81 to 84%, respectively, for all test commodities. The total average of within- and between-day SD and RSDr values for all test commodities ranged from 2.5 to 7.3 mu g/kg and from 4.6 to 6.2%, respectively. HorRat values were < 1.3 for all matrixes examined. The tested method was found to be acceptable for the matrixes examined. C1 [Trucksess, Mary W.; Fu, Wu-Sheng; Oles, Carolyn J.] US FDA, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. [White, Kevin D.] US FDA, Off Regulatory Sci, Div Analyt Chem, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov FU Office of Dietary Supplements, National Institutes of Health, Bethesda, MD; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported in part by the Office of Dietary Supplements, National Institutes of Health, Bethesda, MD, and in part by an appointment to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. We would like to thank Jeanne I. Rader for her support and guidance. NR 16 TC 5 Z9 5 U1 1 U2 7 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 MAR-APR PY 2011 VL 94 IS 2 BP 589 EP 595 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500027 PM 21563694 ER PT J AU Kim, HY Eyheramonho, MB Pichavant, M Cambaceres, CG Matangkasombut, P Cervio, G Kuperman, S Moreiro, R Konduru, K Manangeeswaran, M Freeman, GJ Kaplan, GG DeKruyff, RH Umetsu, DT Rosenzweig, SD AF Kim, Hye Young Belen Eyheramonho, Maria Pichavant, Muriel Gonzalez Cambaceres, Carlos Matangkasombut, Ponpan Cervio, Guillermo Kuperman, Silvina Moreiro, Rita Konduru, Krishnamurthy Manangeeswaran, Mohanraj Freeman, Gordon J. Kaplan, Gerardo G. DeKruyff, Rosemarie H. Umetsu, Dale T. Rosenzweig, Sergio D. TI A polymorphism in TIM1 is associated with susceptibility to severe hepatitis A virus infection in humans SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID KILLER T-CELLS; ACUTE LIVER-FAILURE; AIRWAY HYPERREACTIVITY; MUCIN DOMAIN; NKT CELLS; PHOSPHATIDYLSERINE RECEPTOR; FULMINANT-HEPATITIS; APOPTOTIC CELLS; HIV-1 INFECTION; ATOPIC DISEASE AB During infection with the hepatitis A virus (HAV), most patients develop mild or asymptomatic disease. However,, a small number of patients develop serious, life-threatening hepatitis. We investigated this variability in disease severity by examining 30 Argentinean patients with HAV-induced acute liver failure in a case-control, cross-sectional, observational study. We found that HAV-induced severe liver disease was associated with a 6-amino-acid insertion in TIM1/HAVCR1 (157insMTTTVP), the gene encoding the HAV receptor. This polymorphism was previously shown to be associated with protection against asthma and allergic diseases and with HIV progression. In binding assays, the TIM-1 protein containing the 157insMTTTVP insertion polymorphism bound HAV more efficiently. When expressed by human natural killer T (NKT) cells, this long form resulted in greater NKT cell cytolytic activity against HAV-infected liver cells, compared with the shorter TIM-1 protein without the polymorphism. To our knowledge, the 157insMTTTVP polymorphism in TIM1 is the first genetic susceptibility factor shown to predispose to HAV-induced acute liver failure. Furthermore, these results suggest that HAV infection has driven the natural selection of shorter forms of the TIM-1 protein, which binds HAV less efficiently, thereby protecting against severe HAV-induced disease, but which may predispose toward inflammation associated with asthma and allergy. C1 [Kim, Hye Young; Pichavant, Muriel; Matangkasombut, Ponpan; DeKruyff, Rosemarie H.; Umetsu, Dale T.] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Pediat,Div Immunol, Boston, MA 02115 USA. [Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Immunol, Buenos Aires, DF, Argentina. [Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Liver Transplantat, Buenos Aires, DF, Argentina. [Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Transfus Med, Buenos Aires, DF, Argentina. [Belen Eyheramonho, Maria; Gonzalez Cambaceres, Carlos; Cervio, Guillermo; Kuperman, Silvina; Moreiro, Rita; Rosenzweig, Sergio D.] Hosp Nacl Pediat JP Garrahan, Div Lab Med, Buenos Aires, DF, Argentina. [Konduru, Krishnamurthy; Manangeeswaran, Mohanraj; Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Rosenzweig, Sergio D.] NIAID, Infect Dis Susceptibil Unit, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Umetsu, DT (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol,Karp Labs, Rm 10127,1 Blackfan Circle, Boston, MA 02115 USA. EM dale.umetsu@childrens.harvard.edu; srosenzweig@niaid.nih.gov FU Fortabat Endowment of the David Rockefeller Center for Latin American Studies at Harvard University; NIH [P01 AI054456]; FDA FX We thank Leslie Kalish for help with the statistical analysis; and Mirta Ciocca, Miriam Cuarterolo, Oscar Imventarza, Javier Goni, Ana Del Pozo, Jorge Sasbon, Stefania Pittaluga, and Maria T. de Davila for valuable comments and support. These studies were supported by the de Fortabat Endowment of the David Rockefeller Center for Latin American Studies at Harvard University, by a grant from the NIH (P01 AI054456), and with FDA intramural funds. The findings and conclusions in this article have not been formally disseminated by the FDA and should not be construed to represent any Agency determination or policy. NR 47 TC 36 Z9 38 U1 1 U2 3 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR PY 2011 VL 121 IS 3 BP 1111 EP 1118 DI 10.1172/JCI44182 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 729YQ UT WOS:000287991000029 PM 21339644 ER PT J AU Huang, X Ning, YM Gulley, JL Kluetz, PG Adelberg, D Mulquin, M Madan, RA Bassim, C Figg, WD Dahut, WL AF Huang, X. Ning, Y. M. Gulley, J. L. Kluetz, P. G. Adelberg, D. Mulquin, M. Madan, R. A. Bassim, C. Figg, W. D. Dahut, W. L. TI Phase II trial of bevacizumab (A), lenalidomide (R), docetaxel (D), and prednisone (P) in patients (pts)with metastatic castration-resistant prostate cancer (mCRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, US FDA, Silver Spring, MD USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniolfacial Res, NIH, Bethesda, MD USA. NCI, Mol Pharmacol Sect, NIH, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2011 VL 29 IS 7 SU S MA 138 PG 1 WC Oncology SC Oncology GA V31JU UT WOS:000208880700139 PM 27968512 ER PT J AU Burall, LS Simpson, AC Datta, AR AF Burall, Laurel S. Simpson, Alexandra C. Datta, Atin R. TI Evaluation of a Serotyping Scheme Using a Combination of an Antibody-Based Serogrouping Method and a Multiplex PCR Assay for Identifying the Major Serotypes of Listeria monocytogenes SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GENOME DNA MICROARRAY; UNITED-STATES; STRAINS; IDENTIFICATION; VIRULENCE; FOOD; DISCRIMINATION; VALIDATION; STANDARD; SEROVARS AB To evaluate a simplified serotyping scheme, we used a combination of an antibody-based serogrouping assay that identified only type 1 and type 4 strains and a multiplex PCR-based serogrouping assay to analyze 362 L. monocytogenes isolates collected over more than 20 years. The multiplex PCR assay also incorporated a set of primers specific for L. monocyto genes hlyA gene to verify the species identification of these isolates. A subset (n = 120) of these isolates were also serotyped with the Denka Seiken serotyping scheme, which is often considered the "gold standard" for serotyping of L. monocytogenes. The results indicate that the multiplex PCR-based assay, in combination with an antibody-based serogrouping assay, correctly identified serotypes of 96% of the previously serotyped isolates. Compared with the Denka Seiken method, the combination method also performed better in identifying serotypes of 120 previously unserotyped L. monocytogenes isolates. Thus, the combination scheme appears to be a simple and rapid way to identify serotypes 1/2a, 1/2b, 1/2c, 3a, 3b, 3c, and 4b isolates, which are the predominant L. monocytogenes serotypes found in food, environmental, and clinical samples. C1 [Burall, Laurel S.; Simpson, Alexandra C.; Datta, Atin R.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Datta, AR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM atin.datta@fda.hhs.gov FU University of Maryland, Joint Institute of Food Safety and Nutrition FX We thank Lewis Graves and Martin Wiedman for several strains used in this study. We also thank the anonymous reviewers for their valuable comments. A. C. Simpson was supported by the University of Maryland, Joint Institute of Food Safety and Nutrition student internship program. NR 35 TC 12 Z9 12 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2011 VL 74 IS 3 BP 403 EP 409 DI 10.4315/0362-028X.JFP-10-355 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 734DK UT WOS:000288313200008 PM 21375876 ER PT J AU Zheng, N Zhang, XY Rosania, GR AF Zheng, Nan Zhang, Xinyuan Rosania, Gus R. TI Effect of Phospholipidosis on the Cellular Pharmacokinetics of Chloroquine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CELLS; TRANSPORTER; KIDNEY; BIOGENESIS; LYSOSOMES; DRUG; AMODIAQUINE; METABOLISM; EXPRESSION; PREDICTION AB In vivo, the weakly basic, lipophilic drug chloroquine (CQ) accumulates in the kidney to concentrations more than a thousand-fold greater than those in plasma. To study the cellular pharmacokinetics of chloroquine in cells derived from the distal tubule, Madin-Darby canine kidney cells were incubated with CQ under various conditions. CQ progressively accumulated without exhibiting steady-state behavior. Experiments failed to yield evidence that known active transport mechanisms mediated CQ uptake at the plasma membrane. CQ induced a phospholipidosis-like phenotype, characterized by the appearance of numerous multivesicular and multilamellar bodies (MLBs/MVBs) within the lumen of expanded cytoplasmic vesicles. Other induced phenotypic changes including changes in the volume and pH of acidic organelles were measured, and the integrated effects of all these changes were computationally modeled to establish their impact on intracellular CQ mass accumulation. Based on the passive transport behavior of CQ, the measured phenotypic changes fully accounted for the continuous, nonsteady-state CQ accumulation kinetics. Consistent with the simulation results, Raman confocal microscopy of live cells confirmed that CQ became highly concentrated within induced, expanded cytoplasmic vesicles that contained multiple MLBs/MVBs. Progressive CQ accumulation was increased by sucrose, a compound that stimulated the phospholipidosis-like phenotype, and was decreased by bafilomycin A1, a compound that inhibited this phenotype. Thus, phospholipidosis-associated changes in organelle structure and intracellular membrane content can exert a major influence on the local bioaccumulation and biodistribution of drugs. C1 [Zheng, Nan; Rosania, Gus R.] Univ Michigan, Dept Pharmaceut Sci, Coll Pharm, Ann Arbor, MI 48109 USA. [Zhang, Xinyuan] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rosania, GR (reprint author), Univ Michigan, Dept Pharmaceut Sci, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. EM grosania@umich.edu FU National Institutes of Health National Institute of General Medical Sciences [R01-GM078200] FX This work was supported by the National Institutes of Health National Institute of General Medical Sciences [Grant R01-GM078200] (to G.R.R). NR 40 TC 21 Z9 22 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAR PY 2011 VL 336 IS 3 BP 661 EP 671 DI 10.1124/jpet.110.175679 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 723AI UT WOS:000287477200009 PM 21156819 ER PT J AU Ohashi, M Bertke, AS Patel, A Krause, PR AF Ohashi, Masahiro Bertke, Andrea S. Patel, Amita Krause, Philip R. TI Spread of Herpes Simplex Virus to the Spinal Cord Is Independent of Spread to Dorsal Root Ganglia SO JOURNAL OF VIROLOGY LA English DT Article ID EXPERIMENTAL GENITAL-INFECTION; REACTIVATION; TYPE-2; HSV-1; MODEL; EXPRESSION; PHENOTYPES; SITE; MICE AB Levels of herpes simplex virus 1 (HSV-1) and HSV-2 DNA in dorsal root ganglia (DRG) and spinal cord (SC) were quantified after inoculation of guinea pig genitals and footpads. In genital infection, viral DNA reached SC and DRG simultaneously (at 2 to 3 days after inoculation) but was more abundant in SC than in DRG. After inoculation of footpads, which lack parasympathetic innervation, the viruses spread more efficiently to DRG than to SC. These results show important differences between genital and footpad infections, including independence of spread to DRG and SC, and imply that autonomic neurons may play an important role in the pathogenesis of viral latency after genital inoculation. C1 [Ohashi, Masahiro; Bertke, Andrea S.; Patel, Amita; Krause, Philip R.] FDA CBER, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), FDA CBER, HFM 457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 FU Japan Herpesvirus Infectious Forum Scholarship Awards in Herpesvirus Infections Research FX M.O. acknowledges financial support from the Japan Herpesvirus Infectious Forum Scholarship Awards in Herpesvirus Infections Research. NR 19 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 6 BP 3030 EP 3032 DI 10.1128/JVI.02426-10 PG 3 WC Virology SC Virology GA 735AT UT WOS:000288386500055 PM 21159869 ER PT J AU Cadieux, N Parra, M Cohen, H Maric, D Morris, SL Brennan, MJ AF Cadieux, Nathalie Parra, Marcela Cohen, Hannah Maric, Dragan Morris, Sheldon L. Brennan, Michael J. TI Induction of cell death after localization to the host cell mitochondria by the Mycobacterium tuberculosis PE_PGRS33 protein SO MICROBIOLOGY-SGM LA English DT Article ID PE-PGRS PROTEINS; GENOME SEQUENCE; VII SECRETION; MACROPHAGES; EXPRESSION; NECROSIS; APOPTOSIS; VIRULENCE; SYSTEM; FAMILY AB PE_PGRS33 is the most studied member of the unique PE family of mycobacterial proteins. These proteins are composed of a PE domain (Pro-Glu motif), a linker region and a PGRS domain (polymorphic GC-rich-repetitive sequence). Previous studies have shown that PE_PGRS33 is surface-exposed, constitutively expressed during growth and infection, involved in creating antigenic diversity, and able to induce death in transfected or infected eukaryotic cells. In this study, we showed that PE_PGRS33 co-localizes to the mitochondria of transfected cells, a phenomenon dependent on the linker region and the PGRS domain, but not the PE domain. Using different genetic fusions and chimeras, we also demonstrated a direct correlation between localization to the host mitochondria and the induction of cell death. Finally, although all constructs localizing to the mitochondria did induce apoptosis, only the wild-type PE_PGRS33 with its own PE domain also induced primary necrosis, indicating a potentially important role for the PE domain. Considering the importance of primary necrosis in Mycobacterium tuberculosis dissemination during natural infection, the PE_PGRS33 protein may play a crucial role in the pathogenesis of tuberculosis. C1 [Cadieux, Nathalie; Brennan, Michael J.] AERAS Global TB Vaccine Fdn, Rockville, MD USA. [Cadieux, Nathalie; Parra, Marcela; Cohen, Hannah; Morris, Sheldon L.; Brennan, Michael J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Maric, Dragan] Natl Inst Neurol Disorders & Stroke, NIH, Flow Cytometry Core Facil, Bethesda, MD USA. RP Cadieux, N (reprint author), AERAS Global TB Vaccine Fdn, Rockville, MD USA. EM ncadieux@aeras.org FU National Vaccine Program Office of the Department of Health and Human Services FX We would like to thank Veerabadran Dheenadhayalan, Karen Meysick and Jackie Muller for invaluable discussions during this study. This work was supported in part by a grant from the National Vaccine Program Office of the Department of Health and Human Services to M. j. B. NR 45 TC 29 Z9 30 U1 0 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD MAR PY 2011 VL 157 BP 793 EP 804 DI 10.1099/mic.0.041996-0 PN 3 PG 12 WC Microbiology SC Microbiology GA 740ZN UT WOS:000288833000018 PM 21081760 ER PT J AU Strader, MB Costantino, N Elkins, CA Chen, CY Patel, I Makusky, AJ Choy, JS Court, DL Markey, SP Kowalak, JA AF Strader, Michael Brad Costantino, Nina Elkins, Christopher A. Chen, Cai Yun Patel, Isha Makusky, Anthony J. Choy, John S. Court, Donald L. Markey, Sanford P. Kowalak, Jeffrey A. TI A Proteomic and Transcriptomic Approach Reveals New Insight into beta-methylthiolation of Escherichia coli Ribosomal Protein S12 SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TRANSFER-RNA; MASS-SPECTROMETRY; POSTTRANSLATIONAL MODIFICATION; STRUCTURAL INSIGHTS; GENE-EXPRESSION; MESSENGER-RNA; 70S RIBOSOME; MIAB PROTEIN; FNR; METHYLATION AB beta-methylthiolation is a novel post-translational modification mapping to a universally conserved Asp 88 of the bacterial ribosomal protein S12. This S12 specific modification has been identified on orthologs from multiple bacterial species. The origin and functional significance was investigated with both a proteomic strategy to identify candidate S12 interactors and expression microarrays to search for phenotypes that result from targeted gene knockouts of select candidates. Utilizing an endogenous recombinant E. coli S12 protein with an affinity tag as bait, mass spectrometric analysis identified candidate S12 binding partners including RimO (previously shown to be required for this post-translational modification) and YcaO, a conserved protein of unknown function. Transcriptomic analysis of bacterial strains with deleted genes for RimO and YcaO identified an overlapping transcriptional phenotype suggesting that YcaO and RimO likely share a common function. As a follow up, quantitative mass spectrometry additionally indicated that both proteins dramatically impacted the modification status of S12. Collectively, these results indicate that the YcaO protein is involved in beta-methylthiolation of S12 and its absence impairs the ability of RimO to modify S12. Additionally, the proteomic data from this study provides direct evidence that the E. coli specific beta-methylthiolation likely occurs when S12 is assembled as part of a ribosomal subunit. Molecular & Cellular Proteomics 10: 10.1074/mcp.M110.005199, 1-10, 2011. C1 [Strader, Michael Brad; Chen, Cai Yun; Makusky, Anthony J.; Markey, Sanford P.; Kowalak, Jeffrey A.] NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. [Costantino, Nina; Court, Donald L.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. [Elkins, Christopher A.; Patel, Isha] US FDA, Laurel, MD 20708 USA. [Choy, John S.] NCI, Bethesda, MD 20892 USA. RP Strader, MB (reprint author), NIMH, Lab Neurotoxicol, Bldg 10 Ctr Dr,Room 3D42,10 Ctr Dr,MSC 1262, Bethesda, MD 20892 USA. EM straderm@mail.nih.gov FU National Institute of Mental Health [1ZIAMH000274] FX This work was supported by the Intramural Research Program of the National Institute of Mental Health(1ZIAMH000274). NR 45 TC 6 Z9 8 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD MAR PY 2011 VL 10 IS 3 AR M110.005199 DI 10.1074/mcp.M110.005199 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 728AY UT WOS:000287847200022 PM 21169565 ER PT J AU Dickson, PI Pariser, AR Groft, SC Ishihara, RW McNeil, DE Tagle, D Griebel, DJ Kaler, SG Mink, JW Shapiro, EG Bjoraker, KJ Krivitzky, L Provenzale, JM Gropman, A Orchard, P Raymond, G Cohen, BH Steiner, RD Goldkind, SF Nelson, RM Kakkis, E Patterson, MC AF Dickson, P. I. Pariser, A. R. Groft, S. C. Ishihara, R. W. McNeil, D. E. Tagle, D. Griebel, D. J. Kaler, S. G. Mink, J. W. Shapiro, E. G. Bjoraker, K. J. Krivitzky, L. Provenzale, J. M. Gropman, A. Orchard, P. Raymond, G. Cohen, B. H. Steiner, R. D. Goldkind, S. F. Nelson, R. M. Kakkis, E. Patterson, M. C. TI Research challenges in central nervous system manifestations of inborn errors of metabolism SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE Inborn errors of metabolism; Central nervous system; Rare disease; Orphan drug designation; Translational research ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; UREA CYCLE DISORDERS; X-LINKED ADRENOLEUKODYSTROPHY; ENZYME REPLACEMENT THERAPY; INFANTILE KRABBES-DISEASE; HURLER-SYNDROME; MUCOPOLYSACCHARIDOSIS-I; MENKES-DISEASE; INITIAL-EXPERIENCE AB The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups. Published by Elsevier Inc. C1 [Ishihara, R. W.; Griebel, D. J.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, Silver Spring, MD 20993 USA. [Dickson, P. I.] Harbor UCLA, Dept Pediat, LA Biomed Res Inst, Torrance, CA 90502 USA. [Groft, S. C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [McNeil, D. E.] US FDA, Off Orphan Prod Dev, Off Commissioner, Silver Spring, MD 20993 USA. [Tagle, D.] NINDS, NIH, Ctr Neurosci, Bethesda, MD 20892 USA. [Kaler, S. G.] NICHHD, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Mink, J. W.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. [Mink, J. W.] Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. [Shapiro, E. G.] Univ Minnesota, Dept Neurol, Minneapolis, MN 55455 USA. [Shapiro, E. G.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Bjoraker, K. J.] Univ Colorado, Childrens Hosp Denver, Aurora, CO 80045 USA. [Krivitzky, L.] Natl Rehabil Hosp, Childrens Res Inst, Ctr Res Neurosci, Childrens Natl Med Ctr, Washington, DC 20010 USA. [Provenzale, J. M.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Provenzale, J. M.] Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. [Provenzale, J. M.] Emory Univ, Sch Med, Dept Oncol, Atlanta, GA 30322 USA. [Provenzale, J. M.] Emory Univ, Sch Med, Dept Biomed Engn, Atlanta, GA 30322 USA. [Gropman, A.] Childrens Natl Med Ctr, Neurogenet Program, Washington, DC 20010 USA. [Orchard, P.] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. [Orchard, P.] Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. [Raymond, G.] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Raymond, G.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21205 USA. [Cohen, B. H.] Cleveland Clin, Neurol Inst, Brain Tumor & Neurooncol Ctr, Cleveland, OH 44195 USA. [Steiner, R. D.] Oregon Hlth & Sci Univ, Dept Pediat, Portland, OR 97239 USA. [Steiner, R. D.] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Doembecher Childrens Hosp, Portland, OR 97239 USA. [Goldkind, S. F.] US FDA, Off Good Clin Practice, Off Commissioner, Silver Spring, MD 20993 USA. [Nelson, R. M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Kakkis, E.] Kakkis EveryLife Fdn, Novato, CA 94949 USA. [Patterson, M. C.] Mayo Clin, Div Child & Adolescent Neurol, Rochester, MN 55905 USA. RP Pariser, AR (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Div Gastroenterol Prod, 10903 New Hampshire Ave,WO22-6474, Silver Spring, MD 20993 USA. EM Pdickson@ucla.edu; Anne.pariser@fda.hhs.gov; Stephen.groft@nih.gov; Richard.ishihara@fda.hhs.gov; Dawn.mcneil@fda.hhs.gov; Tagled@ninds.nih.gov; Donna.griebel@fda.hhs.gov; Kalers@mail.nih.gov; Jonathan_Mink@rochester.edu; Shapi004@umn.edu; Bjoraker.kendra@tchden.org; LKrivitz@cnmc.org; Prove001@mc.duke.edu; Agropman@cnmc.org; Orcha001@umn.edu; Raymond@kennedykrieger.org; Bhcohenmd@aol.com; Steinerr@ohsu.edu; Sara.goldkind@fda.hhs.gov; Robert.nelson@fda.hhs.gov; Ekakkis@kakkis.org; Patterson.marc@mayo.edu OI Steiner, Robert/0000-0003-4177-4590; Patterson, Marc/0000-0002-1116-126X FU NIH Office Rare Diseases Research, National Institute of Neurological Disorders and Stroke; FDA Center for Drug Evaluation and Research, Division of Gastroenterology; National Institute of Child Health and Development Intramural Research Program; Batten Disease Support and Research Association [R01NS060022]; Lysosomal Disease Network; NS065768-01; Urea Cycle Disorders Consortium NIH [RR019453]; National Institute of Neurological Disorders and Stroke [NS054242]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [HD057136]; Food and Drug Administration [FD003450]; Genzyme Corporation; Stem Cells Inc. FX The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was funded by the NIH Office Rare Diseases Research, National Institute of Neurological Disorders and Stroke, and the FDA Center for Drug Evaluation and Research, Division of Gastroenterology Products. Research presented was funded by: National Institute of Child Health and Development Intramural Research Program (SGK), Batten Disease Support and Research Association (JWM, R01NS060022), the Lysosomal Disease Network U54 (EGS, NS065768-01), the Urea Cycle Disorders Consortium NIH U54 (RR019453), the National Institute of Neurological Disorders and Stroke (PID, NS054242), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (GR, HD057136), the Food and Drug Administration (PID, FD003450), Genzyme Corporation, and Stem Cells Inc. NR 44 TC 8 Z9 9 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAR PY 2011 VL 102 IS 3 BP 326 EP 338 DI 10.1016/j.ymgme.2010.11.164 PG 13 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 727CA UT WOS:000287773800156 PM 21176882 ER PT J AU Paule, MG Li, M Allen, RR Liu, F Zou, X Hotchkiss, C Hanig, JP Patterson, TA Slikker, W Wang, C AF Paule, M. G. Li, M. Allen, R. R. Liu, F. Zou, X. Hotchkiss, C. Hanig, J. P. Patterson, T. A. Slikker, W., Jr. Wang, C. TI Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Developmental neurotoxicity; Brain function; Ketamine anesthesia; Cognition; Nonhuman primate ID DEVELOPING RAT-BRAIN; INDUCED DEVELOPMENTAL NEUROAPOPTOSIS; CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTOR ANTAGONISTS; BEHAVIORAL-TEST BATTERY; EXCITATORY AMINO-ACIDS; OPERANT TEST BATTERY; NEURONAL CELL-DEATH; APOPTOTIC NEURODEGENERATION; NONHUMAN-PRIMATES AB Previously our laboratory has shown that ketamine exposure (24 h of clinically relevant anesthesia) causes significant increases in neuronal cell death in perinatal rhesus monkeys. Sensitivity to this ketamine-induced neurotoxicity was observed on gestational days 120-123 (in utero exposure via maternal anesthesia) and on postnatal days (PNDs) 5-6, but not on PNDs 35-37. In the present study, six monkeys were exposed on PND 5 or 6 to intravenous ketamine anesthesia to maintain a light surgical plane for 24 h and six control animals were unexposed. At 7 months of age all animals were weaned and began training to perform a series of cognitive function tasks as part of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB). The OTB tasks used here included those for assessing aspects of learning, motivation, color discrimination, and short-term memory. Subjects responded for banana-flavored food pellets by pressing response levers and press-plates during daily (M-F) test sessions (50 min) and were assigned training scores based upon their individual performance. As reported earlier (Paule et al., 2009) beginning around 10 months of age, control animals significantly outperformed (had higher training scores than) ketamine-exposed animals for approximately the next 10 months. For animals now over 3 and one-half years of age, the cognitive impairments continue to manifest in the ketamine-exposed group as poorer performance in the OTB learning and color and position discrimination tasks, as deficits in accuracy of task performance, but also in response speed. There are also apparent differences in the motivation of these animals which may be impacting OTB performance. These observations demonstrate that a single 24-h episode of ketamine anesthesia, occurring during a sensitive period of brain development, results in very long-lasting deficits in brain function in primates and provide proof-of-concept that general anesthesia during critical periods of brain development can result in subsequent functional deficits. Supported by NICHD, CDER/FDA and NCTR/FDA. Published by Elsevier Inc. C1 [Paule, M. G.; Li, M.; Liu, F.; Zou, X.; Patterson, T. A.; Slikker, W., Jr.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Allen, R. R.] Peak Stat Serv, Evergreen, CO USA. [Hotchkiss, C.] Bionetics Corp, Jefferson, AR USA. [Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM merle.paule@fda.hhs.gov 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), Center for Drug Evaluation and Research (CDER)/FDA and the National Institute of Child Health and Human Development (NICHD). NR 86 TC 172 Z9 182 U1 2 U2 20 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 MAR-APR PY 2011 VL 33 IS 2 BP 220 EP 230 DI 10.1016/j.ntt.2011.01.001 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 766YC UT WOS:000290821500005 PM 21241795 ER PT J AU Cuevas, E Lantz, SM Tobon-Velasco, JC Newport, GD Wu, QG Virmani, A Ali, SF Santamaria, A AF Cuevas, Elvis Lantz, Susan M. Cesar Tobon-Velasco, J. Newport, Glenn D. Wu, Qiangen Virmani, Ashraf Ali, Syed F. Santamaria, Abel TI On the in vivo early toxic properties of A beta(25-35) peptide in the rat hippocampus: Involvement of the Receptor-for-Advanced Glycation-End-Products and changes in gene expression SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Receptor-for-Advanced Glycation-End-Products; Amyloid-beta(25-35); Oxidative stress; Gene expression; Neurotoxicity; Neurodegeneration ID AMYLOID-BETA-PEPTIDE; E-DEFICIENT MICE; NF-KAPPA-B; ALZHEIMERS-DISEASE; OXIDATIVE STRESS; AGE-RAGE; ACTIVATION; INFLAMMATION; IDENTIFICATION; NEUROTOXICITY AB Amyloid-beta peptide (A beta) deposition is assumed to play a pathogenic role in the brain of Alzheimer's disease patients. To date, the precise mechanisms underlying A beta toxicity are not fully understood. A recent hypothesis suggesting that the Receptor-for-Advanced-Glycation-End-Products (RAGE)-a trans-membrane protein signaling for oxidative stress-is involved in A beta toxicity is gaining attention. Early A beta toxicity could indeed help to explain the deleterious events further produced by this molecule in the brain. In this work, we evaluated the pattern of early expression of RAGE in the toxic model induced by A beta(25-35) in rat CA1 region. Intrahippocampal injections of A beta(25-35) in rats increased the RAGE expression at 24 h post-injection; this event was accompanied by increased components of RAGE downstream signaling in hippocampal cells, such as enhanced expression of the pro-apoptotic factor NF-kappa B, increased nitric oxide production. LDH leakage, mitochondrial dysfunction, increased TNF-alpha expression, antioxidant genes down-regulation, and augmented neurodegeneration. Our findings support an active role of RAGE during the early stages of A beta(25-35) toxicity in the hippocampus. (C) 2010 Elsevier Inc. All rights reserved. C1 [Cuevas, Elvis; Cesar Tobon-Velasco, J.; Santamaria, Abel] SSA, Lab Aminoacidos Excitadores, Inst Nacl Neurol & Neurociurgia Manuel Velasco Su, Mexico City 14269, DF, Mexico. [Cuevas, Elvis; Lantz, Susan M.; Newport, Glenn D.; Ali, Syed F.; Santamaria, Abel] Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. [Wu, Qiangen] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Virmani, Ashraf] Sigma Tau Hlth Sci, I-00040 Pomezia, Italy. RP Santamaria, A (reprint author), SSA, Lab Aminoacidos Excitadores, Inst Nacl Neurol & Neurociurgia Manuel Velasco Su, Mexico City 14269, DF, Mexico. EM absada@yahoo.com RI Wu, Qiangen/F-7581-2014 OI Wu, Qiangen/0000-0002-7595-2837 NR 45 TC 10 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2011 VL 33 IS 2 BP 288 EP 296 DI 10.1016/j.ntt.2010.12.002 PG 9 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 766YC UT WOS:000290821500013 PM 21216281 ER PT J AU Abu-Asab, MS Chaouchi, M Alesci, S Galli, S Laassri, M Cheema, AK Atouf, F VanMeter, J Amri, H AF Abu-Asab, Mones S. Chaouchi, Mohamed Alesci, Salvatore Galli, Susana Laassri, Majid Cheema, Amrita K. Atouf, Fouad VanMeter, John Amri, Hakima TI Biomarkers in the Age of Omics: Time for a Systems Biology Approach SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Review ID BREAST-CANCER PATIENTS; PROSTATE-CANCER; MUTATOR PHENOTYPE; EVOLUTION; DISCOVERY; HETEROGENEITY; DISEASE; MICROARRAYS; CARCINOMAS; LIKELIHOOD AB Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology. Second, the lack of serious consideration for the scope of disease heterogeneity. Third, the refusal of the biomedical community to borrow from other biological disciplines their well established methods for dealing with heterogeneity. Therefore, real progress in biomarker discovery will be attained when we recognize that an omics biomarker cannot be assigned and validated without a priori data modeling and subtyping of the disease itself to reveal the extent of its heterogeneity, and its omics' clonal aberrations (drivers) underlying its subtypes and pathways' diversity. To further support our viewpoints, we are contributing a novel a systems biology method such as parsimony phylogenetic approach for disease modeling prior to biomarker circumscription. As an analytical approach that has been successfully used for a half of a century in other biological disciplines, parsimony phylogenetics simultaneously achieves several objectives: it provides disease modeling in a hierarchical phylogenetic classification, identifies biomarkers as the shared derived expressions or mutations-synapomorphies, constructs the omics profiles of specimens based on the most parsimonious arrangement of their heterogeneous data, and permits network profiling of affected signaling pathways as the biosignature of disease classes. C1 [Chaouchi, Mohamed; Amri, Hakima] Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. [Abu-Asab, Mones S.; Galli, Susana] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Alesci, Salvatore] Pfizer, Discovery Translat Med, Collegeville, PA USA. [Laassri, Majid] US FDA, Lab Methods Dev, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Cheema, Amrita K.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. [Atouf, Fouad] US Pharmacopeia, Biol & Biotechnol, Rockville, MD USA. [VanMeter, John] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. RP Amri, H (reprint author), Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. EM amrih@georgetown.edu OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 57 TC 33 Z9 33 U1 1 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD MAR PY 2011 VL 15 IS 3 BP 105 EP 112 DI 10.1089/omi.2010.0023 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 730XY UT WOS:000288072100003 PM 21319991 ER PT J AU Yang, L Wang, KJ Chen, JA Jegga, AG Luo, H Shi, LM Wan, CL Guo, XZ Qin, SY He, GA Feng, GY He, L AF Yang, Lun Wang, Kejian Chen, Jian Jegga, Anil G. Luo, Heng Shi, Leming Wan, Chunling Guo, Xizhi Qin, Shengying He, Guang Feng, Guoyin He, Lin TI Exploring Off-Targets and Off-Systems for Adverse Drug Reactions via Chemical-Protein Interactome - Clozapine-Induced Agranulocytosis as a Case Study SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID DIFFERENT ETHNIC-GROUPS; INDUCED TOXICITY; LIVER-INJURY; RISK-FACTORS; GENOME-WIDE; DATABASE; GENE; PREDICTION; HYPERSENSITIVITY; DETERMINANTS AB In the era of personalized medical practice, understanding the genetic basis of patient-specific adverse drug reaction (ADR) is a major challenge. Clozapine provides effective treatments for schizophrenia but its usage is limited because of life-threatening agranulocytosis. A recent high impact study showed the necessity of moving clozapine to a first line drug, thus identifying the biomarkers for drug-induced agranulocytosis has become important. Here we report a methodology termed as antithesis chemical-protein interactome (CPI), which utilizes the docking method to mimic the differences in the drug-protein interactions across a panel of human proteins. Using this method, we identified HSPA1A, a known susceptibility gene for CIA, to be the off-target of clozapine. Furthermore, the mRNA expression of HSPA1A-related genes (off-target associated systems) was also found to be differentially expressed in clozapine treated leukemia cell line. Apart from identifying the CIA causal genes we identified several novel candidate genes which could be responsible for agranulocytosis. Proteins related to reactive oxygen clearance system, such as oxidoreductases and glutathione metabolite enzymes, were significantly enriched in the antithesis CPI. This methodology conducted a multi-dimensional analysis of drugs' perturbation to the biological system, investigating both the off-targets and the associated off-systems to explore the molecular basis of an adverse event or the new uses for old drugs. C1 [Yang, Lun; Wang, Kejian; Chen, Jian; Luo, Heng; Wan, Chunling; Guo, Xizhi; Qin, Shengying; He, Guang; Feng, Guoyin; He, Lin] Shanghai Jiao Tong Univ, Bio X Ctr, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. [Yang, Lun; He, Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [Yang, Lun; Shi, Leming] Fudan Univ, Sch Pharm, Shanghai 200433, Peoples R China. [Jegga, Anil G.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH USA. [Jegga, Anil G.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Jegga, Anil G.] Univ Cincinnati, Dept Comp Sci, Cincinnati, OH 45221 USA. [He, Lin] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. RP Yang, L (reprint author), US FDA, Ctr Bioinformat, Natl Ctr Toxicol Res, Jefferson, AZ USA. EM lun.yang@gmail.com; helinhelin3@gmail.com RI Yang, Lun/B-4859-2012; Jegga, Anil/H-6140-2011; Luo, Heng/D-3616-2016 OI Jegga, Anil/0000-0002-4881-7752; Luo, Heng/0000-0001-5192-8878 FU National Natural Science Foundation of China (NSFC) [30900841]; 973 Program [2010CB529600, 2007CB947300]; 863 Program [2006AA02A407, 2009AA022701]; Shanghai Municipal Commission of Science and Technology [09DJ1400601]; National Key Project for the Investigation of New Drugs [2008ZX09312-003]; Shanghai Leading Academic Discipline Project [B205] FX This work was mainly supported by National Natural Science Foundation of China (NSFC grant No. 30900841). This work was also supported in part by the 973 Program (2010CB529600, 2007CB947300), the 863 Program (2006AA02A407, 2009AA022701), the Shanghai Municipal Commission of Science and Technology Program (09DJ1400601), the National Key Project for the Investigation of New Drugs 2008ZX09312-003 and the Shanghai Leading Academic Discipline Project (B205). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 74 TC 58 Z9 61 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7358 J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD MAR PY 2011 VL 7 IS 3 AR e1002016 DI 10.1371/journal.pcbi.1002016 PG 13 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 743CU UT WOS:000288995500035 PM 21483481 ER PT J AU Deyton, LR AF Deyton, Lawrence R. TI FDA Tobacco Product Regulations: A Powerful Tool for Tobacco Control SO PUBLIC HEALTH REPORTS LA English DT Editorial Material ID UNITED-STATES; SMOKING C1 US FDA, Ctr Tobacco Prod, Rockville, MD 20850 USA. RP Deyton, LR (reprint author), US FDA, Ctr Tobacco Prod, 9200 Corp Blvd, Rockville, MD 20850 USA. EM ctpexecsec@fda.hhs.gov NR 7 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 MAR-APR PY 2011 VL 126 IS 2 BP 167 EP 169 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 723ZX UT WOS:000287547000006 PM 21387945 ER PT J AU Anderson, AL Verrill, LA Sahyoun, NR AF Anderson, Amy L. Verrill, Linda A. Sahyoun, Nadine R. TI Food Safety Perceptions and Practices of Older Adults SO PUBLIC HEALTH REPORTS LA English DT Article ID FOODBORNE ILLNESS; BEHAVIORS; CONSUMER; RISK; CONSUMPTION; KNOWLEDGE; HEALTH; PATHOGENS; STATES AB Objectives. Older adults are considered more vulnerable to foodborne illness due to lowered immune function. We compared the food safety perceptions and practices of older and younger adults and determined associations with demographic characteristics. Methods. We focused on 1,317 participants years of age from the U.S. Food and Drug Administration's 2006 Food Safety Survey, a telephone survey of a nationally representative sample of American consumers. We used data on participants <60 years of age to compare younger and older adults, and used Pearson's Chi-square tests to determine whether perceptions and practices differed by age, gender, level of education, living arrangement, and race/ethnicity. We conducted multiple logistic regression analysis to assess relationships of demographic characteristics and food safety perceptions with food safety practices of older adults. Results. We found that adults years of age were more likely to follow recommended food safety practices than those <60 years of age. Sixty-six percent of adults years of age reported eating potentially hazardous foods in the past year compared with 81% of adults <60 years of age. Among people >= 60 years of age, women, those with less education, and nonwhite individuals generally had better food safety practices and a greater awareness of food safety risk. Conclusions. These findings suggest that certain subsets of the older adult population are less likely to follow recommended food safety practices and, thus, are at greater risk of foodborne illness. Food safety education for older adults should target men and those with more education and higher incomes. C1 [Anderson, Amy L.; Sahyoun, Nadine R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Verrill, Linda A.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Anderson, AL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM aanders3@umd.edu RI Sahyoun, Nadine/G-2608-2011 FU U.S. Department of Agriculture; National Institute of Food and Agriculture; U.S. Food and Drug Administration; Center for Food Safety and Applied Nutrition FX This study was supported by the U.S. Department of Agriculture, National Institute of Food and Agriculture, and the U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition. NR 26 TC 9 Z9 10 U1 1 U2 7 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 MAR-APR PY 2011 VL 126 IS 2 BP 220 EP 227 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 723ZX UT WOS:000287547000013 PM 21387952 ER PT J AU Hricak, H Brenner, DJ Adelstein, SJ Frush, DP Hall, EJ Howell, RW McCollough, CH Mettler, FA Pearce, MS Suleiman, OH Thrall, JH Wagner, LK AF Hricak, Hedvig Brenner, David J. Adelstein, S. James Frush, Donald P. Hall, Eric J. Howell, Roger W. McCollough, Cynthia H. Mettler, Fred A. Pearce, Mark S. Suleiman, Orhan H. Thrall, James H. Wagner, Louis K. TI Managing Radiation Use in Medical Imaging : A Multifaceted Challenge SO RADIOLOGY LA English DT Article ID ATOMIC-BOMB SURVIVORS; CARDIAC COMPUTED-TOMOGRAPHY; FLUOROSCOPICALLY GUIDED PROCEDURES; CORONARY-ARTERY-DISEASE; MULTISLICE HELICAL CT; MULTIDETECTOR-ROW CT; LOW-DOSE RADIATION; BREAST-CANCER; IONIZING-RADIATION; DECISION-SUPPORT AB This special report aims to inform the medical community about the many challenges involved in managing radiation exposure in a way that maximizes the benefit-risk ratio. The report discusses the state of current knowledge and key questions in regard to sources of medical imaging radiation exposure, radiation risk estimation, dose reduction strategies, and regulatory options. C1 [Hricak, Hedvig] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA. [Brenner, David J.; Hall, Eric J.] Columbia Univ, Ctr Radiol Res, Med Ctr, New York, NY 10032 USA. [Adelstein, S. James] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Frush, Donald P.] Duke Med Ctr, Div Pediat Radiol, Durham, NC USA. [Howell, Roger W.] UMDNJ New Jersey Med Sch Canc Ctr, Dept Radiol, Newark, NJ USA. [McCollough, Cynthia H.] Mayo Clin, Dept Radiol, Rochester, MN USA. [Mettler, Fred A.] Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA. [Pearce, Mark S.] Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Suleiman, Orhan H.] US FDA, Off New Drugs, Silver Spring, MD USA. [Thrall, James H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Wagner, Louis K.] Univ Texas Med Sch Houston, Dept Diagnost & Intervent Imaging, Houston, TX USA. RP Hricak, H (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave,Suite C-278, New York, NY 10021 USA. EM mullnea@mskcc.org RI Frush, Donald/M-6457-2015 OI Frush, Donald/0000-0002-6928-4465 FU NASA [NNJO5H138G]; DOE [SC0001634]; Siemens Medical Solutions; American College of Radiology FX E.J.H. Financial activities related to the present article: institutional grants from NASA NNJO5H138G and DOE-SC0001634. Financial activities not related to the present article: is paid for consultancy (teaching) elsewhere, is paid for employment as professor emeritus at Columbia University, is paid for expert testimony for several court cases, and receives payment for lectures including service on speakers bureaus teaching residents, receives royalties for textbook, receives institutional grants for payment for development of educational presentations, receives money for stock or stock options as part of retirement portfolio, receives money for travel, accommodations, meeting expenses for resident lectures. Other relationships: none to disclose.; C.H.M. Financial activities related to the present article: received institutional payment for travel expenses to the National Academies of Science sponsored Beebe Symposium in December 2009. Financial activities not related to the present article: received research grant related to CT imaging from Siemens Medical Solutions. Other relationships: none to disclose.; Financial activities not related to the present article: receives a stipend for service as board chair from American College of Radiology NR 122 TC 117 Z9 125 U1 3 U2 16 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAR PY 2011 VL 258 IS 3 BP 889 EP 905 DI 10.1148/radiol.10101157 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 724JX UT WOS:000287573100026 PM 21163918 ER PT J AU Laughren, T Levin, R AF Laughren, Thomas Levin, Robert TI Food and Drug Administration Commentary on Methodological Issues in Negative Symptom Trials SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material C1 [Laughren, Thomas; Levin, Robert] US FDA, Div Psychiat Prod, Silver Spring, MD USA. RP Laughren, T (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Thomas.Laughren@fda.hhs.gov NR 3 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAR PY 2011 VL 37 IS 2 BP 255 EP 256 DI 10.1093/schbul/sbq162 PG 2 WC Psychiatry SC Psychiatry GA 726SB UT WOS:000287745300007 PM 21245124 ER PT J AU Bradford, BU Lock, EF Kosyk, O Kim, S Uehara, T Harbourt, D DeSimone, M Threadgill, DW Tryndyak, V Pogribny, IP Bleyle, L Koop, DR Rusyn, I AF Bradford, Blair U. Lock, Eric F. Kosyk, Oksana Kim, Sungkyoon Uehara, Takeki Harbourt, David DeSimone, Michelle Threadgill, David W. Tryndyak, Volodymyr Pogribny, Igor P. Bleyle, Lisa Koop, Dennis R. Rusyn, Ivan TI Interstrain Differences in the Liver Effects of Trichloroethylene in a Multistrain Panel of Inbred Mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE trichloroethylene; metabolism; genetics; peroxisome proliferator-activated receptor alpha; acute exposure; gene expression ID ACTIVATED-RECEPTOR-ALPHA; TANDEM MASS-SPECTROMETRY; GENE-EXPRESSION; TRICHLOROACETIC-ACID; DICHLOROACETIC ACID; MOUSE-LIVER; PPAR-ALPHA; TUMOR-INDUCTION; LIQUID-CHROMATOGRAPHY; HUMAN VOLUNTEERS AB Trichloroethylene (TCE) is a widely used industrial chemical and a common environmental contaminant. It is a well-known carcinogen in rodents and a probable carcinogen in humans. Studies utilizing panels of mouse inbred strains afford a unique opportunity to understand both metabolic and genetic basis for differences in responses to TCE. We tested the hypothesis that strain- and liver-specific toxic effects of TCE are genetically controlled and that the mechanisms of toxicity and susceptibility can be uncovered by exploring responses to TCE using a diverse panel of inbred mouse strains. TCE (2100 mg/kg) or corn oil vehicle was administered by gavage to 6- to 8-week-old male mice of 15 mouse strains. Serum and liver were collected at 2, 8, and 24 h postdosing and were analyzed for TCE metabolites, hepatocellular injury, and gene expression of liver. TCE metabolism, as evident from the levels of individual oxidative and conjugative metabolites, varied considerably between strains. TCE treatment-specific effect on the liver transcriptome was strongly dependent on genetic background. Peroxisome proliferator-activated receptor-mediated molecular networks, consisting of the metabolism genes known to be induced by TCE, represent some of the most pronounced molecular effects of TCE treatment in mouse liver that are dependent on genetic background. Conversely, cell death, liver necrosis, and immune-mediated response pathways, which are altered by TCE treatment in liver, are largely genetic background independent. These studies provide better understanding of the mechanisms of TCE-induced toxicity anchored on metabolism and genotype-phenotype correlations that may define susceptibility or resistance. C1 [Bradford, Blair U.; Kosyk, Oksana; Kim, Sungkyoon; Uehara, Takeki; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Lock, Eric F.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27599 USA. [Harbourt, David; DeSimone, Michelle; Threadgill, David W.; Rusyn, Ivan] Univ N Carolina, Dept Curriculum Toxicol, Chapel Hill, NC 27599 USA. [Threadgill, David W.] N Carolina State Univ, Dept Genet, Raleigh, NC 27695 USA. [Tryndyak, Volodymyr; Pogribny, Igor P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Bleyle, Lisa; Koop, Dennis R.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, 0031 Michael Hooker Res Ctr, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016; Threadgill, David/N-4425-2013 OI Threadgill, David/0000-0003-3538-1635 FU National Institutes of Health [P42 ES005948] FX National Institutes of Health grant (P42 ES005948). NR 58 TC 20 Z9 20 U1 2 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 MAR PY 2011 VL 120 IS 1 BP 206 EP 217 DI 10.1093/toxsci/kfq362 PG 12 WC Toxicology SC Toxicology GA 726SZ UT WOS:000287747800019 PM 21135412 ER PT J AU Tubaro, A Durando, P Del Favero, G Ansaldi, F Icardi, G Deeds, JR Sosa, S AF Tubaro, A. Durando, P. Del Favero, G. Ansaldi, F. Icardi, G. Deeds, J. R. Sosa, S. TI Case definitions for human poisonings postulated to palytoxins exposure SO TOXICON LA English DT Article DE Palytoxin; Seafood poisoning; Marine aerosol; Aquarium zoanthids; Ostreopsis; Palythoa; Case definition; Case report ID DINOFLAGELLATE OSTREOPSIS-SIAMENSIS; MEDITERRANEAN SEA; PUTATIVE PALYTOXIN; MASS-SPECTROMETRY; COASTAL WATERS; TYRRHENIAN SEA; MOUSE BIOASSAY; HUMAN FATALITY; CORAL-REEF; TOXIN AB A series of case reports and anecdotal references describe the adverse effects on human health ascribed to the marine toxin palytoxin (PLTX) after different exposure routes. They include poisonings after oral intake of contaminated seafood, but also inhalation and cutaneous/systemic exposures after direct contact with aerosolized seawater during Ostreopsis blooms and/or through maintaining aquaria containing cnidarian zoanthids. The symptoms commonly recorded during PLTX intoxication are general malaise and weakness, associated with myalgia, respiratory effects, impairment of the neuromuscular apparatus and abnormalities in cardiac function. Systemic symptoms are often recorded together with local damages whose intensity varies according to the route and length of exposure. Gastrointestinal malaise or respiratory distress is common for oral and inhalational exposure, respectively. In addition, irritant properties of PLTX probably account for the inflammatory reactions typical of cutaneous and inhalational contact. Unfortunately, the toxin identification and/or quantification are often incomplete or missing and cases of poisoning are indirectly ascribed to PLTXs, according only to symptoms, anamnesis and environmental/epidemiological investigations (i.e. zoanthid handling or ingestion of particular seafood). Based on the available literature, we suggest a "case definition of PLTX poisonings" according to the main exposure routes, and, we propose the main symptoms to be checked, as well as, hemato-clinical analysis to be carried out. We also suggest the performance of specific analyses both on biological specimens of patients, as well as, on the contaminated materials responsible for the poisoning. A standardized protocol for data collection could provide a more rapid and reliable diagnosis of palytoxin-poisoning, but also the collection of necessary data for the risk assessment for this family of toxins. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Tubaro, A.; Del Favero, G.; Sosa, S.] Univ Trieste, Dept Mat & Nat Resources, I-34127 Trieste, Italy. [Durando, P.; Ansaldi, F.; Icardi, G.] Univ Genoa, Dept Hlth Sci, Sect Hyg & Prevent Med, I-16132 Genoa, Italy. [Durando, P.; Ansaldi, F.; Icardi, G.] San Martino Univ Hosp Genoa, I-16132 Genoa, Italy. [Deeds, J. R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Tubaro, A (reprint author), Univ Trieste, Dept Mat & Nat Resources, Via A Valerio 6, I-34127 Trieste, Italy. EM tubaro@units.it FU Italian Ministry of Education, University and Research (MIUR) FX This work was supported by a grant of the Italian Ministry of Education, University and Research (MIUR). Authors thank Cristiano Alicino, MD, post-graduate student at the School of Specialization in Hygiene and Preventive Medicine of the University of Genoa (Italy) who contributed to the drawing up of the section 5 entitled "Poisonings after postulated exposure to seawater and/or aerosol during Ostreopsis blooms" of the manuscript. NR 88 TC 89 Z9 91 U1 3 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD MAR 1 PY 2011 VL 57 IS 3 SI SI BP 478 EP 495 DI 10.1016/j.toxicon.2011.01.005 PG 18 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 747LP UT WOS:000289321600014 PM 21255599 ER PT J AU Tang, SX Zhao, JQ Viswanath, R Nyambi, PN Redd, AD Dastyar, A Spacek, LA Quinn, TC Wang, X Wood, O Gaddam, D Devadas, K Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Viswanath, Ragupathy Nyambi, Phillipe N. Redd, Andrew D. Dastyar, Armeta Spacek, Lisa A. Quinn, Thomas C. Wang, Xue Wood, Owen Gaddam, Durga Devadas, Krishnakumar Hewlett, Indira K. TI Absence of detectable xenotropic murine leukemia virus-related virus in plasma or peripheral blood mononuclear cells of human immunodeficiency virus Type 1-infected blood donors or individuals in Africa SO TRANSFUSION LA English DT Article ID CHRONIC-FATIGUE-SYNDROME; HUMAN RETROVIRUS XMRV; PROSTATE-CANCER AB BACKGROUND: Since the identification of xenotropic murine leukemia virus-related virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. In this study, we screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected individuals to gain evidence of XMRV infection in this geographic region. STUDY DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50 culture supernatants from PBMNCs of blood donors from Cameroon found to be infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV infection using a sensitive nested polymerase chain reaction (PCR) or reverse transcription (RT)-PCR assay. RESULTS: Using highly sensitive nested PCR or RT-PCR and real-time PCR assays capable of detecting at least 10 copies of XMRV plasmid DNA per reaction, none of the 268 samples tested were found to be XMRV DNA or RNA positive. CONCLUSIONS: Our results failed to demonstrate the presence of XMRV infection in African blood donors or individuals infected with HIV-1. More studies are needed to understand the prevalence, epidemiology, and geographic distribution of XMRV infection worldwide. C1 US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NYU, Sch Med, Dept Pathol, New York, NY USA. Johns Hopkins Univ, Sch Med, Div Intramural Res, NIAID,NIH, Baltimore, MD USA. RP Tang, SX (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20892 USA. EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov FU Division of Intramural Research, NIAID, NIH FX This work was supported in part by Division of Intramural Research, NIAID, NIH. NR 22 TC 21 Z9 21 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2011 VL 51 IS 3 BP 463 EP 468 DI 10.1111/j.1537-2995.2010.02932.x PG 6 WC Hematology SC Hematology GA 732DZ UT WOS:000288166200005 PM 21077909 ER PT J AU Simmons, G Glynn, SA Holmberg, JA Coffin, JM Hewlett, IK Lo, SC Mikovits, JA Switzer, WM Linnen, JM Busch, MP AF Simmons, Graham Glynn, Simone A. Holmberg, Jerry A. Coffin, John M. Hewlett, Indira K. Lo, Shyh-Ching Mikovits, Judy A. Switzer, William M. Linnen, Jeffrey M. Busch, Michael P. CA Blood XMRV Sci Res Working Grp TI The Blood Xenotropic Murine Leukemia Virus-Related Virus Scientific Research Working Group: mission, progress, and plans SO TRANSFUSION LA English DT Editorial Material ID CHRONIC-FATIGUE-SYNDROME; PROSTATE-CANCER; INFECTIOUS RETROVIRUS; MOUSE DNA; XMRV; DISEASE; CONTAMINATION; CELLS; RISK; SEQUENCES C1 [Simmons, Graham] Blood Syst Res Inst, San Francisco, CA 94118 USA. [Simmons, Graham] Univ Calif San Francisco, San Francisco, CA 94118 USA. [Glynn, Simone A.] NHLBI, Transfus Med & Cellular Therapeut Branch, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. US FDA, Off Blood Res & Review, Silver Spring, MD USA. US FDA, Div Cellular & Gene Therapies Review, Silver Spring, MD USA. Univ Nevada, Reno, NV 89557 USA. Whittemore Peterson Inst, Reno, NV USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. Gen Probe Inc, San Diego, CA USA. RP Simmons, G (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA. EM gsimmons@bloodsystems.org; glynnsa@nhlbi.nih.gov RI Simmons, Graham/G-3523-2012 OI Simmons, Graham/0000-0002-9615-7023 FU NHLBI NIH HHS [N01HB-57181, N01HB57181, HHSN268200517181C]; PHS HHS [HHSN268200517181C] NR 40 TC 21 Z9 21 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAR PY 2011 VL 51 IS 3 BP 643 EP 653 DI 10.1111/j.1537-2995.2011.03063.x PG 11 WC Hematology SC Hematology GA 732DZ UT WOS:000288166200028 PM 21366602 ER PT J AU Bruner, DW Hanisch, LJ Reeve, BB Trotti, AM Schrag, D Sit, L Mendoza, TR Minasian, L O'Mara, A Denicoff, AM Rowland, JH Montello, M Geoghegan, C Abernethy, AP Clauser, SB Castro, K Mitchell, SA Burke, L Trentacosti, AM Basch, EM AF Bruner, Deborah Watkins Hanisch, Laura J. Reeve, Bryce B. Trotti, Andy M. Schrag, Deborah Sit, Laura Mendoza, Tito R. Minasian, Lori O'Mara, Ann Denicoff, Andrea M. Rowland, Julia H. Montello, Michael Geoghegan, Cindy Abernethy, Amy P. Clauser, Steven B. Castro, Kathleen Mitchell, Sandra A. Burke, Laurie Trentacosti, Ann Marie Basch, Ethan M. TI Stakeholder perspectives on implementing the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) SO TRANSLATIONAL BEHAVIORAL MEDICINE LA English DT Article DE Patient-reported outcomes; Symptoms; adverse events; Oncology; Cancer; Clinical trials; Toxicity; safety; Tolerability; Comparative effectiveness research; Cooperative groups; National Cancer Institute AB The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty-eight percent felt that patients in clinical trials would be willing to self-report adverse symptoms at clinic visits via computer, and 68% felt patients would self-report weekly from home via the internet or an automated telephone system. Lack of computers and limited space and personnel were seen as potential barriers to in-clinic self-reporting, but these were judged to be surmountable with adequate funding. The PRO-CTCAE items and software are viewed by a majority of survey respondents as a means to improve adverse event data quality and comprehensiveness, enhance clinical decision-making, and foster patient-clinician communication. Research is ongoing to assess the measurement properties and feasibility of implementing this measure in cancer clinical trials. C1 [Bruner, Deborah Watkins] Univ Penn, Abramson Canc Ctr, Sch Nursing, Philadelphia, PA 19104 USA. [Hanisch, Laura J.] Univ Penn, Abramson Canc Ctr, Canc Control & Outcomes Program, Philadelphia, PA 19104 USA. [Reeve, Bryce B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Lineberger Comprehens Canc Ctr, Dept Hlth Policy & Management, Chapel Hill, NC 27599 USA. [Trotti, Andy M.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA. [Schrag, Deborah] Dana Farber Canc Inst, Gastrointestinal Canc Ctr, Boston, MA 02115 USA. [Sit, Laura; Basch, Ethan M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, New York, NY 10065 USA. [Mendoza, Tito R.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA. [Minasian, Lori] NCI, Community Oncol & Prevent Trials Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA. [O'Mara, Ann] NCI, Palliat Care Res Community Oncol & Prevent Trial, Canc Prevent Div, Bethesda, MD 20892 USA. [Denicoff, Andrea M.] NCI, Clin Invest Branch, CTEP, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. [Rowland, Julia H.] NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, NIH,DHHS, Bethesda, MD 20892 USA. [Montello, Michael] NCI, Clin Trials Technol, Bethesda, MD 20892 USA. [Geoghegan, Cindy] Breast Canc Network Strength, Chicago, IL 60603 USA. [Abernethy, Amy P.] Duke Univ, Med Ctr, Sch Med, Dept Med, Durham, NC 27710 USA. [Clauser, Steven B.; Castro, Kathleen; Mitchell, Sandra A.] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Burke, Laurie; Trentacosti, Ann Marie] US FDA, Study Endpoints & Label Dev, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Basch, EM (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, Hlth Outcomes Grp, 307 E 63rd St,2nd Floor, New York, NY 10065 USA. EM basche@mskcc.org OI Abernethy, Amy/0000-0001-6930-8722 FU National Cancer Institute [HHSN261200800043C] FX This work was supported by the National Cancer Institute under contract HHSN261200800043C awarded to Dr. Ethan Basch, PI. NR 26 TC 16 Z9 17 U1 0 U2 2 PU SPRINGER INTERNATIONAL PUBLISHING AG PI CHAM PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND SN 1869-6716 EI 1613-9860 J9 TRANSL BEHAV MED JI Transl. Behav. Med. PD MAR PY 2011 VL 1 IS 1 BP 110 EP 122 DI 10.1007/s13142-011-0025-3 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA V39LG UT WOS:000209411900019 PM 24073038 ER PT J AU Lu, HX Khurana, S Verma, N Manischewitz, J King, L Beigel, JH Golding, H AF Lu, Hanxin Khurana, Surender Verma, Nitin Manischewitz, Jody King, Lisa Beigel, John H. Golding, Hana TI A Rapid Flp-In System for Expression of Secreted H5N1 Influenza Hemagglutinin Vaccine Immunogen in Mammalian Cells SO PLOS ONE LA English DT Article ID EFFICACY; SAFETY; PURIFICATION; ANTIBODIES; ADULTS; VIRUS; DUCKS AB Background: Continuing transmissions of highly pathogenic H5N1 viruses in poultry and humans underscores the need for a rapid response to potential pandemic in the form of vaccine. Recombinant technologies for production of immunogenic hemagglutinin (HA) could provide an advantage over the traditional inactivated vaccine manufacturing process. Generation of stably transfected mammalian cells secreting properly folded HA proteins is important for scalable controlled manufacturing. Methodology/Principal Findings: We have developed a Flp-In based 293 stable cell lines through targeted site-specific recombination for expression of secreted hemagglutinin (HA) proteins and evaluated their immunogenicity. H5N1 globular domain HA1(1-330) and HA0(1-500) proteins were purified from the supernatants of 293 Flp-In stable cell lines. Both proteins were properly folded as confirmed by binding to H5N1-neutralizing conformation-dependent human monoclonal antibodies. The HA0 (with unmodified cleavage site) was monomeric, while the HA1 contained oligomeric forms. Upon rabbit immunization, both HA proteins elicited neutralizing antibodies against the homologous virus (A/Vietnam/1203/2004, clade 1) as well as cross-neutralizing antibodies against heterologous H5N1 clade 2 strains, including A/Indonesia/5/2005. These results exceeded the human antibody responses against the inactivated sub-virion H5N1 vaccine. Conclusions/Significance: Our data suggest that the 293 Flp-In system could serve as a platform for rapid expression of HA immunogens in mammalian cells from emerging influenza strains. C1 [Lu, Hanxin; Khurana, Surender; Verma, Nitin; Manischewitz, Jody; King, Lisa; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Beigel, John H.] NIAID, Immunoregulat Lab, Div Intramural Res, SAIC Frederick,NCI Frederick, Frederick, MD USA. RP Lu, HX (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM hana.golding@fda.hhs.gov OI Tripp, Ralph/0000-0002-2924-9956 FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This project was funded in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E and in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 23 TC 14 Z9 16 U1 0 U2 4 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 FEB 28 PY 2011 VL 6 IS 2 AR e17297 DI 10.1371/journal.pone.0017297 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 729EM UT WOS:000287931400050 PM 21386997 ER PT J AU Wu, HQ White, M Khan, MA AF Wu, Huiquan White, Maury Khan, Mansoor A. TI Quality-by-Design (QbD): An integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and process design space development SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Quality-by-Design (QbD); Process analytical technology (PAT); Co-precipitation; Real-time process monitoring; Critical process variable; Design space ID PARTICLE-SIZE DISTRIBUTION; MULTIVARIATE CALIBRATION; FORMULATION VARIABLES; LASER BACKSCATTERING; AGITATED SUSPENSIONS; FBRM; CRYSTALLIZATION; QUANTIFICATION; OPTIMIZATION; PRODUCT AB The aim of this work was to develop an integrated process analytical technology (PAT) approach for a dynamic pharmaceutical co-precipitation process characterization and design space development. A dynamic co-precipitation process by gradually introducing water to the ternary system of naproxen-Eudragit L100-alcohol was monitored at real-time in situ via Lasentec FBRM and PVM. 3D map of count-time-chord length revealed three distinguishable process stages: incubation, transition, and steady-state. The effects of high risk process variables (slurry temperature, stirring rate, and water addition rate) on both derived co-precipitation process rates and final chord-length-distribution were evaluated systematically using a 3(3) full factorial design. Critical process variables were identified via ANOVA for both transition and steady state. General linear models (GLM) were then used for parameter estimation for each critical variable. Clear trends about effects of each critical variable during transition and steady state were found by GLM and were interpreted using fundamental process principles and Nyvlt's transfer model. Neural network models were able to link process variables with response variables at transition and steady state with R(2) of 0.88-0.98. PVM images evidenced nucleation and crystal growth. Contour plots illustrated design space via critical process variables' ranges. It demonstrated the utility of integrated PAT approach for QbD development. Published by Elsevier B.V. C1 [Wu, Huiquan; White, Maury; Khan, Mansoor A.] OTR OPS CDER FDA, HFD 940, DPQR, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), OTR OPS CDER FDA, HFD 940, DPQR, FDA White Oak Campus,Life Sci Bldg 64,Room 1080, Silver Spring, MD 20993 USA. EM Huiquan.Wu@fda.hhs.gov NR 48 TC 43 Z9 46 U1 2 U2 31 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 FEB 28 PY 2011 VL 405 IS 1-2 BP 63 EP 78 DI 10.1016/j.ijpharm.2010.11.045 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 720KK UT WOS:000287279400008 PM 21138762 ER PT J AU Jeannot, E Pogribny, IP Beland, FA Rusyn, I AF Jeannot, Emmanuelle Pogribny, Igor P. Beland, Frederick A. Rusyn, Ivan TI Chronic administration of ethanol leads to an increased incidence of hepatocellular adenoma by promoting H-ras-mutated cells SO CANCER LETTERS LA English DT Article DE Alcohol; Liver tumors; H-ras; beta-Catenin; HNF1 alpha ID MOUSE-LIVER TUMORS; OXIDATIVE DNA-DAMAGE; MUTATIONAL ANALYSIS; MITOCHONDRIAL-DNA; LUNG-TUMORS; ALCOHOL; MICE; CARCINOGENESIS; EXPRESSION; ONCOGENE AB This study used tissue samples from male B6C3F1 mice treated with ethanol in drinking water (0%, 2.5%, or 5%) for 4 or 104 weeks. We tested whether chronic alcohol drinking promotes oxidative stress in the liver and characterized the mutation profile of spontaneous and ethanol-induced tumors. We show that ethanol does not cause detectable oxidative stress in the liver at any time point and acts by promoting H-ras mutated cells. (c) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Jeannot, Emmanuelle; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Pogribny, Igor P.; Beland, Frederick A.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU NIH [ES005948, ES012689, ES015241] FX This work was supported, in part, by grants from NIH (ES005948, ES012689, and ES015241). The views expressed in this paper do not necessarily represent those of the US Food and Drug Administration. None of the authors has any actual or potential competing financial interests. NR 52 TC 5 Z9 5 U1 0 U2 1 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 FEB 28 PY 2011 VL 301 IS 2 BP 161 EP 167 DI 10.1016/j.canlet.2010.11.010 PG 7 WC Oncology SC Oncology GA 724CY UT WOS:000287554900005 PM 21168264 ER PT J AU Hamburg, MA AF Hamburg, Margaret A. TI Advancing Regulatory Science SO SCIENCE LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Hamburg, MA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 42 Z9 42 U1 0 U2 14 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 FEB 25 PY 2011 VL 331 IS 6020 BP 987 EP 987 DI 10.1126/science.1204432 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 726DM UT WOS:000287699000001 PM 21350129 ER PT J AU Pearson, RJ Gatti, PJ Sahibzada, N Massari, VJ Gillis, RA AF Pearson, Rebecca J. Gatti, Philip J. Sahibzada, Niaz Massari, V. John Gillis, Richard A. TI Ultrastructural evidence for selective GABAergic innervation of CNS vagal projections to the antrum of the rat SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article DE GABA; GAD67; Ultrastructure; Immunohistochemistry; Brainstem; Gastrointestinal; Antrum; Vagus; Motoneuron ID DORSAL MOTOR NUCLEUS; FUNCTIONAL DYSPEPSIA; ELECTRON-MICROSCOPY; TRACTUS-SOLITARIUS; SYNAPTIC CURRENTS; BRAIN-STEM; NEURONS; VAGUS; RECEPTORS; CISAPRIDE AB We reported pharmacological data suggesting that stimulation of a vago-vagal reflex activates GABAergic neurons in the hindbrain that inhibit dorsal motor nucleus of the vagus (DMV) neurons projecting to the antrum, but not to the fundus (Ferreira et al., 2002). The purpose of this study was to use an ultrastructural approach to test the hypothesis that GABAergic terminals form synapses with DMV antrum-projecting neurons, but not with DMV fundus-projecting neurons. A retrograde tracer, CTB-HRP, was injected into the gastric smooth muscle of either the fundus or the antrum of anesthetized rats. Animals were re-anesthetized 48 h later and perfusion-fixed with acrolein and paraformaldehyde. Brainstems were processed histochemically for CTB-HRP, and immunocytochemically for glutamic acid decarboxylase isoenzyme 67 immunoreactivity (GAD67-IR) by dual-labeling electron microscopic methods. Most cell bodies and dendrites of neurons that were retrogradely labeled from the stomach occurred at the level of the area postrema. Examination of 214 synapses on 195 neurons that projected to the antrum revealed that 23.0 +/- 3.6% (n = 4) of synaptic contacts were with GAD67-IR terminals. The examination of 220 synapses on 203 fundus-projecting neurons revealed that only 7.9 +/- 3.1% (n = 4) of synaptic contacts were with GAD67-IR terminals. The difference between GAD67-IR synaptic contacts with antrum- and fundus-projecting neurons was statistically significant (p < 0.05). These data suggest that brainstem circuitry controlling the antrum involves GABAergic transmission. (C) 2010 Elsevier B.V. All rights reserved. C1 [Pearson, Rebecca J.; Sahibzada, Niaz; Gillis, Richard A.] Georgetown Univ, Dept Pharmacol, Med Ctr, Washington, DC 20057 USA. [Gatti, Philip J.; Massari, V. John] Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. [Gatti, Philip J.] FDA CDER, Dept Pharmacol, Div Cardiorenal Prod, Silver Spring, MD USA. RP Gillis, RA (reprint author), Georgetown Univ, Dept Pharmacol, Med Ctr, 3900 Reservoir Rd NW, Washington, DC 20057 USA. EM gillisr@georgetown.edu OI Sahibzada, Niaz/0000-0002-4169-370X FU NIH [R01 DK57105, R01 DK56925, R24MH067627, U54NS039407, F31NS049786]; Division of Research Infrastructure, National Center for Research Resources, NIH [2 G12 RR003048] FX NIH grant #'s: R01 DK57105 (RAG). R01 DK56925 (RAG), R24MH067627 (VJM), U54NS039407 (VJM), and F31NS049786 (RJP). Supported in part by grant 2 G12 RR003048 from the RCMI Program, Division of Research Infrastructure, National Center for Research Resources, NIH. NR 31 TC 2 Z9 3 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD FEB 24 PY 2011 VL 160 IS 1-2 BP 21 EP 26 DI 10.1016/j.autneu.2010.10.010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 729XZ UT WOS:000287989000004 PM 21112817 ER PT J AU Mody, RK Greene, SA Gaul, L Sever, A Pichette, S Zambrana, I Dang, T Gass, A Wood, R Herman, K Cantwell, LB Falkenhorst, G Wannemuehler, K Hoekstra, RM McCullum, I Cone, A Franklin, L Austin, J Delea, K Behravesh, CB Sodha, SV Yee, JC Emanuel, B Al-Khaldi, SF Jefferson, V Williams, IT Griffin, PM Swerdlow, DL AF Mody, Rajal K. Greene, Sharon A. Gaul, Linda Sever, Adrianne Pichette, Sarah Zambrana, Ingrid Dang, Thi Gass, Angie Wood, Rene Herman, Karen Cantwell, Laura B. Falkenhorst, Gerhard Wannemuehler, Kathleen Hoekstra, Robert M. McCullum, Isaac Cone, Amy Franklin, Lou Austin, Jana Delea, Kristin Behravesh, Casey Barton Sodha, Samir V. Yee, J. Christopher Emanuel, Brian Al-Khaldi, Sufian F. Jefferson, Val Williams, Ian T. Griffin, Patricia M. Swerdlow, David L. TI National Outbreak of Salmonella Serotype Saintpaul Infections: Importance of Texas Restaurant Investigations in Implicating Jalapeno Peppers SO PLOS ONE LA English DT Article ID INTERNATIONAL OUTBREAK; FRESH PRODUCE; UNITED-STATES; MULTISTATE OUTBREAK; CONSUMPTION; TOMATOES; GROWTH AB Background: In May 2008, PulseNet detected a multistate outbreak of Salmonella enterica serotype Saintpaul infections. Initial investigations identified an epidemiologic association between illness and consumption of raw tomatoes, yet cases continued. In mid-June, we investigated two clusters of outbreak strain infections in Texas among patrons of Restaurant A and two establishments of Restaurant Chain B to determine the outbreak's source. Methodology/Principal Findings: We conducted independent case-control studies of Restaurant A and B patrons. Patients were matched to well controls by meal date. We conducted restaurant environmental investigations and traced the origin of implicated products. Forty-seven case-patients and 40 controls were enrolled in the Restaurant A study. Thirty case-patients and 31 controls were enrolled in the Restaurant Chain B study. In both studies, illness was independently associated with only one menu item, fresh salsa (Restaurant A: matched odds ratio [mOR], 37; 95% confidence interval [CI], 7.2-386; Restaurant B: mOR, 13; 95% CI 1.3-infinity). The only ingredient in common between the two salsas was raw jalapeno peppers. Cultures of jalapeno peppers collected from an importer that supplied Restaurant Chain B and serrano peppers and irrigation water from a Mexican farm that supplied that importer with jalapeno and serrano peppers grew the outbreak strain. Conclusions/Significance: Jalapeno peppers, contaminated before arrival at the restaurants and served in uncooked fresh salsas, were the source of these infections. Our investigations, critical in understanding the broader multistate outbreak, exemplify an effective approach to investigating large foodborne outbreaks. Additional measures are needed to reduce produce contamination. C1 [Mody, Rajal K.; Sever, Adrianne] Ctr Dis Control & Prevent, Sci Educ & Profess Dev Program Off, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Mody, Rajal K.; Greene, Sharon A.; Herman, Karen; Cantwell, Laura B.; Falkenhorst, Gerhard; Wannemuehler, Kathleen; Hoekstra, Robert M.; McCullum, Isaac; Austin, Jana; Behravesh, Casey Barton; Sodha, Samir V.; Williams, Ian T.; Griffin, Patricia M.; Swerdlow, David L.] Ctr Dis Control & Prevent, Div Foodborne Waterborne & Environm Dis, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. [Gaul, Linda; Dang, Thi] Texas Dept State Hlth Serv, Austin, TX USA. [Pichette, Sarah; Zambrana, Ingrid; Yee, J. Christopher; Emanuel, Brian; Al-Khaldi, Sufian F.; Jefferson, Val] US FDA, Silver Spring, MD USA. [Gass, Angie; Wood, Rene; Cone, Amy; Franklin, Lou] Wichita Falls Wichita Cty Publ Hlth Dist, Wichita Falls, TX USA. [Delea, Kristin] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Mody, RK (reprint author), Ctr Dis Control & Prevent, Sci Educ & Profess Dev Program Off, Epidem Intelligence Serv, Atlanta, GA 30333 USA. EM rmody@cdc.gov FU core government FX This work was supported by core government funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 24 TC 29 Z9 29 U1 1 U2 9 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 FEB 23 PY 2011 VL 6 IS 2 AR e16579 DI 10.1371/journal.pone.0016579 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 725PJ UT WOS:000287657500012 PM 21373185 ER PT J AU Kim, DH Song, CG Ilev, IK Kang, JU AF Kim, Do-Hyun Song, Chul-Gyu Ilev, Ilko K. Kang, Jin U. TI Axial-scanning low-coherence interferometer method for noncontact thickness measurement of biological samples SO APPLIED OPTICS LA English DT Article ID REFRACTIVE-INDEX; TISSUE; LIGHT AB We investigated a high-precision optical method for measuring the thickness of biological samples regardless of their transparency. The method is based on the precise measurement of optical path length difference of the end surfaces of objects, using a dual-arm axial-scanning low-coherence interferometer. This removes any consideration of the shape, thickness, or transparency of testing objects when performing the measurement. Scanning the reference simplifies the measurement setup, resulting in unambiguous measurement. Using a 1310 nm wavelength superluminescent diode, with a 65 nm bandwidth, the measurement accuracy was as high as 11.6 mu m. We tested the method by measuring the thickness of both transparent samples and nontransparent soft biological tissues. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Silver Spring, MD 20993 USA. [Song, Chul-Gyu] Chonbuk Natl Univ, Ctr Adv Image & Informat Technol, Jeonju 561756, Jeonbuk, South Korea. [Kang, Jin U.] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov RI Kang, Jin/A-3228-2010 NR 11 TC 6 Z9 6 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 FEB 20 PY 2011 VL 50 IS 6 BP 970 EP 974 DI 10.1364/AO.50.000970 PG 5 WC Optics SC Optics GA 724KI UT WOS:000287574600023 PM 21343978 ER PT J AU Collier, JW Shah, RB Bryant, AR Habib, MJ Khan, MA Faustino, PJ AF Collier, J. W. Shah, R. B. Bryant, A. R. Habib, M. J. Khan, M. A. Faustino, P. J. TI Development and application of a validated HPLC method for the analysis of dissolution samples of levothyroxine sodium drug products SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Levothyroxine; Dissolution; Drug product; HPLC; Validation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY METHOD; CONTENT UNIFORMITY; TABLET FORMULATIONS; THYROXINE; PHASE; QUANTIFICATION; STABILITY; ASSAY; TRIIODOTHYRONINE AB A rapid, selective, and sensitive gradient HPLC method was developed for the analysis of dissolution samples of levothyroxine sodium tablets. Current USP methodology for levothyroxine (L-T(4)) was not adequate to resolve co-elutants from a variety of levothyroxine drug product formulations. The USP method for analyzing dissolution samples of the drug product has shown significant intra- and inter-day variability. The sources of method variability include chromatographic interferences introduced by the dissolution media and the formulation excipients. In the present work, chromatographic separation of levothyroxine was achieved on an Agilent 1100 Series HPLC with a Waters Nova-pak column (250 mm x 3.9 mm) using a 0.01 M phosphate buffer (pH 3.0)-methanol (55:45, v/v) in a gradient elution mobile phase at a flow rate of 1.0 mL/min and detection UV wavelength of 225 nm. The injection volume was 800 mu L and the column temperature was maintained at 28 degrees C. The method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, specificity, linearity, and analytical range. The standard curve was found to have a linear relationship (r(2) > 0.99) over the analytical range of 0.08-0.8 mu g/mL. Accuracy ranged from 90 to 110% for low quality control (QC) standards and 95 to 105% for medium and high QC standards. Precision was <2% at all QC levels. The method was found to be accurate, precise, selective, and linear for L-T(4) over the analytical range. The HPLC method was successfully applied to the analysis of dissolution samples of marketed levothyroxine sodium tablets. Published by Elsevier B.V. C1 [Collier, J. W.; Shah, R. B.; Bryant, A. R.; Khan, M. A.; Faustino, P. J.] US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Collier, J. W.; Habib, M. J.] Howard Univ, Dept Pharmaceut Sci, Sch Pharm, Washington, DC 20059 USA. RP Faustino, PJ (reprint author), US FDA, Div Prod Qual Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov FU NCRR NIH HHS [G12 RR003048, G12 RR003048-22] NR 21 TC 9 Z9 10 U1 2 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD FEB 20 PY 2011 VL 54 IS 3 BP 433 EP 438 DI 10.1016/j.jpba.2010.08.025 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 687YL UT WOS:000284814300001 PM 20947276 ER PT J AU Dunn, JD Gryniewicz-Ruzicka, CM Kauffman, JF Westenberger, BJ Buhse, LF AF Dunn, Jamie D. Gryniewicz-Ruzicka, Connie M. Kauffman, John F. Westenberger, Benjamin J. Buhse, Lucinda F. TI Using a portable ion mobility spectrometer to screen dietary supplements for sibutramine SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Ion mobility spectrometry; Portable; Hand-held; Weight loss drugs; Herbal dietary supplements ID CHEMICAL WARFARE AGENTS; SYNTHETIC ADULTERANTS; MASS-SPECTROMETRY; WEIGHT-LOSS; ESI-MS; DRUGS; SWABS AB In response to recent incidents of undeclared sibutramine, an appetite suppressant found in dietary supplements, we developed a method to detect sibutramine using hand-held ion mobility spectrometers with an analysis time of 15s. Ion mobility spectrometry is a high-throughput and sensitive technique that has been used for illicit drug, explosive, volatile organic compound and chemical warfare detection. We evaluated a hand-held ion mobility spectrometer as a tool for the analysis of supplement extracts containing sibutramine. The overall instrumental limit of detection of five portable ion mobility spectrometers was 2 ng of sibutramine HCl. When sample extractions containing 30 ng/mu l or greater of sibutramine were analyzed, saturation of the ionization chamber of the spectrometer occurred and the instrument required more than three cleaning cycles to remove the drug. Hence, supplement samples suspected of containing sibutramine should be prepared at concentrations of 2-20 ng/mu l. To obtain this target concentration range for products containing unknown amounts of sibutramine, we provided a simple sample preparation procedure, allowing the U.S. Food and Drug Administration or other agencies to screen products using the portable ion mobility spectrometer. Published by Elsevier B.V. C1 [Dunn, Jamie D.; Gryniewicz-Ruzicka, Connie M.; Kauffman, John F.; Westenberger, Benjamin J.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Dunn, JD (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM Jamie.Dunn@fda.hhs.gov FU U.S. FDA Center for Drug Evaluation and Research FX We would like to thank the U.S. FDA ORA scientists, Gary Dzidowski, Mark Henry, Sarah McMullen, Temar Williams and Valentino Fiorella and the DPA scientists Terry Moore and Wei Ye for participating in the study. Funding was provided by the U.S. FDA Center for Drug Evaluation and Research Critical Path program. NR 32 TC 28 Z9 30 U1 2 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD FEB 20 PY 2011 VL 54 IS 3 BP 469 EP 474 DI 10.1016/j.jpba.2010.09.017 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 687YL UT WOS:000284814300007 PM 20940091 ER PT J AU Robertson, JS Nicolson, C Harvey, R Johnson, R Major, D Guilfoyle, K Roseby, S Newman, R Collin, R Wallis, C Engelhardt, OG Wood, JM Le, JH Manojkumar, R Pokorny, BA Silverman, J Devis, R Bucher, D Verity, E Agius, C Camuglia, S Ong, C Rockman, S Curtis, A Schoofs, P Zoueva, O Xie, H Li, X Lin, ZS Ye, ZP Chen, LM O'Neill, E Balishe, A Lipatov, AS Guo, Z Isakova, I Davis, CT Rivailler, P Gustin, KM Belser, JA Maines, TR Tumpey, TM Xu, XY Katz, JM Klimov, A Cox, NJ Donis, RO AF Robertson, James S. Nicolson, Carolyn Harvey, Ruth Johnson, Rachel Major, Diane Guilfoyle, Kate Roseby, Sarah Newman, Robert Collin, Rebecca Wallis, Chantal Engelhardt, Othmar G. Wood, John M. Le, Jianhua Manojkumar, Ramanunninair Pokorny, Barbara A. Silverman, Jeanmarie Devis, Rene Bucher, Doris Verity, Erin Agius, Catherine Camuglia, Sarina Ong, Chi Rockman, Steven Curtis, Anne Schoofs, Peter Zoueva, Olga Xie, Hang Li, Xing Lin, Zhengshi Ye, Zhiping Chen, Li-Mei O'Neill, Eduardo Balishe, Amanda Lipatov, Aleksandr S. Guo, Zhu Isakova, Irina Davis, Charles T. Rivailler, Pierre Gustin, Kortney M. Belser, Jessica A. Maines, Taronna R. Tumpey, Terrence M. Xu, Xiyan Katz, Jacqueline M. Klimov, Alexander Cox, Nancy J. Donis, Ruben O. TI The development of vaccine viruses against pandemic A(H1N1) influenza SO VACCINE LA English DT Article DE Influenza vaccines; Candidate vaccine viruses; Reverse genetics; High growth reassortants; HA antigen yield ID A VIRUS; REVERSE GENETICS; GENERATION; RECOMBINANTS; SYSTEM; EGG; DNA AB Wild type human influenza viruses do not usually grow well in embryonated hens' eggs, the substrate of choice for the production of inactivated influenza vaccine, and vaccine viruses need to be developed specifically for this purpose. In the event of a pandemic of influenza, vaccine viruses need to be created with utmost speed. At the onset of the current A(H1N1) pandemic in April 2009, a network of laboratories began a race against time to develop suitable candidate vaccine viruses. Two approaches were followed, the classical reassortment approach and the more recent reverse genetics approach. This report describes the development and the characteristics of current pandemic H1N1 candidate vaccine viruses. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Robertson, James S.; Nicolson, Carolyn; Harvey, Ruth; Johnson, Rachel; Major, Diane; Guilfoyle, Kate; Roseby, Sarah; Newman, Robert; Collin, Rebecca; Wallis, Chantal; Engelhardt, Othmar G.; Wood, John M.] Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. [Le, Jianhua; Manojkumar, Ramanunninair; Pokorny, Barbara A.; Silverman, Jeanmarie; Devis, Rene; Bucher, Doris] New York Med Coll, Dept Microbiol & Immunol, Valhalla, NY 10595 USA. [Zoueva, Olga; Xie, Hang; Li, Xing; Lin, Zhengshi; Ye, Zhiping] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Chen, Li-Mei; O'Neill, Eduardo; Balishe, Amanda; Lipatov, Aleksandr S.; Guo, Zhu; Isakova, Irina; Davis, Charles T.; Rivailler, Pierre; Gustin, Kortney M.; Belser, Jessica A.; Maines, Taronna R.; Tumpey, Terrence M.; Xu, Xiyan; Katz, Jacqueline M.; Klimov, Alexander; Cox, Nancy J.; Donis, Ruben O.] Ctr Dis Control & Prevent, Influenza Div, Atlanta, GA 30333 USA. RP Robertson, JS (reprint author), Natl Inst Biol Stand & Controls, Div Virol, Blanche Lane, Potters Bar EN6 3QG, Herts, England. EM jim.robertson@nibsc.hpa.org.uk RI Isakova-Sivak, Irina/C-1034-2014 OI Isakova-Sivak, Irina/0000-0002-2801-1508 NR 28 TC 49 Z9 53 U1 2 U2 8 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 FEB 17 PY 2011 VL 29 IS 9 BP 1836 EP 1843 DI 10.1016/j.vaccine.2010.12.044 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 730TV UT WOS:000288058500015 PM 21199698 ER PT J AU Getie-Kebtie, M Lazarev, A Eichelberger, M Alterman, M AF Getie-Kebtie, Melkamu Lazarev, Alexander Eichelberger, Maryna Alterman, Michail TI Label-free mass spectrometry-based relative quantification of proteins separated by one-dimensional gel electrophoresis SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Label-free; Protein quantification; In-gel digestion; Pressure cycling technology; MALDI-TOF/TOF ID LASER-DESORPTION/IONIZATION TIME; QUANTITATIVE PROTEOMICS; ABSOLUTE QUANTIFICATION; LIQUID-CHROMATOGRAPHY; CYTOCHROME-P450 ISOZYMES; MALDI; IDENTIFICATION; PERFORMANCE; MIXTURES; EXPRESSION AB Here we present a matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF)-based label-free relative protein quantification strategy that involves sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation of proteins followed by in-gel trypsin digestion. The main problem encountered in gel-based protein quantification is the difficulty in achieving complete and consistent proteolytic digestion. To solve this problem, we developed a high-pressure-assisted in-gel trypsin digestion method that is based on pressure cycling technology (PCT). The PCT approach performed at least as well as the conventional overnight in-gel trypsin digestion approach in parameters such as number of peaks detected, number of peptides identified, and sequence coverage, and the digestion time was reduced to 45 min. The gel/mass spectrometry (MS)-based label-free protein quantification method presented in this work proved the applicability of the signal response factor concept for relative protein quantification previously demonstrated by other groups using the liquid chromatography (LC)/MS platform. By normalizing the average signal intensities of the three most intense peptides of each protein with the average intensities of spiked synthetic catalase tryptic peptides, which we used as an internal standard, we observed spot-to-spot and lane-to-lane coefficients of variation of less than 10 and 20%, respectively. We also demonstrated that the method can be used for determining the relative quantities of proteins comigrating during electrophoretic separation. Published by Elsevier Inc. C1 [Getie-Kebtie, Melkamu; Alterman, Michail] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Lazarev, Alexander] Pressure BioSci, S Easton, MA 02375 USA. [Eichelberger, Maryna] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alterman, M (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM michail.alterman@fda.hhs.gov FU CBER Pandemic Influenza Unmet Needs; Biomedical Advanced Research and Development Authority FX The authors gratefully acknowledge critical reading of the manuscript by Dr. V. Gross. This project was supported by funding provided by CBER Pandemic Influenza Unmet Needs and by the Biomedical Advanced Research and Development Authority. NR 36 TC 10 Z9 10 U1 1 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD FEB 15 PY 2011 VL 409 IS 2 BP 202 EP 212 DI 10.1016/j.ab.2010.10.023 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 719CH UT WOS:000287176600006 PM 20971051 ER PT J AU Stein, WD Gulley, JL Schlom, J Madan, RA Dahut, W Figg, WD Ning, YM Arlen, PM Price, D Bates, SE Fojo, T AF Stein, Wilfred D. Gulley, James L. Schlom, Jeff Madan, Ravi A. Dahut, William Figg, William D. Ning, Yang-min Arlen, Phil M. Price, Doug Bates, Susan E. Fojo, Tito TI Tumor Regression and Growth Rates Determined in Five Intramural NCI Prostate Cancer Trials: The Growth Rate Constant as an Indicator of Therapeutic Efficacy SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; RADICAL PROSTATECTOMY; PLUS THALIDOMIDE; CLINICAL-TRIALS; DOUBLING TIME; WORKING GROUP; SURVIVAL; DOCETAXEL; VACCINE; RECOMMENDATIONS AB Purpose: In solid tumors such as prostate cancer, novel paradigms are needed to assess therapeutic efficacy. We utilized a method estimating tumor growth and regression rate constants from serial PSA measurements, and assessed its potential in patients with metastatic castration resistant prostate carcinoma (mCRPC). Experimental Design: Patients were enrolled in five phase II studies, including an experimental vaccine trial, representing the evolution of therapy in mCRPC. PSA measurements obtained before, and during, therapy were used. Data analysis using a two-phase mathematical equation yielded concomitant PSA growth and regression rate constants. Results: Growth rate constants (g) can be estimated while patients receive therapy and in such patients g is superior to PSA-DT in predicting OS. Incremental reductions in growth rate constants were recorded in successive trials with a 10-fold slower g in the most recent combination therapy trial (log g = 10(-3.17)) relative to single-agent thalidomide (log g = 10(-2.08)) more than a decade earlier. Growth rate constants correlated with survival, except in patients receiving vaccine-based therapy where the evidence demonstrates prolonged survival presumably due to immunity developing subsequent to vaccine administration. Conclusion: Incremental reductions in tumor growth rate constants suggest increased efficacy in successive chemotherapy trials. The derived growth rate constant correlates with survival, and may be used to assess efficacy. The PSA-TRICOM vaccine appears to have provided marked benefit not apparent during vaccination, but consistent with subsequent development of a beneficial immune response. If validated as a surrogate for survival, growth rate constants would offer an important new efficacy endpoint for clinical trials. Clin Cancer Res; 17(4); 907-17. (C) 2010 AACR. C1 [Stein, Wilfred D.; Madan, Ravi A.; Dahut, William; Figg, William D.; Price, Doug; Bates, Susan E.; Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Gulley, James L.; Schlom, Jeff; Madan, Ravi A.; Arlen, Phil M.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Stein, Wilfred D.] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. [Ning, Yang-min] US FDA, DDOP OODP CDER, Silver Spring, MD USA. RP Fojo, T (reprint author), NCI, Med Oncol Branch, NIH, NIH Bldg 10,RM 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 37 TC 115 Z9 115 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 15 PY 2011 VL 17 IS 4 BP 907 EP 917 DI 10.1158/1078-0432.CCR-10-1762 PG 11 WC Oncology SC Oncology GA 728ZM UT WOS:000287913200030 PM 21106727 ER PT J AU Jelinek, I Leonard, JN Price, GE Brown, KN Meyer-Manlapat, A Goldsmith, PK Wang, Y Venzon, D Epstein, SL Segal, DM AF Jelinek, Ivett Leonard, Joshua N. Price, Graeme E. Brown, Kevin N. Meyer-Manlapat, Anna Goldsmith, Paul K. Wang, Yan Venzon, David Epstein, Suzanne L. Segal, David M. TI TLR3-Specific Double-Stranded RNA Oligonucleotide Adjuvants Induce Dendritic Cell Cross-Presentation, CTL Responses, and Antiviral Protection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-3; BONE-MARROW CULTURES; ANTIGEN PRESENTATION; INNATE IMMUNITY; IN-VIVO; ADAPTIVE IMMUNITY; CUTTING EDGE; RECOGNITION; ACTIVATION; CD8(+) AB Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA required to activate DC and the expression patterns of TLR3 protein in DC subsets have not been established. In this article, we show that cross-priming CD8 alpha(+) and CD103(+) DC subsets express much greater levels of TLR3 than other DC. In resting DC, TLR3 is located in early endosomes and other intracellular compartments but migrates to LAMP1(+) endosomes on stimulation with a TLR3 ligand. Using homogeneous dsRNA oligonucleotides (ONs) ranging in length from 25 to 540 bp, we observed that a minimum length of similar to 90 bp was sufficient to induce CD86, IL-12p40, IFN-beta, TNF-alpha, and IL-6 expression, and to mature DC into APC that cross-presented exogenous Ags to CD8(+) T cells. TLR3 was essential for activation of DC by dsRNA ONs, and the potency of activation increased with dsRNA length and varied between DC subsets. In vivo, dsRNA ONs, in a size-dependent manner, served as adjuvants for the generation of Ag-specific CTL and for inducing protection against lethal challenge with influenza virus when given with influenza nucleoprotein as an immunogen. These results provide the basis for the development of TLR3-specific adjuvants capable of inducing immune responses tailored for viral pathogens. The Journal of Immunology, 2011, 186: 2422-2429. C1 [Jelinek, Ivett; Leonard, Joshua N.; Brown, Kevin N.; Meyer-Manlapat, Anna; Wang, Yan; Segal, David M.] NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Price, Graeme E.; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Goldsmith, Paul K.] NCI, Antibody & Prot Purificat Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Segal, DM (reprint author), NCI, Expt Immunol Branch, Ctr Canc Res, NIH, Bldg 10,Room 4B36,10 Ctr Dr, Bethesda, MD 20892 USA. EM dave_segal@nih.gov RI Leonard, Joshua/B-7649-2009 FU National Cancer Institute; National Institute of Allergy and Infectious Diseases FX This work was supported by the Intramural Research Program of the National Cancer Institute and by a National Institutes of Health/Food and Drug Administration Intramural Biodefense Award from the National Institute of Allergy and Infectious Diseases. NR 64 TC 81 Z9 83 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2011 VL 186 IS 4 BP 2422 EP 2429 DI 10.4049/jimmunol.1002845 PG 8 WC Immunology SC Immunology GA 715KF UT WOS:000286882700062 PM 21242525 ER PT J AU Kanswal, S Katsenelson, N Allman, W Uslu, K Blake, MS Akkoyunlu, M AF Kanswal, Sunita Katsenelson, Nora Allman, Windy Uslu, Kadriye Blake, Milan S. Akkoyunlu, Mustafa TI Suppressive Effect of Bacterial Polysaccharides on BAFF System Is Responsible for Their Poor Immunogenicity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDEPENDENT TYPE-2 ANTIGENS; PLASMA-CELL DIFFERENTIATION; NECROSIS-FACTOR FAMILY; B-CELLS; IMMUNE-RESPONSE; STREPTOCOCCUS-PNEUMONIAE; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSE; CONJUGATE VACCINE; CPG OLIGODEOXYNUCLEOTIDES AB Capsular polysaccharides of encapsulated bacteria are weakly immunogenic T cell-independent type 2 (TI-2) Ags. Recent findings suggest that BAFF system molecules have a critical role in the development of Ab responses against TI-2 Ags. In this study, we investigated the effect of bacterial polysaccharides on B cell responses to BAFF and a proliferation-inducing ligand (APRIL). We determined that B cells exposed to meningococcal type C polysaccharide (MCPS) or group B Streptococcus serotype V (GBS-V) were unresponsive to BAFF- and APRIL-induced Ig secretion. Moreover, MCPS and GBS-V strongly downregulated transmembrane activator and calcium-modulator and cyclophilin ligand interactor, the BAFF and APRIL receptor that is responsible for Ab development against TI-2 Ags. Interestingly, (4-hydroxy-3-nitrophenyl) acetyl-Ficoll (NP-Ficoll), a prototype TI-2 Ag, did not manifest a suppressive effect on B cells. Paradoxically, whereas GBS-V and MCPS inhibited IFN-gamma-induced BAFF production from dendritic cells, NP-Ficoll strongly increased BAFF secretion. TLR 9 agonist CpG deoxyoligonucleotide (ODN) was able to reverse the MCPS-mediated transmembrane activator and calcium-modulator and cyclophilin ligand interactor suppression but could not rescue the Ig secretion in BAFF- or APRIL-stimulated B cells. In support of these in vitro observations, it was observed that CpG ODN could help augment the Ab response against NP in mice immunized with a CpG ODN-containing NP-Ficoll vaccine but exhibited only marginal adjuvant activity for MCPS vaccine. Collectively, these results suggest a mechanism for the weak immunogenicity of bacterial polysaccharides and explain the previously observed differences between bacterial polysaccharide and NP-Ficoll immunogenicity. The Journal of Immunology, 2011, 186: 2430-2443. C1 [Kanswal, Sunita; Katsenelson, Nora; Allman, Windy; Uslu, Kadriye; Blake, Milan S.; Akkoyunlu, Mustafa] US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, CBER, Rockville, MD 20852 USA. RP Akkoyunlu, M (reprint author), US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, CBER, 29 Lincoln Dr,HFM 428,Bldg 29,Room 516-B, Rockville, MD 20852 USA. EM Mustafa.Akkoyunlu@fda.hhs.gov RI Akkoyunlu, Mustafa/I-5712-2012 NR 56 TC 19 Z9 19 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2011 VL 186 IS 4 BP 2430 EP 2443 DI 10.4049/jimmunol.1002976 PG 14 WC Immunology SC Immunology GA 715KF UT WOS:000286882700063 PM 21248261 ER PT J AU Slager, SL Rabe, KG Achenbach, SJ Vachon, CM Goldin, LR Strom, SS Lanasa, MC Spector, LG Rassenti, LZ Leis, JF Camp, NJ Glenn, M Kay, NE Cunningham, JM Hanson, CA Marti, GE Weinberg, JB Morrison, VA Link, BK Call, TG Caporaso, NE Cerhan, JR AF Slager, Susan L. Rabe, Kari G. Achenbach, Sara J. Vachon, Celine M. Goldin, Lynn R. Strom, Sara S. Lanasa, Mark C. Spector, Logan G. Rassenti, Laura Z. Leis, Jose F. Camp, Nicola J. Glenn, Martha Kay, Neil E. Cunningham, Julie M. Hanson, Curtis A. Marti, Gerald E. Weinberg, J. Brice Morrison, Vicki A. Link, Brian K. Call, Timothy G. Caporaso, Neil E. Cerhan, James R. TI Genome-wide association study identifies a novel susceptibility locus at 6p21.3 among familial CLL SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKIN-LYMPHOMA; FOLLICULAR LYMPHOMA; RISK; VARIANTS; GENES AB Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values <= 3.37 x 10(-8)), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 x 10(-9)). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies. (Blood. 2011;117(6):1911-1916) C1 [Slager, Susan L.; Rabe, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Leis, Jose F.; Kay, Neil E.; Cunningham, Julie M.; Hanson, Curtis A.; Call, Timothy G.; Cerhan, James R.] Mayo Clin, Coll Med, Rochester, MN 55905 USA. [Goldin, Lynn R.; Caporaso, Neil E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Strom, Sara S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Lanasa, Mark C.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA. [Spector, Logan G.; Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Rassenti, Laura Z.] Univ Calif San Diego, Med Ctr, Moores Canc Ctr, La Jolla, CA 92093 USA. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Sch Med, Salt Lake City, UT USA. [Marti, Gerald E.] US FDA, Bethesda, MD 20014 USA. [Weinberg, J. Brice] Durham Vet Adm Med Ctr, Durham, NC USA. [Morrison, Vicki A.] Minneapolis Vet Adm Med Ctr, Minneapolis, MN USA. [Link, Brian K.] Univ Iowa, Iowa City, IA USA. RP Slager, SL (reprint author), Mayo Clin, Coll Med, 200 1st St SW, Rochester, MN 55905 USA. EM slager@mayo.edu OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU National Institutes of Health (NIH) [CA118444, CA92153]; NIH, NCI; Veterans Affairs Research Service; Chronic Lymphocytic Leukemia Research Consortium; National Center for Research Resources; NIH Roadmap for Medical Research [1 UL1 RR024150]; NCI [CA15083, N01-PC-35 141]; University of Utah Huntsman Cancer Institute; Utah State Department of Health; University of Utah; Leukemia & Lymphoma Society; Bernstein Family Fund for Leukemia and Lymphoma Research FX This work was supported by National Institutes of Health (NIH) grants CA118444 and CA92153; the Intramural Research Program of the NIH, NCI; the Veterans Affairs Research Service, and the Chronic Lymphocytic Leukemia Research Consortium. Additional support was provided by the National Center for Research Resources, a component of NIH and the NIH Roadmap for Medical Research (1 UL1 RR024150) and by the NCI (CA15083). Data collection in Utah was made possible by the Utah Population Database and the Utah Registry. Partial support for all data in the Utah Population Database was provided by the University of Utah Huntsman Cancer Institute. The Utah Cancer Registry is funded by contract N01-PC-35 141 from the NCI Surveillance Epidemiology and End Results program with additional support from the Utah State Department of Health and the University of Utah. Sample collection at Duke University was supported by a Leukemia & Lymphoma Society Career Development Award (to M.C.L.) and by the Bernstein Family Fund for Leukemia and Lymphoma Research. NR 17 TC 61 Z9 64 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD FEB 10 PY 2011 VL 117 IS 6 BP 1911 EP 1916 DI 10.1182/blood-2010-09-308205 PG 6 WC Hematology SC Hematology GA 719HA UT WOS:000287192300026 PM 21131588 ER PT J AU Behrman, RE Benner, JS Brown, JS McClellan, M Woodcock, J Platt, R AF Behrman, Rachel E. Benner, Joshua S. Brown, Jeffrey S. McClellan, Mark Woodcock, Janet Platt, Richard TI Developing the Sentinel System - A National Resource for Evidence Development SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SAFETY C1 [Behrman, Rachel E.; Woodcock, Janet] US FDA, Silver Spring, MD USA. [Benner, Joshua S.; McClellan, Mark] Brookings Inst, Engelberg Ctr Hlth Care Reform, Washington, DC 20036 USA. [Brown, Jeffrey S.; Platt, Richard] Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA. [Brown, Jeffrey S.; Platt, Richard] Harvard Univ, Sch Med, Boston, MA USA. RP Behrman, RE (reprint author), US FDA, Silver Spring, MD USA. NR 5 TC 138 Z9 140 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 10 PY 2011 VL 364 IS 6 BP 498 EP 499 DI 10.1056/NEJMp1014427 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 718QH UT WOS:000287139900003 PM 21226658 ER PT J AU Yakes, BJ Deeds, J White, K DeGrasse, SL AF Yakes, Betsy Jean Deeds, Jonathan White, Kevin DeGrasse, Stacey L. TI Evaluation of Surface Plasmon Resonance Biosensors for Detection of Tetrodotoxin in Food Matrices and Comparison to Analytical Methods SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Tetrodotoxin; surface plasmon resonance; Immunoassay; food matrices ID SELF-ASSEMBLED MONOLAYERS; RECEPTOR-BINDING ASSAY; PARALYTIC SHELLFISH; TAKIFUGU-OBLONGUS; SPR SENSOR; TOXINS; MILK; IMMUNOSENSOR; SAXITOXIN; MARINE AB Tetrodotoxin (TTX) is a low molecular weight neurotoxin found in a number of animal species, including pufferfish. One emerging method for TTX detection employs surface plasmon resonance (SPR) immunosensors. SPR, an optical technique that allows for label-free, real-time, multiplexed analysis, can have detection limits that rival many of the conventional transduction methods. Preliminary SPR approaches for TTX were successful, yet suffered from low throughput and used noncommercial instrumentation. To advance this method for broader use, the immunoassay was transferred to a commercial instrument and optimized for improved detection. This manuscript outlines the assay development and results for complex matrices relevant to seafood safety (pufferfish) and food adulteration (milk, apple juice). In addition, results are compared to those obtained using receptor binding assay, ELISA, HPLC-FD, and LC/MS/MS detection techniques. Results highlight the advantages of SPR assays, including rapid screening capability with low reagent consumption and low- to subppb detection limits. C1 [Yakes, Betsy Jean; Deeds, Jonathan; White, Kevin; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. 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 RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 FU CFSAN; U.S. Department of Energy; U.S. Food and Drug Administration FX B.J.Y. was supported during the initial part of this project in part by an appointment with the Research Participation Program at CFSAN administered by the Oak Ridge Institute for Science and Education operated under an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 42 TC 16 Z9 16 U1 3 U2 47 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 FEB 9 PY 2011 VL 59 IS 3 BP 839 EP 846 DI 10.1021/jf103779k PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 712ZR UT WOS:000286705300009 PM 21192708 ER PT J AU Hellberg, RSR Naaum, AM Handy, SM Hanner, RH Deeds, JR Yancy, HF Morrissey, MT AF Hellberg, Rosalee S. Rasmussen Naaum, Amanda M. Handy, Sara M. Hanner, Robert H. Deeds, Jonathan R. Yancy, Haile F. Morrissey, Michael T. TI Interlaboratory Evaluation of a Real-Time Multiplex Polymerase Chain Reaction Method for Identification of Salmon and Trout Species in Commercial Products SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Real-time PCR; interlaboratory study; salmon; trout; species identification; multiplex PCR ID HADDOCK MELANOGRAMMUS-AEGLEFINUS; DNA BARCODES; FISH; PCR; PROBES; QUANTIFICATION; SEAFOOD AB This interlaboratory study evaluated a real-time multiplex polymerase chain reaction (PCR) method for identification of salmon and trout species in a range of commercial products in North America. Eighty salmon and trout products were tested with this method by three independent laboratories. Samples were collected in the United States and Canada, and only the collecting institution was aware of the species declaration. Following analysis with real-time PCR, all three laboratories were able to identify species in 79 of the 80 products, with 100% agreement on species assignment. A low level of fraud was detected, with only four products (5%) found to be substituted or mixtures of two species. The results for two of the fraudulent products were confirmed with alternate methods, but the other two products were heavily processed and could not be verified with methods other than real-time PCR. Overall, the results of this study show the usefulness and versatility of this real-time PCR method for the identification of commercial salmon and trout species. C1 [Hellberg, Rosalee S. Rasmussen; Morrissey, Michael T.] Oregon State Univ, Food Innovat Ctr, Portland, OR 97211 USA. [Naaum, Amanda M.; Hanner, Robert H.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada. [Handy, Sara M.; Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Yancy, Haile F.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Hellberg, RSR (reprint author), Oregon State Univ, Food Innovat Ctr, 1207 NW Naito Pkwy, Portland, OR 97211 USA. EM rosalee.hellberg@gmail.com RI Handy, Sara/C-6195-2008 FU Oregon Innovation Council; Advanced Foods and Materials Network (AFMNet) FX This project was funded by the Oregon Innovation Council. We also acknowledge support for A.M.N. and R.H.H. from the Advanced Foods and Materials Network (AFMNet). NR 35 TC 7 Z9 7 U1 3 U2 14 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 FEB 9 PY 2011 VL 59 IS 3 BP 876 EP 884 DI 10.1021/jf103241y PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 712ZR UT WOS:000286705300014 ER PT J AU Gregori, L AF Gregori, Luisa TI A prototype assay to detect vCJD-infected blood SO LANCET LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; INFECTIVITY C1 US FDA, Rockville, MD 20852 USA. RP Gregori, L (reprint author), US FDA, Rockville, MD 20852 USA. EM luisa.gregori@fda.hhs.gov NR 11 TC 8 Z9 8 U1 0 U2 1 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 FEB 5 PY 2011 VL 377 IS 9764 BP 444 EP 446 DI 10.1016/S0140-6736(11)60057-3 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 721TX UT WOS:000287381800006 PM 21295340 ER PT J AU Chakrabarty, S Snyder, JT Shen, JJ Azmi, H Hu, PQ Chen, QA Ragheb, JA AF Chakrabarty, Sagarika Snyder, James T. Shen, Jijia Azmi, Hooman Hu, Paul Q. Chen, Qian Ragheb, Jack A. TI Human CD14(hi) monocytes and myeloid dendritic cells provide a cell contact-dependent costimulatory signal for early CD40 ligand expression SO BLOOD LA English DT Article ID ACTIVATED T-CELLS; GERMINAL CENTER FORMATION; IL-2 MESSENGER-RNA; RESTING B-CELLS; CD40-CD40 LIGAND; ANTIGEN PRESENTATION; HUMORAL IMMUNITY; CD154 EXPRESSION; GAMMA PRODUCTION; IGM SYNDROME AB CD40L on CD4(+) T cells plays a vital role in the activation of antigen-presenting cells, thus catalyzing a positive feedback loop for T-cell activation. Despite the pivotal juxtaposition of CD40L between antigen-presenting cells and T-cell activation, only a T-cell receptor stimulus is thought to be required for early CD40L surface expression. We show, for the first time, that CD40L expression on peripheral blood CD4(+) T cells is highly dependent on a cell-cell interaction with CD14(hi)CD16(-) monocytes. Interactions with ICAM-1, LFA-3, and to a lesser extent CD80/CD86 contribute to this enhancement of CD40L expression but are not themselves sufficient. The contact-mediated increase in CD40L expression is dependent on new mRNA and protein synthesis. Circulating myeloid dendritic cells also possess this costimulatory activity. By contrast, CD14(lo)CD16(+) monocytes, plasmacytoid dendritic cells, B-cell lymphoma lines, and resting, activated, and Epstein-Barr virus-immortalized primary B cells all lack the capacity to up-regulate early CD40L. The latter indicates that a human B cell cannot activate its cognate T cell to deliver CD40L-mediated help. This finding has functional implications for the role of biphasic CD40L expression, suggesting that the early phase is associated with antigen-presenting cell activation, whereas the late phase is related to B-cell activation. (Blood. 2011; 117(5): 1585-1594) C1 [Chakrabarty, Sagarika; Snyder, James T.; Shen, Jijia; Azmi, Hooman; Hu, Paul Q.; Chen, Qian; Ragheb, Jack A.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Ragheb, Jack A.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biol Prod,Ctr Drug Evaluat & Res,Dept Hlth &, Bethesda, MD 20014 USA. RP Ragheb, JA (reprint author), 29 Lincoln Dr,Bldg 29B,Rm 4G13,HFD 122, Bethesda, MD 20892 USA. EM jr50b@nih.gov FU Department of Health and Human Services FX This work was supported by the Department of Health and Human Services (intramural funding). NR 68 TC 3 Z9 3 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 FEB 3 PY 2011 VL 117 IS 5 BP 1585 EP 1594 DI 10.1182/blood-2008-01-130252 PG 10 WC Hematology SC Hematology GA 715WV UT WOS:000286925500025 PM 20634374 ER PT J AU Gamalo, MA Tiwari, RC AF Gamalo, Mark A. Tiwari, Ram C. TI Testing Noninferiority Through Generalized p-values SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Generalized test function; Noninferiority; Sample size; Type I error ID NON-INFERIORITY TRIALS; BEHRENS-FISHER PROBLEM; ACTIVE-CONTROL TRIALS; VARIANCE-COMPONENTS; CONFIDENCE-INTERVALS; STATISTICAL-METHODS; PLACEBO; ISSUES; CHOICE; DESIGN AB Testing for noninferiority of a new experimental drug compared to a standard reference drug has generally been carried out through statistical tests assuming equal variances. In this article, we present a generalized p-value approach for assessing noninferiority that gives exact tail probabilities when variances are not equal between treatments. Two generalized test functions are constructed corresponding to the fixed-margin and synthesis approaches of retaining a fraction of the reference treatment's effect relative to placebo in historical trials. Monte Carlo simulations are used to compute the p-value. Performance of these test functions are evaluated and results indicate that the generalized test function for the fixed-margin retention performs well in terms of maintaining the Type I error probabilities. Its power also increases and approaches 1 as both the sample size and the parameter denoting the fraction of the effect of the reference drug with respect to placebo increase. Furthermore, confidence intervals (CI's) can be easily constructed using duality between CI's and accepting or rejecting noninferiority. C1 [Gamalo, Mark A.; Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Gamalo, MA (reprint author), US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM mark.gamalo@fda.hhs.gov NR 31 TC 1 Z9 1 U1 1 U2 4 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 FEB PY 2011 VL 3 IS 1 BP 87 EP 96 DI 10.1198/sbr.2010.09028 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791HS UT WOS:000292656400008 ER PT J AU Naum, M Brown, EW Mason-Gamer, RJ AF Naum, Marianna Brown, Eric W. Mason-Gamer, Roberta J. TI Is a robust phylogeny of the enterobacterial plant pathogens attainable? SO CLADISTICS LA English DT Letter ID HORIZONTAL GENE-TRANSFER; 16S RIBOSOMAL-RNA; MOLECULAR PHYLOGENY; ESCHERICHIA-COLI; ENTERIC BACTERIA; COMB-NOV; ERWINIA; EVOLUTION; SEQUENCES; SALMONELLA AB Sequences from gapA, gyrA and ompA were used to evaluate the relationships of the enterobacterial plant pathogens, and assess whether a robust phylogeny can be ascertained using this group of housekeeping genes. Up to 48 taxa were included in a combined phylogenetic analysis to explore the evolutionary distribution of plant pathogenic species across the family Enterobacteriaceae. Phylogenies were reconstructed from gapA, gyrA and ompA gene sequences using maximum parsimony and maximum likelihood algorithms, and phylogenetic congruence was evaluated by the incongruence length difference test and the partition addition bootstrap alteration approach. The resulting gene trees were found to be incongruent, with gapA supporting a monophyletic origin for the plant pathogenic species. In contrast, gyrA and ompA supported multiple polyphyletic origins of Erwinia, Brenneria, Pectobacterium and Pantoea in conjunction with a previously published 16S rDNA phylogeny. However, none of the trees (not even the published 16S rDNA gene tree) supports the current taxonomic classification of these genera into four clades, with Pantoea forming the only monophyletic group in the gapA, gyrA and 16S rDNA trees. Finally, the gapA, gyrA and previously published 16S rDNA phylogenies differ in the taxonomic placement of several bacterial strains which are separated in the three trees. The observed incongruence among the four gene histories is likely to be the result of horizontal transfer events, confounding the search for a robust set of housekeeping genes with a shared evolutionary history that could be used to confidently characterize the relationships of the plant pathogenic enterobacteria. (C) The Willi Hennig Society 2010. C1 [Naum, Marianna; Mason-Gamer, Roberta J.] Univ Illinois, Dept Biol Sci, Chicago, IL 60611 USA. [Naum, Marianna; Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Naum, M (reprint author), Univ Illinois, Dept Biol Sci, Chicago, IL 60611 USA. EM marianna.naum@fda.hhs.gov NR 55 TC 6 Z9 6 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0748-3007 J9 CLADISTICS JI Cladistics PD FEB PY 2011 VL 27 IS 1 BP 80 EP 93 DI 10.1111/j.1096-0031.2010.00313.x PG 14 WC Evolutionary Biology SC Evolutionary Biology GA 702DQ UT WOS:000285875200010 ER PT J AU Philip, R Carrington, L Chan, M AF Philip, Reena Carrington, Lea Chan, Maria TI US FDA perspective on challenges in co-developing in vitro companion diagnostics and targeted cancer therapeutics SO BIOANALYSIS LA English DT Article AB Recent advances in cancer therapy are based on agents that specifically target the products of the genes mutated in cancer cells. Development of companion diagnostic tests for these agents can simplify the drug-discovery process, make clinical trials more efficient and informative, and be used to individualize the therapy of cancer patients. Companion diagnostic development has Many challenges. Examples include the reluctance of drug companies to restrict the uses of their drugs through biomarker tests, difficulties of developing companion diagnostics from discovery to clinical validation and the regulatory challenges in developing effective mechanisms to synchronize reviews of therapeutics with diagnostic devices used to personalize treatment. This article addresses the various challenges in developing companion diagnostics along with the US FDA's approach to regulation of companion diagnostic devices. C1 [Philip, Reena; Carrington, Lea; Chan, Maria] US FDA, Div Immunol & Hematol Devices, Off In Vitro Diagnost Device Evaluat, Silver Spring, MD 20993 USA. [Philip, Reena; Carrington, Lea; Chan, Maria] US FDA, Safety Ctr Device & Radiol Hlth, Silver Spring, MD 20993 USA. RP Philip, R (reprint author), US FDA, Div Immunol & Hematol Devices, Off In Vitro Diagnost Device Evaluat, 10903 New Hampshire Ave,WO66,Room 5528, Silver Spring, MD 20993 USA. EM reena.philip@fda.hhs.gov NR 16 TC 19 Z9 19 U1 1 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 FEB PY 2011 VL 3 IS 4 BP 383 EP 389 DI 10.4155/BIO.11.1 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 745RF UT WOS:000289182600009 PM 21338257 ER PT J AU Weaver, EV McDowell, E Fisher, B Latimer, KS Suttie, AW AF Weaver, E., V McDowell, E. Fisher, B. Latimer, K. S. Suttie, A. W. TI Comparison of Toxicology Parameters in Pregnant and Nonpregnant Rats SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE reproductive toxicology; clinical and anatomic pathology in pregnant rats; changes in rodent pregnancy C1 [Weaver, E., V; McDowell, E.; Latimer, K. S.; Suttie, A. W.] Covance Labs, Vienna, VA USA. [Fisher, B.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 100 EP 100 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200032 ER PT J AU Cotton, LM Burgess, S Crenshaw, S Stitcher, B Fisher, BR AF Cotton, L. M. Burgess, S. Crenshaw, S. Stitcher, B. Fisher, B. R. TI THE Effects of Ifosfamide and Cypermethrin on the Male Reproductive Systems of New Zealand White (NZW) and Dutch Belted (DB) Rabbits SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE male reproductive system; sperm analysis; New Zealand White and Dutch belted rabbits C1 [Cotton, L. M.; Burgess, S.; Stitcher, B.] Covance Labs, Vienna, VA USA. [Crenshaw, S.] Tauri Grp, Alexandria, VA USA. [Fisher, B. R.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, White Oak, 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 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 101 EP 101 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200035 ER PT J AU McKeon, M Fisher, B Latimer, K Suttie, A Makle, B Williams, C AF McKeon, M. Fisher, B. Latimer, K. Suttie, A. Makle, B. Williams, C. TI The Effects of Continuous Infusion Rates on Pre- and Postnatal Development, Including Maternal Function in Rats SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE developmental and reproductive toxicology; continuous infusion; time-mated rats C1 [McKeon, M.; Fisher, B.; Latimer, K.; Suttie, A.; Makle, B.; Williams, C.] Covance Labs, Vienna, VA USA. [McKeon, M.; Fisher, B.; Latimer, K.; Suttie, A.; Makle, B.; Williams, C.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 111 EP 111 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200060 ER PT J AU Ghantous, H AF Ghantous, Hanan TI Symp Ic Introduction to Division of Anti-Viral Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE FDA; regulatory; pharmacology/toxicology C1 [Ghantous, Hanan] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 115 EP 115 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200073 ER PT J AU O'Shaughnessy, J AF O'Shaughnessy, Jacqueline TI Symp Ia Division of Scientific Investigations (DSI): Inspections of Nonclinical Testing Facilities SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [O'Shaughnessy, Jacqueline] US FDA, CDER, Off Compliance, Div Sci Investigat, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 115 EP 115 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200071 ER PT J AU Wasserman, A AF Wasserman, Adam TI Symp Ib Introduction to Division of Anesthetic and Analgesia Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Wasserman, Adam] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 115 EP 115 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200072 ER PT J AU Jensen, DN AF Jensen, Donald Nick TI Symp Id Introduction to Division of Cardiovascular and Renal Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE FDA; regulatory; pharmacology/toxicology C1 [Jensen, Donald Nick] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 116 EP 116 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200074 ER PT J AU Wasserman, A AF Wasserman, Adam TI Symp Ie Overview of Pharmacology/Toxicology at the Office of New Drugs SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Wasserman, Adam] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 116 EP 116 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200075 ER PT J AU Powell, AM AF Powell, Andrea M. TI Symp IIIa An Introduction to the "Animal Rule"-Approval of New Drug and Biological Products When Human Efficacy Studies are Not Ethical or Feasible SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE animal rule; medical countermeasure; animal efficacy studies C1 [Powell, Andrea M.] US FDA, Off Counter Terrorism & Emergency Coordinat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 117 EP 117 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200079 ER PT J AU Beren, JJ AF Beren, Joel J. TI Symp IVd A Clinical Veterinary Perspective on How to Prepare for Your NHP Study and Get a Good Nights Sleep as a Study Director SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Beren, Joel J.] FDA CBER DVS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2011 VL 30 IS 1 BP 120 EP 120 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200087 ER PT J AU DeFelice, A AF DeFelice, Albert TI Symp VId Use of Ultrasound in Preclinical Hemodynamic and Safety Assessment of Investigational Drugs SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [DeFelice, Albert] US FDA, Off Drug Evaluat 1, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 122 EP 122 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200097 ER PT J AU Harrouk, WA AF Harrouk, Wafa A. TI Symp Xd The Use of Minipigs in FDA-Regulated Products: Experiences From the OND Division of Dermatology and Dental Products SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Harrouk, Wafa A.] US FDA, 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 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 127 EP 127 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200114 ER PT J AU Carrington, CD Bolger, PM AF Carrington, C. D. Bolger, P. M. TI Symp XIVb Elemental Contaminants and Dietary Exposure SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Carrington, C. D.; Bolger, P. M.] US FDA, Chem Hazards Assessment Staff, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 132 EP 132 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200130 ER PT J AU Mamata, D AF Mamata, De TI Symp XIVe Toxicity of Heavy and Trace Metals: Regulatory Perspectives SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Mamata, De] US FDA, 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 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 133 EP 133 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200133 ER PT J AU Bourcier, T AF Bourcier, Todd TI Symp XVIb Regulatory Preclinical Development of Dipeptidyl Peptidase 4 Inhibitors SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE type 2 diabetes; preclinical toxicology; dipeptidyl peptidase-4 inhibitors C1 [Bourcier, Todd] US FDA, CDER, Div Metab & Endocrine Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 134 EP 134 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200137 ER PT J AU El-Hage, J Bourcier, T Carlson, D Hummer, B Timerstein, M AF El-Hage, Jeri Bourcier, Todd Carlson, David Hummer, Brian Timerstein, Mark TI Symp XVIa Therapies for Type 2 Diabetes: Nonclinical Safety Assessments and Risk Evaluation SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [El-Hage, Jeri] Aclairo Pharmaceut Dev Grp, Vienna, VA USA. [Bourcier, Todd; Carlson, David; Hummer, Brian] US FDA, DMEP, Rockville, MD 20857 USA. [Timerstein, Mark] Bristol Myers Squibb Co, New Brunswick, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 134 EP 134 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200136 ER PT J AU Hummer, BT AF Hummer, B. Timothy TI Symp XVIc GLP-1 Receptor Agonists: Extrapolating Nonclinical Data to Human Risk SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE type 2 diabetes; glucagon like peptide-1 (GLP-1); thyroid c-cells C1 [Hummer, B. Timothy] US FDA, CDER, Div Metab & Endocrine Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 134 EP 135 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200138 ER PT J AU Carlson, DB AF Carlson, David B. TI Symp XVId Preclinical Toxicology Of Glucokinase Activators - A Promising New Therapeutic Class for Diabetes? SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol DE glucokinase activators; type 2 diabetes; animal models C1 [Carlson, David B.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 135 EP 135 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200139 ER PT J AU Ghantous, H AF Ghantous, Hanan TI Symp XVIIg A Behind the Scenes Look at FDA Guidances SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Ghantous, Hanan] US FDA, CDER, Div Antiviral Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD FEB PY 2011 VL 30 IS 1 BP 136 EP 136 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200145 ER PT J AU Reid, L AF Reid, Lynnda TI Symp XVIIf FDA Update-Pregnancy and Lactation Labeling Rule SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Reid, Lynnda] US FDA, CDER, Div Reprod & Urol Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 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 FEB PY 2011 VL 30 IS 1 BP 136 EP 136 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200144 ER PT J AU Topper, M AF Topper, Molly (Shea) TI Symp XVIIc Perspective of an FDA Pharmacology/Toxicology Reviewer on Change SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the American-College-of-Toxicology CY NOV 07-10, 2010 CL Baltimore, MD SP Amer Coll Toxicol C1 [Topper, Molly (Shea)] US FDA, CDER, Div Pulm Allergy & Rheumatol Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB PY 2011 VL 30 IS 1 BP 136 EP 136 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200142 ER PT J AU Chen, KJ Felten, R Chen, L Ogden, N AF Chen, Kejing Felten, Richard Chen, Long Ogden, Neil TI REGULATORY PERSPECTIVE OF OPTICAL IMAGING DEVICES: TECHNOLOGY, INDICATIONS, AND FUTURE CHALLENGES SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract C1 [Chen, Kejing; Felten, Richard; Chen, Long; Ogden, Neil] US FDA, Off Device Evaluat, 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD FEB PY 2011 VL 43 SU 23 MA 20 BP 913 EP 913 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 735EK UT WOS:000288396000019 ER PT J AU Jiang, WL Lionberger, R Yu, LX AF Jiang, Wenlei Lionberger, Robert Yu, Lawrence X. TI In vitro and in vivo characterizations of PEGylated liposomal doxorubicin SO BIOANALYSIS LA English DT Review ID ACCELERATED BLOOD CLEARANCE; DRUG-RELEASE; THERAPEUTIC ACTIVITY; ANTITUMOR-ACTIVITY; INTERSTITIAL PH; CHAIN-LENGTH; SOLID TUMORS; PHARMACOKINETICS; PLASMA; FORMULATIONS AB One challenge in developing a nanoparticle drug-delivery system is understanding the critical physicochemical properties that may impact its in vivo performance and establishing analytical techniques that can adequately characterize in vitro and in vivo properties. Doxil (R) /Caelyx (R), a PEGylated liposornal doxorubincin (PLD), is one of the leading approved nanoparticle product used in cancer therapy. In this review, we use PLD as an example to illustrate identification of key in vitro and in vivo characteristics. The following characteristics, including liposome composition, state of encapsulated drug, internal environment of liposome, liposome size distribution, lamellarity, grafted polyethylene glycol at the liposome surface, electrical surface potential or charge, and in vitro leakage, are considered critical to demonstrate the supramolecular structure of PLD and ensure consistent drug delivery to cancer tissues. Corresponding analytical techniques are discussed to determine these liposome characteristics. Furthermore, in vivo stability of the PLD can be determined by plasma pharmacokinetics of both free and liposome-encapsulated drug. A better understanding of the critical in vitro and in vivo liposome characteristics together with improvements in analytical technology will enable generic liposome product development and ensure liposome product quality. C1 [Jiang, Wenlei; Lionberger, Robert; Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Lionberger, R (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM robert.lionberger@fda.hhs.gov NR 69 TC 38 Z9 40 U1 3 U2 64 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD FEB PY 2011 VL 3 IS 3 BP 333 EP 344 DI 10.4155/BIO.10.204 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 730QT UT WOS:000288049900016 PM 21320053 ER PT J AU Agarwal, S Zhang, L Huang, S AF Agarwal, S. Zhang, L. Huang, S. TI RELEVANCE AND VALUE OF IN VITRO P-GP INHIBITION DATA FOR NEW MOLECULAR ENTITIES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Agarwal, S.; Zhang, L.; Huang, S.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. NR 0 TC 1 Z9 1 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 FEB PY 2011 VL 89 SU 1 BP S40 EP S40 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100127 ER PT J AU Bai, JP Lesko, LJ Abernethy, DR AF Bai, J. P. Lesko, L. J. Abernethy, D. R. TI USE OF PHARMACOLOGY, BIOLOGY, AND DISEASE/GENE NETWORKS TO ADVANCE MECHANISM FOR CLINICALLY OBSERVED ADVERSE EVENTS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Bai, J. P.; Lesko, L. J.; Abernethy, D. R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 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 FEB PY 2011 VL 89 SU 1 BP S43 EP S43 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100136 ER PT J AU Chung, S Hand, A Vaidyanathan, J Choe, S Sahajwalla, C AF Chung, S. Hand, A. Vaidyanathan, J. Choe, S. Sahajwalla, C. TI RENAL FUNCTION CHANGE WITH AGING: CROSS-SECTIONAL VERSUS LONGITUDINAL ANALYSIS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Chung, S.; Hand, A.; Vaidyanathan, J.; Choe, S.; Sahajwalla, C.] FDA CDER OTS OCP, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 2 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 FEB PY 2011 VL 89 SU 1 BP S34 EP S34 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100108 ER PT J AU Fan, Y Agarwal, S Zhang, L Lesko, LJ Huang, S AF Fan, Y. Agarwal, S. Zhang, L. Lesko, L. J. Huang, S. TI REVIEW OF TRANSPORTER-RELATED POST-MARKETING REQUIREMENT (PMR)/POST-MARKETING COMMITMENT (PMC) STUDY REPORTS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Fan, Y.; Agarwal, S.; Zhang, L.; Lesko, L. J.; Huang, S.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S37 EP S37 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100117 ER PT J AU Gnjidic, D Hilmer, SN Le Couteur, DG Abernethy, DR AF Gnjidic, D. Hilmer, S. N. Le Couteur, D. G. Abernethy, D. R. TI DRUG BURDEN INDEX AND BEERS CRITERIA: IMPACT ON FUNCTION IN OLDER ADULTS LIVING IN LOW-LEVEL CARE FACILITIES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Gnjidic, D.; Hilmer, S. N.; Le Couteur, D. G.] Univ Sydney, Sydney, NSW 2006, Australia. [Gnjidic, D.; Hilmer, S. N.] Royal N Shore Hosp, Sydney, NSW, Australia. [Le Couteur, D. G.] Concord Hosp, Sydney, NSW, Australia. [Abernethy, D. R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S14 EP S14 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100043 ER PT J AU Kawai, VK Grijalva, C Arbogast, P Curtis, JR Solomon, DH Delzell, E Ouellet-Hellstrom, R Herrinton, L Mitchell, E Chen, L Liu, L Stein, CM Griffin, MR AF Kawai, V. K. Grijalva, C. Arbogast, P. Curtis, J. R. Solomon, D. H. Delzell, E. Ouellet-Hellstrom, R. Herrinton, L. Mitchell, E. Chen, L. Liu, L. Stein, C. M. Griffin, M. R. TI NARCOTIC USE DOES NOT DECREASE AFTER INITIATION OF DMARD THERAPY IN PATIENTS WITH RHEUMATOID ARTHRITIS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Kawai, V. K.; Grijalva, C.; Arbogast, P.; Mitchell, E.; Stein, C. M.; Griffin, M. R.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Curtis, J. R.; Delzell, E.; Chen, L.] Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. [Solomon, D. H.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Ouellet-Hellstrom, R.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Herrinton, L.; Liu, L.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S13 EP S13 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100040 ER PT J AU Morrissey, KM Wen, C Huang, S Zhang, L Giacomini, KM AF Morrissey, K. M. Wen, C. Huang, S. Zhang, L. Giacomini, K. M. TI DEVELOPMENT OF A PUBLIC DRUG TRANSPORTER DATABASE SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Morrissey, K. M.; Wen, C.; Giacomini, K. M.] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Huang, S.; Zhang, L.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S40 EP S40 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100126 ER PT J AU Naraharisetti, SB Nallani, SC Pacanowski, MA Doddapaneni, S AF Naraharisetti, S. B. Nallani, S. C. Pacanowski, M. A. Doddapaneni, S. TI ARE SINGLE NUCLEOTIDE POLYMORPHISMS OF CYP2C9 A RISK FACTOR FOR NSAID-ASSOCIATED ADVERSE EVENTS? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Naraharisetti, S. B.; Nallani, S. C.; Doddapaneni, S.] US FDA, Div Clin Pharmacol 2, Off Clin Pharmacol, Silver Spring, MD USA. [Pacanowski, M. A.] US FDA, Genom Grp, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S74 EP S74 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100237 ER PT J AU Park, EJ Ko, CW Crentsil, V Zhang, J Zhang, L Huang, SM Xiao, S Mehrotra, N Alabi, E Stockbridge, N Xu, NN AF Park, E. J. Ko, C. W. Crentsil, V. Zhang, J. Zhang, L. Huang, S. M. Xiao, S. Mehrotra, N. Alabi, E. Stockbridge, N. Xu, N. N. TI A COMPARISION OF CG AND MDRD EQUATIONS FOR DOSAGE ADJUSTMENT IN RENAL IMPAIRMENT SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Park, E. J.; Ko, C. W.; Crentsil, V.; Zhang, J.; Zhang, L.; Huang, S. M.; Xiao, S.; Mehrotra, N.; Alabi, E.; Stockbridge, N.; Xu, N. N.] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S40 EP S40 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100128 ER PT J AU Park, EJ Pai, MP Zhang, J Dong, T Ko, CW Crentsil, V Stockbridge, NL Xu, NN AF Park, E. J. Pai, M. P. Zhang, J. Dong, T. Ko, C. W. Crentsil, V. Stockbridge, N. L. Xu, N. N. TI ESTIMATION OF CREATININE CLEARANCE (ECLCR) ACROSS ALL WEIGHT STRATA. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Park, E. J.; Zhang, J.; Dong, T.; Ko, C. W.; Crentsil, V.; Stockbridge, N. L.; Xu, N. N.] FDA CDER, Silver Spring, MD USA. [Pai, M. P.] Albany Coll Pharm, Albany, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S32 EP S33 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100103 ER PT J AU Tompkins, LM Zhao, P Zhang, L Huang, S AF Tompkins, L. M. Zhao, P. Zhang, L. Huang, S. TI DIFFERENTIAL EFFECTS OF HEPATIC INSUFFICIENCY ON SENSITIVE CYP SUBSTRATES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Tompkins, L. M.; Zhao, P.; Zhang, L.; Huang, S.] US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S40 EP S41 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100129 ER PT J AU Zhang, L Hu, NL Agarwal, S Huang, S AF Zhang, L. Hu, N. L. Agarwal, S. Huang, S. TI INVESTIGATION OF POSSIBLE FORMULATION EFFECT ON DIGOXIN ABSORPTION. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 112th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-05, 2011 CL Dallas, TX SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhang, L.; Agarwal, S.; Huang, S.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. [Hu, N. L.] Purdue Univ, Coll Pharm, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2011 VL 89 SU 1 BP S39 EP S39 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712DE UT WOS:000286644100125 ER PT J AU Zhang, X Paule, MG Newport, GD Sadovova, N Berridge, MS Apana, SM Kabalka, G Miao, W Slikker, W Wang, C AF Zhang, X. Paule, M. G. Newport, G. D. Sadovova, N. Berridge, M. S. Apana, S. M. Kabalka, G. Miao, W. Slikker, W., Jr. Wang, Cheng TI MicroPET imaging of ketamine-induced neuronal apoptosis with radiolabeled DFNSH SO JOURNAL OF NEURAL TRANSMISSION LA English DT Article DE Ketamine; Apoptosis; MicroPET; DFNSH ID DEVELOPING RAT-BRAIN; EXPERIMENTAL CEREBRAL STROKE; DEATH IN-VIVO; CELL-DEATH; EARLY EXPOSURE; ANNEXIN-V; PET; NEURODEGENERATION; NEUROTOXICITY; ANESTHETICS AB Recent reports indicate that 6-12 h of ketamine anesthesia can trigger neuronal apoptosis in postnatal day (PND) 7 rats. In vitro, ex vivo, and confocal fluorescent imaging studies suggest that dansyl compounds can accumulate within the cytoplasm of the apoptotic cell. High-resolution positron emission tomography (microPET) imaging has been proposed as a minimally invasive method for detecting apoptosis in the rat brain. Compared with [(18)F]-labeled annexin V, which binds to externalized phosphatidylserine (PS) on the outer membrane of apoptotic cells, intracellular uptake of the dansylhydrazone of p-fluorobenzaldehyde (DFNSH) may lead to improved target-to-background contrast ratios. In this study, the effect of ketamine on the uptake and retention of [(18)F]-DFNSH in the rat brain was investigated using microPET imaging. On PND 7, rat pups in the experimental group were exposed, at 2-h intervals, to six subcutaneous injections of ketamine (20 mg/kg) and control rat pups received six injections of saline. On PND 35, [(18)F]-DFNSH (37 MBq) was injected into the tail vein of rats and microPET images were obtained over 2 h following the injection. Radiolabeled tracer accumulation in the region of interest (ROI) in the frontal cortex was converted into standard uptake values (SUVs). The radiotracer was quickly distributed into the brains of both ketamine- and saline-treated rats. Compared with the control group, the uptake of [(18)F]-DFNSH was significantly increased in the ROI, frontal cortex area of ketamine-treated rats. In addition, the wash-out duration of the tracer was prolonged in the ketamine-treated animals. This study demonstrates that microPET imaging is capable of distinguishing differences in retention of [(18)F]-DFNSH in ROI and suggests that this compound may serve as a minimally invasive biomarker of neuronal apoptosis in rodents. C1 [Zhang, X.; Paule, M. G.; Newport, G. D.; Slikker, W., Jr.; Wang, Cheng] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Sadovova, N.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Berridge, M. S.; Apana, S. M.] 3D Imaging LLC, Little Rock, AR 72113 USA. [Kabalka, G.; Miao, W.] Univ Tennessee, Knoxville, TN 37920 USA. RP Wang, C (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cheng.wang@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/US Food and Drug Administration (FDA) FX This document has been reviewed in accordance with United States Food and Drug Administration (FDA) policy and approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The views expressed in this report are those of the authors and do not necessarily reflect the views of the FDA. This work was supported by the National Center for Toxicological Research (NCTR)/US Food and Drug Administration (FDA). The kind provision of a chromatographic standard of DFNSH by Dr. Kabalka is gratefully acknowledged. NR 45 TC 8 Z9 8 U1 1 U2 9 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0300-9564 J9 J NEURAL TRANSM JI J. Neural Transm. PD FEB PY 2011 VL 118 IS 2 BP 203 EP 211 DI 10.1007/s00702-010-0499-z PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 732JE UT WOS:000288180000007 PM 20963452 ER PT J AU Moro, PL Broder, K Zheteyeva, Y Walton, K Rohan, P Sutherland, A Guh, A Haber, P DeStefano, F Vellozzi, C AF Moro, Pedro L. Broder, Karen Zheteyeva, Yenlik Walton, Kimp Rohan, Patricia Sutherland, Andrea Guh, Alice Haber, Penina DeStefano, Frank Vellozzi, Claudia TI Adverse events in pregnant women following administration of trivalent inactivated influenza vaccine and live attenuated influenza vaccine in the Vaccine Adverse Event Reporting System, 1990-2009 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE pregnancy; seasonal influenza vaccine; surveillance; vaccine safety ID BELLS-PALSY; PANDEMIC INFLUENZA; SAFETY; IMMUNIZATION; GUIDELINES; HEALTH; IMPACT; RATES AB OBJECTIVE: The objective of the study was to characterize reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received seasonal influenza vaccines to assess for potential vaccine safety concerns. STUDY DESIGN: We searched VAERS for reports of adverse events (AEs) in pregnant women who received trivalent inactivated influenza vaccine (TIV) from July 1, 1990 through June 30, 2009, or live attenuated influenza vaccine (LAIV) from July 1, 2003, through June 30, 2009. RESULTS: A total of 148 reports after TIV and 27 reports after LAIV were identified. Twenty TIV (13.5%) and 1 LAIV (4%) reports were classified as serious. No specific AEs were reported in 30 TIV (20.3%) and 16 LAIV (59%) reports. The most common pregnancy-specific AE was spontaneous abortion: 17 after TIV (11.5%) and 3 after LAIV (11%). The reporting rate of spontaneous abortion was 1.9 per million pregnant women vaccinated. CONCLUSION: No unusual patterns of pregnancy complications or fetal outcomes were observed in the VAERS reports of pregnant women after the administration of TIV or LAIV. C1 [Moro, Pedro L.; Broder, Karen; Zheteyeva, Yenlik; Walton, Kimp; Guh, Alice; Haber, Penina; 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. [Rohan, Patricia; Sutherland, Andrea] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Silver Spring, MD 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. NR 30 TC 29 Z9 30 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 FEB PY 2011 VL 204 IS 2 AR 146.e1 DI 10.1016/j.ajog.2010.08.050 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 715HV UT WOS:000286874900022 PM 20965490 ER PT J AU Castelan-Vega, J Corvette, L Sirota, L Arciniega, J AF Castelan-Vega, Juan Corvette, Laura Sirota, Lev Arciniega, Juan TI Reduction of Immunogenicity of Anthrax Vaccines Subjected to Thermal Stress, as Measured by a Toxin Neutralization Assay SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROTECTIVE ANTIGEN; LETHAL TOXIN; BACILLUS-ANTHRACIS; INACTIVATION; VALIDATION AB We report that a toxin neutralization assay (TNA) can detect a decrease in the immunogenicity of anthrax vaccines as a consequence of brief exposure to elevated temperature. This attribute of TNA may help in adopting immunogenicity as a replacement of the current potency test, which involves protection from lethal challenge. C1 [Castelan-Vega, Juan; Corvette, Laura; Sirota, Lev; Arciniega, Juan] Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Arciniega, J (reprint author), Ctr Biol Evaluat & Res, Mail Code HFM-443,1401 Rockville Pike, Rockville, MD 20852 USA. EM Juan.Arciniega@fda.hhs.gov FU Biomedical Advanced Research and Development Authority; U. S. Department of Energy; U. S. Food and Drug Administration FX This project was supported by the Biomedical Advanced Research and Development Authority and by J.C.-V.'s appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. J.C.-V. is also grateful for the support from COTEPABE and the Instituto Politecnico Nacional (Mexico). L. S. was supported in part by a CBER director's Critical Path grant. NR 10 TC 9 Z9 9 U1 0 U2 3 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 FEB PY 2011 VL 18 IS 2 BP 349 EP 351 DI 10.1128/CVI.00267-10 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 712GJ UT WOS:000286653900023 PM 21147935 ER PT J AU Wang, SJ Hung, HMJ O'Neill, R AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert TI Adaptive design clinical trials and trial logistics models in CNS drug development SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Review DE Learn-and-Confirm; Learn-versus-Confirm; Sample size re-estimation; Trial logistics model; Two-stage adaptive selection ID MODERN PROTOCOL DESIGN; RECEPTOR ANTAGONIST; SYMPTOM REDUCTION; SUICIDE RISK; SAMPLE-SIZE; MIGRAINE; PLACEBO; ATTRITION; INTERIM AB In central nervous system therapeutic areas, there are general concerns with establishing efficacy thought to be sources of high attrition rate in drug development. For instance, efficacy endpoints are often subjective and highly variable. There is a lack of robust or operational biomarkers to substitute for soft endpoints. In addition, animal models are generally poor, unreliable or unpredictive. To increase the probability of success in central nervous system drug development program, adaptive design has been considered as an alternative designs that provides flexibility to the conventional fixed designs and has been viewed to have the potential to improve the efficiency in drug development processes. In addition, successful implementation of an adaptive design trial relies on establishment of a trustworthy logistics model that ensures integrity of the trial conduct. In accordance with the spirit of the U.S. Food and Drug Administration adaptive design draft guidance document recently released, this paper enlists the critical considerations from both methodological aspects and regulatory aspects in reviewing an adaptive design proposal and discusses two general types of adaptations, sample size planning and re-estimation, and two-stage adaptive design. Literature examples of adaptive designs in central nervous system are used to highlight the principles laid out in the U.S. FDA draft guidance. Four logistics models seen in regulatory adaptive design applications are introduced. In general, complex adaptive designs require simulation studies to access the design performance. For an adequate and well-controlled clinical trial, if a Learn-and-Confirm adaptive selection approach is considered, the study-wise type I error rate should be adhered to. However, it is controversial to use the simulated type I error rate to address a strong control of the study-wise type I error rate. Published by Elsevier B.V. C1 [Wang, Sue-Jane; O'Neill, Robert] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, HFD-700,WO 21,MailStop Room 3562,10903 New Hampsh, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 28 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD FEB PY 2011 VL 21 IS 2 BP 159 EP 166 DI 10.1016/j.euroneuro.2010.09.003 PG 8 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 725BJ UT WOS:000287619900003 PM 20933373 ER PT J AU Wolf, R Voscopolous, C Winston, J Cattaisson, C Darwiche, N Glick, A Weinberg, WC Vogel, JC Goldsmith, P Hennings, H Yuspa, SH AF Wolf, R. Voscopolous, C. Winston, J. Cattaisson, C. Darwiche, N. Glick, A. Weinberg, W. C. Vogel, J. C. Goldsmith, P. Hennings, H. Yuspa, S. H. TI S100A7 (psoriasin) and S100A15 (koebnerisin) marks tumor progression during skin carcinogenesis SO EXPERIMENTAL DERMATOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung CY FEB 17-19, 2011 CL Tuebingen, GERMANY SP Arbeitsgemeinsch Dermatol Forsch C1 [Wolf, R.; Voscopolous, C.; Winston, J.; Cattaisson, C.; Darwiche, N.; Glick, A.; Hennings, H.; Yuspa, S. H.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA. [Wolf, R.] Univ Munich, Dept Dermatol & Allergol, Munich, Germany. [Weinberg, W. C.] US FDA, Bethesda, MD 20014 USA. [Vogel, J. C.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Goldsmith, P.] NCI, Antibody & Prot Purificat Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD FEB PY 2011 VL 20 IS 2 MA P222 BP 197 EP 197 PG 1 WC Dermatology SC Dermatology GA 709UZ UT WOS:000286468200240 ER PT J AU Parsons, BL AF Parsons, Barbara L. TI Monoclonal tumor origin is an underlying misconception of the RESIC approach SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov NR 5 TC 5 Z9 5 U1 0 U2 3 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 FEB 1 PY 2011 VL 108 IS 5 BP E15 EP E15 DI 10.1073/pnas.1017998108 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714JA UT WOS:000286804700001 PM 21239682 ER PT J AU Wang, YJ Dou, JH Cross, KP Valerio, LG AF Wang, Yun-Jan Dou, Jinhui Cross, Kevin P. Valerio, Luis G., Jr. TI Computational analysis for hepatic safety signals of constituents present in botanical extracts widely used by women in the United States for treatment of menopausal symptoms SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Botanicals; Safety; Dietary supplements; Computational science; QSAR; Modeling; Liver toxicity; Women's health; Menopausal symptoms; Menopause; Hormone replacement therapy; Black cohosh; Chasteberry; Hops; Red clover ID URINARY-TRACT TOXICITIES; HOPS HUMULUS-LUPULUS; CIMICIFUGA-RACEMOSA; N-ACETYLCYSTEINE; BLACK COHOSH; DIETARY PHYTOESTROGENS; MOUSE-LIVER; RED-CLOVER; HEPATOTOXICITY; XANTHOHUMOL AB Black cohosh, red clover, hops, and chasteberry are botanicals commonly used to alleviate menopausal symptoms in the US, and are examined in this study as part of a FDA Office of Women's Health research collaboration to expand knowledge on the safety of these botanical products. Computational approaches using classic (quantitative) structure-activity relationships ((Q)SAR), probabilistic reasoning, machine learning methods, and human expert rule-based systems were employed to deliver human hepatobiliary adverse effect predictions. The objective is to profile and analyze constituents that are alerting for the human hepatobiliary adverse effects. Computational analysis of positively predicted constituents showed that common structural features contributing to the hepatobiliary adverse effect predictions contain phenolic, flavone, isoflavone, glucoside conjugated flavone and isoflavone, and 4-hydroxyacetophenone structures. Specifically, protocatechuic acid from black cohosh, benzofuran and 4-vinylphenol from chasteberry, and xanthohumol I from hops were botanical constituents predicted positive for liver toxicity endpoints and were also confirmed with literature findings. However, comparison between the estimated human exposure to these botanical constituents and the LOAEL and NOAEL in published animal liver toxicology studies for these constituents demonstrated varying margins of safety. This study will serve as regulatory decision support information for regulators at the FDA to help with the process of prioritizing chemicals for testing. Published by Elsevier Inc. C1 [Wang, Yun-Jan; Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Yun-Jan] GlobalNet Serv, Rockville, MD 20852 USA. [Dou, Jinhui] US FDA, Bot Review Team, Off Drug Evaluat 6, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Cross, Kevin P.] Leadscope Inc, Columbus, OH 43215 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak 51,Room 4218, Silver Spring, MD 20993 USA. EM Luis.Valerio@fda.hhs.gov FU US FDA, Office of Women's Health FX The authors thank the US FDA, Office of Women's Health for funding this research project. We thank Barbara Minnier for assistance with chemical structures. NR 61 TC 5 Z9 6 U1 1 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD FEB PY 2011 VL 59 IS 1 BP 111 EP 124 DI 10.1016/j.yrtph.2010.09.012 PG 14 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 727BM UT WOS:000287772300012 PM 20920542 ER PT J AU Lanzarotta, A Gratz, S Brueggemeyer, T Witkowski, M AF Lanzarotta, Adam Gratz, Samuel Brueggemeyer, Thomas Witkowski, Mark TI A Targeted Approach to Detect Controlled Substances in Suspect Tablets Using Attenuated Total Internal Reflection Fourier-Transform Infrared Spectroscopic Imaging SO SPECTROSCOPY LA English DT Article ID IDENTIFICATION AB Suspect "ecstasy" tablets have been analyzed using attenuated total internal reflection Fourier-transform infrared (ATR-FT-IR) spectroscopic imaging to confirm the presence of several controlled substances that were first identified using liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS). The ATR-FT-IR method was a targeted approach that involved searching standard FT-IR spectra (of the components already detected by LC-ESI-MS) against each spectrum contained in an ATR-FT-IR image. The method potentially can be used in the future both as an initial screen and as a confirmatory method for other analytical techniques. C1 [Lanzarotta, Adam; Witkowski, Mark] US FDA, Trace Examinat Sect, Forens Chem Ctr, Cincinnati, OH USA. [Gratz, Samuel] US FDA, Separat Sect 2, Forens Chem Ctr, Cincinnati, OH USA. [Brueggemeyer, Thomas] US FDA, Separat Spect & Mol Biol Sect, Forens Chem Ctr, Cincinnati, OH USA. RP Lanzarotta, A (reprint author), US FDA, Trace Examinat Sect, Forens Chem Ctr, Cincinnati, OH USA. EM Adam.Lanzarotta@fda.hhs.gov NR 13 TC 6 Z9 6 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 0887-6703 J9 SPECTROSCOPY-US JI Spectroscopy PD FEB PY 2011 VL 26 IS 2 BP 34 EP + PG 7 WC Spectroscopy SC Spectroscopy GA 724FG UT WOS:000287560900003 ER PT J AU Samuelson, F Gallas, BD Myers, KJ Petrick, N Pinsky, P Sahiner, B Campbell, G Pennello, GA AF Samuelson, Frank Gallas, Brandon D. Myers, Kyle J. Petrick, Nicholas Pinsky, Paul Sahiner, Berkman Campbell, Gregory Pennello, Gene A. TI The Importance of ROC Data SO ACADEMIC RADIOLOGY LA English DT Letter ID PERFORMANCE C1 [Samuelson, Frank; Gallas, Brandon D.; Myers, Kyle J.; Petrick, Nicholas; Pinsky, Paul; Sahiner, Berkman; Campbell, Gregory; Pennello, Gene A.] US FDA, Ctr Devices & Radiol Hlth, Washington, DC 20204 USA. RP Samuelson, F (reprint author), US FDA, Ctr Devices & Radiol Hlth, Washington, DC 20204 USA. OI Gallas, Brandon/0000-0001-7332-1620 NR 5 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD FEB PY 2011 VL 18 IS 2 BP 257 EP 258 DI 10.1016/j.acra.2010.10.016 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 712XI UT WOS:000286699200019 PM 21232688 ER PT J AU Zang, QD Keire, DA Wood, RD Buhse, LF Moore, CMV Nasr, M Al-Hakim, A Trehy, ML Welsh, WJ AF Zang, Qingda Keire, David A. Wood, Richard D. Buhse, Lucinda F. Moore, Christine M. V. Nasr, Moheb Al-Hakim, Ali Trehy, Michael L. Welsh, William J. TI Class Modeling Analysis of Heparin H-1 NMR Spectral Data Using the Soft Independent Modeling of Class Analogy and Unequal Class Modeling Techniques SO ANALYTICAL CHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; OVERSULFATED CHONDROITIN SULFATE; ADVERSE CLINICAL EVENTS; MULTIVARIATE CALIBRATION METHODS; ARTIFICIAL NEURAL-NETWORKS; LOW-MOLECULAR-WEIGHT; ANTICOAGULANT ACTIVITY; CHEMOMETRIC TECHNIQUES; DERMATAN SULFATE; SPECTROSCOPY AB To differentiate heparin samples with varying amounts of dermatan sulfate (DS) impurities and oversulfated chondroitin sulfate (OSCS) contaminants, proton NMR spectral data for heparin sodium active pharmaceutical ingredient samples from different manufacturers were analyzed using multivariate chemometric techniques. A total of 168 samples were divided into three groups: (a) Heparin, [DS] <= 1.0% and [OSCS] = 0%; (b) DS, [DS] > 1.0% and [OSCS] = 0%; (c) OSCS, [OSCS] > 0% with any content of DS. The chemometric models were constructed and validated using two well-established methods: soft independent modeling of class analogy (SIMCA) and unequal class modeling (UNEQ). While SIMCA modeling was conducted using the entire set of variables extracted from the NMR spectral data, UNEQ modeling was combined with variable reduction using stepwise linear discriminant analysis to comply with the requirement that the number of samples per class exceed the number of variables in the model by at least 3-fold. Comparison of the results from these two modeling approaches revealed that UNEQ had greater sensitivity (fewer false positives) while SIMCA had greater specificity (fewer false negatives). For Heparin, DS, and OSCS, respectively, the sensitivity was 78% (56/72),74% (37/50), and 85% (39/46) from SIMCA modeling and 88% (63/72), 90% (45/50), and 91% (42/46) from UNEQ modeling. Importantly, the specificity of both the SIMCA and UNEQ models was 100% (46/46) for Heparin with respect to OSCS; no OSCS-containing sample was misclassified as Heparin. The specificity of the SIMCA model (45/50, or 90%) was superior to that of the UNEQ model (27/50, or 54%) for Heparin with respect to DS samples. However, the overall prediction ability of the UNEQ model (85%) was notably better than that of the SIMCA model (76%) for the Heparin vs DS vs OSCS classes. The models were challenged with blends of heparin spiked with nonsulfated, partially sulfated, or fully oversulfated chondroitin sulfate A, dermatan sulfate, or heparan sulfate at the 1.0, 5.0, and 10.0 wt % levels. The results from the present study indicate that the combination of H-1 NMR spectral data and class modeling techniques (viz., SIMCA and UNEQ) represents a promising strategy for assessing the quality of commercial heparin samples with respect to impurities and contaminants. The methodologies show utility for applications beyond heparin to other complex products. C1 [Zang, Qingda; Keire, David A.; Welsh, William J.] Univ Med & Dent New Jersey, Dept Pharmacol, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Zang, Qingda; Wood, Richard D.] Snowdon Inc, Monmouth Jct, NJ 08852 USA. [Zang, Qingda] 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.] Food & Drug Adm, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Moore, Christine M. V.; Nasr, Moheb; Al-Hakim, Ali] Food & Drug Adm, Ctr Drug Evaluat & Res, Office New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Welsh, WJ (reprint author), Univ Med & Dent New Jersey, Dept Pharmacol, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. EM welshwj@umdnj.edu NR 52 TC 12 Z9 12 U1 2 U2 9 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 FEB 1 PY 2011 VL 83 IS 3 BP 1030 EP 1039 DI 10.1021/ac102832t PG 10 WC Chemistry, Analytical SC Chemistry GA 712TR UT WOS:000286689600057 PM 21192734 ER PT J AU Lu, QJ Malinauskas, RA AF Lu, Qijin Malinauskas, Richard A. TI Comparison of Two Platelet Activation Markers Using Flow Cytometry After In Vitro Shear Stress Exposure of Whole Human Blood SO ARTIFICIAL ORGANS LA English DT Article DE Platelet activation; Flow cytometry; Shear stress; Rheometer; P-selectin; PAC1; Human blood ID VENTRICULAR ASSIST DEVICE; CARDIOPULMONARY BYPASS; HEPARIN; ANTICOAGULANT; THROMBOSIS; PUMP; AGGREGATION; ANTIBODIES AB Platelet activation is the initiating step to thromboembolic complications in blood-contacting medical devices. Currently, there are no widely accepted testing protocols or relevant metrics to assess platelet activation during the in vitro evaluation of new medical devices. In this article, two commonly used platelet activation marker antibodies, CD62P (platelet surface P-selectin) and PAC1 (activated GP IIb/IIIa), were evaluated using flow cytometry. Anticoagulant citrate dextrose solution A (ACDA) and heparin anticoagulated human blood from healthy donors were separately exposed to shear stresses of 0, 10, 15, and 20 Pa for 120 s using a cone-plate rheometer model, and immediately mixed with the platelet marker antibodies for analysis. To monitor for changes in platelet reactivity between donors and over time, blood samples were also evaluated after exposure to 0, 2, and 20 mu M of adenosine diphosphate (ADP). Following ADP stimulation, the percentage of both CD62P and PAC1 positive platelets increased in a dose dependent fashion, even 8 h after the blood was collected. After shear stress stimulation, both CD62P and PAC1 positive platelets increased significantly at shear stress levels of 15 and 20 Pa when ACDA was used as the anticoagulant. However, for heparinized blood, the PAC1 positive platelets decreased with increasing shear stress, while the CD62P positive platelets increased. Besides the anticoagulant effect, the platelet staining buffer also impacted PAC1 response, but had little effect on CD62P positive platelets. These data suggest that CD62P is a more reliable marker compared with PAC1 for measuring shear-dependent platelet activation and it has the potential for use during in vitro medical device testing. C1 [Lu, Qijin; Malinauskas, Richard A.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Lu, QJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM qijin.lu@fda.hhs.gov NR 44 TC 11 Z9 11 U1 1 U2 14 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD FEB PY 2011 VL 35 IS 2 BP 137 EP 144 DI 10.1111/j.1525-1594.2010.01051.x PG 8 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 721ZQ UT WOS:000287398100011 PM 20946295 ER PT J AU Emily, JW Wise, RP Menschik, D Shadomy, SV Iskander, J Beeler, J Varricchio, F Ball, R AF Woo, Emily Jane Wise, Robert P. Menschik, David Shadomy, Sean V. Iskander, John Beeler, Judy Varricchio, Frederick Ball, Robert TI Thrombocytopenia after vaccination: Case reports to the US Vaccine Adverse Event Reporting System, 1990-2008 SO VACCINE LA English DT Article DE Vaccine; Thrombocytopenia; Postmarketing safety; Adverse event ID POSTLICENSURE SAFETY SURVEILLANCE; VARICELLA VACCINE; UNITED-STATES; MMR VACCINE; PURPURA; IMMUNIZATION; RUBELLA; VAERS; DRUG; ANTIBODIES AB We reviewed thrombocytopenia (TP) reports to the US Vaccine Adverse Event Reporting System (VAERS). We examined TP patterns for differences in single versus multiple immunization reports, presence of a live viral vaccine, seriousness, age, and interval to symptom onset. We found 1510 reports of possible TP and after exclusions evaluated 1440 for possible causes. Most (1078; 75%) met the regulatory definition of a serious adverse event. TP was reported after inactivated and live viral vaccines. Platelet counts <10 x 10(9)/L were reported. Identified vaccines could be prioritized for hypothesis-testing studies. Published by Elsevier Ltd. C1 [Woo, Emily Jane; Wise, Robert P.; Menschik, David; Beeler, Judy; Varricchio, Frederick; Ball, Robert] US FDA, CBER, OBE, Rockville, MD 20852 USA. [Shadomy, Sean V.; Iskander, John] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Emily, JW (reprint author), US FDA, CBER, OBE, Food & Drug Adm HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 35 TC 0 Z9 0 U1 0 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 FEB 1 PY 2011 VL 29 IS 6 BP 1319 EP 1323 DI 10.1016/j.vaccine.2010.11.051 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 721FU UT WOS:000287339800030 ER PT J AU Boyce, JA Assa'a, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SE Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'a, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan E. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the diagnosis and management of food allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO NUTRITION LA English DT Article C1 [Plaut, Marshall; Cooper, Susan E.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Dept Med,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Brigham & Womens Hosp, Dept Emergency Med,Div Rheumatol Allergy & Immuno, Massachusetts Gen Hosp,Dept Med, Boston, MA 02115 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Pulm & Crit Med Div, Boston, MA 02115 USA. [Assa'a, Amal] Univ Cincinnati, Div Allergy & Immunol, Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45221 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27706 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27706 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Div Allergy & Immunol, Dept Pediat, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Southampton SO9 5NH, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport PO30 5TG, Isle Of Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton SO16 6YD, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Allergy & Immunol Sect, Dept Pediat, Baton Rouge, LA 70803 USA. [Beck, Lisa A.] Univ Rochester, Med Ctr, Dept Dermatol, Rochester, NY 14642 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Sect Pediat Gastroenterol Hepatol & Nutr, Digest Hlth Inst, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. Univ Colorado, Denver Sch Med, Dept Pediat, Aurora, CO USA. Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. Univ Tennessee, Coll Med, Dept Med, Div Allergy & Immunol, Knoxville, TN 37996 USA. US FDA, Off Food Addit Safety, College Pk, MD USA. Childrens Hosp Orange Cty, Orange, CA USA. Childrens Hosp Boston, Div Immunol, Boston, MA USA. Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB R3T 2N2, Canada. Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. Olmsted Med Ctr, Dept Res, Rochester, MN USA. Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 6503, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU NIAID; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; National Institutes of Health; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; Dey; Novartis; Astellas; Astellas, Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc.; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; AllerGen; Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health, Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious, Diseases: National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX NIAID-sponsored Expert Panel; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoSmithKline and as a speaker for the American College of Allergy, Asthma, and, Immunology, the North East Allergy Society, the Virginia Allergy Society, the New, England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has, received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Dannon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received, funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the, National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G. T. Furuta has served as a consultant and/or speaker to Caption Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J. M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc. Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; F. E. R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health, Research.; S.J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious, Diseases: National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 0 TC 18 Z9 18 U1 1 U2 23 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 EI 1873-1244 J9 NUTRITION JI Nutrition PD FEB PY 2011 VL 27 IS 2 BP 253 EP 267 DI 10.1016/j.nut.2010.12.001 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 710UL UT WOS:000286542400022 PM 21215925 ER PT J AU Shpyleva, SI Tryndyak, VP Kovalchuk, O Starlard-Davenport, A Chekhun, VF Beland, FA Pogribny, IP AF Shpyleva, Svitlana I. Tryndyak, Volodymyr P. Kovalchuk, Olga Starlard-Davenport, Athena Chekhun, Vasyl' F. Beland, Frederick A. Pogribny, Igor P. TI Role of ferritin alterations in human breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Breast cancer; Ferritin; Iron; MicroRNA miR-200 ID H-CHAIN; DIFFERENTIAL EXPRESSION; MESENCHYMAL TRANSITION; MELANOMA PROGRESSION; OXIDATIVE STRESS; DRUG-RESISTANCE; MIR-200 FAMILY; IRON; GENES; OVEREXPRESSION AB Breast cancer is the most common malignancy in women. Successful treatment of breast cancer relies on a better understanding of the molecular mechanisms involved in breast cancer initiation and progression. Recent studies have suggested a crucial role of perturbations in ferritin levels and tightly associated with this, the deregulation of intracellular iron homeostasis; however, the underlying molecular mechanisms for the cancer-linked ferritin alterations remain largely unknown and often with conflicting conclusions. Therefore, this study was undertaken to define the role of ferritin in breast cancer. We determined that human breast cancer cells with an epithelial phenotype, such as MCF-7, MDA-MB-361, T-47D, HCC70 and cells, expressed low levels of ferritin light chain, ferritin heavy chain, transferrin, transferring receptor, and iron-regulatory proteins 1 and 2. In contrast, expression of these proteins was substantially elevated in breast cancer cells with an aggressive mesenchymal phenotype, such as Hs-578T, BT-549, and especially MDA-MB-231 cells. The up-regulation of ferritin light chain and ferritin heavy chain in MDA-MB-231 cells was accompanied by alterations in the subcellular distribution of these proteins as characterized by an increased level of nuclear ferritin and a lower level of the cellular labile iron pool as compared to MCF-7 cells. We established that ferritin heavy chain is a target of miRNA miR-200b, suggesting that its up-regulation in MDA-MB-231 cells may be triggered by the low expression of miR-200b. Ectopic up-regulation of miR-200b by transfection of MDA-MB-231 cells with miR-200b substantially decreased the level of ferritin heavy chain. More importantly, miR-200b-induced down-regulation of ferritin was associated with an increased sensitivity of the MDA-MB-231 cells to the chemotherapeutic agent doxorubicin. These results suggest that perturbations in ferritin levels are associated with the progression of breast cancer toward a more advanced malignant phenotype. C1 [Shpyleva, Svitlana I.; Tryndyak, Volodymyr P.; Starlard-Davenport, Athena; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Shpyleva, Svitlana I.; Chekhun, Vasyl' F.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, UA-03022 Kiev, Ukraine. [Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 42 TC 53 Z9 57 U1 0 U2 17 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD FEB PY 2011 VL 126 IS 1 BP 63 EP 71 DI 10.1007/s10549-010-0849-4 PG 9 WC Oncology SC Oncology GA 709VT UT WOS:000286470200007 PM 20390345 ER PT J AU Khurana, S Verma, S Verma, N Crevar, CJ Carter, DM Manischewitz, J King, LR Ross, TM Golding, H AF Khurana, Surender Verma, Swati Verma, Nitin Crevar, Corey J. Carter, Donald M. Manischewitz, Jody King, Lisa R. Ross, Ted M. Golding, Hana TI Bacterial HA1 Vaccine against Pandemic H5N1 Influenza Virus: Evidence of Oligomerization, Hemagglutination, and Cross-Protective Immunity in Ferrets SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT HEMAGGLUTININ; STRUCTURAL BASIS; BINDING; TRANSPORT; ANTIBODY; RECEPTOR; IMMUNOGENICITY; GLYCOPROTEIN; RESPONSES; PROTEINS AB The impending influenza virus pandemic requires global vaccination to prevent large-scale mortality and morbidity, but traditional influenza virus vaccine production is too slow for rapid responses. We have developed bacterial systems for expression and purification of properly folded functional hemagglutinin as a rapid response to emerging pandemic strains. A recombinant H5N1 (A/Vietnam/1203/2004) hemagglutinin globular domain (HA1) was produced in Escherichia coli under controlled redox refolding conditions. Importantly, the properly folded HA1(1-320), i.e., HA1 lacking amino acids 321 to 330, contained >= 75% functional oligomers without addition of foreign oligomerization sequence. Site-directed mutagenesis mapped the oligomerization signal to the HA1 N-terminal Ile-Cys-Ile residues at positions 3 to 5. The purified HA1 oligomers (but not monomers) bound fetuin and agglutinated red blood cells. Upon immunization of rabbits, the oligomeric HA1(1-320) elicited potent neutralizing antibodies against homologous and heterologous H5N1 viruses more rapidly than HA1(28-320) containing only monomers. Ferrets vaccinated with oligomeric HA1 (but not monomeric HA1 with the N terminus deleted) at 15 and 3 mu g/dose were fully protected from lethality and weight loss after challenge with homologous H5N1 (A/Vietnam/1203/2004, clade 1) virus, as well as heterologous clade 2.2 H5N1 (A/WooperSwan/Mongolia/244/2005) virus. Protection was associated with a significant reduction in viral loads in the nasal washes of homologous and heterologous virus challenged ferrets. This is the first study that describes the presence of an N-terminal oligomerization sequence in the globular domain of influenza virus hemagglutinin. Our findings suggest that functional oligomeric rHA1-based vaccines can be produced efficiently in bacterial systems and can be easily upscaled in response to a pandemic influenza virus threat. C1 [Khurana, Surender; Verma, Swati; Verma, Nitin; Manischewitz, Jody; King, Lisa R.; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Crevar, Corey J.; Carter, Donald M.; Ross, Ted M.] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov FU NIH/NIAID [UO1-AI077771]; DMID, NIH [IAA 224-10-1006] FX This study was funded in part by an American Recovery and Reinvestment Act supplement to NIH/NIAID grant UO1-AI077771 to T. M. R. This study was also partly supported by IAA 224-10-1006 from DMID, NIH. NR 35 TC 37 Z9 42 U1 1 U2 9 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 FEB PY 2011 VL 85 IS 3 BP 1246 EP 1256 DI 10.1128/JVI.02107-10 PG 11 WC Virology SC Virology GA 705PC UT WOS:000286147400009 PM 21084473 ER PT J AU Lyn-Cook, LE Tareke, E Word, B Starlard-Davenport, A Lyn-Cook, BD Hammons, GJ AF Lyn-Cook, Lascelles E., Jr. Tareke, Eden Word, Beverly Starlard-Davenport, Athena Lyn-Cook, Beverly D. Hammons, George J. TI Food contaminant acrylamide increases expression of Cox-2 and nitric oxide synthase in breast epithelial cells SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE Acrylamide; PhIP; nitric oxide synthase; Cox-2; breast ID CANCER; GLYCIDAMIDE; CYCLOOXYGENASE; INFLAMMATION; CARCINOGEN; METABOLITE; EXPOSURE; HUMANS; WOMEN; PHIP AB Acrylamide has been discovered in foods cooked at high temperature. A potentially harmful effect of this dietary component has been suggested by data indicating its association with increased breast cancer. This study investigated the potential effects of acrylamide in nontumorigenic breast cells by assessing expression levels of inducible nitric oxide synthase (iNOS) and cycloogenase-2 (Cox-2) and NOS activity, which are known to be early molecular changes in disease formation. Treatment of cells with acrylamide increased levels of iNOS (both expression and activity) and Cox-2. Its potent metabolite, glycidamide, also induced both iNOS and Cox-2, with induction of iNOS occurring at a lower concentration. 2-Amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP), another food-borne carcinogen, was found to induce Cox-2 expression. Combining acrylamide with PhIP did not result in a further increase. These studies suggest that further research is needed to determine the role of carcinogens formed from cooking foods in inducing early molecular changes associated with breast cancer. C1 [Tareke, Eden; Word, Beverly; Starlard-Davenport, Athena; Lyn-Cook, Beverly D.; Hammons, George J.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lyn-Cook, Lascelles E., Jr.] Univ Arkansas, Little Rock, AR 72204 USA. RP Hammons, GJ (reprint author), Natl Ctr Toxicol Res, HFT 100, Jefferson, AR 72079 USA. EM ghammons@nctr.fda.gov NR 47 TC 8 Z9 8 U1 0 U2 10 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD FEB PY 2011 VL 27 IS 1 BP 11 EP 18 DI 10.1177/0748233710380217 PG 8 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 706FX UT WOS:000286204500002 PM 20713430 ER PT J AU Saylor, DM Guyer, JE Wheeler, D Warren, JA AF Saylor, David M. Guyer, Jonathan E. Wheeler, Daniel Warren, James A. TI Predicting microstructure development during casting of drug-eluting coatings SO ACTA BIOMATERIALIA LA English DT Article DE Microstructure; Coating; Modeling; Simulation; Diffusion ID CONFOCAL RAMAN MICROSCOPY; POLYMER-SOLVENT SYSTEMS; DIFFUSION-COEFFICIENTS; RELEASE; STENT; SOLUBILITY AB We have devised a novel diffuse interface formulation to model the development of chemical and physical inhomogeneities, i.e. microstructure, during the process of casting drug-eluting coatings. These inhomogeneities, which depend on the coating constituents and manufacturing conditions, can have a profound affect on the rate and extent of drug release, and therefore the ability of coated medical devices to function successfully. By deriving the model equations in a time-dependent reference frame, we find that it is computationally viable to probe a wide, physically relevant range of material and process quantities. To illustrate the application of the model, we have evaluated the impact of manufacturing solvent, coating thickness and evaporation rate on microstructure development. Our results suggest that modifying these process conditions can have a strong and nearly discontinuous effect on coating microstructure, and therefore on drug release. Further, we demonstrate that the model can be applied to processes that involve the incremental application of the coating in layers or passes. This new model formulation, which can also be used to predict the kinetics of drug release, provides a tool to elucidate and quantify the relationships between process variables, microstructure and performance. Establishing these relationships can reduce empiricism in materials selection and process design, providing a facile and efficient means to tailor the underlying microstructure and achieve a desired drug-release behavior. Published by Elsevier Ltd. on behalf of Acta materialia Inc. C1 [Saylor, David M.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Guyer, Jonathan E.; Wheeler, Daniel; Warren, James A.] NIST, Div Met, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA. RP Saylor, DM (reprint author), US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM david.saylor@fda.hhs.gov RI Wheeler, Daniel/C-8994-2009; Warren, James/B-1698-2008; Guyer, Jonathan/M-5165-2016 OI Wheeler, Daniel/0000-0002-2653-7418; Warren, James/0000-0001-6887-1206; Guyer, Jonathan/0000-0002-1407-6589 NR 27 TC 3 Z9 3 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1742-7061 EI 1878-7568 J9 ACTA BIOMATER JI Acta Biomater. PD FEB PY 2011 VL 7 IS 2 BP 604 EP 613 DI 10.1016/j.actbio.2010.09.019 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 713AP UT WOS:000286707700016 PM 20858554 ER PT J AU Arzhantsev, S Li, XA Kauffman, JF AF Arzhantsev, Sergey Li, Xiang Kauffman, John F. TI Rapid Limit Tests for Metal Impurities in Pharmaceutical Materials by X-ray Fluorescence Spectroscopy Using Wavelet Transform Filtering SO ANALYTICAL CHEMISTRY LA English DT Article ID ATOMIC-ABSORPTION-SPECTROMETRY; DIETARY CALCIUM SUPPLEMENTS; MASS-SPECTROMETRY; PEAK DETECTION; LEAD CONTENT; PRODUCTS; MEDICINE; CHEMOMETRICS; ELEMENTS; SPECTRA AB We introduce a new method for analysis of X-ray fluorescence (XRF). spectra based on continuous wavelet transform filters, and the method is applied to the determination of toxic metals in, pharmaceutical materials using hand-held XRF spectrometers. The method uses the continuous wavelet transform to filter the signal and noise components of the spectrum. We present a limit test that compares the wavelet domain signal-to-noise ratios at the energies of the elements of interest to an empirically determined signal-to-noise decision threshold. The limit test is advantageous because it does not require the user to measure calibration samples prior to measurement, though system suitability tests are still recommended. The limit test was evaluated in a collaborative study that involved five different hand-held XRF spectrometers used by multiple analysts in six separate laboratories across the United States. In total, more than 1200 measurements were performed. The detection limits estimated for arsenic, lead, mercury, and chromium were 8, 14, 20, and 150 mu g/g, respectively. C1 [Arzhantsev, Sergey; Li, Xiang; Kauffman, John F.] Ctr Drug Evaluat & Res, US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Arzhantsev, S (reprint author), Ctr Drug Evaluat & Res, US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM sergey.arzhantsev@fda.hhs.gov FU Oak Ridge Institute for Science and Education (ORISE); FDA Center for Drug Evaluation and Research FX The authors acknowledge FDA Office of Regulatory Affairs field scientists Luella Rossi, Gary Dzidowski, Mark Henry, Dongping Dai, and Diana C. Mould for participating in the collaborative study. S.A. and X.L. were supported by the Oak Ridge Institute for Science and Education (ORISE). This work was funded by the FDA Center for Drug Evaluation and Research Critical Path Program. The information presented here reflects the current thinking and experience of the authors. However, this is not an official policy document and should not be used in lieu of regulations, published FDA guidances, or direct discussions with the agency. NR 41 TC 27 Z9 28 U1 3 U2 23 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 FEB 1 PY 2011 VL 83 IS 3 BP 1061 EP 1068 DI 10.1021/ac1028598 PG 8 WC Chemistry, Analytical SC Chemistry GA 712TR UT WOS:000286689600061 PM 21222440 ER PT J AU Chen, YH Ross, WH Whiting, RC Van Stelten, A Nightingale, KK Wiedmann, M Scott, VN AF Chen, Yuhuan Ross, William H. Whiting, Richard C. Van Stelten, Anna Nightingale, Kendra K. Wiedmann, Martin Scott, Virginia N. TI Variation in Listeria monocytogenes Dose Responses in Relation to Subtypes Encoding a Full-Length or Truncated Internalin A SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TO-EAT FOODS; QUANTITATIVE RISK-ASSESSMENT; PREGNANT GUINEA-PIGS; INDUCED STILLBIRTHS; INLA; VIRULENCE; MODEL; POLYMORPHISM; DISTINCT; STRAINS AB Internalin A (InlA; encoded by inlA) facilitates the crossing of the intestinal barrier by Listeria monocytogenes. Mutations leading to a premature stop codon (PMSC) in inlA and thus attenuated mammalian virulence have been reported. We recently characterized 502 L. monocytogenes food isolates from a retail survey and 507 human clinical isolates from multiple U. S. states with respect to the presence/absence of inlA mutations. The objective of this study was to investigate the hypothesis that dose responses for human listeriosis vary between L. monocytogenes strains with and those without a PMSC in inlA. Subtype-specific prevalence and concentration distributions in food, along with epidemiologic and consumption data, were input into established dose-response models to generate an r value (probability of a cell causing illness). Under the conservative assumption that L. monocytogenes levels at retail represent levels consumed, mean log(10) r values were -8.1 and -10.7 for L. monocytogenes subtypes with genes encoding a full-length and a truncated InlA, respectively. L. monocytogenes carrying a 5' frameshift mutation in a homopolymeric tract showed a mean log10 r value of -12.1. Confidence intervals for the r values and their differences varied depending on subtypes. When the increase in concentration of L. monocytogenes subtypes between retail and consumption was considered, mean log10 r values were reduced to -10.4, -13.8, and -12.8 for the subtypes with genes encoding a full-length InlA, for the subtypes carrying a PMSC in inlA, and for all L. monocytogenes isolates regardless of subtype, respectively. Our study provides further quantitative evidence that L. monocytogenes subtypes vary in abilities and relative likelihoods of causing human disease, which were mechanistically related to defined genetic markers. C1 [Chen, Yuhuan; Scott, Virginia N.] Grocery Manufacturers Assoc, Washington, DC USA. [Ross, William H.] Hlth Canada, Food Directorate, Ottawa, ON K1A 0L2, Canada. [Whiting, Richard C.] Exponent, Bowie, MD USA. [Van Stelten, Anna; Nightingale, Kendra K.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Wiedmann, Martin] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. RP Chen, YH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Room 2A-009,Mail Code HFS-005,5100 Paint Branch P, College Pk, MD 20740 USA. EM Yuhuan.Chen@fda.hhs.gov RI Wiedmann, Martin/A-9683-2008 OI Wiedmann, Martin/0000-0002-4168-5662 FU National Research Initiative of the USDA Cooperative State Research, Education and Extension Service [2005-35201-16266]; North America Branch of the International Life Sciences Institute Technical Committee on Food Microbiology FX This project was supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service, grant 2005-35201-16266. We thank the North America Branch of the International Life Sciences Institute Technical Committee on Food Microbiology for a grant from which the framework of the growth model in this study was initially developed. NR 48 TC 18 Z9 19 U1 0 U2 8 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 FEB PY 2011 VL 77 IS 4 BP 1171 EP 1180 DI 10.1128/AEM.01564-10 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 717WM UT WOS:000287078100003 PM 21169442 ER PT J AU Gavrielides, MA Gallas, BD Lenz, P Badano, A Hewitt, SM AF Gavrielides, Marios A. Gallas, Brandon D. Lenz, Petra Badano, Aldo Hewitt, Stephen M. TI Observer Variability in the Interpretation of HER2/neu Immunohistochemical Expression With Unaided and Computer-Aided Digital Microscopy SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CELLULAR IMAGING-SYSTEM; IN-SITU HYBRIDIZATION; BREAST-CANCER; TISSUE MICROARRAYS; VIRTUAL MICROSCOPY; INTEROBSERVER REPRODUCIBILITY; QUANTITATIVE-ANALYSIS; PROTEIN EXPRESSION; HER-2/NEU STATUS; RECEPTOR STATUS AB Context.-Observer variability in digital microscopy and the effect of computer-aided digital microscopy are underexamined areas in need of further research, considering the increasing use and future role of digital imaging in pathology. A reduction in observer variability using computer aids could enhance the statistical power of studies designed to determine the utility of new biomarkers and accelerate their incorporation in clinical practice. Objectives.-To quantify interobserver and intraobserver variability in immunohistochemical analysis of HER2/neu with digital microscopy and computer-aided digital microscopy, and to test the hypothesis that observer agreement in the quantitative assessment of HER2/neu immunohistochemical expression is increased with the use of computer-aided microscopy. Design.-A set of 335 digital microscopy images extracted from 64 breast cancer tissue slides stained with a HER2 antibody, were read by 14 observers in 2 reading modes: the unaided mode and the computer-aided mode. In the unaided mode, HER2 images were displayed on a calibrated color monitor with no other information, whereas in the computer-aided mode, observers were shown a HER2 image along with a corresponding feature plot showing computer-extracted values of membrane staining intensity and membrane completeness for the particular image under examination and, at the same time, mean feature values of the different HER2 categories. In both modes, observers were asked to provide a continuous score of HER2 expression. Results.-Agreement analysis performed on the output of the study showed significant improvement in both interobserver and intraobserver agreement when the computer-aided reading mode was used to evaluate preselected image fields. Conclusion.-The role of computer-aided digital microscopy in reducing observer variability in immunohistochemistry is promising. (Arch Pathol Lab Med. 2011;135:233-242) C1 [Gavrielides, Marios A.; Gallas, Brandon D.; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Lenz, Petra; Hewitt, Stephen M.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Gavrielides, MA (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Room 4114, Silver Spring, MD 20993 USA. EM marios.gavrielides@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; Hewitt, Stephen/0000-0001-8283-1788; badano, aldo/0000-0003-3712-6670 NR 43 TC 30 Z9 31 U1 1 U2 7 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD FEB PY 2011 VL 135 IS 2 BP 233 EP 242 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 722KG UT WOS:000287430500017 PM 21284444 ER PT J AU Doughty, E Kertesz-Farkas, A Bodenreider, O Thompson, G Adadey, A Peterson, T Kann, MG AF Doughty, Emily Kertesz-Farkas, Attila Bodenreider, Olivier Thompson, Gary Adadey, Asa Peterson, Thomas Kann, Maricel G. TI Toward an automatic method for extracting cancer- and other disease-related point mutations from the biomedical literature SO BIOINFORMATICS LA English DT Article ID PROSTATE-CANCER; GROWTH-FACTOR; GENE; SYSTEM; VALIDATION; DATABASE; TEXT AB Motivation: A major goal of biomedical research in personalized medicine is to find relationships between mutations and their corresponding disease phenotypes. However, most of the disease-related mutational data are currently buried in the biomedical literature in textual form and lack the necessary structure to allow easy retrieval and visualization. We introduce a high-throughput computational method for the identification of relevant disease mutations in PubMed abstracts applied to prostate (PCa) and breast cancer (BCa) mutations. Results: We developed the extractor of mutations (EMU) tool to identify mutations and their associated genes. We benchmarked EMU against MutationFinder-a tool to extract point mutations from text. Our results show that both methods achieve comparable performance on two manually curated datasets. We also benchmarked EMU's performance for extracting the complete mutational information and phenotype. Remarkably, we show that one of the steps in our approach, a filter based on sequence analysis, increases the precision for that task from 0.34 to 0.59 (PCa) and from 0.39 to 0.61 (BCa). We also show that this high-throughput approach can be extended to other diseases. Discussion: Our method improves the current status of disease-mutation databases by significantly increasing the number of annotated mutations. We found 51 and 128 mutations manually verified to be related to PCa and Bca, respectively, that are not currently annotated for these cancer types in the OMIM or Swiss-Prot databases. EMU's retrieval performance represents a 2-fold improvement in the number of annotated mutations for PCa and BCa. We further show that our method can benefit from full-text analysis once there is an increase in Open Access availability of full-text articles. C1 [Doughty, Emily; Kertesz-Farkas, Attila; Thompson, Gary; Adadey, Asa; Peterson, Thomas; Kann, Maricel G.] Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. [Kertesz-Farkas, Attila] US FDA, Div Imaging & Appl Math, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Bodenreider, Olivier] Natl Lib Med, Bethesda, MD 20894 USA. RP Kann, MG (reprint author), Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. EM mkann@umbc.edu RI Kann, Maricel/E-5701-2012 FU National Institutes of Health (NIH) [1K22CA143148, R01LM009722]; Centre for Devices and Radiological Health; US Food and Drug Administration; NIH, National Library of Medicine FX This work was supported by the National Institutes of Health (NIH) [1K22CA143148, MGK (PI) and R01LM009722, MGK (collaborator)]. A. K. F. acknowledges funding from the Research Fellowship Program of the Centre for Devices and Radiological Health, administrated by the Oak Ridge Associated Universities through a contact with the US Food and Drug Administration. Additional funding (OB) was provided by the Intramural Research Program of the NIH, National Library of Medicine. NR 32 TC 26 Z9 26 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD FEB 1 PY 2011 VL 27 IS 3 BP 408 EP 415 DI 10.1093/bioinformatics/btq667 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 716RN UT WOS:000286991300016 PM 21138947 ER PT J AU He, WW Liu, Y Yuan, JS Yin, JJ Wu, XC Hu, XN Zhang, K Liu, JB Chen, CY Ji, YL Guo, YT AF He, Weiwei Liu, Ying Yuan, Jinshan Yin, Jun-Jie Wu, Xiaochun Hu, Xiaona Zhang, Ke Liu, Jianbo Chen, Chunying Ji, Yinglu Guo, Yuting TI Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays SO BIOMATERIALS LA English DT Article DE Platinum; Nanostructures; Oxidase; Peroxidase; Catalase; Immunoassays ID OXYGEN REDUCTION REACTION; GOLD NANORODS; HYDROGEN-PEROXIDE; GLUCOSE DETECTION; PLATINUM NANOPARTICLES; CATALYTIC-ACTIVITY; SUPEROXIDE ANION; CONTRAST AGENTS; MECHANISM; GROWTH AB In this paper, we demonstrated that Au nanorods coated with a shell composed of Pt nanodots (Au@Pt nanostructures) exhibited intrinsic oxidase-like, peroxidase-like and catalase-like activity, catalyzing oxygen and hydrogen peroxide reduction and the dismutation decomposition of hydrogen peroxide to produce oxygen. Based on these findings, we established an Au@Pt nanostructures based enzyme linked immunosorbent assay (ELISA) for the detection of mouse interleukin 2 (IL-2). In comparison with natural enzymes, Au@Pt nanostructures have advantages of low cost, easy preparation, better stability, and tunable catalytic activity (compared with HRP), which make them a promising enzyme mimetic candidate and may find potential applications in biocatalysis, bioassays, and nano-biomedicine such as reactive oxygen species (ROS)-related fields (anti-aging and therapeutics for neurodegenerative diseases and cancers). (c) 2010 Elsevier Ltd. All rights reserved. C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [He, Weiwei; Wu, Xiaochun; Hu, Xiaona; Zhang, Ke; Liu, Jianbo; Ji, Yinglu; Guo, Yuting] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China. [Liu, Ying; Yuan, Jinshan; Chen, Chunying] Natl Ctr Nanosci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. [He, Weiwei] Xuchang Univ, Inst Surface Micro & Nano Mat, Xuchang 461000, Peoples R China. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM JunJie.Yin@fda.hhs.gov; wuxc@nanoctr.cn; chenchy@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [20773032]; National Basic Research Program of China [2006CB932602, 2006CB705600] FX The work was supported by National Natural Science Foundation of China (Grant No. 20773032) and the National Basic Research Program of China (2006CB932602 and 2006CB705600). NR 40 TC 201 Z9 207 U1 30 U2 222 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2011 VL 32 IS 4 BP 1139 EP 1147 DI 10.1016/j.biomaterials.2010.09.040 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 699PL UT WOS:000285675200021 PM 21071085 ER PT J AU Fan, J Yin, JJ Ning, B Wu, XC Hu, Y Ferrari, M Anderson, GJ Wei, JY Zhao, YL Nie, GJ AF Fan, Jia Yin, Jun-Jie Ning, Bo Wu, Xiaochun Hu, Ye Ferrari, Mauro Anderson, Gregory J. Wei, Jingyan Zhao, Yuliang Nie, Guangjun TI Direct evidence for catalase and peroxidase activities of ferritin-platinum nanoparticles SO BIOMATERIALS LA English DT Article DE Biomimetic enzymes; Catalase activities; ESR; Ferritin; Nanoparticles ID OXIDE NANOPARTICLES; METHANOL OXIDATION; APOFERRITIN; PROTEIN; SUPEROXIDE; TOXICOLOGY; STRESS; CARBON; CERIUM; CAGE AB Using apoferritin (apoFt) as a nucleation substrate, we have successfully synthesized 1-2 nm platinum nanoparticles (Pt-Ft) which are highly stable. By directly measuring the products of Pt-Ft-catalyzed reactions, we showed, with no doubt, Pt-Ft possesses both catalase and peroxidase activities. With hydrogen peroxide as substrate, we observed oxygen gas bubbles were generated from hydrogen peroxide decomposed by Pt-Ft: the generation of oxygen gas strongly supports Pt-Ft reacts as catalase, other than peroxidase. While with organic dyes and hydrogen peroxide as substrates, distinctive color products were formed catalyzed by Pt-Ft, which indicates a peroxidase-like activity. Interestingly, these biomimetic properties showed differential response to pH and temperature for different reaction substrates. Pt-Ft showed a significant increase in catalase activity with increasing pH and temperature. The HRP-like activity of Pt-Ft was optimal at physiological temperature and slightly acidic conditions. Our current study demonstrates that Pt-Ft possesses both catalase and peroxidase activities for different substrates under different conditions. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Fan, Jia; Wei, Jingyan] Jilin Univ, Coll Pharmaceut Sci, Changchun 130021, Peoples R China. [Fan, Jia; Ning, Bo; Wu, Xiaochun; Nie, Guangjun] Natl Ctr Nanosci & Technol, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100190, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hu, Ye; Ferrari, Mauro] Univ Texas Hlth Sci Ctr Houston, Dept Nanomed & Biomed Engn, Houston, TX 77031 USA. [Anderson, Gregory J.] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. [Zhao, Yuliang] Chinese Acad Sci, Inst High Energy Phys, CAS Key Lab Biol Effects Nanomat & Nanosafety, Beijing 100864, Peoples R China. RP Wei, JY (reprint author), Jilin Univ, Coll Pharmaceut Sci, Changchun 130021, Peoples R China. EM jingyanwei@yahoo.com.cn; zhaoyuliang@ihep.ac.cn; niegj@nanoctr.cn RI Yin, Jun Jie /E-5619-2014; Anderson, Gregory/G-4148-2013; OI Anderson, Gregory/0000-0002-8814-5866; nie, guangjun/0000-0001-5040-9793 FU MOST [2009AA03Z335, 2010CB933600, 2011CB933403]; NSFC [10979011, 30900278]; CAS FX This work was supported by grants from MOST 863 (2009AA03Z335), MOST 973 program (2010CB933600, 2011CB933403) and NSFC (10979011; 30900278). GN acknowledges the support of CAS Hundred Talents Program. We thank Herman Lutterodt for help with ESR study and Professor Sarah Perrett for her suggestions. NR 38 TC 109 Z9 116 U1 13 U2 122 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD FEB PY 2011 VL 32 IS 6 BP 1611 EP 1618 DI 10.1016/j.biomaterials.2010.11.004 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 712WX UT WOS:000286698100017 PM 21112084 ER PT J AU Beyer, BK Chernoff, N Danielsson, BR Davis-Bruno, K Harrouk, W Hood, RD Janer, G Liminga, UW Kim, JH Rocca, M Rogers, J Scialli, AR AF Beyer, Bruce K. Chernoff, Neil Danielsson, Bengt R. Davis-Bruno, Karen Harrouk, Wafa Hood, Ronald D. Janer, Gemma Liminga, Ulla Wandel Kim, James H. Rocca, Meredith Rogers, John Scialli, Anthony R. TI ILSI/HESI Maternal Toxicity Workshop Summary: Maternal Toxicity and Its Impact on Study Design and Data Interpretation SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE maternal-fetal interactions; mechanisms of teratogenesis; pharmaceuticals; safety assessment; developmental toxicity; maternal toxicity; prenatal; teratology ID ANTIARRHYTHMIC AGENT ALMOKALANT; EMBRYONIC CARDIAC-ARRHYTHMIA; UTEROPLACENTAL BLOOD-FLOW; DEVELOPMENTAL TOXICITY; FETAL DEVELOPMENT; RHYTHM ABNORMALITIES; INTRAUTERINE GROWTH; BLOCKING ACTIVITY; FOOD RESTRICTION; DIGITAL DEFECTS AB Workshops on maternal toxicity were held at the annual Society of Toxicology, Teratology Society, and European Teratology Society meetings in 2009. Speakers presented background information prior to a general discussion on this topic. The following recommendations/options are based on the outcome of the discussions at the workshops: 1. A comprehensive evaluation of all available data from general toxicity studies, range-finding Developmental and Reproductive Toxicology (DART) studies, class effects, structure-activity relationships, exposure studies, etc. is essential for appropriate dose selection for definitive DART studies. The intent is to avoid marked maternal toxicity leading to mortality or decreased body weight gains of greater than 20% for prolonged periods. (a) Evaluate alternative endpoints for dose selection and data interpretation (e.g., target tissue effects and pharmacology) for biotherapeutics. (b) Evaluate additional maternal parameters based on effects and/or target organs observed in short-term (e.g., 2- or 4-week) general toxicity studies. 2. Evaluate all available data to determine a cause-effect relationship for developmental toxicity. (a) Conduct a pair-feeding/pair-watering study as a follow-up. (b) Evaluate individual data demonstrating maternal toxicity in the mother with adverse embryo-fetal outcomes in the litter associated with the affected mother. (c) Conduct single-dose studies at increasing doses as a complement to conventional embryo-fetal toxicity studies for certain classes of compounds that affect the hERG channel. 3. Support statements that embryo-fetal effects are caused by maternal toxicity and/or exaggerated pharmacology, especially for malformations. (a) Provide mechanistic or other supporting data. (b) Establish the relevance of the DART findings in animals for human exposures. Birth Defects Res (Part B) 92:36-51, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Beyer, Bruce K.] Sanofi Aventis US Inc, Disposit Safety & Anim Res Preclin Safety, Dept Disposit Safety & Anim Res Preclin Safety, Bridgewater, NJ 08807 USA. [Chernoff, Neil; Rogers, John] US EPA, Tox Assessment Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. [Danielsson, Bengt R.] Pharmanet Dev Grp, Consultancy Div, Stockholm, Sweden. [Danielsson, Bengt R.] Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. [Davis-Bruno, Karen; Harrouk, Wafa] US FDA, CDER OND, Silver Spring, MD USA. [Hood, Ronald D.] Univ Alabama, Dept Biol Sci, Tuscaloosa, AL USA. [Hood, Ronald D.] Ronald D Hood & Associates, Toxicol Consultants, Tuscaloosa, AL USA. [Janer, Gemma] Palau Pharma SA, Dept Pharmacol & Toxicol, Palau de Plegamans, Spain. [Liminga, Ulla Wandel] Med Prod Agcy, Sci & Regulatory Strategy, Uppsala, Sweden. [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Rocca, Meredith] Elan Pharmaceut, Dept Nonclin Safety Evaluat, San Francisco, CA USA. [Scialli, Anthony R.] Tetra Tech Sci, Washington, DC USA. RP Beyer, BK (reprint author), Sanofi Aventis US Inc, Disposit Safety & Anim Res Preclin Safety, Dept Disposit Safety & Anim Res Preclin Safety, Mail Stop JR2-103B,1041 Route 202-206,POB 6800, Bridgewater, NJ 08807 USA. EM bruce.beyer@sanofi-aventis.com FU Health and Environmental Sciences Institute (HESI) FX Grant sponsor: Health and Environmental Sciences Institute (HESI). NR 72 TC 14 Z9 14 U1 2 U2 5 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 FEB PY 2011 VL 92 IS 1 BP 36 EP 51 DI 10.1002/bdrb.20281 PG 16 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 729XF UT WOS:000287986900004 PM 21312321 ER PT J AU Hamilton, AS Albertsen, PC Johnson, TK Hoffman, R Morrell, D Deapen, D Penson, DF AF Hamilton, Ann S. Albertsen, Peter C. Johnson, Terri Kang Hoffman, Richard Morrell, Donna Deapen, Dennis Penson, David F. TI Trends in the treatment of localized prostate cancer using supplemented cancer registry data SO BJU INTERNATIONAL LA English DT Article ID QUALITY-OF-LIFE; ANDROGEN-DEPRIVATION THERAPY; RADICAL PROSTATECTOMY; UNITED-STATES; HIGH-RISK; BRACHYTHERAPY; OUTCOMES; MANAGEMENT; RADIATION; DISEASE AB What's known on the subject? and What does the study add? Variation in treatment of localized prostate cancer has been shown to exist according to demographic and clinical factors, patient and provider preference, and region of residence since there is no consensus concerning appropriate treatment. Between 1998 and 2002 the proportion of men choosing watchful waiting declined from 12.6% to 9.0% while those receiving brachytherapy (with or without external beam radiation therapy) increased from 14.9% to 17.7%. Based on Gleason score, PSA, and age at diagnosis, younger African-American men may be receiving less aggressive therapy than indicated, while older men with low risk tumours may be receiving more aggressive therapy than necessary. OBJECTIVE To conduct an analysis of localized prostate cancer treatment in the USA between 1998 and 2002. PATIENTS AND METHODS Results from the National Cancer Institute's Patterns of Care study from 10 regional cancer registries in 1998 and 14 registries in 2002 were compared using univariate and multivariate statistical methods. RESULTS Patients with localized prostate cancer in 2002 were younger, had lower prostate-specific antigen values, and higher Gleason scores compared with those diagnosed in 1998. Little change occurred in age-adjusted percentages of men who were treated with a radical prostatectomy (45-46%) or by external beam radiation (EBRT) alone (19-20%). The proportion receiving brachytherapy (BT), alone or with EBRT, increased from 14.9 to 17.7%, while the proportion receiving watchful waiting declined from 12.6 to 9.0%. Younger African-American men with intermediate/high-risk disease were less likely to receive any type of aggressive therapy in comparison with Non-Hispanic White men. Over 70% of men who were >= 75 years of age, with low-risk disease, were treated with EBRT or BT. CONCLUSIONS Older men with low-risk disease might be overtreated with aggressive therapy, while younger intermediate/high-risk African-American men appear less likely to receive indicated aggressive therapy. C1 [Hamilton, Ann S.] Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, Los Angeles, CA 90089 USA. [Albertsen, Peter C.] Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. [Johnson, Terri Kang] US FDA, Div Biostat, Off Biometr & Surveillance, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Hoffman, Richard] New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM USA. [Hoffman, Richard] Univ New Mexico, Sch Med, Dept Med, Albuquerque, NM 87131 USA. [Penson, David F.] Vanderbilt Univ, Med Ctr, Ctr Surg Qual & Outcomes Res, Nashville, TN USA. RP Hamilton, AS (reprint author), Univ So Calif, Keck Sch Med, USC Norris Comprehens Canc Ctr, 1441 Eastlake Ave,Rm 3427A,MC1975, Los Angeles, CA 90089 USA. EM ahamilt@usc.edu FU NCI [N01-PC-35133, N01-PC-35135, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01PC-35139, N01-PC-35141, N01-PC-35142, N01-PC-35143, N01-PC-35145, N02-PC-15104, N02-PC-15105, N02-PC-15106, N02-PC-15107]; Centers for Disease Control and Preventions National Program of Cancer Registries [U55/CCR921930-02] FX The authors would like to acknowledge the contributions of the participating SEER registries and staffs. Without their dedicated efforts this research could not have been conducted. Each registry was funded by the NCI under the following contract numbers: N01-PC-35133, N01-PC-35135, N01-PC-35136, N01-PC-35137, N01-PC-35138, N01PC-35139, N01-PC-35141, N01-PC-35142, N01-PC-35143, N01-PC-35145, N02-PC-15104, N02-PC-15105, N02-PC-15106 and N02-PC-15107 (see list below for further details). The collection of California cancer incidence data was supported by: the California Department of Health Services, as part of the statewide cancer reporting programme mandated by California Health and Safety Code Section 103885; the NCI SEER programme under contract N01-PC-35139 awarded to the Cancer Prevention Institute of California, contract N01-PC-35139 awarded to the University of Southern California, and contract N02-PC-15105 awarded to the Public Health Institute; and the Centers for Disease Control and Preventions National Program of Cancer Registries, under agreement # U55/CCR921930-02 awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the author(s) and endorsement by the State of California, Department of Health Services, the NCI, and the Centers for Disease Control and Prevention or their contractors and subcontractors is not intended nor should be inferred. NR 36 TC 38 Z9 40 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD FEB PY 2011 VL 107 IS 4 BP 576 EP 584 DI 10.1111/j.1464-410X.2010.09514.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 713WE UT WOS:000286767300010 PM 20735387 ER PT J AU Cho, S Bashaw, ED AF Cho, S. Bashaw, E. D. TI Clinical Pharmacology for Development of Topical Dermatological Products: Present and Future Opportunities for Safety and Efficacy SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The development of topical products for dermatological diseases represents an untapped opportunity for the clinical pharmacologist. Assessment of bioavailability of topical drugs and its utility in weighing benefit vs. risk has been unique and challenging, compared with assessments for conventional systemic drugs. However, with continued advances in analytical methods and growing interests in discovering biomarkers, the future opportunities for clinical pharmacology to advance topical drug development processes are enormous and will be limited only by our drive and determination to push science forward. C1 [Cho, S.; Bashaw, E. D.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Cho, S (reprint author), US FDA, Off Clin Pharmacol, Silver Spring, MD USA. EM seongeun.cho@fda.hhs.gov NR 5 TC 2 Z9 2 U1 1 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 FEB PY 2011 VL 89 IS 2 BP 167 EP 169 DI 10.1038/clpt.2010.283 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 711JA UT WOS:000286585500008 PM 21252932 ER PT J AU Zhao, P Zhang, L Grillo, JA Liu, Q Bullock, JM Moon, YJ Song, P Brar, SS Madabushi, R Wu, TC Booth, BP Rahman, NA Reynolds, KS Berglund, EG Lesko, LJ Huang, SM AF Zhao, P. Zhang, L. Grillo, J. A. Liu, Q. Bullock, J. M. Moon, Y. J. Song, P. Brar, S. S. Madabushi, R. Wu, T. C. Booth, B. P. Rahman, N. A. Reynolds, K. S. Berglund, E. Gil Lesko, L. J. Huang, S-M TI Applications of Physiologically Based Pharmacokinetic (PBPK) Modeling and Simulation During Regulatory Review SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG-DRUG INTERACTIONS; IN-VITRO DATA; TISSUE DISTRIBUTION; MIDAZOLAM CLEARANCE; SILDENAFIL CITRATE; HUMAN-POPULATIONS; RENAL IMPAIRMENT; LIVER-CIRRHOSIS; STEADY-STATE; PREDICTION AB Physiologically based pharmacokinetic (PBPK) modeling and simulation is a tool that can help predict the pharmacokinetics of drugs in humans and evaluate the effects of intrinsic (e. g., organ dysfunction, age, genetics) and extrinsic (e. g., drug-drug interactions) factors, alone or in combinations, on drug exposure. The use of this tool is increasing at all stages of the drug development process. This report reviews recent instances of the use of PBPK in decision-making during regulatory review. The examples are based on Center for Drug Evaluation and Research reviews of several submissions for investigational new drugs (INDs) and new drug applications (NDAs) received between July 2008 and June 2010. The use of PBPK modeling and simulation facilitated the following types of decisions: the need to conduct specific clinical pharmacology studies, specific study designs, and appropriate labeling language. The report also discusses the challenges encountered when PBPK modeling and simulation were used in these cases and recommends approaches to facilitating full utilization of this tool. C1 [Zhao, P.; Zhang, L.; Grillo, J. A.; Liu, Q.; Bullock, J. M.; Moon, Y. J.; Song, P.; Brar, S. S.; Madabushi, R.; Wu, T. C.; Booth, B. P.; Rahman, N. A.; Reynolds, K. S.; Lesko, L. J.; Huang, S-M] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Berglund, E. Gil] Med Prod Agcy, Efficacy & Safety 2, Uppsala, Sweden. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM ShiewMei.Huang@fda.hhs.gov NR 45 TC 169 Z9 178 U1 3 U2 37 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 FEB PY 2011 VL 89 IS 2 BP 259 EP 267 DI 10.1038/clpt.2010.298 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 711JA UT WOS:000286585500024 PM 21191381 ER PT J AU Lee, HW Muniyappa, R Yan, X Yue, LQ Linden, EH Chen, H Hansen, BC Quon, MJ AF Lee, Ho-Won Muniyappa, Ranganath Yan, Xu Yue, Lilly Q. Linden, Ellen H. Chen, Hui Hansen, Barbara C. Quon, Michael J. TI Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys SO ENDOCRINOLOGY LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; DEPENDENT DIABETES-MELLITUS; FASTING PLASMA-GLUCOSE; REDUCES BLOOD-PRESSURE; GREEN TEA POLYPHENOL; METABOLIC SYNDROME; NONHUMAN-PRIMATES; ISLET AMYLOIDOSIS; MACACA-MULATTA; CHECK INDEX AB The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SI(Clamp) (r approximate to 0.4-0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies. (Endocrinology 152: 414-423, 2011) C1 [Lee, Ho-Won; Muniyappa, Ranganath; Chen, Hui; Quon, Michael J.] NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. [Yan, Xu; Yue, Lilly Q.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Linden, Ellen H.; Hansen, Barbara C.] Univ S Florida, Obes Diabet & Aging Res Ctr, Dept Pediat, Coll Med, St Petersburg, FL 33701 USA. [Linden, Ellen H.; Hansen, Barbara C.] Univ S Florida, Dept Internal Med, Coll Med, St Petersburg, FL 33701 USA. RP Lee, HW (reprint author), NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. RI Hansen, Barbara/J-8723-2012; OI Hansen, Barbara/0000-0001-9646-3525; Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU National Center for Complementary and Alternative Medicine, National Institutes of Health; American Diabetes Association FX This work was supported in part by the Intramural Research Program, National Center for Complementary and Alternative Medicine, National Institutes of Health, and in part by a Clinical Research Award from the American Diabetes Association (to M.J.Q.). The primate colony support was via National Institutes of Health National Institute on Aging N01AG3 1012 and continues under National Institutes of Health HHSN263200800022C, institutional, and private funds (to B.C.H.). NR 42 TC 14 Z9 14 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD FEB PY 2011 VL 152 IS 2 BP 414 EP 423 DI 10.1210/en.2010-1164 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 709FA UT WOS:000286422100012 PM 21209021 ER PT J AU Wu, KM Yao, JQ Boring, D AF Wu, Kuei-Meng Yao, Jiaqin Boring, Daniel TI Green Tea Extract-Induced Lethal Toxicity in Fasted but Not in Nonfasted Dogs SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE green tea extract; fasted dogs; polyphenols ID SAFETY AB Recent chronic toxicity studies performed on green tea extracts in fasted dogs have revealed some unique dose-limiting lethal liver, gastrointestinal, and renal toxicities. Key findings included necrosis of hepatic cells, gastrointestinal epithelia and renal tubules, atrophy of reproductive organs, atrophy and necrosis of hematopoietic tissues, and associated hematological changes. The polyphenol cachetins (a mixture of primarily epigallocatechin gallate [>= 55%]; plus up to 10% each of epigallocatechin, epicatechin, and epigallocatechin gallate) appeared to be the causative agents for the observed toxicities because they are the active ingredients of green tea extract studied. Conduct of the study in nonfasted dogs under the same testing conditions and dose levels showed unremarkable results. Assuming both studies were valid, at the identified no observed adverse effect levels (NOAEL) of each study, systemic exposures (based on area under the curve [AUC]) were actually lower in fasted than nonfasted dogs, suggesting that fasting may have rendered the target organ systems potentially more vulnerable to the effects of green tea extract. The toxicity mechanisms that produced lethality are not known, but the results are scientifically intriguing. Because tea drinking has become more popular in the United States and abroad, the mode of action and site of action of green tea extract-induced lethal toxicities during fasting and the role of other phytochemical components of Folia Camellia sinensis (including nonpolyphenol fractions, which are often consumed when whole-leaf products are presented) warrant further investigation. C1 [Wu, Kuei-Meng] US FDA, Div Antiviral Prod, CDER, Silver Spring, MD 20993 USA. [Yao, Jiaqin] US FDA, Div Dermatol & Dent Prod, CDER, Silver Spring, MD 20993 USA. [Boring, Daniel] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA. RP Wu, KM (reprint author), US FDA, Div Antiviral Prod, CDER, Silver Spring, MD 20993 USA. EM kueimeng.wu@fda.hhs.gov NR 9 TC 8 Z9 8 U1 2 U2 2 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 FEB PY 2011 VL 30 IS 1 BP 19 EP 20 DI 10.1177/1091581810387445 PG 2 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 733RJ UT WOS:000288280200002 PM 21098339 ER PT J AU Collison, M Khurana, T Slater, JE AF Collison, M. Khurana, T. Slater, J. E. TI Production of Single Chain Variable Fragment Antibodies (scFv) for the Characterization of German Cockroach (GCr) Extracts SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Collison, M.; Khurana, T.; Slater, J. E.] Lab Immunobiochem DBPAP CBER FDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB119 EP AB119 DI 10.1016/j.jaci.2010.12.476 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400458 ER PT J AU El Fiky, A Perreault, R Kirschman, K Rabin, RL AF El Fiky, A. Perreault, R. Kirschman, K. Rabin, R. L. TI Interferon beta Expression is Attenuated In Human Model of Alternatively Activated Macrophages SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [El Fiky, A.; Perreault, R.; Kirschman, K.; Rabin, R. L.] US FDA, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2011 VL 127 IS 2 SU S BP AB127 EP AB127 DI 10.1016/j.jaci.2010.12.506 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400488 ER PT J AU Hillyer, P Chen, A Navarro, M Schramm, LM Mane, VP Gold, DM Raviv, N Rabin, RL AF Hillyer, P. Chen, A. Navarro, M. Schramm, L. M. Mane, V. P. Gold, D. M. Raviv, N. Rabin, R. L. TI Strain Dependent Differences in Magnitude and Timing of Innate Immune Responses to Respiratory Syncytial Virus (RSV) in Human Monocyte Derived Dendritic Cells (MDDC) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT American-Academy-of-Allergy-Asthma-and-Immunology Annual Meeting CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol C1 [Hillyer, P.; Chen, A.; Navarro, M.; Schramm, L. M.; Mane, V. P.; Gold, D. M.; Raviv, N.; Rabin, R. L.] CBER FDA, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 FEB PY 2011 VL 127 IS 2 SU S BP AB166 EP AB166 DI 10.1016/j.jaci.2010.12.660 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400642 ER PT J AU Khurana, T Collison, M Chew, F Slater, JE AF Khurana, T. Collison, M. Chew, F. Slater, J. E. TI Identification of Novel Allergens of Blatella germanica using Single Chain Variable Fragment Antibodies SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI) CY MAR 18-22, 2011 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol (AAAAI) C1 [Khurana, T.; Collison, M.; Slater, J. E.] Lab Immunobiochem CBER FDA, Bethesda 117548, MD USA. [Chew, F.] Natl Univ Singapore, Dept Biol Sci, Allergy & Mol Immunol Lab, Singapore, Singapore. NR 0 TC 0 Z9 0 U1 3 U2 6 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 FEB PY 2011 VL 127 IS 2 SU S BP AB119 EP AB119 DI 10.1016/j.jaci.2010.12.477 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 832YI UT WOS:000295846400459 ER PT J AU Darney, S Fowler, B Grandjean, P Heindel, J Mattison, D Slikker, W AF Darney, Sally Fowler, Bruce Grandjean, Philippe Heindel, Jerrold Mattison, Donald Slikker, William, Jr. TI Prenatal Programming and Toxicity II (PPTOX II): Role of Environmental Stressors in the Developmental Origins of Disease SO JOURNAL OF DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Editorial Material C1 [Fowler, Bruce] Ctr Dis Control, Div Toxicol & Environm Med, ATSDR, Atlanta, GA 30333 USA. [Grandjean, Philippe] Univ So Denmark, Odense, Denmark. [Heindel, Jerrold] NIEHS, Organs & Syst Pathobiol Branch, Res Triangle Pk, NC USA. [Mattison, Donald] NICHD, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, HHS, Bethesda, MD USA. [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. OI Mattison, Donald/0000-0001-5623-0874 NR 2 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 2040-1744 J9 J DEV ORIG HLTH DIS JI J. Dev. Orig. Health Dis. PD FEB PY 2011 VL 2 IS 1 BP 2 EP 2 DI 10.1017/S2040174411000109 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 755LW UT WOS:000289933800001 ER PT J AU Zou, W Al-Khaldi, SF Branham, WS Han, T Fuscoe, JC Han, J Foley, SL Xu, J Fang, H Cerniglia, CE Nayak, R AF Zou, Wen Al-Khaldi, Sufian F. Branham, William S. Han, Tao Fuscoe, James C. Han, Jing Foley, Steven L. Xu, Joshua Fang, Hong Cerniglia, Carl E. Nayak, Rajesh TI Microarray analysis of virulence gene profiles in Salmonella serovars from food/food animal environment SO JOURNAL OF INFECTION IN DEVELOPING COUNTRIES LA English DT Article DE Salmonella; virulence associated genes; microarray; pathogenicity ID DNA MICROARRAY; PATHOGENICITY ISLANDS; ENTERICA SEROVARS; IDENTIFICATION; STRAINS; DISEASE; HOST AB Introduction: Rapid, accurate and inexpensive analysis of the disease-causing potential of foodborne pathogens is an important consideration in food safety and biodefense, particularly in developing countries. The objective of this study is to demonstrate the use of a robust and inexpensive microarray platform to assay the virulence gene profiles in Salmonella from food and/or the food animal environment, and then use ArrayTrack (TM) for data analysis. Methodology: The spotted array consisted of 69 selected Salmonella-specific virulence gene probes (65bp each). These probes were printed on poly-L-lysine-coated slides. Genomic DNA was digested with Sau3AI, labeled with Cy3 dye, hybridized to the gene probes, and the images were captured and analyzed by GenePix 4000B and ArrayTrack (TM), a free software developed by Food and Drug Administration (FDA) researchers. Results: Nearly 58% of the virulence-associated genes tested were present in all Salmonella strains tested. In general, genes belonging to inv, pip, prg, sic, sip, spa or ttr families were detected in more than 90% of the isolates, while the iacP, avrA, invH, rhuM, sirA, sopB, sopE or sugR genes were detected in 40 to 80% of the isolates. The gene variability was independent of the Salmonella serotype. Conclusions: This hybridization array presents an accurate and cost-effective method for evaluating the disease-causing potential of Salmonella in outbreak investigations by targeting a selective set of Salmonella-associated virulence genes. C1 [Han, Jing; Foley, Steven L.; Cerniglia, Carl E.; Nayak, Rajesh] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Zou, Wen] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Al-Khaldi, Sufian F.] US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Branham, William S.; Han, Tao; Fuscoe, James C.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Xu, Joshua; Fang, Hong] US FDA, Z Tech Corp, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nayak, R (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Rajesh.Nayak@fda.hhs.gov FU Oak Ridge Institute for Science and Education; US Department of Energy; US Food and Drug Administration FX We thank Drs. Mark Walderhaug from the USFDA Center for Food Safety and Applied Nutrition (CFSAN), Brett Kenney from West Virginia University, Doris Farmer from the USFDA Office of Regulatory Affairs (ORA), and Virginia L. Miller from Washington University for providing the Salmonella test and control strains. We thank Dr. Ronald Lorentzen from CFSAN for the travel fund from the USFDA Scientific Collaboration Program between CFSAN and the National Center for Toxicological Research (NCTR). We are grateful to Drs. James J. Chen, John Sutherland, Chris A. Elkins, Huizhong Chen, and Nathan Twaddle for critical reading of this manuscript. Wen Zou and Jing Han acknowledge support of their fellowships from the Oak Ridge Institute for Science and Education, administered through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 31 TC 22 Z9 26 U1 0 U2 5 PU J INFECTION DEVELOPING COUNTRIES PI TRAMANIGLIO PA JIDC CENT OFF PORTO CONTE RICERCHE RES CTR, S P 55, PORTO CONTE CAPO CACCIA KM 8.400 LOC, TRAMANIGLIO, 07041, ITALY SN 1972-2680 J9 J INFECT DEV COUNTR JI J. Infect. Dev. Ctries. PD FEB PY 2011 VL 5 IS 2 BP 94 EP 105 PG 12 WC Infectious Diseases SC Infectious Diseases GA 905BR UT WOS:000301246800003 PM 21389588 ER PT J AU Macintyre, HL Stutes, AL Smith, WL Dorsey, CP Abraham, A Dickey, RW AF Macintyre, Hugh L. Stutes, Adrienne L. Smith, William L. Dorsey, Carol P. Abraham, Ann Dickey, Robert W. TI Environmental correlates of community composition and toxicity during a bloom of Pseudo-nitzschia spp. in the northern Gulf of Mexico SO JOURNAL OF PLANKTON RESEARCH LA English DT Article DE Pseudo-nitzschia; bloom; pigment; domoic acid; temperature; groundwater discharge ID DOMOIC ACID PRODUCTION; INORGANIC CARBON ACQUISITION; HARMFUL ALGAL BLOOMS; MARINE-PHYTOPLANKTON; RUBISCO ACTIVASE; ELECTRON-TRANSPORT; PHOTOSYNTHETIC PARAMETERS; TEMPERATURE ADAPTATION; SILICATE LIMITATION; SPECTRAL ABSORPTION AB The potentially toxic diatom genus Pseudo-nitzschia is a common component of the microalgal assemblage in the northern Gulf of Mexico. We characterized community structure in Mobile Bay and the adjacent littoral Gulf in a bloom year (2005) and non-bloom year (2006). In both cases, a shift from domination by eukaryotes to cyanobacteria was correlated with seasonal changes in temperature, whereas the overall biomass was correlated with total nutrient concentrations down the estuarine salinity gradient. The bloom of Pseudo-nitzschia spp. followed a period of high discharge from local aquifers that are highly contaminated with nitrate. The diatom assemblage in both bloom and non-bloom years was dominated by a suite of 12 common genera that formed three distinct clusters. The first cluster contained a single centric genus and dominated only a small fraction of samples. The second comprised four benthic and tychopelagic genera and was most common inside the shallow waters of Mobile Bay. The third comprised seven planktonic genera, including Pseudo-nitzschia spp., which was most closely associated with two well-described bloom-forming genera, Chaeloceros and Skeletonema. We argue that these occupy a ruderal niche, blooming after peaks in discharge of submarine groundwater along the littoral Gulf of Mexico. The 2005 bloom of Pseudo-nitzschia spp. was toxic, with domoic acid concentrations reaching 8.0 mu g L(-1) and mean cell toxin quotas reaching 4.9 pg cell(-1). The mean cell toxin quotas were highly correlated (R = 0.97) with a multivariate statistic based on environmental data and were maximal at low silicate concentration, high salinity and dissolved inorganic carbon, and high irradiance. The correlations are consistent with photoacclimative status, with toxicity being highest under conditions likely to lead to excess "photon pressure", an imbalance between generation of photosynthetic reductant and its consumption downstream. C1 [Macintyre, Hugh L.; Stutes, Adrienne L.] Dauphin Isl Sea Lab, Dauphin Isl, AL 36528 USA. [Macintyre, Hugh L.] Dalhousie Univ, Dept Oceanog, Halifax, NS B3H 4J1, Canada. [Stutes, Adrienne L.] Hart Crowser Inc, Seattle, WA 98109 USA. [Smith, William L.; Dorsey, Carol P.; Abraham, Ann] Alabama Dept Publ Hlth, Mobile Div Lab, Mobile, AL 36608 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Macintyre, HL (reprint author), Dauphin Isl Sea Lab, 101 Bienville Blvd, Dauphin Isl, AL 36528 USA. EM hugh.macintyre@dal.ca RI MacIntyre, Hugh/B-4555-2011 OI MacIntyre, Hugh/0000-0002-8852-6984 FU EPA Alabama Center for Estuarine Research; Alabama Oyster Reef Restoration Program; Mobile Bay National Estuary Program FX Aspects of this work were supported by grants from EPA Alabama Center for Estuarine Research, Alabama Oyster Reef Restoration Program and the Mobile Bay National Estuary Program to HM. NR 123 TC 22 Z9 22 U1 3 U2 43 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0142-7873 J9 J PLANKTON RES JI J. Plankton Res. PD FEB PY 2011 VL 33 IS 2 BP 273 EP 295 DI 10.1093/plankt/fbq146 PG 23 WC Marine & Freshwater Biology; Oceanography SC Marine & Freshwater Biology; Oceanography GA 716FC UT WOS:000286953500007 ER PT J AU Plinston, C Hart, P Chong, A Hunter, N Foster, J Piccardo, P Manson, JC Barron, RM AF Plinston, Chris Hart, Patricia Chong, Angela Hunter, Nora Foster, James Piccardo, Pedro Manson, Jean C. Barron, Rona M. TI Increased Susceptibility of Human-PrP Transgenic Mice to Bovine Spongiform Encephalopathy Infection following Passage in Sheep SO JOURNAL OF VIROLOGY LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; HUMAN PRION PROTEIN; HUMAN TRANSMISSION; BSE INFECTIVITY; SCRAPIE AGENT; VARIANT CJD; STRAIN; BRAIN; VCJD; GOAT AB The risk of the transmission of ruminant transmissible spongiform encephalopathy (TSE) to humans was thought to be low due to the lack of association between sheep scrapie and the incidence of human TSE. However, a single TSE agent strain has been shown to cause both bovine spongiform encephalopathy (BSE) and human vCJD, indicating that some ruminant TSEs are transmissible to humans. While the transmission of cattle BSE to humans in transgenic mouse models has been inefficient, indicating the presence of a significant transmission barrier between cattle and humans, BSE has been transmitted to a number of other species. Here, we aimed to further investigate the human transmission barrier following the passage of BSE in a sheep. Following inoculation with cattle BSE, gene-targeted transgenic mice expressing human PrP showed no clinical or pathological signs of TSE disease. However, following inoculation with an isolate of BSE that had been passaged through a sheep, TSE-associated vacuolation and proteinase K-resistant PrP deposition were observed in mice homozygous for the codon 129-methionine PRNP gene. This observation may be due to higher titers of the BSE agent in sheep or an increased susceptibility of humans to BSE prions following passage through a sheep. However, these data confirm that, contrary to previous predictions, it is possible that a sheep prion is transmissible to humans and that BSE from other species is a public health risk. C1 [Plinston, Chris; Hart, Patricia; Chong, Angela; Hunter, Nora; Foster, James; Piccardo, Pedro; Manson, Jean C.; Barron, Rona M.] Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Roslin EH25 9PS, Midlothian, Scotland. [Plinston, Chris; Hart, Patricia; Chong, Angela; Hunter, Nora; Foster, James; Piccardo, Pedro; Manson, Jean C.; Barron, Rona M.] Univ Edinburgh, RDSVS, Roslin EH25 9PS, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Lab Bacterial & TSE Agents, Rockville, MD 20857 USA. RP Barron, RM (reprint author), Univ Edinburgh, Roslin Inst, Neuropathogenesis Div, Roslin EH25 9PS, Midlothian, Scotland. EM rona.barron@roslin.ed.ac.uk RI Barron, Rona/C-7703-2013; OI Barron, Rona/0000-0003-4512-9177; Hart, Patricia/0000-0002-9634-3483 FU United Kingdom Department for Environment, Food and Rural Affairs (Defra) [SE1439, SE1441]; NIH-NIAID [Y1-A1-4893-02, 224-05-1307] FX This work was funded by contracts SE1439 and SE1441 from the United Kingdom Department for Environment, Food and Rural Affairs (Defra), and NIH-NIAID agreement Y1-A1-4893-02 and FDA agreement 224-05-1307. NR 31 TC 26 Z9 26 U1 0 U2 7 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 FEB PY 2011 VL 85 IS 3 BP 1174 EP 1181 DI 10.1128/JVI.01578-10 PG 8 WC Virology SC Virology GA 705PC UT WOS:000286147400002 PM 21084466 ER PT J AU Freed, M de Zwart, JA Loud, JT El Khouli, RH Myers, KJ Greene, MH Duyn, JH Badano, A AF Freed, Melanie de Zwart, Jacco A. Loud, Jennifer T. El Khouli, Riham H. Myers, Kyle J. Greene, Mark H. Duyn, Jeff H. Badano, Aldo TI An anthropomorphic phantom for quantitative evaluation of breast MRI SO MEDICAL PHYSICS LA English DT Article DE breast imaging; phantom; standardization; MRI ID CONTRAST-ENHANCED MRI; PREOPERATIVE ASSESSMENT; PARAMETER-ESTIMATION; SURGICAL-MANAGEMENT; DIAGNOSTIC-ACCURACY; RELAXATION-TIMES; CANCER; TISSUE; IMPACT; OPTIMIZATION AB Purpose: In this study, the authors aim to develop a physical, tissue-mimicking phantom for quantitative evaluation of breast MRI protocols. The objective of this phantom is to address the need for improved standardization in breast MRI and provide a platform for evaluating the influence of image protocol parameters on lesion detection and discrimination. Quantitative comparisons between patient and phantom image properties are presented. Methods: The phantom is constructed using a mixture of lard and egg whites, resulting in a random structure with separate adipose- and glandular-mimicking components. T(1) and T(2) relaxation times of the lard and egg components of the phantom were estimated at 1.5 T from inversion recovery and spin-echo scans, respectively, using maximum-likelihood methods. The image structure was examined quantitatively by calculating and comparing spatial covariance matrices of phantom and patient images. A static, enhancing lesion was introduced by creating a hollow mold with stereolithography and filling it with a gadolinium-doped water solution. Results: Measured phantom relaxation values fall within 2 standard errors of human values from the literature and are reasonably stable over 9 months of testing. Comparison of the covariance matrices of phantom and patient data demonstrates that the phantom and patient data have similar image structure. Their covariance matrices are the same to within error bars in the anterior-posterior direction and to within about two error bars in the right-left direction. The signal from the phantom's adipose-mimicking material can be suppressed using active fat-suppression protocols. A static, enhancing lesion can also be included with the ability to change morphology and contrast agent concentration. Conclusions: The authors have constructed a phantom and demonstrated its ability to mimic human breast images in terms of key physical properties that are relevant to breast MRI. This phantom provides a platform for the optimization and standardization of breast MRI imaging protocols for lesion detection and characterization. [DOI: 10.1118/1.3533899] C1 [Freed, Melanie; Myers, Kyle J.; 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.; Duyn, Jeff H.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA. [Loud, Jennifer T.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [El Khouli, Riham H.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA. [El Khouli, Riham H.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. [El Khouli, Riham H.] Suez Canal Univ, Sch Med, Dept Diagnost Radiol, Ismailia, Egypt. 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 Office of Women's Health at the Food and Drug Administration; Center for Devices and Radiological Health; U.S. Department of Energy; U.S. Food and Drug Administration; NINDS/NIH; NCI FX The authors thank Rachel Brem (GWU Hospital), Brian Garra (FDA/CDRH), and Eileen Thompson (GWU Hospital) for acquisition of GE clinical images of the phantom; Eugene O'Bryan, Randy Bidinger, and Bruce Fleharty (FDA/CDRH) for advice on design and construction of custom phantom jars; Brandon D. Gallas (FDA/CDRH) for discussions on covariance matrices and maximum-likelihood estimation; Christian Graff for discussions on bounded maximization; and Han Wen (NHLBI/NIH) for providing MRI scan time. The authors also acknowledge the use of facilities in Radiology and Imaging Sciences at the NIH Clinical Center. This study was supported, in part, by a research grant from the Office of Women's Health at the Food and Drug Administration. This project was supported, in part, by an appointment to the Research Participation Program at the Center for Devices and Radiological Health administered by 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. J. T. Loud and M. H. Greene were supported by funding from the NCI Intramural Research Program. NR 60 TC 13 Z9 13 U1 0 U2 10 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 FEB PY 2011 VL 38 IS 2 BP 743 EP 753 DI 10.1118/1.3533899 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 716DI UT WOS:000286945000022 PM 21452712 ER PT J AU Armato, SG McLennan, G Bidaut, L McNitt-Gray, MF Meyer, CR Reeves, AP Zhao, BS Aberle, DR Henschke, CI Hoffman, EA Kazerooni, EA MacMahon, H van Beek, EJR Yankelevitz, D Biancardi, AM Bland, PH Brown, MS Engelmann, RM Laderach, GE Max, D Pais, RC Qing, DPY Roberts, RY Smith, AR Starkey, A Batra, P Caligiuri, P Farooqi, A Gladish, GW Jude, CM Munden, RF Petkovska, I Quint, LE Schwartz, LH Sundaram, B Dodd, LE Fenimore, C Gur, D Petrick, N Freymann, J Kirby, J Hughes, B Casteele, AV Gupte, S Sallam, M Heath, MD Kuhn, MH Dharaiya, E Burns, R Fryd, DS Salganicoff, M Anand, V Shreter, U Vastagh, S Croft, BY Clarke, LP AF Armato, Samuel G., III McLennan, Geoffrey Bidaut, Luc McNitt-Gray, Michael F. Meyer, Charles R. Reeves, Anthony P. Zhao, Binsheng Aberle, Denise R. Henschke, Claudia I. Hoffman, Eric A. Kazerooni, Ella A. MacMahon, Heber van Beek, Edwin J. R. Yankelevitz, David Biancardi, Alberto M. Bland, Peyton H. Brown, Matthew S. Engelmann, Roger M. Laderach, Gary E. Max, Daniel Pais, Richard C. Qing, David P-Y Roberts, Rachael Y. Smith, Amanda R. Starkey, Adam Batra, Poonam Caligiuri, Philip Farooqi, Ali Gladish, Gregory W. Jude, C. Matilda Munden, Reginald F. Petkovska, Iva Quint, Leslie E. Schwartz, Lawrence H. Sundaram, Baskaran Dodd, Lori E. Fenimore, Charles Gur, David Petrick, Nicholas Freymann, John Kirby, Justin Hughes, Brian Casteele, Alessi Vande Gupte, Sangeeta Sallam, Maha Heath, Michael D. Kuhn, Michael H. Dharaiya, Ekta Burns, Richard Fryd, David S. Salganicoff, Marcos Anand, Vikram Shreter, Uri Vastagh, Stephen Croft, Barbara Y. Clarke, Laurence P. TI The Lung Image Database Consortium, (LIDC) and Image Database Resource Initiative (IDRI): A Completed Reference Database of Lung Nodules on CT Scans SO MEDICAL PHYSICS LA English DT Article DE lung nodule; computed tomography (CT); thoracic imaging; interobserver variability; computer-aided diagnosis (CAD) ID COMPUTED-TOMOGRAPHY SCANS; PULMONARY NODULES; SCREENING TRIAL; AIDED DETECTION; CANCER; TRUTH; PERFORMANCE; SELECTION; NELSON; CAD AB Purpose: The development of computer-aided diagnostic (CAD) methods for lung nodule detection, classification, and quantitative assessment can be facilitated through a well-characterized repository of computed tomography (CT) scans. The Lung Image Database Consortium (LIDC) and Image Database Resource Initiative (IDRI) completed such a database, establishing a publicly available reference for the medical imaging research community. Initiated by the National Cancer Institute (NCI), further advanced by the Foundation for the National Institutes of Health (FNIH), and accompanied by the Food and Drug Administration (FDA) through active participation, this public-private partnership demonstrates the success of a consortium founded on a consensus-based process. Methods: Seven academic centers and eight medical imaging companies collaborated to identify, address, and resolve challenging organizational, technical, and clinical issues to provide a solid foundation for a robust database. The LIDC/IDRI Database contains 1018 cases, each of which includes images from a clinical thoracic CT scan and an associated XML file that records the results of a two-phase image annotation process performed by four experienced thoracic radiologists. In the initial blinded-read phase, each radiologist independently reviewed each CT scan and marked lesions belonging to one of three categories ("nodule >= 3 mm," "nodule < 3 mm," and "non-nodule >= 3 mm"). In the subsequent unblinded-read phase, each radiologist independently reviewed their own marks along with the anonymized marks of the three other radiologists to render a final opinion. The goal of this process was to identify as completely as possible all lung nodules in each CT scan without requiring forced consensus. Results: The Database contains 7371 lesions marked "nodule" by at least one radiologist. 2669 of these lesions were marked "nodule >= 3 mm" by at least one radiologist, of which 928 (34.7%) received such marks from all four radiologists. These 2669 lesions include nodule outlines and subjective nodule characteristic ratings. Conclusions: The LIDC/IDRI Database is expected to provide an essential medical imaging research resource to spur CAD development, validation, and dissemination in clinical practice. [DOI: 10.1118/1.3528204] C1 [Armato, Samuel G., III; MacMahon, Heber; Engelmann, Roger M.; Roberts, Rachael Y.; Caligiuri, Philip] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [McLennan, Geoffrey] Univ Iowa, Carver Coll Med, Dept Internal Med, Div Pulm, Iowa City, IA 52242 USA. [McNitt-Gray, Michael F.; Aberle, Denise R.; Brown, Matthew S.; Pais, Richard C.; Qing, David P-Y; Batra, Poonam; Jude, C. Matilda; Petkovska, Iva] Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol Sci, Los Angeles, CA 90024 USA. [Meyer, Charles R.] Univ Michigan, Dept Radiol, Sch Med, Ann Arbor, MI 48109 USA. [Reeves, Anthony P.; Biancardi, Alberto M.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY 14853 USA. [Zhao, Binsheng] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10065 USA. [Henschke, Claudia I.; Yankelevitz, David; Max, Daniel; Farooqi, Ali] Mt Sinai Sch Med, Dept Radiol, New York, NY 10029 USA. [Hoffman, Eric A.; van Beek, Edwin J. R.; Smith, Amanda R.] Univ Iowa, Carver Coll Med, Dept Radiol, Iowa City, IA 52242 USA. [Kazerooni, Ella A.] Univ Michigan Hlth Syst, Dept Radiol, Cardiovasc Ctr 5482, Ann Arbor, MI 48109 USA. [Bland, Peyton H.; Laderach, Gary E.] Univ Michigan, Dept Radiol, BSRB A502, Ann Arbor, MI 48109 USA. [Gladish, Gregory W.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Radiol, Unit 1478, Houston, TX 77030 USA. [Munden, Reginald F.] Univ Texas MD Anderson Canc Ctr, Dept Diagnost Imaging, Unit 1478, Houston, TX 77030 USA. [Schwartz, Lawrence H.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10065 USA. [Sundaram, Baskaran] Univ Michigan Hlth Syst, Dept Radiol, CVC 5481, Ann Arbor, MI 48109 USA. [Fenimore, Charles] NIST, Informat Access Div, Gaithersburg, MD 20899 USA. [Gur, David] Univ Pittsburgh, Dept Radiol, Pittsburgh, PA 15213 USA. [Petrick, Nicholas] US FDA, Silver Spring, MD 20993 USA. [Freymann, John; Kirby, Justin] SAIC Frederick Inc, Bethesda, MD 20892 USA. [Hughes, Brian] TerpSys, Rockville, MD 20852 USA. [Casteele, Alessi Vande] Agfa HealthCare NV, B-2640 Mortsel, Belgium. [Gupte, Sangeeta] FUJIFILM Med Syst USA Inc, Stamford, CT 06902 USA. [Sallam, Maha] iCAD Inc, Nashua, NH 03062 USA. [Heath, Michael D.] Carestream Hlth Inc, Rochester, NY 14615 USA. [Kuhn, Michael H.] Philips Med Syst DMC GmbH, D-22315 Hamburg, Germany. [Dharaiya, Ekta] Philips Healthcare, Highland Hts, OH 44143 USA. [Burns, Richard; Fryd, David S.] Riverain Med, Miamisburg, OH 45342 USA. [Salganicoff, Marcos; Anand, Vikram] Siemens Med Solut USA Inc, Malvern, PA 19355 USA. [Shreter, Uri] GE Healthcare, Waukesha, WI 53188 USA. [Vastagh, Stephen] Med Imaging & Technol Alliance, Arlington, VA 22209 USA. [Croft, Barbara Y.; Clarke, Laurence P.] NCI, Canc Imaging Program, Bethesda, MD 20892 USA. [Henschke, Claudia I.] Weill Cornell Med Coll, Dept Radiol, New York, NY USA. RP Armato, SG (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave,MC 2026, Chicago, IL 60637 USA. EM s-armato@uchicago.edu RI Croft, Barbara/D-1248-2013; OI Croft, Barbara/0000-0003-2544-150X; Bidaut, Luc/0000-0001-8253-2606; Munden, Reginald/0000-0003-3836-5067; Aberle, Denise/0000-0002-8858-3401 FU USPHS [U01CA091085, U01CA091090, U01CA091099, U01CA091100, U01CA091103]; NCI [HHSN261200800001E]; Foundation for the National Institutes of Health; University of Chicago; American Legacy Foundation; Flight Attendants' Medical Research Institute; AstraZeneca, Inc.; GlaxoSmithKline and Carestream Health Inc. FX This paper is dedicated to the memory of Geoffrey McLennan, M. D., Ph.D., who served as the Chair of the LIDC/IDRI Steering Committee since the inception of the project. Dr. McLennan provided the constant source of motivation, perspective, and determination that moved this database from an idea to reality. His extraordinary scientific and clinical vision, combined with his unfettered perseverance and uncompromising optimism, will be greatly missed by all his co-authors, colleagues, and friends. The authors would like express their sincere appreciation to the late Robert F. Wagner, Ph.D., whose enlightened perspective on medical image analysis performance studies provided the foundation for the statistical considerations on which the LIDC/IDRI Database was founded. Supported in part by USPHS Grant Nos. U01CA091085, U01CA091090, U01CA091099, U01CA091100, and U01CA091103 and by NCI Contract No. HHSN261200800001E. Funding was obtained through the Foundation for the National Institutes of Health from contributions provided by the medical imaging companies that participated in the IDRI. Disclosure statement: S. G. A. and H. M. receive royalties and licensing fees through the University of Chicago related to computer-aided diagnosis. H. M. is a consultant to Riverain, a company that produces software for lung nodule detection. A. P. R. is a paid consultant of and holds stock in VisionGate, Inc. A. P. R. is a coinventor on a patent and other pending patents owned by Cornell Research Foundation which are non-exclusively licensed to General Electric and are related to technology involving computer-aided diagnostic methods, including measurement of nodules. A. P. R. receives research support in the form of grants and contracts from: NCI, American Legacy Foundation, Flight Attendants' Medical Research Institute, AstraZeneca, Inc., GlaxoSmithKline and Carestream Health Inc. D.Y. is a named inventor on a number of patents and patent applications relating to the evaluation of diseases of the chest including measurement of nodules. Some of these, which are owned by Cornell Research Foundation (CRF) are nonexclusively licensed to General Electric. As an inventor of these patents, D.Y. is entitled to a share of any compensation which CRF may receive from its commercialization of these patents. NR 45 TC 139 Z9 144 U1 3 U2 38 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 FEB PY 2011 VL 38 IS 2 BP 915 EP 931 DI 10.1118/1.3528204 PG 17 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 716DI UT WOS:000286945000038 PM 21452728 ER PT J AU Kurhanewicz, J Vigneron, DB Brindle, K Chekmenev, EY Comment, A Cunningham, CH DeBerardinis, RJ Green, GG Leach, MO Rajan, SS Rizi, RR Ross, BD Warren, WS Malloy, CR AF Kurhanewicz, John Vigneron, Daniel B. Brindle, Kevin Chekmenev, Eduard Y. Comment, Arnaud Cunningham, Charles H. DeBerardinis, Ralph J. Green, Gary G. Leach, Martin O. Rajan, Sunder S. Rizi, Rahim R. Ross, Brian D. Warren, Warren S. Malloy, Craig R. TI Analysis of Cancer Metabolism by Imaging Hyperpolarized Nuclei: Prospects for Translation to Clinical Research SO NEOPLASIA LA English DT Article ID MAGNETIC-RESONANCE-SPECTROSCOPY; C-13 MR SPECTROSCOPY; TUMOR-CELL GROWTH; IN-VIVO; CARBOXYPEPTIDASE G2; NMR-SPECTROSCOPY; CONTRAST AGENT; BREAST-CANCER; PARA-HYDROGEN; BRAIN-TUMORS AB A major challenge in cancer biology is to monitor and understand cancer metabolism in vivo with the goal of improved diagnosis and perhaps therapy. Because of the complexity of biochemical pathways, tracer methods are required for detecting specific enzyme-catalyzed reactions. Stable isotopes such as C-13 or N-15 with detection by nuclear magnetic resonance provide the necessary information about tissue biochemistry, but the crucial metabolites are present in low concentration and therefore are beyond the detection threshold of traditional magnetic resonance methods. A solution is to improve sensitivity by a factor of 10,000 or more by temporarily redistributing the populations of nuclear spins in a magnetic field, a process termed hyperpolarization. Although this effect is short-lived, hyperpolarized molecules can be generated in an aqueous solution and infused in vivo where metabolism generates products that can be imaged. This discovery lifts the primary constraint on magnetic resonance imaging for monitoring metabolism-poor sensitivity-while preserving the advantage of biochemical information. The purpose of this report was to briefly summarize the known abnormalities in cancer metabolism, the value and limitations of current imaging methods for metabolism, and the principles of hyperpolarization. Recent preclinical applications are described. Hyperpolarization technology is still in its infancy, and current polarizer equipment and methods are suboptimal. Nevertheless, there are no fundamental barriers to rapid translation of this exciting technology to clinical research and perhaps clinical care. C1 [Kurhanewicz, John; Vigneron, Daniel B.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94158 USA. [Brindle, Kevin] Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. [Chekmenev, Eduard Y.] Vanderbilt Univ, Dept Radiol, Nashville, TN USA. [Cunningham, Charles H.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Toronto, ON, Canada. [Comment, Arnaud] Ecole Polytech Fed Lausanne, Lab Funct & Metab Imaging, Lausanne, Switzerland. [DeBerardinis, Ralph J.] UT SW Med Ctr, Dept Pediat, Dallas, TX USA. [Green, Gary G.] Univ York, York Neuroimaging Ctr, York YO10 5DD, N Yorkshire, England. [Leach, Martin O.] Royal Marsden Hosp, Inst Canc Res, London SW3 6JJ, England. [Rajan, Sunder S.] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA. [Rizi, Rahim R.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Ross, Brian D.] Huntington Med Res Inst, Dept Magnet Resonance Spect, Pasadena, CA USA. [Warren, Warren S.] Duke Univ, Dept Chem, Durham, NC 27706 USA. [Malloy, Craig R.] UT SW Med Ctr, Adv Imaging Res Ctr, Dallas, TX USA. [Malloy, Craig R.] VA N Texas Healthcare Syst, Dallas, TX USA. RP Kurhanewicz, J (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, Mission Bay Campus,Byers Hall,Room 203E,1700 4th, San Francisco, CA 94158 USA. EM John.Kurhanewicz@radiology.ucsf.edu RI leach, martin/C-2248-2008; Comment, Arnaud/G-5693-2011; Green, Gary/D-3543-2009; Chekmenev, Eduard/J-5908-2013 OI Chekmenev, Eduard/0000-0002-8745-8801; leach, martin/0000-0002-0756-5368; Comment, Arnaud/0000-0002-8484-3448; Green, Gary/0000-0003-1977-7509; FU NCRR NIH HHS [P41 RR002584]; NIBIB NIH HHS [R01 EB002122] NR 151 TC 309 Z9 312 U1 10 U2 81 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD FEB PY 2011 VL 13 IS 2 BP 81 EP 97 DI 10.1593/neo.101102 PG 17 WC Oncology SC Oncology GA 716DC UT WOS:000286944300001 PM 21403835 ER PT J AU Liu, YX Lo, YC Qian, L Crews, FT Wilson, B Chen, HL Wu, HM Chen, SH Wei, K Lu, RB Ali, S Hong, JS AF Liu, Yuxin Lo, Yi-Ching Qian, Li Crews, Fulton Tim Wilson, Belinda Chen, Hui-Ling Wu, Hung-Ming Chen, Shih-Heng Wei, Ke Lu, Ru-Band Ali, Syed Hong, Jau-Shyong TI Verapamil protects dopaminergic neuron damage through a novel anti-inflammatory mechanism by inhibition of microglial activation SO NEUROPHARMACOLOGY LA English DT Article DE Calcium channel blocker; Oxidative stress and neuroinflammation ID CALCIUM-CHANNEL BLOCKERS; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; NITRIC-OXIDE SYNTHASE; SUPEROXIDE GENERATION; RACEMIC VERAPAMIL; CEREBRAL-ISCHEMIA; HUMAN-NEUTROPHILS; NEUROPROTECTION; EXPRESSION; ANTAGONISTS AB Verapamil has been shown to be neuroprotective in several acute neurotoxicity models due to blockade of calcium entry into neurons. However, the potential use of veraparnil to treat chronic neurodegenerative diseases has not been reported. Using rat primary mesencephalic neuron/glia cultures, we report that verapamil significantly inhibited LPS-induced dopaminergic neurotoxicity in both pre- and post-treatment experiments. Reconstituted culture studies revealed that the presence of microglia was essential in verapamil-elicited neuroprotection. Mechanistic studies showed that decreased production of inflammatory mediators from LPS-stimulated microglia underlay neuroprotective property of verapamil. Further studies demonstrated that microglial NADPH oxidase (PHOX), the key superoxide-producing enzyme, but not calcium channel in neurons, is the site of action for the neuroprotective effect of verapamil. This conclusion was supported by the following two observations: 1) Verapamil failed to show protective effect on LPS-induced dopaminergic neurotoxicity in PHOX-deficient (deficient in the catalytic subunit of gp91(phox)) neuron/glia cultures: 2) Ligand binding studies showed that the binding of [H-3]Verapamil onto gp91(phox) transfected COS7 cell membranes was higher than the non-transfected control. The calcium channel-independent neuroprotective property of verapamil was further supported by the finding that R(+)-verapamil, a less active form in blocking calcium channel, showed the same potency in neuroprotection, inhibition of pro-inflammatory factors production and binding capacity to gp91(phox) membranes as R(-)-verapamil, the active isomer of calcium channel blocker. In conclusion, our results demonstrate a new indication of verapamil-mediated neuroprotection through a calcium channel-independent pathway and provide a valuable avenue for the development of therapy for inflammation-related neurodegenerative diseases. Published by Elsevier Ltd. C1 [Liu, Yuxin; Lo, Yi-Ching; Qian, Li; Wilson, Belinda; Chen, Hui-Ling; Wu, Hung-Ming; Chen, Shih-Heng; Wei, Ke; Hong, Jau-Shyong] Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. [Lo, Yi-Ching] Kaohsiung Med Univ, Dept Pharmacol, Kaohsiung 807, Taiwan. [Crews, Fulton Tim] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. [Liu, Yuxin] Hebei Univ, Sch Pharmaceut Sci, Lab Cell Pharmacol, Baoding, Peoples R China. [Chen, Hui-Ling; Wu, Hung-Ming; Chen, Shih-Heng; Lu, Ru-Band] Natl Cheng Kung Univ & Hosp, Dept Psychiat, Tainan, Taiwan. [Ali, Syed] Neurochem Lab NCTR, Jefferson, AR USA. RP Hong, JS (reprint author), Natl Inst Environm Hlth Sci, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov FU National Institutes of Health, National Institute of Environmental Health Sciences, U.S.A.; NIAAA; UNC Bowles Center for Alcohol Studies, U.S.A.; National Science Council, Taiwan [NSC-96-2320-B-037-039-MY3] FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences, U.S.A.; the Extramural grants from NIAAA (FTC) as well as The UNC Bowles Center for Alcohol Studies (YL and FTC), U.S.A.; and the National Science Council (grant NSC-96-2320-B-037-039-MY3), Taiwan. NR 34 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD FEB-MAR PY 2011 VL 60 IS 2-3 BP 373 EP 380 DI 10.1016/j.neuropharm.2010.10.002 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 717NL UT WOS:000287054600021 PM 20950631 ER PT J AU Mendrick, DL AF Mendrick, Donna L. TI Transcriptional profiling to identify biomarkers of disease and drug response SO PHARMACOGENOMICS LA English DT Review DE biomarkers; blood gene expression; genomics; microarray; miRNA; personalized; medicine pharmacogenomics; PMN translational ID GENE-EXPRESSION PROFILES; BLOOD MONONUCLEAR-CELLS; JUVENILE IDIOPATHIC ARTHRITIS; CORONARY-ARTERY-DISEASE; INDUCED LIVER-INJURY; PERIPHERAL-BLOOD; HUNTINGTONS-DISEASE; ISCHEMIC-STROKE; MOLECULAR CLASSIFICATION; CIRCULATING MICRORNAS AB The discovery, biological qualification and analytical validation of genomic biomarkers requires extensive collaborations between individuals with expertise in biology, statistics, bioinformatics, chemistry, clinical medicine, regulatory science and so on. For clinical utility, blood-borne biomarkers (e.g., mRNA and miRNA) of organ damage, drug toxicity and/or response would be preferred to those that are tissue based. Currently used biomarkers such as serum creatinine (indicating renal dysfunction) denote organ damage whether caused by disease, physical injury or drugs. Therefore, it is anticipated that studies of disease will discover biomarkers that can also be used to identify drug-induced injury and vice versa. This article describes transcriptomic blood-borne biomarkers that have been reported to be connected with disease and drug toxicity. Much more qualification and validation needs to be carried out before many of these biomarkers can prove useful. Discussed here are some of the lessons learned and roadblocks to success. C1 US FDA, Div Syst Biol, HFT 230, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mendrick, DL (reprint author), US FDA, Div Syst Biol, HFT 230, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM donna.mendrick@fda.hhs.gov NR 89 TC 21 Z9 21 U1 0 U2 11 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 FEB PY 2011 VL 12 IS 2 BP 235 EP 249 DI 10.2217/PGS.10.184 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 741RE UT WOS:000288881000015 PM 21332316 ER PT J AU Jacob, CC Reimschuessel, R Von Tungeln, LS Olson, GR Warbritton, AR Hattan, DG Beland, FA da Costa, GG AF Jacob, Cristina C. Reimschuessel, Renate Von Tungeln, Linda S. Olson, Greg R. Warbritton, Alan R. Hattan, David G. Beland, Frederick A. da Costa, Goncalo Gamboa TI Dose-Response Assessment of Nephrotoxicity from a 7-Day Combined Exposure to Melamine and Cyanuric Acid in F344 Rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE melamine; cyanuric acid; melamine cyanurate; nephrotoxicity ID TOXICITY; CATS AB The intentional adulteration of pet food with melamine and derivatives, including cyanuric acid, has been implicated in the kidney failure and death of a large number of cats and dogs in the United States. Although individually these compounds present low toxicity, coexposure can lead to the formation of melamine cyanurate crystals in the nephrons and eventual kidney failure. To determine the dose-response for nephrotoxicity upon coadministration of melamine and cyanuric acid, groups of male and female F344 rats (six animals per sex per group) were fed 0 (control), 7, 23, 69, 229, or 694 ppm of both melamine and cyanuric acid; 1388 ppm melamine; or 1388 ppm cyanuric acid in the diet for 7 days. No toxicity was observed in the rats exposed to the individual compounds, whereas anorexia and a statistically significant increase in blood urea nitrogen and serum creatinine levels was observed in the animals treated with 229 and 694 ppm melamine and cyanuric acid. The kidneys of these animals were grossly enlarged and pale yellow. Large numbers of crystalline structures deposited in the tubules were seen on sections in kidneys from all rats in these treatment groups. No significant changes were detected in the remaining treatment groups exposed to both melamine and cyanuric acid. In the melamine-only treatment group, 5 of 12 rats had scattered crystals present in renal tubules when examined by wet mount. These were not observed by histopathology. The observed adverse effect level (8.6 mg/kg bw [body weight]/day) and benchmark dose modeling data (8.4-10.9 mg/kg bw/day) determined in this study suggest that the tolerable daily intake values derived from studies conducted with melamine alone may underestimate the risk from coexposures to melamine and cyanuric acid. C1 [Jacob, Cristina C.; Von Tungeln, Linda S.; Beland, Frederick A.; da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Reimschuessel, Renate] Ctr Vet Med, Laurel, MD 20708 USA. [Olson, Greg R.; Warbritton, Alan R.] Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Hattan, David G.] Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP da Costa, GG (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HET 233,3900 NCTR Rd, Jefferson, AR 72079 USA. EM goncalo.gamboa@fda.hhs.gov RI Jacob, Cristina/A-3885-2015 OI Jacob, Cristina/0000-0003-2652-3865 FU National Center for Toxicological Research/Food and Drug Administration [224-07-0007]; National Institute for Environmental Health Sciences/National Toxicology Program FX National Center for Toxicological Research/Food and Drug Administration (Interagency Agreement No. 224-07-0007) with the National Institute for Environmental Health Sciences/National Toxicology Program. NR 22 TC 32 Z9 33 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2011 VL 119 IS 2 BP 391 EP 397 DI 10.1093/toxsci/kfq333 PG 7 WC Toxicology SC Toxicology GA 710XH UT WOS:000286549800013 PM 21030430 ER PT J AU Fux, E Smith, JL Tong, MM Guzman, L Anderson, DM AF Fux, Elie Smith, Juliette L. Tong, Mengmeng Guzman, Leonardo Anderson, Donald M. TI Toxin profiles of five geographical isolates of Dinophysis spp. from North and South America SO TOXICON LA English DT Article DE Dinophysis; Diarrhetic shellfish poisoning; Okadaic acid; Dinophysistoxin ID CHROMATOGRAPHY-MASS-SPECTROMETRY; SHELLFISH POISONING TOXINS; PECTENOTOXIN-2 SECO ACID; MUSSELS MYTILUS-EDULIS; DIARRHETIC SHELLFISH; OKADAIC ACID; LIQUID-CHROMATOGRAPHY; PROROCENTRUM-LIMA; NEW-ZEALAND; CAUSATIVE TOXIN AB Marine dinoflagellates of the genus Dinophysis can produce toxins of the okadaic acid (OA) and pectenotoxin (PTX) groups. These lipophilic toxins accumulate in filter-feeding shellfish and cause an illness in consumers called diarrhetic shellfish poisoning (DSP). In 2008, a bloom of Dinophysis led to the closure of shellfish harvesting areas along the Texas coast, one of the first DSP-related closures in the U.S. This event resulted in a broad study of toxin production in isolates of Dinophysis spp. from U.S. waters. In the present study, we compared toxin profiles in geographical isolates of Dinophysis collected in the U.S. (Eel Pond, Woods Hole MA; Martha's Vineyard, MA; and Port Aransas Bay, Texas), and in those from Canada (Blacks Harbour, Bay of Fundy) and Chile (Reloncavi Estuary), when cultured in the laboratory under the same conditions. For each isolate, the mitochondrial cox1 gene was sequenced to assist in species identification. Strains from the northeastern U.S. and Canada were all assigned to Dinophysis acuminata, while those from Chile and Texas were most likely within the D. acuminata complex whereas precise species designation could not be made with this marker. Toxins were detected in all Dinophysis isolates and each isolate had a different profile. Toxin profiles of isolates from Eel Pond, Martha's Vineyard, and Bay of Fundy were most similar, in that they all contained OA. DTX1, and PTX2. The Eel Pond isolate also contained OA-D8 and DTX1-D7, and low levels (unconfirmed structurally) of DTX1-D8 and DTX1-D9. D. acuminata from Martha's Vineyard produced DTX1-D7, along with OA, DTX1, and PTX2, as identified in both the cells and the culture medium. D. acuminata from the Bay of Fundy produced DTX1 and PTX2, as found in both cells and culture medium, while only trace amounts of OA were detected in the medium. The Dinophysis strain from Texas only produced OA, and the one from Chile only PTX2, as confirmed in both cells and culture medium. Published by Elsevier Ltd. C1 [Fux, Elie] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Smith, Juliette L.; Tong, Mengmeng; Anderson, Donald M.] Woods Hole Oceanog Inst, Dept Biol, Woods Hole, MA 02543 USA. [Tong, Mengmeng] Nankai Univ, Coll Environm Sci & Engn, Tianjin 300071, Peoples R China. [Guzman, Leonardo] Inst Fomento Pesquero, Balmaceda 252, Puerto Montt, Chile. RP Fux, E (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM eliefux@hotmail.com RI tong, mengmeng/B-2669-2012; Toxinas, Inct/I-1933-2013 FU NSF [OCE-0850421]; Ocean Life Institute; Coastal Ocean Institute at the Woods Hole Oceanographic Institution; Woods Hole Center for Oceans and Human Health through NSF [OCE-0430724]; NIEHS [1 P50 ES012742]; Ministry of Education, People's Republic of China [707011]; China Scholarship Council; Food and Drug Administration FX Funding was provided by NSF Grant OCE-0850421, the Ocean Life Institute and the Coastal Ocean Institute at the Woods Hole Oceanographic Institution, and the Woods Hole Center for Oceans and Human Health through NSF grant OCE-0430724 and NIEHS grant 1 P50 ES012742. MMT would like to thank the Ministry of Education, People's Republic of China for financial support as a Grand Fostering Project (No. 707011) and the China Scholarship Council. This project was supported in part by an appointment to the Research Participation Program administered by the Oak Ridge Institute for Science and Education through an agreement with the for the Food and Drug Administration. We also thank Dr. Jeremiah D. Hackett (Department of Ecology and Evolutionary Biology, University of Arizona, USA) who helped in the isolation of Dinophysis and Dr. Christopher Miles (Norway's National Veterinary Institute) and Dr. Michael Quilliam (NRC - Canada) for their generous gifts of PTX11 and OA-D8, respectively. We also would like to thank Deana L Erdner from the University of Texas Marine Science Institute, Port Aransas, for supplying the isolate from this location as well as Dave Kulis (Woods Hole Oceanographic Institution) for collecting the samples from the Bay of Fundy. Thanks to Dr. Steve Plakas from the FDA, Gulf Coast Seafood laboratory, Dauphin Island, USA, for his very valuable comments on this manuscript. NR 70 TC 42 Z9 42 U1 0 U2 24 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD FEB PY 2011 VL 57 IS 2 BP 275 EP 287 DI 10.1016/j.toxicon.2010.12.002 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 725FA UT WOS:000287629400011 PM 21147146 ER PT J AU Dasgupta, S Banerjee, RK Hariharan, P Myers, MR AF Dasgupta, Subhashish Banerjee, Rupak K. Hariharan, Prasanna Myers, Matthew R. TI Beam localization in HIFU temperature measurements using thermocouples, with application to cooling by large blood vessels SO ULTRASONICS LA English DT Article DE HIFU; Beam positioning error; Thermocouple artifacts; Blood flow cooling; Thermal dose ID INTENSITY FOCUSED ULTRASOUND; FUNCTION MINIMIZATION; TISSUE; EQUATION; RADIOFREQUENCY; HYPERTHERMIA; SIMULATIONS; CALIBRATION; ABLATION; FIELD AB Experimental studies of thermal effects in high-intensity focused ultrasound (HIFU) procedures are often performed with the aid of fine wire thermocouples positioned within tissue phantoms. Thermocouple measurements are subject to several types of error which must be accounted for before reliable inferences can be made on the basis of the measurements. Thermocouple artifact due to viscous heating is one source of error. A second is the uncertainty regarding the position of the beam relative to the target location or the thermocouple junction, due to the error in positioning the beam at the junction. This paper presents a method for determining the location of the beam relative to a fixed pair of thermocouples. The localization technique reduces the uncertainty introduced by positioning errors associated with very narrow HIFU beams. The technique is presented in the context of an investigation into the effect of blood flow through large vessels on the efficacy of HIFU procedures targeted near the vessel. Application of the beam localization method allowed conclusions regarding the effects of blood flow to be drawn from previously inconclusive (because of localization uncertainties) data. Comparison of the position-adjusted transient temperature profiles for flow rates of 0 and 400 ml/min showed that blood flow can reduce temperature elevations by more than 10%, when the HIFU focus is within a 2 mm distance from the vessel wall. At acoustic power levels of 17.3 and 24.8 W there is a 20- to 70-fold decrease in thermal dose due to the convective cooling effect of blood flow, implying a shrinkage in lesion size. The beam-localization technique also revealed the level of thermocouple artifact as a function of sonication time, providing investigators with an indication of the quality of thermocouple data for a given exposure time. The maximum artifact was found to be double the measured temperature rise, during initial few seconds of sonication. (C) 2010 Elsevier B.V. All rights reserved. C1 [Dasgupta, Subhashish; Banerjee, Rupak K.] Univ Cincinnati, Dept Mech Engn, Cincinnati, OH 45220 USA. [Banerjee, Rupak K.] Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH 45220 USA. [Hariharan, Prasanna; Myers, Matthew R.] US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Banerjee, RK (reprint author), Univ Cincinnati, Dept Mech Ind & Nucl Engn, 593 Rhodes Hall,ML 0072, Cincinnati, OH 45221 USA. EM rupak.banerjee@uc.edu FU National Science Foundation [0552036] FX Financial support from the National Science Foundation (Grant No. 0552036) is greatly acknowledged. NR 32 TC 14 Z9 14 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0041-624X J9 ULTRASONICS JI Ultrasonics PD FEB PY 2011 VL 51 IS 2 BP 171 EP 180 DI 10.1016/j.ultras.2010.07.007 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 682KC UT WOS:000284400900009 PM 20817250 ER PT J AU Xie, H Jing, XH Li, X Lin, ZS Plant, E Zoueva, O Yang, H Ye, ZP AF Xie, Hang Jing, Xianghong Li, Xing Lin, Zhengshi Plant, Ewan Zoueva, Olga Yang, Hong Ye, Zhiping TI Immunogenicity and Cross-Reactivity of 2009-2010 Inactivated Seasonal Influenza Vaccine in US Adults and Elderly SO PLOS ONE LA English DT Article ID LABORATORY-CONFIRMED INFLUENZA; ANTIBODY-RESPONSES; UNITED-STATES; VIRUS; CHILDREN; AGE; INFECTION; STRAINS; SERUM; MATCH AB The campaign of 2009-2010 Northern Hemisphere seasonal vaccination was concurrent with the 2009 H1N1 pandemic. Using a hemagglutination inhibition (HAI) assay, we evaluated the immunogenicity and cross-reactivity of 2009-2010 inactivated trivalent influenza vaccine (TIV) in US adult and elderly populations. Vaccination of TIV resulted in a robust boost on the antibody response of all subjects to seasonal A/Brisbane/59/2007 (H1N1) and A/Uruguay/716/2007 (H3N2) with over 70% of recipients reaching a seroprotective titer of 40. B/Brisbane/60/2008 was the least immunogenic among the three seasonal vaccine strains with <30% of TIV recipients reaching a seroprotective titer of 40. TIV vaccination also induced a moderate boost on the pandemic specific antibody responses. Twenty-four percent of adults and 36% of elderly reached a seroprotective HAI titer of 40 or more against pandemic A/South Carolina/18/2009 (H1N1) after receiving TIV compared to 4% and 7% at the beginning of vaccination, respectively. In addition, 22% of adults and 34% of elderly showed an increase of 4-fold or more in A/South Carolina/18/2009 specific HAI titers after TIV vaccination. The pandemic specific cross-reactive antibodies strongly correlated with the post-vaccination HAI titers against the seasonal H3N2 vaccine strain in all subjects. C1 [Xie, Hang; Jing, Xianghong; Li, Xing; Lin, Zhengshi; Plant, Ewan; Zoueva, Olga; Ye, Zhiping] US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review, Bethesda, MD 20014 USA. [Yang, Hong] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Bethesda, MD USA. RP Xie, H (reprint author), US FDA, Lab Resp Viral Dis, Div Viral Prod, Off Vaccine Res & Review, Bethesda, MD 20014 USA. EM Hang.Xie@fda.hhs.gov; Zhiping.Ye@fda.hhs.gov OI Plant, Ewan/0000-0003-0166-5939 FU Center for Biologics Evaluation; Research/Food and Drug Administration FX This study was supported by Center for Biologics Evaluation and Research/Food and Drug Administration institutional research funds. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 27 TC 20 Z9 20 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 JAN 31 PY 2011 VL 6 IS 1 AR e16650 DI 10.1371/journal.pone.0016650 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 714UK UT WOS:000286834300109 PM 21304946 ER PT J AU Ghosh, P Ghosh, K Tiwari, RC AF Ghosh, Pulak Ghosh, Kaushik Tiwari, Ram C. TI Bayesian approach to cancer-trend analysis using age-stratified Poisson regression models SO STATISTICS IN MEDICINE LA English DT Article DE cancer mortality; cancer incidence; cancer surveillance; joinpoint regression; SEER program; Dirichlet process prior ID INFORMATION; SELECTION; MIXTURES; RATES AB Annual Percentage Change (APC) summarizes trends in age-adjusted cancer rates over short time-intervals. This measure implicitly assumes linearity of the log-rates over the intervals in question, which may not be valid, especially for relatively longer time-intervals. An alternative is the Average Annual Percentage Change (AAPC), which computes a weighted average of APC values over intervals where log-rates are piece-wise linear. In this article, we propose a Bayesian approach to calculating APC and AAPC values from age-adjusted cancer rate data. The procedure involves modeling the corresponding counts using age-specific Poisson regression models with a log-link function that contains unknown joinpoints. The slope-changes at the joinpoints are assumed to have a mixture distribution with point mass at zero and the joinpoints are assumed to be uniformly distributed subject to order-restrictions. Additionally, the age-specific intercept parameters are modeled nonparametrically using a Dirichlet process prior. The proposed method can be used to construct Bayesian credible intervals for AAPC using age-adjusted mortality rates. This provides a significant improvement over the currently available frequentist method, where variance calculations are done conditional on the joinpoint locations. Simulation studies are used to demonstrate the success of the method in capturing trend-changes. Finally, the proposed method is illustrated using data on prostate cancer incidence. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Ghosh, Kaushik] Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Syst, Bangalore 560076, Karnataka, India. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Ghosh, K (reprint author), Univ Nevada, Dept Math Sci, 4505 Maryland Pkwy,Box 454020, Las Vegas, NV 89154 USA. EM kaushik.ghosh@unlv.edu NR 29 TC 2 Z9 2 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2011 VL 30 IS 2 BP 127 EP 139 DI 10.1002/sim.4077 PG 13 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 701TU UT WOS:000285847100002 PM 20839366 ER PT J AU Koenig, HC Sutherland, A Izurieta, HS McGonagle, D AF Koenig, Helen C. Sutherland, Andrea Izurieta, Hector S. McGonagle, Dennis TI Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination SO VACCINE LA English DT Article DE Autoimmune diseases; Immunological disease continuum; Vaccine safety surveillance; Vaccine adverse events ID GUILLAIN-BARRE-SYNDROME; TOLL-LIKE RECEPTORS; ARTHRITIS FOLLOWING TETANUS; HEPATITIS-B VACCINATION; REPORTING SYSTEM VAERS; CENTRAL-NERVOUS-SYSTEM; REACTIVE ARTHRITIS; ADVERSE EVENTS; MOLECULAR MIMICRY; IMMUNE-COMPLEXES AB In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post-licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination. (C) 2010 Published by Elsevier Ltd. C1 [McGonagle, Dennis] Chapel Allerton Hosp, Leeds Inst Mol Med, Sect Musculoskeletal Dis, Leeds LS7 4SA, W Yorkshire, England. [Koenig, Helen C.; Sutherland, Andrea; Izurieta, Hector S.] Ctr Biol Evaluat & Res, Food & Drug Adm, Rockville, MD USA. [McGonagle, Dennis] Univ Leeds, Leeds NIHR Biomed Res Unit, Leeds Inst Mol Med, Leeds, W Yorkshire, England. RP McGonagle, D (reprint author), Chapel Allerton Hosp, Leeds Inst Mol Med, Sect Musculoskeletal Dis, Chapeltown Rd, Leeds LS7 4SA, W Yorkshire, England. EM d.g.mcgonagle@leeds.ac.uk FU UK National Institute of Health Research; WELMEC; Wellcome Trust; EPSRC [WT 088908/Z/09/Z]; UK National Institute of Health Research and Arthritis Research UK FX We would like to thank Drs. Douglas Pratt, Alexandra S. Worobec and Jay Slater, from the Center for Biologics Evaluation and Research, Food and Drug Administration, and Dr. Noel Rose, from Johns Hopkins Bloomberg School of Public Health, for their critical review of this manuscript. Dr. McGonagle's work is funded in part by the UK National Institute of Health Research and in part through WELMEC, a Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC, under grant number WT 088908/Z/09/Z.; Dr. McGonagle is funded by the UK National Institute of Health Research and Arthritis Research UK. There were no other funding sources for the preparation of this manuscript. NR 101 TC 7 Z9 7 U1 0 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 JAN 29 PY 2011 VL 29 IS 5 BP 913 EP 919 DI 10.1016/j.vaccine.2010.10.044 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 720QS UT WOS:000287295800009 PM 21036134 ER PT J AU Delmonte, P Kia, ARF Kramer, JKG Mossoba, MM Sidisky, L Rader, JI AF Delmonte, Pierluigi Kia, Ali-Reza Fardin Kramer, John K. G. Mossoba, Magdi M. Sidisky, Len Rader, Jeanne I. TI Separation characteristics of fatty acid methyl esters using SLB-IL111, a new ionic liquid coated capillary gas chromatographic column SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Ionic liquids; Gas chromatography (GC); GLC; trans fat; Fatty acids; Conjugated linoleic acid (CLA); cis- and trans-MUFA; Separation of synthetic CLA isomers; Separation of synthetic MUFA isomers; GC separations on ionic liquid columns; SP-2560; CP-Sil-88; SLB-IL111 ID CONJUGATED LINOLEIC ACIDS; THIN-LAYER-CHROMATOGRAPHY; TRANS-OCTADECENOIC ACID; HUMAN-MILK LIPIDS; CP-SIL 88; STATIONARY PHASES; OCTADECADIENOIC ACID; POSITIONAL ISOMERS; FISH-OIL; CIS AB The ionic liquid SLB-IL111 column, available from Supelco Inc., is a novel fused capillary gas chromatography (GC) column capable of providing enhanced separations of fatty acid methyl esters (FAMEs) compared to the highly polar cyanopropyl siloxane columns currently recommended for the separation of cis- and trans isomers of fatty acids (FAs), and marketed as SP-2560 and CP-Sil 88. The SLB-IL111 column was operated isothermal at 168 degrees C, with hydrogen as carrier gas at 1.0 mL/min, and the elution profile was characterized using authentic GC standards and synthetic mono-unsaturated fatty acids (MUFAs) and conjugated linoleic acid (CLA) isomers as test mixtures. The SLB-IL111 column provided an improved separation of cis- and trans-18:1 and cis/trans CLA isomers. This is the first direct GC separation of c9,t11-from t7,c9-CLA, and t15-18:1 from c9-18:1, both of which previously required complimentary techniques for their analysis using cyanopropyl siloxane columns. The SLB-IL111 column also provided partial resolution of t13/t14-18:1, c8- from c6/c7-18:1, and for several t,t-CLA isomer pairs. This column also provided elution profiles of the geometric and positional isomers of the 16:1, 20:1 and 18:3 FAMEs that were complementary to those obtained using the cyanopropyl siloxane columns. However, on the SLB-IL111 column the saturated FAs eluted between the cis- and trans MUFAs unlike cyanopropyl siloxane columns that gave a clear separation of most saturated FAs. These differences in elution pattern can be exploited to obtain a more complete analysis of complex lipid mixtures present in ruminant fats. Published by Elsevier B.V. C1 [Delmonte, Pierluigi; Kia, Ali-Reza Fardin; Mossoba, Magdi M.; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kramer, John K. G.] Agr & Agri Food Canada, Guelph Food Res Ctr, Guelph, ON, Canada. [Sidisky, Len] Supelco Sigma Aldrich, Bellefonte, PA USA. RP Delmonte, P (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, HFS-717,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Pierluigi.delmonte@fda.hhs.gov; jkgkramer@rogers.com NR 40 TC 80 Z9 84 U1 2 U2 64 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 JAN 21 PY 2011 VL 1218 IS 3 BP 545 EP 554 DI 10.1016/j.chroma.2010.11.072 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 712QI UT WOS:000286680900022 PM 21176911 ER PT J AU Jin, QH Yu, LR Wang, LF Zhang, ZJ Kasper, LH Lee, JE Wang, CC Brindle, PK Dent, SYR Ge, K AF Jin, Qihuang Yu, Li-Rong Wang, Lifeng Zhang, Zhijing Kasper, Lawryn H. Lee, Ji-Eun Wang, Chaochen Brindle, Paul K. Dent, Sharon Y. R. Ge, Kai TI Distinct roles of GCN5/PCAF-mediated H3K9ac and CBP/p300-mediated H3K18/27ac in nuclear receptor transactivation SO EMBO JOURNAL LA English DT Article DE CBP and p300; GCN5 and PCAF; histone acetylation; nuclear receptor ID HISTONE H3; GENE-EXPRESSION; TRANSCRIPTIONAL REGULATION; HUMAN GENOME; CHROMATIN; ACETYLATION; COMPLEX; P300; ACETYLTRANSFERASE; ACTIVATION AB Histone acetyltransferases (HATs) GCN5 and PCAF (GCN5/PCAF) and CBP and p300 (CBP/p300) are transcription co-activators. However, how these two distinct families of HATs regulate gene activation remains unclear. Here, we show deletion of GCN5/PCAF in cells specifically and dramatically reduces acetylation on histone H3K9 (H3K9ac) while deletion of CBP/p300 specifically and dramatically reduces acetylations on H3K18 and H3K27 (H3K18/27ac). A ligand for nuclear receptor (NR) PPAR delta induces sequential enrichment of H3K18/27ac, RNA polymerase II (Pol H) and H3K9ac on PPAR delta target gene Angptl4 promoter, which correlates with a robust Angptl4 expression. Inhibiting transcription elongation blocks ligand-induced H3K9ac, but not H3K18/27ac, on the Angptl4 promoter. Finally, we show GCN5/PCAF and GCN5/PCAF-mediated H3K9ac correlate with, but are surprisingly dispensable for, NR target gene activation. In contrast, CBP/p300 and their HAT activities are essential for ligand-induced Pol II recruitment on, and activation of, NR target genes. These results highlight the substrate and site specificities of HATs in cells, demonstrate the distinct roles of GCN5/PCAF- and CBP/p300-mediated histone acetylations in gene activation, and suggest an important role of CBP/p300-mediated H3K18/27ac in NR-dependent transcription. The EMBO Journal (2011) 30, 249-262. doi:10.1038/emboj.2010.318; Published online 3 December 2010 C1 [Jin, Qihuang; Wang, Lifeng; Lee, Ji-Eun; Wang, Chaochen; Ge, Kai] NIDDK, Nucl Receptor Biol Sect, CEB, NIH, Bethesda, MD 20892 USA. [Yu, Li-Rong] US FDA, Ctr Excellence Prote, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Zhang, Zhijing; Dent, Sharon Y. R.] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Kasper, Lawryn H.] St Jude Childrens Hosp, Dept Biochem, Memphis, TN 38105 USA. RP Ge, K (reprint author), NIDDK, Nucl Receptor Biol Sect, CEB, NIH, Bldg 10,Room 8N307C,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kaig@niddk.nih.gov RI Lee, Ji-Eun/F-7891-2011; Wang, Lifeng/I-4888-2012; OI Lee, Ji-Eun/0000-0002-3768-7016; Wang, Lifeng/0000-0003-4752-6547; Ge, Kai/0000-0002-7442-5138 FU NIDDK, NIH; NIH [R01GM067718, DE018183] FX We thank Y Barak and R Evans for providing PPAR deltaflox/flox mice, Z Wang and K Zhao for validated histone modification antibodies, R Roeder for Ada2b, SPT3 and Ada2a antibodies, and D Mendrick for critical reading of the paper. This work was supported by the Intramural Research Program of the NIDDK, NIH to KG, NIH R01GM067718 to SYRD and NIH DE018183 to PKB. NR 55 TC 209 Z9 214 U1 5 U2 19 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JAN 19 PY 2011 VL 30 IS 2 BP 249 EP 262 DI 10.1038/emboj.2010.318 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 719DE UT WOS:000287179100004 PM 21131905 ER PT J AU Hillebrenner, MG Swain, JA Zuckerman, B AF Hillebrenner, Matthew G. Swain, Julie A. Zuckerman, Bram TI VARC Consensus Report: The FDA Perspective SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material C1 [Hillebrenner, Matthew G.; Swain, Julie A.; Zuckerman, Bram] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Silver Spring, MD 20993 USA. RP Hillebrenner, MG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, 10903 New Hampshire Ave,WO66-1232, Silver Spring, MD 20993 USA. EM matthew.hillebrenner@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JAN 18 PY 2011 VL 57 IS 3 BP 270 EP 271 DI 10.1016/j.jacc.2010.12.004 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 705LS UT WOS:000286133900004 PM 21216554 ER PT J AU Chen, QY Snapper, CM Sen, G AF Chen, Quanyi Snapper, Clifford M. Sen, Goutam TI Endogenous IL-1R1 Signaling Is Critical for Cognate CD4(+) T Cell Help for Induction of In Vivo Type 1 and Type 2 Antipolysaccharide and Antiprotein Ig Isotype Responses to Intact Streptococcus pneumoniae, but Not to a Soluble Pneumococcal Conjugate Vaccine (Retraction of vol 177, pg 6044, 2006) SO JOURNAL OF IMMUNOLOGY LA English DT Correction C1 [Chen, Quanyi; Snapper, Clifford M.] Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. [Sen, Goutam] Ctr Biol Evaluat & Res, Food & Drug Adm, Rockville, MD USA. RP Chen, QY (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 1 TC 0 Z9 0 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2011 VL 186 IS 2 BP 1289 EP 1289 DI 10.4049/jimmunol.1090127 PG 1 WC Immunology SC Immunology GA 702TB UT WOS:000285917700068 PM 21209288 ER PT J AU Edison, SE Lin, LA Gamble, BM Wong, J Zhang, K AF Edison, Sara. E. Lin, Lora A. Gamble, Bryan M. Wong, Jon Zhang, Kai TI Surface swabbing technique for the rapid screening for pesticides using ambient pressure desorption ionization with high-resolution mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID ION-SOURCE; IDENTIFICATION; RESIDUES; MS AB A rapid screening method for pesticides has been developed to promote more efficient processing of produce entering the United States. Foam swabs were used to recover a multiclass mixture of 132 pesticides from the surfaces of grapes, apples, and oranges. The swabs were analyzed using direct analysis in real time (DART) ionization coupled with a high-resolution Exactive Orbitrap (TM) mass spectrometer. By using a DART helium temperature gradient from 100-350 degrees C over 3 min, a minimal separation of analytes based on volatility differences was achieved. This, combined with the Exactive's mass resolution of 100 000, allowed the chromatographic step, along with the typical compositing and extraction steps associated with gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry (LC/MS) approaches, to be eliminated. Detection of 86% of the analytes present was consistently achieved at levels of 2 ng/g (per each apple or orange) and 10 ng/g (per grape). A resolution study was conducted with four pairs of isobaric compounds analyzed at a mass resolution of 100 000. Baseline separation was achieved with analyte ions differing in mass by 25ppm and analyte ions with a mass difference of 10ppm were partially resolved. In addition, field samples that had undergone traditional sample preparation using QuEChERS (quick, easy, cheap, rugged, and safe) were analyzed using both LC/MS and DART-MS and the results from the two techniques were found to be comparable in terms of identification of the pesticides present. The use of swabs greatly increased sample throughput by reducing sample preparation and analysis time. Published in 2010 by John Wiley & Sons, Ltd. C1 [Edison, Sara. E.; Lin, Lora A.; Gamble, Bryan M.] US FDA, Forens Chem Ctr, Cincinnati, OH USA. [Wong, Jon; Zhang, Kai] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Edison, SE (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH USA. EM sara.edison@fda.hhs.gov NR 18 TC 51 Z9 57 U1 9 U2 49 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD JAN 15 PY 2011 VL 25 IS 1 BP 127 EP 139 DI 10.1002/rcm.4831 PG 13 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 694QY UT WOS:000285313900017 PM 21157860 ER PT J AU Gannavaram, S Sharma, P Duncan, RC Salotra, P Nakhasi, HL AF Gannavaram, Sreenivas Sharma, Paresh Duncan, Robert C. Salotra, Poonam Nakhasi, Hira L. TI Mitochondrial Associated Ubiquitin Fold Modifier-1 Mediated Protein Conjugation in Leishmania donovani SO PLOS ONE LA English DT Article ID PLASMODIUM-FALCIPARUM; TRYPANOSOMA-CRUZI; PARASITIC PROTOZOA; LIGASE; IDENTIFICATION; SYSTEM; PROTEASOME; EXPRESSION; GENES; TARENTOLAE AB In this report, we demonstrate the existence of the ubiquitin fold modifier-1 (Ufm1) and its conjugation pathway in trypanosomatid parasite Leishmania donovani. LdUfm1 is activated by E1-like enzyme LdUba5. LdUfc1 (E2) specifically interacted with LdUfm1 and LdUba5 to conjugate LdUfm1 to proteinaceous targets. Mass spectrometry analysis revealed that LdUfm1 is conjugated to Leishmania protein targets that are associated with mitochondria. Immunofluorescence experiments showed that Leishmania Ufm1, Uba5 and Ufc1 are associated with the mitochondria. The demonstration that all the components of this system as well as the substrates are associated with mitochondrion suggests it may have physiological roles not yet described in any other organism. Overexpression of a non-conjugatable form of LdUfm1 and an active site mutant of LdUba5 resulted in reduced survival of Leishmania in the macrophage. Since mitochondrial activities are developmentally regulated in the life cycle of trypanosomatids, Ufm1 mediated modifications of mitochondrial proteins may be important in such regulation. Thus, Ufm1 conjugation pathway in Leishmania could be explored as a potential drug target in the control of Leishmaniasis. C1 [Gannavaram, Sreenivas; Duncan, Robert C.; Nakhasi, Hira L.] US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Sharma, Paresh; Salotra, Poonam] Inst Pathol ICMR, New Delhi, India. RP Gannavaram, S (reprint author), US FDA, Lab Emerging Pathogens, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM salotra@vsnl.com; hira.nakhasi@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 44 TC 8 Z9 9 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 JAN 14 PY 2011 VL 6 IS 1 AR e16156 DI 10.1371/journal.pone.0016156 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 710MS UT WOS:000286516500032 PM 21264253 ER PT J AU Herishanu, Y Perez-Galan, P Liu, DL Biancotto, A Pittaluga, S Vire, B Gibellini, F Njuguna, N Lee, E Stennett, L Raghavachari, N Liu, PC McCoy, JP Raffeld, M Stetler-Stevenson, M Yuan, C Sherry, R Arthur, DC Maric, I White, T Marti, GE Munson, P Wilson, WH Wiestner, A AF Herishanu, Yair Perez-Galan, Patricia Liu, Delong Biancotto, Angelique Pittaluga, Stefania Vire, Berengere Gibellini, Federica Njuguna, Ndegwa Lee, Elinor Stennett, Lawrence Raghavachari, Nalini Liu, Poching McCoy, J. Philip Raffeld, Mark Stetler-Stevenson, Maryalice Yuan, Constance Sherry, Richard Arthur, Diane C. Maric, Irina White, Therese Marti, Gerald E. Munson, Peter Wilson, Wyndham H. Wiestner, Adrian TI The lymph node microenvironment promotes B-cell receptor signaling, NF-kappa B activation, and tumor proliferation in chronic lymphocytic leukemia SO BLOOD LA English DT Article ID TOLL-LIKE RECEPTORS; GENE-EXPRESSION; ZAP-70 EXPRESSION; GENOMIC ABERRATIONS; DISEASE PROGRESSION; ANTIGEN RECEPTOR; MUTATION STATUS; CROSS-LINKING; SURVIVAL; IGM AB Chronic lymphocytic leukemia (CLL), an incurable malignancy of mature B lymphocytes, involves blood, bone marrow, and secondary lymphoid organs such as the lymph nodes (LN). A role of the tissue microenvironment in the pathogenesis of CLL is hypothesized based on in vitro observations, but its contribution in vivo remains ill-defined. To elucidate the effects of tumor-host interactions in vivo, we purified tumor cells from 24 treatment-naive patients. Samples were obtained concurrently from blood, bone marrow, and/or LN and analyzed by gene expression profiling. We identified the LN as a key site in CLL pathogenesis. CLL cells in the LN showed up-regulation of gene signatures, indicating B-cell receptor (BCR) and nuclear factor-kappa B activation. Consistent with antigen-dependent BCR signaling and canonical nuclear factor-kappa B activation, we detected phosphorylation of SYK and I kappa B alpha, respectively. Expression of BCR target genes was stronger in clinically more aggressive CLL, indicating more effective BCR signaling in this subtype in vivo. Tumor proliferation, quantified by the expression of the E2F and c-MYC target genes and verified with Ki67 staining by flow cytometry, was highest in the LN and was correlated with clinical disease progression. These data identify the disruption of tumor microenvironment interactions and the inhibition of BCR signaling as promising therapeutic strategies in CLL. This study is registered at http://clinicaltrials.gov as NCT00019370. (Blood. 2011;117(2):563-574) C1 [Herishanu, Yair; Perez-Galan, Patricia; Vire, Berengere; Gibellini, Federica; Njuguna, Ndegwa; Lee, Elinor; Stennett, Lawrence; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. [Biancotto, Angelique; McCoy, J. Philip] NIH, Ctr Human Immunol, Bethesda, MD 20892 USA. [Pittaluga, Stefania; Raffeld, Mark; Stetler-Stevenson, Maryalice; Yuan, Constance; Arthur, Diane C.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Sherry, Richard] NCI, Surg Branch, Bethesda, MD 20892 USA. [Maric, Irina] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. [White, Therese] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. [Marti, Gerald E.; Wilson, Wyndham H.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Wiestner, A (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,CRC 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM wiestnera@mail.nih.gov FU American Physician Fellowship (APF); NIH, the National Heart, Lung, and Blood Institute; National Cancer Institute FX Foremost we thank our patients for their willingness to undergo additional or more extensive procedures to make this research possible. We thank Dr Lou Staudt for lymphochip microarrays, the NCI surgery team for performing excisional lymph node biopsies, and Theresa Davies-Hill for assistance in processing biopsy specimens. We thank Drs Lou Staudt, Neal Young, Cindy Dunbar, and Clifton Mo for helpful discussions and critical reading of the manuscript. We gratefully acknowledge the American Physician Fellowship (APF) for support of Y.H.; This research was also supported by the Intramural Research Program of the NIH, the National Heart, Lung, and Blood Institute, and the National Cancer Institute. NR 50 TC 327 Z9 336 U1 5 U2 23 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 JAN 13 PY 2011 VL 117 IS 2 BP 563 EP 574 DI 10.1182/blood-2010-05-284984 PG 12 WC Hematology SC Hematology GA 705ZD UT WOS:000286178700026 PM 20940416 ER PT J AU Savan, R McFarland, AP Reynolds, DA Feigenbaum, L Ramakrishnan, K Karwan, M Shirota, H Klinman, DM Dunleavy, K Pittaluga, S Anderson, SK Donnelly, RP Wilson, WH Young, HA AF Savan, Ram McFarland, Adelle P. Reynolds, Della A. Feigenbaum, Lionel Ramakrishnan, Karthika Karwan, Megan Shirota, Hidekazu Klinman, Dennis M. Dunleavy, Kieron Pittaluga, Stefania Anderson, Stephen K. Donnelly, Raymond P. Wilson, Wyndham H. Young, Howard A. TI A novel role for IL-22R1 as a driver of inflammation SO BLOOD LA English DT Article ID LARGE-CELL LYMPHOMA; EFFECTIVE THERAPY; NPM-ALK; CHAIN; ACTIVATION; EXPRESSION; KINASE; TRANSLOCATION; CONTRIBUTES; ANTIBODY AB The interleukin (IL)-22R1 chain of the heterodimeric IL-22 receptor is not expressed on normal leukocytes, but this receptor is expressed on T cells from anaplastic lymphoma kinase-positive (ALK(+)) anaplastic large cell lymphoma (ALCL) patients. To investigate the consequences of aberrant expression of this receptor on lymphocytes, we generated transgenic mice that express IL-22R1 on lymphocytes. The health of these animals progressively deteriorated at 8 to 12 weeks of age, as they displayed respiratory distress, rough coat and sluggish movement, and subsequent lethality due to multiorgan inflammation. The IL-22R1 transgenic animals developed neutrophilia that correlated with increased levels of circulating IL-17 and granulocyte colony-stimulating factor. In addition, these mice had increased serum IL-22 levels, suggesting that T cells expressing IL-22R1 generate IL-22 in a positive autoregulatory loop. As a result of the mouse model findings, we analyzed circulating cytokine levels in ALK(+)ALCL patients and detected elevated levels of IL-22, IL-17, and IL-8 in untreated patient samples. Importantly, IL-22 and IL-17 were undetectable in all patients who were in complete remission after chemotherapy. This study documents a previously unknown role of IL-22R1 in inflammation and identifies the involvement of IL-22R1/IL-22 in ALK(+)ALCL. (Blood. 2011;117(2):575-584) C1 [Savan, Ram; McFarland, Adelle P.; Reynolds, Della A.; Ramakrishnan, Karthika; Shirota, Hidekazu; Klinman, Dennis M.; Anderson, Stephen K.; Young, Howard A.] Ctr Canc Res, Canc & Inflammat Program, Frederick, MD 21702 USA. [Feigenbaum, Lionel; Karwan, Megan] NCI, Lab Anim Sci Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Metab Branch, Lymphoma Therapeut Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, Hematopathol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Young, HA (reprint author), Ctr Canc Res, Canc & Inflammat Program, POB B,Bldg 560, Frederick, MD 21702 USA. EM savanr@mail.nih.gov; YoungHow@mail.nih.gov RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 FU NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [HHSN261200800001E] 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 28 TC 27 Z9 28 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 JAN 13 PY 2011 VL 117 IS 2 BP 575 EP 584 DI 10.1182/blood-2010-05-285908 PG 10 WC Hematology SC Hematology GA 705ZD UT WOS:000286178700027 PM 20971950 ER PT J AU Fan, XH Shao, L Fang, H Tong, WD Cheng, YY AF Fan, Xiaohui Shao, Li Fang, Hong Tong, Weida Cheng, Yiyu TI Cross-Platform Comparison of Microarray-Based Multiple-Class Prediction SO PLOS ONE LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; DNA MICROARRAYS; QUALITY-CONTROL; OLIGONUCLEOTIDE; CANCER; TECHNOLOGIES; CLASSIFIERS; CONSISTENCY; CALIBRATION; PROGNOSIS AB High-throughput microarray technology has been widely applied in biological and medical decision-making research during the past decade. However, the diversity of platforms has made it a challenge to re-use and/or integrate datasets generated in different experiments or labs for constructing array-based diagnostic models. Using large toxicogenomics datasets generated using both Affymetrix and Agilent microarray platforms, we carried out a benchmark evaluation of cross-platform consistency in multiple-class prediction using three widely-used machine learning algorithms. After an initial assessment of model performance on different platforms, we evaluated whether predictive signature features selected in one platform could be directly used to train a model in the other platform and whether predictive models trained using data from one platform could predict datasets profiled using the other platform with comparable performance. Our results established that it is possible to successfully apply multiple-class prediction models across different commercial microarray platforms, offering a number of important benefits such as accelerating the possible translation of biomarkers identified with microarrays to clinically-validated assays. However, this investigation focuses on a technical platform comparison and is actually only the beginning of exploring cross-platform consistency. Further studies are needed to confirm the feasibility of microarray-based cross-platform prediction, especially using independent datasets. C1 [Fan, Xiaohui; Shao, Li; Cheng, Yiyu] Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. [Fang, Hong] Z Tech Corp, Jefferson, AZ USA. [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AZ USA. RP Fan, XH (reprint author), Zhejiang Univ, Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou 310003, Zhejiang, Peoples R China. EM weida.tong@fda.hhs.gov; chengyy@zju.edu.cn FU National Science Foundation of China [30801556]; Higher Education of China [20090101110126]; Science Foundation of Chinese University [2009QNA7031] FX This work was supported by the National Science Foundation of China (No. 30801556), the Research Fund for the Doctoral Program of Higher Education of China (No. 20090101110126), and Science Foundation of Chinese University (No. 2009QNA7031). The funders or the sponsor (Z-Tech Corporation) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 30 TC 10 Z9 11 U1 0 U2 9 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 JAN 11 PY 2011 VL 6 IS 1 AR e16067 DI 10.1371/journal.pone.0016067 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 710LU UT WOS:000286514000019 PM 21264309 ER PT J AU Posnack, NG Lee, NH Brown, R Sarvazyan, N AF Posnack, Nikki Gillum Lee, Norman H. Brown, Ronald Sarvazyan, Narine TI Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity SO TOXICOLOGY LA English DT Article DE Cardiac myocyte; Microarray; Gene expression; Phthalate; Connexin-43; Calcium handling; Arrhythmia ID CARDIAC MYOCYTES; DI(2-ETHYLHEXYL) PHTHALATE; GAP-JUNCTIONS; MONO-(2-ETHYLHEXYL) PHTHALATE; RYANODINE RECEPTOR; HUMAN-REPRODUCTION; CALCIUM-RELEASE; HEART; PROTEINS; INFANTS AB Background: Di-(2-ethylhexyl)-phthalate (DEHP) is a widely used plasticizer that imparts flexibility to polyvinyl chloride. We have recently reported that clinically relevant concentrations of DEHP can affect electrical coupling between cardiac myocytes causing significant rhythm disturbances. The underlying causes for this effect are currently unknown. Objectives: To use data on global mRNA expression as a tool to reveal possible pathways leading to arrhythmogenic effects of DEHP. Methods: Rat neonatal cardiomyocytes were treated with 50 DEHP for 72 h. Extracted RNA samples were hybridized onto Affymetrix Rat Gene 1.0 ST arrays. The mRNA expression of a subset of genes was validated by qRT-PCR. In a second set of experiments, cells were treated in a concentration dependent manner to identify genes affected by low DEHP concentrations. Results: DEHP exposure is associated with global changes in mRNA expression, with differentially expressed genes overrepresented in 47 Gene Ontology categories. Modified expression was detected for genes associated with cell electrical activity, calcium handling, adhesion and microtubular transport. For a number of key proteins, including kinesin, TGF beta 2, alpha-tubulin, and alpha 1 & beta 1 integrins, changes in mRNA levels were confirmed on the level of the protein expression. A number of genes associated with cell adhesion and electrical activity were identified as early DEHP targets as they were affected by concentrations as low as 1 mu g/mL Conclusions: Exposure of neonatal rat cardiomyocytes to clinically relevant DEHP concentrations leads to global changes in mRNA expression. These changes help to explain the arrhythmogenic effects of phthalates on these cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved. C1 [Posnack, Nikki Gillum; Lee, Norman H.; Sarvazyan, Narine] George Washington Univ, Dept Physiol & Pharmacol, Washington, DC 20037 USA. [Brown, Ronald] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Sarvazyan, N (reprint author), George Washington Univ, Dept Physiol & Pharmacol, 2300 Eye St, Washington, DC 20037 USA. EM phynas@gmail.com RI Posnack, Nikki/F-1170-2013 OI Posnack, Nikki/0000-0002-3880-7200 FU National Institutes of Health [HL076722, 1F32ES019057, CA120316]; GWU Catherine Birch McCormick Center FX The authors thank Luther Swift for isolation of cardiomyocytes and Yi Lian and Dr. Sydney Fu for their assistance with microarray processing. This work was supported by the National Institutes of Health (HL076722 to NS, 1F32ES019057 to NGP and CA120316 to NHL) and the GWU Catherine Birch McCormick Center. NR 43 TC 16 Z9 17 U1 1 U2 5 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 JAN 11 PY 2011 VL 279 IS 1-3 BP 54 EP 64 DI 10.1016/j.tox.2010.09.007 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 718GU UT WOS:000287109900007 PM 20920545 ER PT J AU Van Dole, KB West, SL Mease, M Olsen, A AF Van Dole, Kristen B. West, Suzanne L. Mease, Mary Olsen, Axel TI Perception of Drug Safety and Knowledge Influences Drug Selection SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID BENEFITS; RISKS C1 [Van Dole, Kristen B.; West, Suzanne L.] Univ N Carolina, Dept Epidemiol, Gillings Sch Publ Hlth, Chapel Hill, NC USA. [Mease, Mary] US FDA, Ctr Drug & Evaluat Res, Silver Spring, MD USA. [Olsen, Axel] Pharmaceut Safety Inst, Newtown, PA USA. RP Van Dole, KB (reprint author), GlaxoSmithKline Inc, Worldwide Epidemiol Dept, POB 13398,5 Moore Dr, Res Triangle Pk, NC 27709 USA. EM kristen.b.van-dole@gsk.com NR 3 TC 0 Z9 0 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JAN 10 PY 2011 VL 171 IS 1 BP 90 EP 91 DI 10.1001/archinternmed.2010.470 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 703YO UT WOS:000286018100018 PM 21220667 ER PT J AU Dreyer, ZE Dinndorf, PA Camitta, B Sather, H La, MK Devidas, M Hilden, JM Heerema, NA Sanders, JE McGlennen, R Willman, CL Carroll, AJ Behm, F Smith, FO Woods, WG Godder, K Reaman, GH AF Dreyer, Zoann E. Dinndorf, Patricia A. Camitta, Bruce Sather, Harland La, Mei K. Devidas, Meenakshi Hilden, Joanne M. Heerema, Nyla A. Sanders, Jean E. McGlennen, Ron Willman, Cheryl L. Carroll, Andrew J. Behm, Fred Smith, Franklin O. Woods, William G. Godder, Kamar Reaman, Gregory H. TI Analysis of the Role of Hematopoietic Stem-Cell Transplantation in Infants With Acute Lymphoblastic Leukemia in First Remission and MLL Gene Rearrangements: A Report From the Children's Oncology Group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; PROGNOSTIC-FACTORS; CLINICAL-TRIALS; POOR-PROGNOSIS; CANCER GROUP; CHILDHOOD; IRRADIATION AB Purpose Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage leukemia (MLL) gene rearrangements, is only 30% to 40%. Relapse has been the major source of treatment failure for these patients. The parallel Children's Cancer Group (CCG) 1953 and Pediatric Oncology Group (POG) 9407 studies were designed to test the hypothesis that more intensive therapy, including dose intensification of chemotherapy, and hematopoietic stem-cell transplantation (HSCT) would improve the outcome for this group of patients. Patients and Methods One hundred eighty-nine infants (CCG 1953, n = 115; POG 9407, n = 74) were enrolled between October 1996 and August 2000. For infants with the MLL gene rearrangement and an appropriate donor, HSCT was the preferred treatment on CCG 1953 and investigator option on POG 9407 after completion of the second phase of therapy. Fifty-three infants underwent HSCT. Results The 5-year EFS rate was 48.8% (95% CI, 33.9% to 63.7%) in patients who received HSCT and 48.7% (95% CI, 33.8% to 63.6%) in patients treated with chemotherapy alone (P = .60). Transplantation outcomes were not affected by the preparatory regimen or donor source. Conclusion Our data suggest that routine use of HSCT for infants with MLL-rearranged ALL is not indicated. However, limited by small numbers, this study should not be considered the definitive answer to this question. J Clin Oncol 29:214-222. (C) 2010 by American Society of Clinical Oncology C1 Texas Childrens Hosp, Houston, TX 77030 USA. US FDA, Silver Spring, MD USA. Midwest Childrens Canc Ctr, Milwaukee, WI USA. Childrens Oncol Grp, Arcadia, CA USA. Peyton Manning Childrens Hosp St Vincent, Indianapolis, IN USA. Nationwide Childrens Hosp, Columbus, OH USA. Seattle Childrens Hosp, Seattle, WA USA. Univ Minnesota Med Sch, Minneapolis, MN USA. Univ New Mexico Sch Med, Albuquerque, NM USA. Univ Alabama, Birmingham, AL USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ Illinois, Chicago, IL USA. Emory Univ Childrens Healthcare Atlanta, Aflac Canc Ctr, Atlanta, GA USA. Virginia Commonwealth Univ Hlth Care Syst, Med Coll Virginia, Richmond, VA USA. RP Dreyer, ZE (reprint author), 6621 Fannin, Houston, TX 77030 USA. EM zedreyer@txccc.org FU National Cancer Institute, National Institutes of Health, Bethesda, MD [U10 CA98543, U10 CA98413] FX Supported by Chair Grant No. U10 CA98543 and Statistics and Data Center Grant No. U10 CA98413 to the Children's Oncology Group from the National Cancer Institute, National Institutes of Health, Bethesda, MD. NR 28 TC 31 Z9 34 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 10 PY 2011 VL 29 IS 2 BP 214 EP 222 DI 10.1200/JCO.2009.26.8938 PG 9 WC Oncology SC Oncology GA 703GC UT WOS:000285965400026 PM 21135279 ER PT J AU Ali, MM Amialchuk, A Dwyer, DS AF Ali, Mir M. Amialchuk, Aliaksandr Dwyer, Debra S. TI The Social Contagion Effect of Marijuana Use among Adolescents SO PLOS ONE LA English DT Article ID DRUG-USE; SUBSTANCE USE; ALCOHOL-CONSUMPTION; HEALTH AB Background: Research on adolescent substance use has consistently identified a strong relationship between adolescent behavior and the behavior of their peers. However, peer effects are difficult to estimate and causal interpretations must be undertaken with caution since individuals in most cases choose with whom to associate. In this paper we seek to empirically quantify the causal role of peer social networks in explaining marijuana usage among adolescents. Methods and Findings: Using data from a nationally representative sample of adolescents we utilize a multivariate structural model with school-level fixed effects to account for the problems of contextual effects, correlated effects and peer selections to purge the potential biases from the estimates of peer influence. Our peer group measures are drawn not only from the nomination of close friends (N = 6,377), but also from classmates (N = 19,335). Marijuana usage among the peer groups were constructed using the peers' own report of their marijuana consumption. Controlling for parent level characteristics, and other demographic parameters, we find that a 10% increase in the proportion of close friends and classmates who use marijuana increases the probability that an individual chooses to use marijuana by 5%. Conclusion: Our findings indicate that peer effects are important determinants of marijuana use even after controlling for potential biases We also found evidence to show that the influence of close friends and the more exogenous classmates are quite similar in magnitude under our preferred specification, supporting theory predicting the importance of peer influence. Effective policy aimed at reducing marijuana usage among adolescents would consider these significant 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. [Ali, Mir M.] US FDA, Off Regulat Policy & Social Sci, College Pk, MD USA. RP Ali, MM (reprint author), Univ Toledo, Dept Econ, 2801 W Bancroft St, Toledo, OH 43606 USA. EM mir.ali@fda.hhs.gov FU National Institute of Child Health and Human Development [P01- HD31921] FX The views expressed here are those of the authors and do not necessarily reflect the views of the Food and Drug Administration. 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 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 23 TC 14 Z9 14 U1 1 U2 10 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 JAN 10 PY 2011 VL 6 IS 1 AR e16183 DI 10.1371/journal.pone.0016183 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 710LL UT WOS:000286513100030 PM 21264337 ER PT J AU Hinchey, J Jeon, BY Alley, H Chen, B Goldberg, M Derrick, S Morris, S Jacobs, WR Porcelli, SA Lee, S AF Hinchey, Joseph Jeon, Bo Y. Alley, Holly Chen, Bing Goldberg, Michael Derrick, Steven Morris, Sheldon Jacobs, William R., Jr. Porcelli, Steven A. Lee, Sunhee TI Lysine Auxotrophy Combined with Deletion of the SecA2 Gene Results in a Safe and Highly Immunogenic Candidate Live Attenuated Vaccine for Tuberculosis SO PLOS ONE LA English DT Article ID CD8(+) T-CELLS; MYCOBACTERIUM-TUBERCULOSIS; FUNCTIONAL IMPAIRMENT; IMMUNE-RESPONSE; VIRAL-INFECTION; BCG; SMEGMATIS; DIAMINOPIMELATE; GENERATION; EFFECTOR AB Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a major global health problem, despite the widespread use of the M. bovis Bacille Calmette-Guerin (BCG) vaccine and the availability of drug therapies. In recent years, the high incidence of coinfection of M. tuberculosis and HIV, as well as escalating problems associated with drug resistance, has raised ominous concerns with regard to TB control. Vaccination with BCG has not proven highly effective in controlling TB, and also has been associated with increasing concerns about the potential for the vaccine to cause disseminated mycobacterial infection in HIV infected hosts. Thus, the development of an efficacious and safe TB vaccine is generally viewed as a critical to achieving control of the ongoing global TB pandemic. In the current study, we have analyzed the vaccine efficacy of an attenuated M. tuberculosis strain that combines a mutation that enhances T cell priming (Delta secA2) with a strongly attenuating lysine auxotrophy mutation (Delta lysA). The Delta secA2 mutant was previously shown to be defective in the inhibition of apoptosis and markedly increased priming of antigen-specific CD8(+) T cells in vivo. Similarly, the Delta secA2 Delta lysA strain retained enhanced apoptosis and augmented CD8+ T cell stimulatory effects, but with a noticeably improved safety profile in immunosuppressed mice. Thus, the M. tuberculosis Delta secA2 Delta lysA mutant represents a live attenuated TB vaccine strain with the potential to deliver increased protection and safety compared to standard BCG vaccination. C1 [Hinchey, Joseph; Chen, Bing; Goldberg, Michael; Jacobs, William R., Jr.; Porcelli, Steven A.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. [Jeon, Bo Y.] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea. [Alley, Holly; Lee, Sunhee] Duke Human Vaccine Inst, Durham, NC USA. [Derrick, Steven; Morris, Sheldon] US FDA, Ctr Biol Evaluat, Bethesda, MD 20014 USA. [Jacobs, William R., Jr.] Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA. [Porcelli, Steven A.] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Hinchey, J (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA. EM sunhee.lee@duke.edu FU NIH [U54 AI057157, AI063537]; Einstein Cancer Center (NIH/NCI) [NIH/NCI CA013330]; Einstein Center for AIDS Research (NIH) [NIH AI-51519] FX SL was supported by NIH grant U54 AI057157. SAP and WRJ were supported by NIH Program Project Grant AI063537. Flow cytometry studies were carried out using core facilities supported by the Einstein Cancer Center (NIH/NCI CA013330) and the Einstein Center for AIDS Research (NIH AI-51519). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 32 TC 21 Z9 22 U1 1 U2 7 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 JAN 10 PY 2011 VL 6 IS 1 AR e15857 DI 10.1371/journal.pone.0015857 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 710LL UT WOS:000286513100014 PM 21264335 ER PT J AU Sejvar, JJ Kohl, KS Gidudu, J Amato, A Bakshi, N Baxter, R Burwen, DR Cornblath, DR Cleerbout, J Edwards, KM Heininger, U Hughes, R Khuri-Bulos, N Korinthenberg, R Law, BJ Munro, U Maltezou, HC Nell, P Oleske, J Sparks, R Velentgas, P Vermeer, P Wiznitzer, M AF Sejvar, James J. Kohl, Katrin S. Gidudu, Jane Amato, Anthony Bakshi, Nandini Baxter, Roger Burwen, Dale R. Cornblath, David R. Cleerbout, Jan Edwards, Kathryn M. Heininger, Ulrich Hughes, Richard Khuri-Bulos, Najwa Korinthenberg, Rudolf Law, Barbara J. Munro, Ursula Maltezou, Helena C. Nell, Patricia Oleske, James Sparks, Robert Velentgas, Priscilla Vermeer, Patricia Wiznitzer, Max CA Brighton Collaboration GBS Working TI Guillain-Barre syndrome and Fisher syndrome: Case definitions and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE Guillain-Barre syndrome; Neuropathy; Fisher syndrome; Acute inflammatory demyelinating polyradiculoneuropathy; Adverse event; Immunization; Guidelines; Case definition ID MEDIATED NEUROLOGIC DISEASE; MOTOR AXONAL NEUROPATHY; MOLECULAR MIMICRY; INFLUENZA VACCINATION; UNITED-STATES; ELECTRODIAGNOSTIC CRITERIA; CAMPYLOBACTER-JEJUNI; DIAGNOSTIC-CRITERIA; RABIES VACCINATION; EPIDEMIOLOGY C1 [Sejvar, James J.; Kohl, Katrin S.; Gidudu, Jane] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Amato, Anthony] Brigham & Womens Hosp, Dept Neurol, Div Neuromuscular Dis, Boston, MA 02115 USA. [Velentgas, Priscilla] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. [Bakshi, Nandini; Baxter, Roger] NCK Kaiser Permanente, Oakland, CA USA. [Burwen, Dale R.] US FDA, Rockville, MD 20857 USA. [Cornblath, David R.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Cleerbout, Jan] GlaxoSmithKline Biol, Rixensart, Belgium. [Edwards, Kathryn M.] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. [Heininger, Ulrich] Univ Childrens Hosp, Basel, Switzerland. [Hughes, Richard] Kings Coll London, Sch Med, London WC2R 2LS, England. [Khuri-Bulos, Najwa] Jordan Univ Hosp, Amman, Jordan. [Korinthenberg, Rudolf] Univ Hosp Freiburg, Freiburg, Germany. [Law, Barbara J.] Publ Hlth Agcy Canada, Ottawa, ON, Canada. [Munro, Ursula] Sanofi Pasteur MSD GmbH, Walldorf, Germany. [Maltezou, Helena C.] Hellen Ctr Dis Control & Prevent, Athens, Greece. [Nell, Patricia] USAF, Airforce Reserve Command, Sturgeon Bay, WI USA. [Oleske, James] Univ Hosp, New Jersey Med Sch, Morris Plains, NJ USA. [Sparks, Robert] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Velentgas, Priscilla] Harvard Pilgrim Hlth Care, Boston, MA USA. [Vermeer, Patricia] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Wiznitzer, Max] Univ Hosp Cleveland, Dept Neurol, Cleveland, OH 44106 USA. RP Sejvar, JJ (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org OI Korinthenberg, Rudolf/0000-0002-4638-3460 FU WHO FX The authors are grateful for the support and helpful comments from members of Brighton Collaboration Steering Committee during the time of the development of this document, who are not already included as authors (Mike Blum, Paul Heath, Hector Izurieta, Brigitte Keller Stanislawski, Katrin Kohl Odile Leroy), and the participants in the Reference Group (Adam Rudiger, Adderson Elisabeth, Aguilar Maria, Aldrovandi Grace, Allen Mary, Bachtiar Novilia Sjafri, Barami A. A. Salim, Baxter Roger, Bettinger Julie, Bilynsky Roman, Blum Michael, Bonhoeffer Jan, Brady Michael, Buettcher Michael, Buttery Jim, Cane Alejandro, Chang Soju, Chatterjee Arani, Chawla Krishan, Cherian Thomas, Cleerbout Jan, Close Philippe, Condit Richard, Cornblath David, Couch Robert B., da Costa Christopher, Davis Larry, de Menezes Martins Reinaldo, de Vries Corinne, Deotti Sandra Maria, Dimitrijevic Dragana, Dong Duo, Evengard Birgitta, Falup-Pecurariu Cristian, Fernandopulle Rohini, Ferreira Germano, Fisher Margaret C, Galama Jochem, Gallegos Karl, Gershman Mark, Gibbs Neville, Gidudu Jane, Gurwith Marc, Halsey Neal, Hanlon Erin, Hitchcock William, Hossain Shah, Huang Wan-Ting, Hunter Deborah, Isaacs David, Jacobson Robert, Johann-Liang Rosemary, Jones Barbara, Jovancevic Milivoj, Kaisar Mahfuzul Islam, Kang Gagandeep, Klug Bettina, Korinthenberg Rudolf, Kulcsar Andrea, Lee Grace, Lievano Fabio, MacDonald Noni, Mahmood Asif, Maltezou Helena, Martin Martin Susana, McIntosh G David, Mentzer Dirk, Meredith Stefanie, Meszner Zsofia, Milstien Julie, Minor Mary, Modlin John, Montgomery Jay, Morse Ann, Munro Ursula, Nalin David, Nell Patricia, Nimmannitya Suchitra, Nisslein Thomas, Nokleby Hanne, Nwosu Kenneth, Oleske James M., Patnaik Badri, Pinheiro Luis, Pourmalek Farshad, Ramasamy Ranjan, Rump Eva-Beate, Samson Heather, Santos Eliane, Schuller Elisabeth, Schultze Viola, Sidhu Maninder K., Sillan Francoise, Sliman Joseph, Soh Bee Leng Sally, Sparks Robert, Sprenger Ralf, Steele Russell, Stoller Rudolf, Storsaeter Jann, Suznjevic Vladimir, Tebaa Amina, Tridente Giuseppe, Trimis Georgios, Uhnoo Ingrid, Van Dinther Kristy, Varricchio Frederick, Ventura Rafael, Vilella Anna, Warden Beverly, Weston William, Wimalaratne Omala, Wong Virginia, Chun-Nei, Zajdowicz Thad, Zaman Khalequz, Zanoni Giovanna, Zielinski Andrzej, and Zuber Patrick and harmonization work by Michael Buettcher, Sabine Faisst, and Jan Bonhoeffer. We are also grateful for the support of WHO and ECDC for creating this document. Finally, we would like to thank the members of the WHO/CIOMS Working Group on Vaccine Pharmacovigilance (http://www.cioms.ch/frame current programme. htm) for the review of, constructive comments on, and endorsement of this document. NR 84 TC 120 Z9 123 U1 3 U2 13 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 JAN 10 PY 2011 VL 29 IS 3 BP 599 EP 612 DI 10.1016/j.vaccine.2010.06.003 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 715AQ UT WOS:000286853200031 PM 20600491 ER PT J AU Imam, SZ Zhou, Q Yamamoto, A Valente, AJ Ali, SF Bains, M Roberts, JL Kahle, PJ Clark, RA Li, SL AF Imam, Syed Z. Zhou, Qing Yamamoto, Ayako Valente, Anthony J. Ali, Syed F. Bains, Mona Roberts, James L. Kahle, Philipp J. Clark, Robert A. Li, Senlin TI Novel Regulation of Parkin Function through c-Abl-Mediated Tyrosine Phosphorylation: Implications for Parkinson's Disease SO JOURNAL OF NEUROSCIENCE LA English DT Article ID UBIQUITIN LIGASE ACTIVITY; PROTECTIVE FUNCTION; S-NITROSYLATION; PROTEIN LIGASE; CELL-DEATH; MUTATIONS; SUBSTRATE; STRESS; NEURODEGENERATION; PATHOGENESIS AB Mutations in parkin, an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in striatum of adult C57BL/6 mice. Activated c-Abl was found in the striatum of PD patients. Concomitantly, parkin was tyrosine-phosphorylated, causing loss of its ubiquitin ligase and cytoprotective activities, and the accumulation of parkin substrates, AIMP2(aminoacyl tRNA synthetase complex-interacting multifunctional protein 2) (p38/JTV-1) and FBP-1.STI-571, a selective c-Abl inhibitor, prevented tyrosine phosphorylation of parkin and restored its E3 ligase activity and cytoprotective function both in vitro and in vivo. Our results suggest that tyrosine phosphorylation of parkin by c-Abl is a major post-translational modification that leads to loss of parkin function and disease progression in sporadic PD. Moreover, inhibition of c-Abl offers new therapeutic opportunities for blocking PD progression. C1 [Imam, Syed Z.; Zhou, Qing; Valente, Anthony J.; Clark, Robert A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Imam, Syed Z.; Bains, Mona; Roberts, James L.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA. [Imam, Syed Z.; Roberts, James L.; Clark, Robert A.; Li, Senlin] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Imam, Syed Z.; Clark, Robert A.; Li, Senlin] S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. [Yamamoto, Ayako; Kahle, Philipp J.] Univ Clin Tubingen, Lab Funct Neurogenet, Dept Neurodegenerat, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany. [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Imam, SZ (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM imam@uthscsa.edu; lis1@uthscsa.edu FU US National Institutes of Health; Department of Veterans Affairs; Michael J. Fox Foundation; Parkinson's Disease Foundation; San Antonio Area Foundation; American Parkinson Disease Association; Executive Research Council of University of Texas Health Science Center; San Antonio (UTHSCSA); German National Genome Research Network [NGFN-2]; European Union FX This work was supported by grants from the US National Institutes of Health, Department of Veterans Affairs, Michael J. Fox Foundation, Parkinson's Disease Foundation, San Antonio Area Foundation, American Parkinson Disease Association, Executive Research Council of University of Texas Health Science Center, San Antonio (UTHSCSA), the German National Genome Research Network (NGFN-2), and the European Union (N)EUROPARK consortium. The technical assistance of Xuyean Liao, Doran Pearson, Lora Judge, Heather Dudley, and Wuqiong Ma is acknowledged. We thank F. Fiesel (Hertie Institute, Tubingen, Germany) for helpful suggestions, and S.T. Weintraub and K. Hakala for MS analyses (UTHSCSA Institutional Mass Spectrometry Laboratory). Parkin plasmids and constructs, antibodies to AIMP2, and postmortem human samples were kind gifts from Ted M. Dawson (Johns Hopkins University, Baltimore, MD). We also thank Dr. Dawson's lab for processing of some human samples. c-Abl and Arg constructs were kind gifts from B. Li (Institute of Molecular and Cell Biology, Singapore), D. Kufe (Dana-Farber Cancer Institute, Harvard Medical School, Cambridge, MA), and Z. M. Yuan (Harvard School of Public Health). Recombinant tyrosine kinase fragment of c-Abl was a kind gift from M. Seeliger and J. Kuriyan (Howard Hughes Medical Institute, University of California, Berkeley, CA). FBP-1 cDNA was kindly provided by D. Levens (National Cancer Institute, National Institutes of Health, Bethesda, MD). Lenti-shRNA to parkin was kindly provided by P. Aebischer and R. Zuffrey (Ecole Polytechnique Federale Lausanne, Lausanne, Switzerland). STI-571 was provided by Novartis Pharma. NR 30 TC 58 Z9 58 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JAN 5 PY 2011 VL 31 IS 1 BP 157 EP 163 DI 10.1523/JNEUROSCI.1833-10.2011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 702SH UT WOS:000285915100018 PM 21209200 ER PT J AU Whittlesey, KJ Lee, MH Dang, JYM Colehour, M Arcidiacono, J Lazarus, E Kaplan, DS Fink, D Durfor, CN Batra, A Hilbert, SL Grayeski, DL McFarland, R Witten, C AF Whittlesey, Kevin J. Lee, Mark H. Dang, Jiyoung M. Colehour, Maegen Arcidiacono, Judith Lazarus, Ellen Kaplan, David S. Fink, Donald Durfor, Charles N. Batra, Ashok Hilbert, Stephen L. Grayeski, Deborah Lavoie McFarland, Richard Witten, Celia BE Atala, A Lanza, R Thomson, JA Nerem, R TI Overview of the FDA Regulatory Process SO PRINCIPLES OF REGENERATIVE MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID ADENOVIRUS VECTORS; IN-VITRO; CELLS; KERATINOCYTES; REQUIREMENTS; STANDARDS; PRODUCTS; FRZB-1; WNT-8 C1 [Whittlesey, Kevin J.] US FDA, Off Commissioner, Silver Spring, MD USA. [Lee, Mark H.; Arcidiacono, Judith; Lazarus, Ellen; Fink, Donald; McFarland, Richard; Witten, Celia] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Dang, Jiyoung M.; Colehour, Maegen; Kaplan, David S.; Durfor, Charles N.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Batra, Ashok] SUNY Syracuse, Syracuse, NY USA. [Batra, Ashok] US Biotechnol & Pharma Consulting Grp, Potomac, MD USA. [Hilbert, Stephen L.] Childrens Mercy Hosp, Kansas City, MO 64108 USA. [Grayeski, Deborah Lavoie] M Squared Associates Inc, Alexandria, VA USA. RP Whittlesey, KJ (reprint author), US FDA, Off Commissioner, Silver Spring, MD USA. NR 70 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-12-381423-4 PY 2011 BP 1145 EP 1168 DI 10.1016/B978-0-12-381422-7.10063-X PG 24 WC Cell & Tissue Engineering; Developmental Biology SC Cell Biology; Developmental Biology GA BCS97 UT WOS:000311305200063 ER PT S AU Platisa, L Marchessoux, C Kimpe, T Vansteenkiste, E Badano, A Philips, W AF Platisa, Ljiljana Marchessoux, Cedric Kimpe, Tom Vansteenkiste, Ewout Badano, Aido Philips, Wilfried GP IEEE TI Channelized Hotelling Observers for Signal Detection in Stack-Mode Reading of Volumetric Images on Medical Displays with Slow Response Time SO 2011 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors CY OCT 23-29, 2011 CL Valencia, SPAIN SP IEEE, Inst Elect & Elect Engineers Nucl & Plasma Sci Soc (IEEE NPSS) ID BOOTSTRAP; NOISE AB Volumetric medical images are commonly read in stack-browsing mode. However, previous studies suggest that slow temporal response of medical liquid crystal displays may degrade the diagnostic accuracy (lesion detectability) at browsing rates as low as 10 frames per second (fps). Recently, a multi-slice channelized Hotelling observer (msCHO) model was proposed to estimate the detection performance in 3D images. This implementation of the msCHO restricted the analysis to the luminance of a display pixel at the end of the frame time (end-of-frame luminance) while ignoring the luminance transition within the frame time (intra-frame luminance). Such an approach fails to differentiate between, for example, the commonly found case of two displays with different temporal profiles of luminance as long as their end-of-frame luminance levels are the same. In order to overcome this limitation of the msCHO, we propose a new upsampled msCHO (umsCHO) which acts on images obtained using both the intra-frame and the end-of-frame luminance information. The two models are compared on a set of synthesized 3D images for a range of browsing rates (16.67, 25 and 50 fps). Our results demonstrate that, depending on the details of the luminance transition profiles, neglecting the intra-frame luminance information may lead to over-or underestimation of lesion detectability. Therefore, we argue that using the umsCHO rather than msCHO model is more appropriate for estimating the detection performance in the stack-browsing mode. C1 [Platisa, Ljiljana; Vansteenkiste, Ewout] Univ Ghent, Dept Telecommun & Informat Proc TELIN IPI IBBT, Grp Image Proc & Interpretat, St Pietersnieuwstr 41, B-9000 Ghent, Belgium. [Marchessoux, Cedric; Kimpe, Tom] Technol & Innovat Grp, Hlth Div, B-8500 Kortrijk, Belgium. [Badano, Aido] CDRH, Off Sci & Engn Labs, Div Imaging & Appl Math, FDA, Silver Spring, MD 20993 USA. RP Platisa, L (reprint author), Univ Ghent, Dept Telecommun & Informat Proc TELIN IPI IBBT, Grp Image Proc & Interpretat, St Pietersnieuwstr 41, B-9000 Ghent, Belgium. EM Ljiljana.Platisa@telin.ugent.be NR 15 TC 0 Z9 0 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-0120-6 J9 IEEE NUCL SCI CONF R PY 2011 BP 2697 EP 2702 PG 6 WC Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAM64 UT WOS:000304755602194 ER PT S AU Calderon, SN AF Calderon, Silvia N. BE Nagase, H TI Nonpeptidic Delta (delta) Opioid Agonists and Antagonists of the Diarylmethylpiperazine Class: What Have We Learned? SO CHEMISTRY OF OPIOIDS SE Topics in Current Chemistry LA English DT Review; Book Chapter DE delta Agonists; delta Antagonists; Diphenylmethylpiperazines; Nonpeptidic delta ligands; SNC 80 ID RECEPTOR-MEDIATED PHENOMENA; N-SUBSTITUTED BENZOTRIAZOLES; DISPLAYS SELECTIVE BINDING; MESSAGE-ADDRESS CONCEPT; PHARMACOLOGICAL CHARACTERIZATION; HIGHLY POTENT; HIGH-AFFINITY; LIGANDS; SNC-80; ANALOGS AB The discovery of the selective delta (delta) opioid agonists SNC 80 and BW373U86, which possess a diarylmethylpiperazine structure unique among opioids, represented a major advance in the field of delta-opioid ligands. Extensive research has recently been performed to uncover the structure-activity relationships (SAR) of this class of ligands, thereby providing valuable tools for the pharmacological characterization of the delta opioid receptor. This review focuses on the SAR of this unique series of ligands, and provides an overview of the various chemical routes that have been developed and optimized through the years to allow the syntheses of these ligands on a multigram scale. The search for selective delta opioid agonists and antagonists, as well as for those with mixed opioid agonist properties with potential therapeutic value, continues. Several questions regarding the interaction at the molecular level of diphenylmethylpiperazine derivatives and related analogs with opioid receptors and in particular with the delta opioid system still remain unanswered. Indeed, the development and pharmacological characterization of novel nonpeptidic delta opioid ligands remains an active area of research, as it may provide a better understanding of the role of this receptor in multiple disease states and disorders. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Calderon, SN (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM silvia.calderon@fda.hhs.gov NR 61 TC 2 Z9 2 U1 1 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0340-1022 BN 978-3-642-18107-8 J9 TOP CURR CHEM JI Top. Curr. Chem. PY 2011 VL 299 BP 121 EP 140 DI 10.1007/128_2010_83 D2 10.1007/978-3-642-18107-8 PG 20 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA BAZ17 UT WOS:000306137700006 PM 21630509 ER PT S AU Woodruff, RS Yan, J Jones, MY Watanabe, F Biris, A Chen, T AF Woodruff, Robert S. Yan, Jian Jones, Margie Y. Watanabe, Fumiya Biris, Alexandru Chen, Tao BE Tarasenko, O TI "Evaluation of Genotoxicity of Titanium Dioxide Nanoparticles using the Ames Test and In Vitro Comet Assay" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Woodruff, Robert S.] US FDA, Div Microbiol, Arkansas Reg Lab, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 35 EP 36 PG 2 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100015 ER PT S AU Pogribna, M Nichols, J Cozart, C Siitonen, P Walker, NJ Boudreau, M AF Pogribna, Marta Nichols, J. Cozart, C. Siitonen, P. Walker, N. J. Boudreau, Mary BE Tarasenko, O TI "Tissue Distribution of Different Sizes of Silver Nanoparticles in Sprague-Dawley Rats" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Pogribna, Marta; Nichols, J.; Cozart, C.; Siitonen, P.; Boudreau, Mary] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 59 EP 60 PG 2 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100063 ER PT S AU Alusta, P Buzatu, D Tarasenko, O Wilkes, J Darsey, J AF Alusta, Pierre Buzatu, Dan Tarasenko, Olga Wilkes, Jon Darsey, Jerry BE Tarasenko, O TI DIRECT IMPACT CORONA IONIZATION OF BACTERIA FOR RAPID, REPRODUCIBLE IDENTIFICATION VIA SPECTRAL PATTERN RECOGNITION SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club DE direct impact corona ionization; mass spectrometry; rapid bacterial identification ID PYROLYSIS-MASS-SPECTROMETRY AB A novel atmospheric pressure ionization process, Direct Impact Corona Ionization (DICI), is described here. In this process, a corona impinges onto the flat surface of a stainless steel pin carrying a thin film of dried bacterial suspension, the analyte. Two electrodes - a corona electrode and the sample pin - are immersed in hot inert He gas flux, flowing past them towards a 0.4 mm orifice leading to a mass spectrometer analyzer. An electric potential of 1.5 - 3.0 kV is placed between the two. At distances less than 1 cm, an intermittent arc is formed. At approximately 4 mm, the arc becomes a continuous corona discharge (plasma). The plasma is hot enough to: A) locally melt the impact zone on the steel pin, and B) ablate the dry thin bacterial film deposited on the metal pin. Biomolecular ions as heavy as 790 m/z are generated. Mass spectral fingerprints of bacteria are obtained with a high degree of reproducibility by selecting the highest intensity of an "indicator ion", 560.5 m/z or another relatively heavy ion whose appearance signals efficient vaporization of low volatility components. C1 [Alusta, Pierre; Buzatu, Dan; Wilkes, Jon] US FDA, Ctr Innovat Technol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Alusta, P (reprint author), US FDA, Ctr Innovat Technol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. FU ORISE (Oak Ridge, TN); ORISE; NCTR; IBC [09093.] FX This study was supported by ORISE (Oak Ridge, TN). Sincere appreciation is extended to Bruce Pearce, Richard Beger, Tom Schmitt, Randal Tucker, Tom Heinze, Richard Rassmussen, Reggie Hall, Don Paine, John Sutherland, Mohammed Nawaz, Rajesh Nayak, Steven Foley, Ricky Holland, Fumiya Watanabe, Nysia George and the Array Track TM development team at the NCTR for their scientific and computational insights. This study conforms to the IBC protocol # 09093. NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 128 EP 134 DI 10.1063/1.3587468 PG 7 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100075 ER PT S AU Eassa, S Bose, C Alusta, P Tarasenko, O AF Eassa, Souzan Bose, Chhanda Alusta, Pierre Tarasenko, Olga BE Tarasenko, O TI DETECTION METHOD OF TOXOPLASMA GONDII TACHYZOITES SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Proceedings Paper CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club ID RISK-FACTORS; INFECTION; OLIGOSACCHARIDES; GLYCOSYLATION; RECOGNITION; PREGNANCY; ROLES AB Tachyzoites are considered to be the most important stage of Toxoplasma gondii which causes toxoplasmosis. T. gondii is, an obligate intracellular parasite which infects a wide range of cells. The present study was designed to develop a method for an early detection of T. gondii tachyzoites. The method comprised of a binding assay which was analyzed using principal component and cluster analysis. Our data showed that glycoconjugates GC1, GC2, GC3 and GC10 exhibit a significantly higher binding affinity for T. gondii tachyzoites as compared to controls (T. gondii only, PAA only, GC 1, 2, 3, and 10 only). C1 [Eassa, Souzan; Tarasenko, Olga] Univ Arkansas, Little Rock, AR 72204 USA. [Bose, Chhanda; Alusta, Pierre] Cent Arkansas Vet Healthcare Syst, Little Rock, AR 72204 USA. [Alusta, Pierre] Natl Ctr Toxicol Res, FDA Labs, Jefferson, AR USA. RP Eassa, S (reprint author), Univ Arkansas, Little Rock, AR 72204 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 157 EP 164 DI 10.1063/1.3587472 PG 8 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100079 ER PT B AU Robertson, SM Piscitelli, SC Struble, KA AF Robertson, Sarah M. Piscitelli, Stephen C. Struble, Kimberly A. BE Piscitelli, SC Rodvold, KA Pai, MP TI Drug Interactions with Antiretrovirals for HIV Infection SO DRUG INTERACTIONS IN INFECTIOUS DISEASES, THIRD EDITION SE Infectious Disease LA English DT Article; Book Chapter ID TENOFOVIR DISOPROXIL FUMARATE; IMMUNODEFICIENCY-VIRUS PROTEASE; PHARMACOKINETIC INTERACTION; HEALTHY-VOLUNTEERS; NEGATIVE VOLUNTEERS; CYP3A4 INHIBITORS; PLASMA-LEVELS; RALTEGRAVIR; RITONAVIR; MARAVIROC AB Despite great strides in human immunodeficiency virus (HIV) drug development, the management of drug interactions remains a key component of patient care. A number of new drugs have been approved in the past 5 years, including two new classes of antiretrovirals: CCR5 antagonists and integrase inhibitors. HIV treatment is complex, generally requiring at least three antiretrovirals in addition to medications for supportive care and concomitant infections. Many antiretrovirals have clinically significant drug interactions that require dosage adjustment. This chapter reviews important drug interactions for the newest antiretrovirals and provides detailed tables to guide clinicians on patient management. C1 [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Struble, Kimberly A.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Piscitelli, Stephen C.] GlaxoSmithKline Inc, Clin Pharmacol, Infect Dis, Res Triangle Pk, NC USA. RP Robertson, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak Bldg 22, Silver Spring, MD 20993 USA. EM Sarah.Robertson@fda.hhs.gov NR 95 TC 5 Z9 5 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-212-0 J9 INFECT DIS PY 2011 BP 425 EP 470 DI 10.1007/978-1-61779-213-7_13 D2 10.1007/978-1-61779-213-7 PG 46 WC Infectious Diseases; Medicine, General & Internal; Pharmacology & Pharmacy SC Infectious Diseases; General & Internal Medicine; Pharmacology & Pharmacy GA BYU08 UT WOS:000300328700013 ER PT S AU Wang, SJ Anugu, V Nguyen, T Rose, N Burns, J McKenna, M Petrick, N Summers, RM AF Wang, Shijun Anugu, Vishal Tan Nguyen Rose, Natalie Burns, Joseph McKenna, Matthew Petrick, Nicholas Summers, Ronald M. GP IEEE TI FUSION OF MACHINE INTELLIGENCE AND HUMAN INTELLIGENCE FOR COLONIC POLYP DETECTION IN CT COLONOGRAPHY SO 2011 8TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 8th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAR 30-APR 02, 2011 CL Chicago, IL SP Inst Elect & Electron Engn, Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc (SPS) DE Computed tomographic colonography; computer aided detection; Amazon MTurk; alpha -integration; classifier fusion ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; COMPUTER-AIDED DETECTION; FALSE POSITIVES; REDUCTION AB In this paper, we proposed a novel method to improve colonic polyp detection in computed tomographic colonography. Utilizing the human knowledge workers via the Amazon Mechanical Turk (MTurk) webservice, we distributed polyp detections from a computer-aided detection system (CAD) to anonymous online knowledge workers and asked them to distinguish true and false polyp candidates. We combined decisions from the CAD system (machine intelligence) and the MTurk workers (human intelligence) using alpha-integration. Preliminary experimental results indicated that the combined decisions were superior to either alone, with area under the receiver operating characteristic curve improving by 5.8% and 7.0% compared with CAD and MTurk workers alone, respectively. C1 [Wang, Shijun; Anugu, Vishal; Tan Nguyen; Rose, Natalie; Burns, Joseph; McKenna, Matthew; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA. [Petrick, Nicholas] U S Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Burns, Joseph] Univ Calif, Irvine Med Ctr, Dept Radiol Sci, Orange, CA 92868 USA. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Ctr Clin, Bldg 10,Room 1C224,MSC 1182, Bethesda, MD 20892 USA. EM rms@mail.nih.gov FU Intramural Research Programs of the NIH Clinical Center; U.S. Food and Drug Administration FX This research was supported by the Intramural Research Programs of the NIH Clinical Center and the U.S. Food and Drug Administration (NP). NR 12 TC 7 Z9 7 U1 0 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-4128-0 J9 I S BIOMED IMAGING PY 2011 BP 160 EP 164 PG 5 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BYH79 UT WOS:000298849400038 ER PT S AU Vidal, C Beggs, D Younes, L Jain, SK Jedynak, B AF Vidal, Camille Beggs, Dale Younes, Laurent Jain, Sanjay K. Jedynak, Bruno GP IEEE TI INCORPORATING USER INPUT IN TEMPLATE-BASED SEGMENTATION SO 2011 8TH IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO SE IEEE International Symposium on Biomedical Imaging LA English DT Proceedings Paper CT 8th IEEE International Symposium on Biomedical Imaging (ISBI) - From Nano to Macro CY MAR 30-APR 02, 2011 CL Chicago, IL SP Inst Elect & Electron Engn, Engn Med & Biol Soc (EMBS), IEEE Signal Proc Soc (SPS) DE Registration; Template-based Segmentation; User Input; Diseased Organs AB We present a simple and elegant method to incorporate user input in a template-based segmentation method for diseased organs. The user provides a partial segmentation of the organ of interest, which is used to guide the template towards its target. The user also highlights some elements of the background that should be excluded from the final segmentation. We derive by likelihood maximization a registration algorithm from a simple statistical image model in which the user labels are modeled as Bernoulli random variables. The resulting registration algorithm minimizes the sum of square differences between the binary template and the user labels, while preventing the template from shrinking, and penalizing for the inclusion of background elements into the final segmentation. We assess the performance of the proposed algorithm on synthetic images in which the amount of user annotation is controlled. We demonstrate our algorithm on the segmentation of the lungs of Mycobacterium tuberculosis infected mice from mu CT images. C1 [Vidal, Camille] US FDA, Div Imaging & Appl Math, CDRH, Rockville, MD 20857 USA. [Younes, Laurent; Jedynak, Bruno] US FDA, Ctr Imaging Sci, Rockville, MD 20857 USA. [Beggs, Dale; Younes, Laurent; Jedynak, Bruno] Johns Hopkins Univ, Dept Appl Math & Stat, Baltimore, MD 21218 USA. [Jain, Sanjay K.] Johns Hopkins Univ, Ctr Tuberculosis Res, Baltimore, MD 21218 USA. RP Vidal, C (reprint author), US FDA, Div Imaging & Appl Math, CDRH, Rockville, MD 20857 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1945-7928 BN 978-1-4244-4128-0 J9 I S BIOMED IMAGING PY 2011 BP 1434 EP 1437 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BYH79 UT WOS:000298849400326 ER PT S AU Sanders, ME Levy, DD AF Sanders, Mary Ellen Levy, Dan D. BA Sanders, ME Levy, DD BF Sanders, ME Levy, DD TI The science and regulations of probiotic food and supplement product labeling SO PROBIOTIC FOODS AND SUPPLEMENTS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Probiotic Foods and Supplements - The Science and Regulations of Labeling CY JUN 12, 2010 CL New York Acad Sci, New York, NY HO New York Acad Sci DE probiotics; dietary supplements; FDA; structure/function claims ID IRRITABLE-BOWEL-SYNDROME; LACTOBACILLUS AB Presented by the New York Academy of Sciences, the U.S. Food and Drug Administration (FDA), and the U.S. Office of Dietary Supplements of the National Institutes of Health, the symposium "Probiotic Foods and Supplements: The Science and Regulations of Labeling," was held on June 12, 2010 at the New York Academy of Sciences, New York, NY, the goals of which were to facilitate the exchange of ideas regarding labeling and substantiation of claims for probiotics among academic, industry, and regulatory professionals, and to discuss ways to translate and communicate research results in a truthful way to the consumer and to such health professionals as physicians, pharmacists, and dieticians. The target audience for this symposium included academicians interested in conducting research on the health benefits of probiotics; scientists; communications personnel, and regulatory specialists from companies involved in, or interested in, the marketing of probiotics; U. S. government regulatory experts tasked with oversight of probiotic foods and dietary supplement products; and other experts in the field interested in the development of probiotics for the U. S. market. C1 [Sanders, Mary Ellen] Dairy & Food Culture Technol, Centennial, CO 80122 USA. [Levy, Dan D.] US FDA, New Dietary Ingredient Review Team, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sanders, ME (reprint author), Dairy & Food Culture Technol, 7119 S Glencoe Ct, Centennial, CO 80122 USA. EM mes@mesanders.com; Dan.Levy@fda.hhs.gov; mes@mesanders.com; Dan.Levy@fda.hhs.gov FU National Center for Complementary and Alternative Medicine, a component of the National Institutes of Health FX This conference report was made possible, in part, by support from the National Center for Complementary and Alternative Medicine, a component of the National Institutes of Health. The views expressed in written conference materials or publications and by speakers and moderators do not necessarily reflect the official policies of the National Institutes of Health; nor do mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government. NR 24 TC 13 Z9 15 U1 3 U2 15 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 0077-8923 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2011 VL 1219 IS S1 BP E1 EP E23 DI 10.1111/j.1749-6632.2010.05956.x PG 23 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA BZD70 UT WOS:000301188100001 PM 21332758 ER PT J AU Huang, Y Zhang, K Kang, JU Calogero, D James, RH Ilev, IK AF Huang, Yong Zhang, Kang Kang, Jin U. Calogero, Don James, Robert H. Ilev, Ilko K. GP IEEE TI A Novel Non-Contact Common-Path Fourier Domain Optical Coherence Tomography Method for Intraocular Lens Power Measurement In-Vitro SO 2011 IEEE PHOTONICS CONFERENCE (PHO) LA English DT Proceedings Paper CT IEEE Photonics Conference (PHO) CY OCT 09-13, 2011 CL Arlington, VA SP IEEE DE cataract; intraocular lens dioptric power; common-path Fourier domain optical coherence tomography AB We developed a novel non-contact common path FD-OCT method to measure the dioptric power of intraocular lenses in-vitro. This method can be applied to a wide range of IOLs. C1 [Huang, Yong; Calogero, Don; James, Robert H.; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Huang, Y (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yhuang60@jhu.edu RI Kang, Jin/A-3228-2010 NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-8939-8 PY 2011 BP 727 EP 728 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA BYQ41 UT WOS:000299750700364 ER PT J AU Bumbaugh, AC Lacher, DW AF Bumbaugh, Alyssa C. Lacher, David W. BE Walk, ST Feng, PCH TI Gene Acquisition and Loss in the Phylogenetic Lineages of the Invasive Escherichia coli SO POPULATION GENETICS OF BACTERIA: A TRIBUTE TO THOMAS S. WHITTAM LA English DT Article; Book Chapter ID SHIGELLA-FLEXNERI 2A; SHE PATHOGENICITY ISLAND; COMPLETE GENOME SEQUENCE; BACTERIAL PATHOGENS; IRON TRANSPORT; EVOLUTIONARY RELATIONSHIPS; MOLECULAR CHARACTERIZATION; GENOTYPIC CHARACTERIZATION; SALMONELLA-TYPHIMURIUM; ANTIVIRULENCE LOCI C1 [Bumbaugh, Alyssa C.] Shippensburg Univ, Dept Biol, Shippensburg, PA 17257 USA. [Lacher, David W.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Bumbaugh, AC (reprint author), Shippensburg Univ, Dept Biol, Shippensburg, PA 17257 USA. NR 89 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-711-4 PY 2011 BP 135 EP 156 PG 22 WC Evolutionary Biology; Microbiology SC Evolutionary Biology; Microbiology GA BYN76 UT WOS:000299463700011 ER PT J AU Abu-Ali, GS Springman, AC Ouellette, LM Wick, L Qi, WH Vanaja, SK Bergholz, TM Lacher, DW Walk, ST Tietjen, JA Steinsland, H Riordan, JT Manning, SD AF Abu-Ali, Galeb S. Springman, A. Cody Ouellette, Lindsey M. Wick, Lukas Qi, Weihong Vanaja, Sivapriya Kalisan Bergholz, Teresa M. Lacher, David W. Walk, Seth T. Tietjen, Jillian A. Steinsland, Hans Riordan, James T. Manning, Shannon D. BE Walk, ST Feng, PCH TI Molecular Evolution of Enterohemorrhagic Escherichia coli and Application to Epidemiology SO POPULATION GENETICS OF BACTERIA: A TRIBUTE TO THOMAS S. WHITTAM LA English DT Article; Book Chapter ID HEMOLYTIC-UREMIC SYNDROME; HEMORRHAGIC COLITIS; GENOMIC DIVERSITY; GENETIC DIVERSITY; O157-H7 INFECTION; MASSIVE OUTBREAK; HUMAN-DISEASE; SAKAI CITY; EMERGENCE; SEQUENCE C1 [Abu-Ali, Galeb S.; Lacher, David W.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Springman, A. Cody; Ouellette, Lindsey M.; Manning, Shannon D.] Michigan State Univ, E Lansing, MI 48824 USA. [Wick, Lukas] Biosynth AG, CH-9422 Staad, Switzerland. [Qi, Weihong] Swiss Fed Inst Technol, Funct Genom Ctr Zurich Uni, CH-8057 Zurich, Switzerland. [Vanaja, Sivapriya Kalisan] Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. [Bergholz, Teresa M.] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Walk, Seth T.] Univ Michigan Hlth Syst, Dept Internal Med, Div Infect Dis, Ann Arbor, MI 48109 USA. [Tietjen, Jillian A.] Univ Michigan, Genet Counseling Dept, Ann Arbor, MI 48109 USA. [Steinsland, Hans] Univ Bergen, Dept Biomed, N-5009 Bergen, Norway. [Riordan, James T.] Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL 33063 USA. RP Abu-Ali, GS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RI Bergholz, Teresa/A-2815-2010 OI Bergholz, Teresa/0000-0002-3976-5858 NR 42 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-711-4 PY 2011 BP 287 EP 302 PG 16 WC Evolutionary Biology; Microbiology SC Evolutionary Biology; Microbiology GA BYN76 UT WOS:000299463700019 ER PT S AU Chen, WJ Petrick, N Sahiner, B AF Chen, Weijie Petrick, Nicholas Sahiner, Berkman BE Manning, DJ Abbey, CK TI Assessment of updated CAD without a new reader study: effect of calibration of computer output on the computer-aided reader performance in CADx SO MEDICAL IMAGING 2011: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 16-17, 2011 CL Lake Buena Vista, FL SP SPIE, Dynasil Corp/RMD Res, AAPM - Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc DE calibration; CADx; assessment; ROC analysis AB It is very resource-demanding to assess each new version of a CAD system through a new reader study. We conjecture that the aided reader performance on a new version can be predicted by using certain characteristics of the computer output and the reader study conducted when the CAD system was initially introduced. This would likely reduce the need for additional reader studies. However, investigations are needed to develop a sound scientific foundation to test this conjecture. In this work, we consider a CADx system that outputs a disease score to aid the physician in making a diagnostic decision on a located lesion. Our major contribution is to show that calibration, reflected as a change in scale, is a characteristic of the computer output that needs to be considered in order to predict the aided reader performance in a new CADx version without a reader study. We used a bivariate-bi-beta distribution to model the joint distribution of the decision variable underlying the reader without aid and the decision variable underlying the version 1 computer output in the initial version. We then applied a monotonic transformation to the computer output to simulate the computer output in a new version, i.e., the scores in the two versions differ only in calibration (specifically a change in scale). By further modeling certain mechanisms that the human reader may use for combining the computer output and the reader-alone scores, we computed the aided reader performance in terms of AUC for the new version of the CADx system. Our results show that the aided reader performance could depend on the degree of calibration difference between the two CAD system outputs. We conclude that for the purpose of predicting the aided reader performance of a new version of the CADx system, ROC performance (or any other rank-based metric) of the stand-alone CADx system may not be sufficient by itself. C1 [Chen, Weijie; Petrick, Nicholas; Sahiner, Berkman] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs CDRH, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs CDRH, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-508-3 J9 PROC SPIE PY 2011 VL 7966 AR 79661P DI 10.1117/12.878278 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BXL76 UT WOS:000296320800055 ER PT S AU Sahiner, B Petrick, N Paquerault, S Chen, WJ Nguyen, T AF Sahiner, Berkman Petrick, Nicholas Paquerault, Sophie Chen, Weijie Tien Nguyen BE Manning, DJ Abbey, CK TI Agreement Between Two Versions of a CADx System: A Simulation Study SO MEDICAL IMAGING 2011: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 16-17, 2011 CL Lake Buena Vista, FL SP SPIE, Dynasil Corp/RMD Res, AAPM - Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc DE Agreement; concordance; standalone performance; CAD system update ID SUPPORT VECTOR MACHINES; CLASSIFICATION AB A simulation study was conducted to investigate the agreement between original and updated versions of a computer-aided diagnosis (CADx) system. Performances of two versions of a CADx system are traditionally compared using metrics derived from the receiver operating characteristic (ROC) curve. These aggregate standalone performance measures may reveal the overall improvement of the CADx system due to the update, but do not provide information about the specific change in CADx output for individual cases. To address this issue, we used the concordance measure, which compares the ordering of scores for pairs of cases between system versions (i.e., before and after the update of the system). In this preliminary study, the system update that we investigated was an enlargement of the training data set, which is often encountered in the development of a subsequent CADx system version for improving performance. We separately studied the effect of the size of the original training set, the number of features, and the distribution and separation of the two classes in the feature space on the concordance and AUC measures. When the effect of an update was compared among datasets with differences in intrinsic class separation, concordance was in general larger when the intrinsic class separation was larger. The amount of change in AUC between the original and updated CADx system did not always predict the degree of agreement between the two system versions. A large improvement in AUC could be accompanied with either a larger or smaller agreement between the original and updated systems. Quantification of the degree of agreement in standalone performance between different versions of a CADx system may serve to define a major algorithm update, and better depict the impact of that update. C1 [Sahiner, Berkman; Petrick, Nicholas; Paquerault, Sophie; Chen, Weijie; Tien Nguyen] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Sahiner, B (reprint author), 10903 New Hampshire Ave WO62-4106, Silver Spring, MD 20993 USA. EM berkman.sahiner@fda.hhs.gov NR 10 TC 0 Z9 0 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-508-3 J9 PROC SPIE PY 2011 VL 7966 AR 79660J DI 10.1117/12.877727 PG 8 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BXL76 UT WOS:000296320800018 ER PT J AU Van Dort, ME Kande, G Rauch, JN John, CS Comeau, A Bowen, WD Rehemtulla, A Ross, BD AF Van Dort, M. E. Kande, G. Rauch, J. N. John, C. S. Comeau, A. Bowen, W. D. Rehemtulla, A. Ross, B. D. TI Development of [F-18]-labeled Benzamides as Sigma Receptor Radioligands for Tumor Imaging SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Van Dort, M. E.; Kande, G.; Rauch, J. N.; Ross, B. D.] Univ Michigan, Sch Med, Dept Radiol, Ann Arbor, MI USA. [Rehemtulla, A.] Univ Michigan, Sch Med, Dept Radiat Oncol, Ann Arbor, MI USA. [John, C. S.] CDER, Off Clin Pharmacol, Silver Spring, MD USA. [Comeau, A.; Bowen, W. D.] Brown Univ, Dept Mol Pharmacol, Providence, RI 02912 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2011 VL 54 SU 1 BP S216 EP S216 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 833RC UT WOS:000295901600216 ER PT J AU Trehy, ML Ye, W Hadwiger, ME Moore, TW Allgire, JF Woodruff, JT Ahadi, SS Black, JC Westenberger, BJ AF Trehy, Michael L. Ye, Wei Hadwiger, Michael E. Moore, Terry W. Allgire, James F. Woodruff, Jeffrey T. Ahadi, Shafiq S. Black, John C. Westenberger, Benjamin J. TI ANALYSIS OF ELECTRONIC CIGARETTE CARTRIDGES, REFILL SOLUTIONS, AND SMOKE FOR NICOTINE AND NICOTINE RELATED IMPURITIES SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE anatabine; cigarette; cotinine; e-cigarette; nicotine; smokeless ID FREE-BASE NICOTINE; PARTICULATE MATTER; CHROMATOGRAPHY; DELIVERY AB The objective of this study was to determine nicotine and the nicotine related impurities, that is, cotinine, myosmine, anatabine, anabasine, and beta-nicotyrine, in electronic cigarette cartridges, the liquid used to fill the cartridges, and from smoke generated using the electronic cigarette devices. An HPLC method was validated for the determination. Samples of nicotine containing products were purchased via the internet from NJOY, Smoking Everywhere, CIXI, and Johnson Creek. Electronic cigarette devices were purchased from NJOY, Smoking Everywhere, and CIXI. The results from the testing found that (1) the nicotine content labeling was not accurate with some manufacturers, (2) nicotine is present in the "smoke" from electronic cigarettes, and (3) nicotine related impurities contents in cartridges and refills were found to vary by electronic cigarette manufacturer. C1 [Trehy, Michael L.; Ye, Wei; Hadwiger, Michael E.; Moore, Terry W.; Allgire, James F.; Woodruff, Jeffrey T.; Ahadi, Shafiq S.; Black, John C.; Westenberger, Benjamin J.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Trehy, ML (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM Michael.Trehy@fda.hhs.gov NR 17 TC 108 Z9 112 U1 11 U2 105 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2011 VL 34 IS 14 BP 1442 EP 1458 DI 10.1080/10826076.2011.572213 PG 17 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 837UU UT WOS:000296230900012 ER PT J AU Abliz, E Collins, JE Bell, H Tata, DB AF Abliz, Erkinay Collins, Joshua E. Bell, Howard Tata, Darrell B. TI Novel applications of diagnostic X-rays in activating a clinical photodynamic drug: Photofrin II through X-ray induced visible luminescence from "rare-earth" formulated particles SO JOURNAL OF X-RAY SCIENCE AND TECHNOLOGY LA English DT Article DE X-ray induced luminescence; photodynamic therapy; reactive oxygen species detection; singlet oxygen; Photofrin II; Gadolinium Oxysulfide particles ID ABSOLUTE EFFICIENCY; SINGLET OXYGEN; NANOPARTICLES; RADIATION; THERAPY; SCREENS; CANCER; CELLS; PORPHYRINS AB Introduction: In this communication we report on a novel non-invasive methodology in utilizing "soft" energy diagnostic X-rays to indirectly activate a photo-agent utilized in photodynamic therapy (PDT): Photofrin II (Photo II) through X-ray induced luminescence from Gadolinium Oxysulfide (20 micron dimension) particles doped with Terbium: Gd(2)O(2)S:Tb. Photodynamic agents such as Photo II utilized in PDT possess a remarkable property to become preferentially retained within the tumor's micro-environment. Upon the photo-agent's activation through (visible light) photon absorption, the agents exert their cellular cytotoxicity through type I and type II pathways through extensive generation of reactive oxygen species (ROS); namely, singlet oxygen (1)O(2), superoxide anion O(2)(-), and hydrogen peroxide H(2)O(2), within the intra-tumoral environment. Unfortunately, due to shallow visible light penetration depth (similar to 2 mm to 5 mm) in tissues, the current PDT strategy has largely been restricted to the treatment of surface tumors, such as the melanomas. Additional invasive strategies through optical fibers are currently utilized in getting the visible light into the intended deep seated targets within the body for PDT. Methods: X-ray induced visible luminescence from Gd(2)O(2)S:Tb particles were spectroscopically characterized, and the potential in-vitro cellular cytotoxicity of Gd(2)O(2)S:Tb particles on human glioblastoma cells (due to 48 Hrs Gd(2)O(2)S:Tb particle exposure) was screened through the MTS cellular metabolic assay. In-vitro human glioblastoma cellular exposures in presence of Photo II with Gd(2)O(2)S:Tb particles were performed in the dark in sterile 96 well tissue culture plates, and the corresponding changes in the metabolic activities of the glioblastoma due to 15 minutes of (diagnostic energy) X-ray exposure was determined 48 Hrs after treatment through the MTS assay. Results: Severe suppression (> 90% relative to controls) in the cellular metabolic activity of human glioblastoma was measured due to the treatment of clinically relevant concentrations of 20 mu g/ml Photo II, with Gd(2)O(2)S:Tb particles, and (120 kVp) diagnostic X-rays. Taken together, the in-vitro findings herein provide the basis for future studies in determining the safety and efficacy of this non-invasive X-ray induced luminescence strategy in activating photo-agent in deep seated tumors. C1 [Tata, Darrell B.] US FDA, Silver Spring, MD USA. [Abliz, Erkinay] George Washington Univ, Dept Elect & Comp Engn, Washington, DC USA. [Collins, Joshua E.; Bell, Howard] Intelligent Mat Inc, Princeton, NJ USA. RP Tata, DB (reprint author), US FDA, White Oak Campus, Silver Spring, MD USA. EM Darayash.Tata@fda.hhs.gov NR 26 TC 6 Z9 6 U1 1 U2 35 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0895-3996 J9 J X-RAY SCI TECHNOL JI J. X-Ray Sci. Technol. PY 2011 VL 19 IS 4 BP 521 EP 530 DI 10.3233/XST-2011-0311 PG 10 WC Instruments & Instrumentation; Optics; Physics, Applied SC Instruments & Instrumentation; Optics; Physics GA 836VZ UT WOS:000296146500008 PM 25214384 ER PT J AU Rubin, DB AF Rubin, Daniel B. TI An Alternative to Pooling Kaplan-Meier Curves in Time-to-Event Meta-Analysis SO INTERNATIONAL JOURNAL OF BIOSTATISTICS LA English DT Article DE meta-analysis; survival analysis; Simpson's paradox ID TYPE-2 DIABETES-MELLITUS; MYOCARDIAL-INFARCTION; ROSIGLITAZONE; RISK; REGRESSION; ESTIMATOR; DEATH AB A meta-analysis that uses individual-level data instead of study-level data is widely considered to be a gold standard approach, in part because it allows a time-to-event analysis. Unfortunately, with the common practice of presenting Kaplan-Meier survival curves after pooling subjects across randomized trials, using individual-level data can actually be a step backwards; a Simpson's paradox can occur in which pooling incorrectly reverses the direction of an association. We introduce a nonparametric procedure for synthesizing survival curves across studies that is designed to avoid this difficulty and preserve the integrity of randomization. The technique is based on a counterfactual formulation in which we ask what pooled survival curves would look like if all subjects in all studies had been assigned treatment, or if all subjects had been assigned to control arms. The method is related to a Kaplan-Meier adjustment proposed in 2005 by Xie and Liu to correct for confounding in nonrandomized studies, but is formulated for the meta-analysis setting. The procedure is discussed in the context of examining rosiglitazone and cardiovascular adverse events. C1 Food & Drug Adm, Rockville, MD 20857 USA. RP Rubin, DB (reprint author), Food & Drug Adm, Rockville, MD 20857 USA. NR 26 TC 1 Z9 1 U1 1 U2 6 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1557-4679 J9 INT J BIOSTAT JI Int. J. Biostat. PY 2011 VL 7 IS 1 AR 18 DI 10.2202/1557-4679.1289 PG 27 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 832FX UT WOS:000295789600018 ER PT B AU Wen, ZN Su, ZQ Liu, J Ning, BT Guo, L Tong, WD Shi, LM AF Wen, Zhining Su, Zhenqiang Liu, Jie Ning, Baitang Guo, Lei Tong, Weida Shi, Leming BE Lu, HHS Scholkopf, B Zhao, HY TI The MicroArray Quality Control (MAQC) Project and Cross-Platform Analysis of Microarray Data SO HANDBOOK OF STATISTICAL BIOINFORMATICS SE Springer Handbooks of Computational Statistics LA English DT Article; Book Chapter ID GENE-EXPRESSION MEASUREMENTS; BIG BLUE RATS; DNA MICROARRAY; ARRAYS; REPRODUCIBILITY; CONSISTENCY; LIVER; MUTAGENICITY; RIDDELLIINE; SPECIFICITY AB As a powerful tool for genome-wide gene expression analysis, DNA microarray technology is widely used in biomedical research. One important application of microarrays is to identify differentially expressed genes (DEGs) between two distinct biological conditions, e.g. disease versus normal or treatment versus control, so that the underlying molecular mechanism differentiating the two conditions maybe revealed. Mechanistic interpretation of microarray results requires the identification of reproducible and reliable lists of DEGs, because irreproducible lists of DEGs may lead to different biological conclusions. Many vendors are providing microarray platforms of different characteristics for gene expression analysis, and the widely publicized apparent lack of intra- and cross-platform concordance in DEGs from microarray analysis of the same sets of study samples has been of great concerns to the scientific community and regulatory agencies like the US Food and Drug Administration (FDA). In this chapter, we describe the study design of and the main findings from the FDA-led MicroArray Quality Control (MAQC) project that aims to objectively assess the performance of different microarray platforms and the advantages and limitations of various competing statistical methods in identifying DEGs from microarray data. Using large data sets generated on two human reference RNA samples established by the MAQC project, we show that the levels of concordance in inter-laboratory and cross-platform comparisons are generally high. Furthermore, the levels of concordance largely depend on the statistical criteria used for ranking and selecting DEGs, irrespective of the chosen platforms or test sites. Importantly, a straightforward method combining fold-change ranking with a non-stringent P-value cutoff produces more reproducible lists of DEGs than those by t-test P-value ranking. Similar conclusions are reached when microarray data sets from a rat toxicogenomics study are analyzed. The availability of the MAQC reference RNA samples and the large reference data sets provides a unique resource for the gene expression community to reach consensus on the "best practices" for the generation, analysis, and applications of microarray data in drug development and personalized medicine. C1 [Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@fda.hhs.gov NR 42 TC 3 Z9 3 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-3-642-16344-9 J9 SPR HBK COMPU STAT PY 2011 BP 171 EP 192 DI 10.1007/978-3-642-16345-6_9 D2 10.1007/978-3-642-16345-6 PG 22 WC Computer Science, Theory & Methods; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Computer Science; Mathematical & Computational Biology; Medical Informatics; Mathematics GA BVV63 UT WOS:000292903100009 ER PT J AU Kim, BS Kim, JN Cerniglia, CE AF Kim, Bong-Soo Kim, Jong Nam Cerniglia, Carl E. TI In Vitro Culture Conditions for Maintaining a Complex Population of Human Gastrointestinal Tract Microbiota SO JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY LA English DT Article ID 16S RIBOSOMAL-RNA; GRADIENT GEL-ELECTROPHORESIS; HUMAN GUT; INTESTINAL MICROFLORA; BACTERIAL-POPULATIONS; GENTIAN-VIOLET; PCR PRIMERS; COMMUNITIES; DIVERSITY; COLON AB A stable intestinal microbiota is important in maintaining human physiology and health. Although there have been a number of studies using in vitro and in vivo approaches to determine the impact of diet and xenobiotics on intestinal microbiota, there is no consensus for the best in vitro culture conditions for growth of the human gastrointestinal microbiota. To investigate the dynamics and activities of intestinal microbiota, it is important for the culture conditions to support the growth of a wide range of intestinal bacteria and maintain a complex microbial community representative of the human gastrointestinal tract. Here, we compared the bacterial community in three culture media: brain heart infusion broth and high-and low-carbohydrate medium with different growth supplements. The bacterial community was analyzed using denaturing gradient gel electrophoresis (DGGE), pyrosequencing and real-time PCR. Based on the molecular analysis, this study indicated that the 3% fecal inoculum in low-concentration carbohydrate medium with 1% autoclaved fecal supernatant provided enhanced growth conditions to conduct in vitro studies representative of the human intestinal microbiota. C1 [Kim, Bong-Soo; Kim, Jong Nam; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM carl.cerniglia@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 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 Food and Drug Administration. The views presented in this paper are not necessarily those of the Food and Drug Administration. Bong-Soo Kim and Jong Nam Kim contributed equally to this work. NR 38 TC 12 Z9 12 U1 1 U2 22 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1110-7243 J9 J BIOMED BIOTECHNOL JI J. Biomed. Biotechnol. PY 2011 AR 838040 DI 10.1155/2011/838040 PG 10 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 816YI UT WOS:000294637600001 ER PT S AU Zeng, RP Myers, KJ AF Zeng, Rongping Myers, Kyle J. BE Pelc, NJ Samei, E Nishikawa, RM TI Task-based comparative study of iterative image reconstruction methods for limited-angle x-ray tomography SO MEDICAL IMAGING 2011: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2011 - Physics of Medical Imaging CY FEB 13-17, 2011 CL Lake Buena Vista, FL SP Dynasil Corp/RMD Res, Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc, SPIE AB For tomography that has available only projection views from a limited angular span, such as is the case in an x-ray tomosynthesis system, the image reconstruction problem is ill-posed. Reconstruction methods play an important role in optimizing the image quality for human interpretation. In this work we compare three popular iterative image reconstruction methods that have been applied to digital tomosynthesis systems: the simultaneous algebraic reconstruction technique (SART), the maximum-likelihood (ML) and the total-variation regularized least-square reconstruction method (TVLS). Quality of the images reconstructed from these three methods is assessed through task-based performance. Two tasks are considered in this work: lesion detection and shape discrimination. Area under the ROC curve (AUC) is used as the figure-of-merit. Our simulation results indicate that TVLS and SART perform very similarly and better than the ML in terms of lesion detectability, while the ML performs better than the other two in terms of shape discrimination ability. C1 [Zeng, Rongping] US FDA, Off Sci, Rockville, MD 20857 USA. RP Zeng, RP (reprint author), US FDA, Off Sci, Rockville, MD 20857 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8503-8 J9 PROC SPIE PY 2011 VL 7961 AR 796137 DI 10.1117/12.878098 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BWL08 UT WOS:000294178500106 ER PT B AU Todd, ECD Bartleson, CA Guzewich, JJ Tan, A Lee, M Nazarowec-White, M AF Todd, Ewen C. D. Bartleson, Charles A. Guzewich, John J. Tan, Agnes Lee, Marilyn Nazarowec-White, Maria CA Int Assoc Food Protection GP CFIIAFP TI Procedures to Investigate Foodborne Illness Sixth Edition 2011 SO PROCEDURES TO INVESTIGATE FOODBORNE ILLNESS, SIXTH EDITION 2011 LA English DT Article; Book Chapter ID RISK-BASED APPROACH; UNITED-STATES; FOOD WORKERS; DISEASE OUTBREAKS; SURVEILLANCE; INFECTIONS; SPREAD; GASTROENTERITIS; LIMITATIONS; PATHOGENS C1 [Todd, Ewen C. D.] Ewen Todd Consulting, Okemos, MI USA. [Bartleson, Charles A.] Washington State Dept Hlth, Olympia, WA USA. [Guzewich, John J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Tan, Agnes] Univ Melbourne, Dept Microbiol & Immunol, Publ Hlth Lab, Microbiol Diagnost Unit, Melbourne, Vic, Australia. [Lee, Marilyn] Ryerson Univ, Sch Occupat & Publ Hlth, Toronto, ON, Canada. [Nazarowec-White, Maria] Hlth Canada, Hlth Prod & Food Branch, Ottawa, ON K1A 0L2, Canada. [Nazarowec-White, Maria] Bur Microbiol Hazards, Ottawa, ON, Canada. RP Todd, ECD (reprint author), Ewen Todd Consulting, Okemos, MI USA. OI Todd, Ewen/0000-0001-7266-279X NR 45 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-8395-4 PY 2011 BP 1 EP + PG 161 WC Food Science & Technology SC Food Science & Technology GA BVZ32 UT WOS:000293199800001 ER PT S AU Petrick, N Kim, HJG Clunie, D Borradaile, K Ford, R Zeng, RP Gavrielides, MA McNitt-Gray, MF Fenimore, C Lu, ZQJ Zhao, BS Buckler, AJ AF Petrick, Nicholas Kim, Hyun J. Grace Clunie, David Borradaile, Kristin Ford, Robert Zeng, Rongping Gavrielides, Marios A. McNitt-Gray, Michael F. Fenimore, Charles Lu, Z. Q. John Zhao, Binsheng Buckler, Andrew J. BE Summers, RM VanGinneken, B TI Evaluation of 1D, 2D and 3D nodule size estimation by radiologists for spherical and non-spherical nodules through CT thoracic phantom imaging SO MEDICAL IMAGING 2011: COMPUTER-AIDED DIAGNOSIS SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2011 - Computer-Aided Diagnosis CY FEB 15-17, 2011 CL Lake Buena Vista, FL SP SPIE, Dynasil Corp/RMD Res, Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc DE Size Estimation; Lung Nodules; CT Imaging; Phantom Study; Reader Study; Reader Variability ID LUNG-CANCER; VOLUMETRIC CT; SOLID TUMORS; BIOMARKER; QUALIFICATION AB The purpose of this work was to estimate bias in measuring the size of spherical and non-spherical lesions by radiologists using three sizing techniques under a variety of simulated lesion and reconstruction slice thickness conditions. We designed a reader study in which six radiologists estimated the size of 10 synthetic nodules of various sizes, shapes and densities embedded within a realistic anthropomorphic thorax phantom from CT scan data. In this manuscript we report preliminary results for the first four readers (Readers 1-4). Two repeat CT scans of the phantom containing each nodule were acquired using a Philips 16-slice scanner at a 0.8 and 5 mm slice thickness. The readers measured the sizes of all nodules for each of the 40 resulting scans (10 nodules x 2 slice thickness x 2 repeat scans) using three sizing techniques (1D longest in-slice dimension; 2D area from longest in-slice dimension and corresponding longest perpendicular dimension; 3D semi-automated volume) in each of 2 reading sessions. The normalized size was estimated for each sizing method and an inter-comparison of bias among methods was performed. The overall relative biases (standard deviation) of the 1D, 2D and 3D methods for the four readers subset (Readers 1-4) were -13.4 (20.3), -15.3 (28.4) and 4.8 (21.2) percentage points, respectively. The relative biases for the 3D volume sizing method was statistically lower than either the 1D or 2D method (p<0.001 for 1D vs. 3D and 2D vs. 3D). C1 [Petrick, Nicholas; Zeng, Rongping; Gavrielides, Marios A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Petrick, N (reprint author), WO62-4118,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nicholas.petrick@fda.hhs.gov OI Ford, Robert/0000-0002-0958-1505; Buckler, Andrew/0000-0002-0786-4835 NR 12 TC 2 Z9 2 U1 2 U2 5 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-505-2 J9 PROC SPIE PY 2011 VL 7963 AR 79630D DI 10.1117/12.878265 PG 7 WC Engineering, Electrical & Electronic; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BWL95 UT WOS:000294211100011 ER PT J AU Karmakar, A Xu, Y Mahmood, MW Zhang, YB Saeed, LM Mustafa, T Ali, S Biris, AR Biris, AS AF Karmakar, Alokita Xu, Yang Mahmood, Meena W. Zhang, Yongbin Saeed, Lamya Mohammed Mustafa, Thikra Ali, Syed Biris, Alexandru R. Biris, Alexandru S. TI Radio-frequency induced in vitro thermal ablation of cancer cells by EGF functionalized carbon-coated magnetic nanoparticles SO JOURNAL OF MATERIALS CHEMISTRY LA English DT Article ID IRON-OXIDE NANOPARTICLES; DRUG-DELIVERY; ROCK-I; NANOTUBES; APOPTOSIS; VIVO; CASPASE-3; ASSAYS; LINES; FRAGMENTATION AB Carbon-shelled, iron-based magnetic nanoparticles (C/Fe MNPs) were found to act as strong heat generating agents when exposed to radio-frequency (RF) energy with the ability to thermally destroy cancer cells. In order to efficiently deliver MNPs to cancer cells and to enhance the effectiveness of the RF treatment, human epidermal growth factor (EGF) was bioconjugated with the C/Fe MNPs for their specific delivery to two cancer cell lines, MCF-7 breast cancer cells and Panc-1 pancreatic cancer cells, respectively. These cell lines overexpress the epidermal growth factor receptors (EGFRs) and were used in this study as models. EGF-MNPs have shown higher surface binding efficiency towards the MCF-7 cells based on the comparative zeta-potential measurements. Confocal optical microscopy further confirmed that EGF-bioconjugated MNPs highly accumulated around and inside of these cancer cells. RF treatment was found to destroy 92.8% of MCF-7 breast cancer cells during 10 minutes of treatment when EGF was bound to the nanoparticles, while 37.3% of cells died when MNPs alone were used in identical conditions. Panc-1 cancer cells exhibit a higher resistance than MCF-7 cells when they were exposed to MNPs or RF treatment. Cytotoxicity studies demonstrated that the EGF-C/Fe MNP bioconjugates present lower toxicity compared to the C/Fe MNP. Caspase assay studies demonstrated that the MCF-7 cancer cells underwent an apoptotic process by the caspase 3 deficiency pathway showing no evidence of morphological changes such as membrane blebbing. C1 [Karmakar, Alokita; Xu, Yang; Mahmood, Meena W.; Saeed, Lamya Mohammed; Mustafa, Thikra; Biris, Alexandru S.] Univ Arkansas, Nanotechnol Ctr, Little Rock, AR 72204 USA. [Zhang, Yongbin] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. [Ali, Syed] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. [Biris, Alexandru R.] Natl Inst Res & Dev Isotop & Mol Technol, RO-3400 Cluj Napoca, Romania. RP Xu, Y (reprint author), Univ Arkansas, Nanotechnol Ctr, 2801 S Univ Ave, Little Rock, AR 72204 USA. EM yxxu@ualr.edu; asbiris@ualr.edu FU Arkansas Science and Technology Authority (ASTA) [08-CAT-03]; US Army TATRC program FX Support for this research received from the Arkansas Science and Technology Authority (ASTA) grant # 08-CAT-03 is greatly appreciated. The financial support provided by the US Army TATRC program is highly appreciated. NR 40 TC 12 Z9 12 U1 3 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0959-9428 J9 J MATER CHEM JI J. Mater. Chem. PY 2011 VL 21 IS 34 BP 12761 EP 12769 DI 10.1039/c1jm10569h PG 9 WC Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 807LC UT WOS:000293898300027 ER PT J AU Manirarora, JN Parnell, SA Hu, YH Kosiewicz, MM Alard, P AF Manirarora, Jean N. Parnell, Sarah A. Hu, Yoon-Hyeon Kosiewicz, Michele M. Alard, Pascale TI NOD Dendritic Cells Stimulated with Lactobacilli Preferentially Produce IL-10 versus IL-12 and Decrease Diabetes Incidence SO CLINICAL & DEVELOPMENTAL IMMUNOLOGY LA English DT Article ID REGULATORY T-CELLS; ORGAN-SPECIFIC AUTOIMMUNITY; ANTIGEN-PRESENTING CELLS; PRONE MOUSE STRAINS; KAPPA-B ACTIVITY; IN-VITRO; INTERLEUKIN-10 PRODUCTION; IMMUNE-SYSTEM; APC FUNCTION; MICE AB Dendritic cells (DCs) from NOD mice produced high levels of IL-12 that induce IFN gamma-producing T cells involved in diabetes development. We propose to utilize the microorganism ability to induce tolerogenic DCs to abrogate the proinflammatory process and prevent diabetes development. NOD DCs were stimulated with Lactobacilli (nonpathogenic bacteria targeting TLR2) or lipoteichoic acid (LTA) from Staphylococcus aureus (TLR2 agonist). LTA-treated DCs produced much more IL-12 than IL-10 and accelerated diabetes development when transferred into NOD mice. In contrast, stimulation of NOD DCs with L. casei favored the production of IL-10 over IL-12, and their transfer decreased disease incidence which anti-IL-10R antibodies restored. These data indicated that L. casei can induce NOD DCs to develop a more tolerogenic phenotype via production of the anti-inflammatory cytokine, IL-10. Evaluation of the relative production of IL-10 and IL-12 by DCs may be a very useful means of identifying agents that have therapeutic potential. C1 [Manirarora, Jean N.; Parnell, Sarah A.; Hu, Yoon-Hyeon; Kosiewicz, Michele M.; Alard, Pascale] Univ Louisville HSC, Dept Microbiol & Immunol, Louisville, KY 40202 USA. [Manirarora, Jean N.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Alard, P (reprint author), Univ Louisville HSC, Dept Microbiol & Immunol, 319 Abraham Flexner Way, Louisville, KY 40202 USA. EM p0alar01@gwise.louisville.edu FU University of Louisville School of Medicine; NIH [R56DK075892]; Ruth L. Kirschstein NRSA FX This research was supported by funds from the University of Louisville School of Medicine, and NIH R56DK075892 (PA). J.N. Manirarora was supported by a Ruth L. Kirschstein NRSA. The authors thank Mike Myers and Jason L. Hudkins for technical assistance; Chris Worth for cell sorting; the staff of the animal facility for animal care. J.N. Manirarora and S. A. Parnell contributed equally to this work. NR 63 TC 5 Z9 5 U1 0 U2 1 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1740-2522 J9 CLIN DEV IMMUNOL JI Clin. Dev. Immunol. PY 2011 AR 630187 DI 10.1155/2011/630187 PG 12 WC Immunology SC Immunology GA 803LW UT WOS:000293583800001 ER PT J AU Xu, AQ Zhang, YT Amato, PR AF Xu, Anqi Zhang, Yuanting Amato, Paul R. TI A Comparison of Divorce Risk Models, in China and the United States SO JOURNAL OF COMPARATIVE FAMILY STUDIES LA English DT Article AB Divorce has become more common in China. However, studies of Chinese marriage and family life have lagged because relevant data are sparse. Using a divorce risk model, this study compares China and the United States. Chinese data came from a 2007-2008 Shanghai study containing 1,070 married or cohabiting respondents. The U.S. data came from the 2000 Survey of Marriage and Family Life containing 2,100 married individuals. In both countries, marital quality (happiness) was higher when couples frequently shared activities, reported few arguments, had not experienced marital violence, thought it would be difficult to replace their current spouses, and grew up with happily married parents. Moreover, in both countries, divorce risk (thinking about divorce) was negatively associated with marital quality, marital duration, believing that marriage is for life, reporting few quarrels, and the absence of marital violence. Differences between samples also emerged, which may reflect unique cultural aspects of Chinese and American society. C1 [Xu, Anqi] Shanghai Acad Social Sci, Inst Sociol, Shanghai 200020, Peoples R China. [Zhang, Yuanting] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Amato, Paul R.] Penn State Univ, Dept Sociol, University Pk, PA 16802 USA. RP Xu, AQ (reprint author), Shanghai Acad Social Sci, Inst Sociol, 599-7-622 Huaihai Rd M, Shanghai 200020, Peoples R China. NR 8 TC 1 Z9 1 U1 1 U2 10 PU J COMPARATIVE FAMILY STUDIES PI CALGARY PA UNIV CALGARY-DEPT SOCIOLOGY 2500 UNIVERSITY DRIVE NW, CALGARY, AB T2N 1N4, CANADA SN 0047-2328 J9 J COMP FAM STUD JI J. Comp. Fam. Stud. PY 2011 VL 42 IS 2 BP 289 EP + PG 8 WC Family Studies SC Family Studies GA 797FK UT WOS:000293109700009 ER PT J AU Wang, WW Scharfstein, D Wang, CG Daniels, M Needham, D Brower, R AF Wang, Weiwei Scharfstein, Daniel Wang, Chenguang Daniels, Michael Needham, Dale Brower, Roy TI Estimating the causal effect of low tidal volume ventilation on survival in patients with acute lung injury SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Bayesian inference; Causal inference; Dynamic treatment regime; G-computation formula ID RESPIRATORY-DISTRESS-SYNDROME; DYNAMIC TREATMENT REGIMES; MARGINAL STRUCTURAL MODELS; MECHANICAL VENTILATION; INFERENCE; TRIALS; PARAMETERS; MORTALITY; OUTCOMES; ARDS AB Acute lung injury is a condition that is characterized by acute onset of severe hypoxaemia and bilateral pulmonary infiltrates. Patients typically require mechanical ventilation in an intensive care unit. Low tidal volume ventilation (LTVV), which is a time varying dynamic treatment regime, has been recommended as an effective ventilation strategy. This recommendation was based on the results of a randomized clinical trial designed to compare low versus high tidal volume strategies by the Acute Respiratory Distress Syndrome Network. After publication of the trial, some critics focused on the high non-adherence rates in the LTVV arm suggesting that non-adherence occurred because treating physicians felt that deviating from the prescribed regime would improve patients' outcomes. We seek to address this controversy by estimating the survival distribution in the counterfactual setting where all patients assigned to LTVV followed the regime. Inference is based on a fully Bayesian implementation of Robins's G-computation formula. In addition to reanalysing data from the original trial, we also apply our methodology to data from a subsequent trial, which implemented the LTVV regime in both of its study arms and also suffered from non-adherence. C1 [Scharfstein, Daniel] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. [Wang, Weiwei] Univ Texas Hlth Sci Ctr, Houston, TX USA. [Wang, Chenguang] Food & Drug Adm, Silver Spring, MD USA. [Daniels, Michael] Univ Florida, Gainesville, FL USA. [Needham, Dale; Brower, Roy] Johns Hopkins Sch Med, Baltimore, MD USA. RP Scharfstein, D (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM dscharf@jhsph.edu FU National Institutes of Health [NO1-HR-46046-64, NO1-HR-16146-54, R01-CA-85295, R01-AI-078835, P30-MH-086043] FX This research was sponsored by National Institutes of Health contracts NO1-HR-46046-64, NO1-HR-16146-54, R01-CA-85295, R01-AI-078835 and P30-MH-086043. NR 43 TC 2 Z9 3 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2011 VL 60 BP 475 EP 496 DI 10.1111/j.1467-9876.2010.00757.x PN 4 PG 22 WC Statistics & Probability SC Mathematics GA 798TT UT WOS:000293235800001 PM 22025809 ER PT B AU Padilla, F Wear, K AF Padilla, Frederic Wear, Keith BE Laugier, P Haiat, G TI Scattering by Trabecular Bone SO BONE QUANTITATIVE ULTRASOUND LA English DT Article; Book Chapter DE Anisotropy; Apparent backscatter coefficient; Attenuation; Role of scattering; Autocorrelation; Backcatter; Backscatter coefficient measurement; Binary mixture model; Born approximation; Broadband Ultrasound Backscatter; Faran cylinder model; Multiple scattering; Shear waves; Thin cylinder model; Trabecular thickness; Velocity dispersion; Weak scattering model ID BOVINE CANCELLOUS BONE; ULTRASONIC BACKSCATTER COEFFICIENT; FREQUENCY-DEPENDENCE; IN-VITRO; HUMAN CALCANEUS; ACOUSTIC PROPERTIES; MIMICKING PHANTOMS; QUANTITATIVE ULTRASOUND; MECHANICAL-PROPERTIES; SPECTRUM ANALYSIS AB This chapter reviews models for scattering of ultrasound by cancellous bone, methods for measuring scattering, and empirical results. Theory and measurements are presented for the dependence of backscatter on frequency and mean trabecular thickness. Additional topics discussed include the inverse problem (that is, estimating cancellous bone properties based on scattering measurements), the extent of multiple scattering in cancellous bone, and the role of scattering in determining attenuation. The potential advantages and intrinsic difficulties of backscatter as a clinical measurement are discussed. Results of clinical trials are presented. C1 [Padilla, Frederic] Univ Paris 06, CNRS, Lab Imagerie Parametr, UMR 7623, F-75006 Paris, France. [Padilla, Frederic] Univ Michigan, Med Ctr, Dept Radiol, Ann Arbor, MI 48109 USA. [Wear, Keith] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Padilla, F (reprint author), Univ Paris 06, CNRS, Lab Imagerie Parametr, UMR 7623, F-75006 Paris, France. EM fpadilla@umich.edu; keith.wear@fda.hhs.gov NR 95 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY BN 978-94-007-0016-1 PY 2011 BP 123 EP 145 DI 10.1007/978-94-007-0017-8_6 D2 10.1007/978-94-007-0017-8 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BSU37 UT WOS:000285825800007 ER PT J AU Li, F Nie, L Wu, G Qiao, JJ Zhang, WW AF Li, Feng Nie, Lei Wu, Gang Qiao, Jianjun Zhang, Weiwen TI Prediction and Characterization of Missing Proteomic Data in Desulfovibrio vulgaris SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article ID TANDEM MASS-SPECTROMETRY; MESSENGER-RNA EXPRESSION; INTEGRATIVE ANALYSIS; UNDETECTED PROTEINS; SEQUENCE FEATURES; GENE-EXPRESSION; NEURAL-NETWORKS; ABUNDANCE; GENOMICS; HILDENBOROUGH AB Proteomic datasets are often incomplete due to identification range and sensitivity issues. It becomes important to develop methodologies to estimate missing proteomic data, allowing better interpretation of proteomic datasets and metabolic mechanisms underlying complex biological systems. In this study, we applied an artificial neural network to approximate the relationships between cognate transcriptomic and proteomic datasets of Desulfovibrio vulgaris, and to predict protein abundance for the proteins not experimentally detected, based on several relevant predictors, such as mRNA abundance, cellular role and triple codon counts. The results showed that the coefficients of determination for the trained neural network models ranged from 0.47 to 0.68, providing better modeling than several previous regression models. The validity of the trained neural network model was evaluated using biological information (i.e. operons). To seek understanding of mechanisms causing missing proteomic data, we used a multivariate logistic regression analysis and the result suggested that some key factors, such as protein instability index, aliphatic index, mRNA abundance, effective number of codons (N-c) and codon adaptation index (CAI) values may be ascribed to whether a given expressed protein can be detected. In addition, we demonstrated that biological interpretation can be improved by use of imputed proteomic datasets. C1 [Qiao, Jianjun; Zhang, Weiwen] Tianjin Univ, Sch Chem Engn & Technol, Tianjin 300072, Peoples R China. [Li, Feng] Off Biometr OTS CDER FDA, Div Biometr 2, Silver Spring, MD 20993 USA. [Nie, Lei] Off Biometr OTS CDER FDA, Div Biometr 4, Silver Spring, MD 20993 USA. [Wu, Gang] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA. RP Zhang, WW (reprint author), Tianjin Univ, Sch Chem Engn & Technol, Tianjin 300072, Peoples R China. EM Weiwen.Zhang@asu.edu FU National Basic Research Program of China [2011CBA00803] FX The research work of J. QIAO and W. ZHANG was supported by National Basic Research Program of China (2011CBA00803). This paper reflects the views of F. Li and L. Nie should not be construed to represent FDA's view or policies. NR 40 TC 4 Z9 4 U1 0 U2 3 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PY 2011 AR 780973 DI 10.1155/2011/780973 PG 16 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 787ON UT WOS:000292386700001 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Utility of Microbiological Testing for Safety and Quality SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 12 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 3 EP 11 DI 10.1007/978-1-4419-9374-8_1 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500001 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Validation of Control Measures SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID TEMPERATURE C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 25 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 13 EP 32 DI 10.1007/978-1-4419-9374-8_2 PG 20 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500002 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Verification of Process Control SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 14 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 33 EP 40 DI 10.1007/978-1-4419-9374-8_3 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500003 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Verification of Environmental Control SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 4 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 41 EP 45 DI 10.1007/978-1-4419-9374-8_4 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500004 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Corrective Actions to Reestablish Control SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 47 EP 54 DI 10.1007/978-1-4419-9374-8_5 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500005 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Microbiological Testing in Customer-Supplier Relations SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 55 EP 60 DI 10.1007/978-1-4419-9374-8_6 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500006 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Applications and Use of Criteria and Other Tests SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID MICROBIOLOGICAL CRITERIA C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 63 EP 73 DI 10.1007/978-1-4419-9374-8_7 PG 11 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500007 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Meat Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 19 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 75 EP 93 DI 10.1007/978-1-4419-9374-8_8 PG 19 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500008 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Poultry Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID BROILER CARCASSES; RISK-ASSESSMENT; CAMPYLOBACTER C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 27 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 95 EP 106 DI 10.1007/978-1-4419-9374-8_9 PG 12 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500009 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Fish and Seafood Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID BIOGENIC-AMINES C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 22 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 107 EP 133 DI 10.1007/978-1-4419-9374-8_10 PG 27 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500010 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Feeds and Pet Food SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157; CONTAMINATED DRY DOG; ANIMAL FEED; SALMONELLA-ENTERICA; PELLETING PROCESS; UNITED-STATES; HUMAN HEALTH; BY-PRODUCTS; BSE AGENT; CAT FOOD C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 135 EP 145 DI 10.1007/978-1-4419-9374-8_11 PG 11 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500011 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Vegetables and Vegetable Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID MICROBIAL RISK-ASSESSMENT; LISTERIA-MONOCYTOGENES; IRRIGATION WATER; MICROBIOLOGICAL QUALITY; CONSUMPTION; PATHOGENS; MUSHROOMS; SPROUTS; GROWTH; FRUIT C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 41 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 147 EP 176 DI 10.1007/978-1-4419-9374-8_12 PG 30 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500012 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Fruits and Fruit Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157-H7; LISTERIA-MONOCYTOGENES; CHLORINE DIOXIDE; SALMONELLA-MONTEVIDEO; REDUCING SALMONELLA; FROZEN RASPBERRIES; FRESH CANTALOUPES; UNITED-STATES; RAW TOMATOES; GROWTH C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 71 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 177 EP 195 DI 10.1007/978-1-4419-9374-8_13 PG 19 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500013 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Spice, Dry Soups and Asian Flavorings SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID BIOGENIC-AMINES C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 27 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 197 EP 208 DI 10.1007/978-1-4419-9374-8_14 PG 12 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500014 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Cereals and Cereal Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID BACILLUS-CEREUS; QUALITY; RICE C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 22 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 209 EP 225 DI 10.1007/978-1-4419-9374-8_15 PG 17 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500015 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Nuts, Oilseeds, Dried Legumes and Coffee SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID SALMONELLA-ENTERITIDIS; ASPERGILLUS-FLAVUS; OCHRATOXIN-A; PEANUT BUTTER; AFLATOXIN; ALMONDS; OUTBREAK; SURVIVAL; KERNELS; QUALITY C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 48 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 227 EP 239 DI 10.1007/978-1-4419-9374-8_16 PG 13 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500016 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Cocoa, Chocolate and Confectionery SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID OCHRATOXIN-A; INTERNATIONAL OUTBREAK; SALMONELLA; FUNGI; QUALITY; BEANS C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 22 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 241 EP 246 DI 10.1007/978-1-4419-9374-8_17 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500017 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Oil- and Fat-Based Foods SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID MEAN PARTICLE DIAMETERS C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 247 EP 261 DI 10.1007/978-1-4419-9374-8_18 PG 15 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500018 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Sugar, Syrups and Honey SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID INFANT BOTULISM; CLOSTRIDIUM-BOTULINUM C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 16 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 263 EP 268 DI 10.1007/978-1-4419-9374-8_19 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500019 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Water SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID DRINKING-WATER; PSEUDOMONAS-AERUGINOSA; RISK-ASSESSMENT; OUTBREAKS; TASTE; ODOR C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 281 EP 289 DI 10.1007/978-1-4419-9374-8_21 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500021 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Eggs and Egg Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 19 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 291 EP 303 DI 10.1007/978-1-4419-9374-8_22 PG 13 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500022 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Milk and Dairy Products SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID RAW-MILK; PARATUBERCULOSIS; SAMPLES C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 37 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 305 EP 327 DI 10.1007/978-1-4419-9374-8_23 PG 23 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500023 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Shelf-Stable Heat Treated Foods SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID SPICES; BACTERIAL; SPORES; JUICE C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 29 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 329 EP 337 DI 10.1007/978-1-4419-9374-8_24 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500024 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Dry Foods for Infants and Young Children SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID WEANING FOOD; MICROBIOLOGICAL EVALUATION; NUTRITION; AFRICA C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 26 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 339 EP 348 DI 10.1007/978-1-4419-9374-8_25 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500025 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Combination Foods SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 4 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 349 EP 354 DI 10.1007/978-1-4419-9374-8_26 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500026 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Sampling Considerations and Statistical Aspects of Sampling Plans SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID MICROBIOLOGICAL ANALYSIS; FOOD; PERFORMANCE; VALIDATION C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 17 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 355 EP 364 DI 10.1007/978-1-4419-9374-8 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500027 ER PT B AU Chen, Y Brown, E Knabel, SJ AF Chen, Yi Brown, Eric Knabel, Stephen J. BE Wiedmann, M Zhang, W TI Molecular Epidemiology of Foodborne Pathogens SO GENOMICS OF FOODBORNE BACTERIAL PATHOGENS SE Food Microbiology and Food Safety LA English DT Article; Book Chapter ID FIELD GEL-ELECTROPHORESIS; FRAGMENT-LENGTH-POLYMORPHISM; SINGLE-NUCLEOTIDE POLYMORPHISMS; MULTILOCUS ENZYME ELECTROPHORESIS; LISTERIA-MONOCYTOGENES STRAINS; ESCHERICHIA-COLI O157-H7; COMMERCIAL SOFTWARE PACKAGES; VIRULENCE-ASSOCIATED GENES; TANDEM REPEAT ANALYSIS; SEQUENCE TYPING MLST C1 [Chen, Yi; Brown, Eric] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Knabel, Stephen J.] Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM yi.chen@fda.hhs.gov; eric.brown@fda.hhs.gov; sjk9@psu.edu NR 145 TC 2 Z9 2 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-7685-7 J9 FOOD MICROBIOL FOOD PY 2011 BP 403 EP 453 DI 10.1007/978-1-4419-7686-4_12 D2 10.1007/978-1-4419-7686-4 PG 51 WC Food Science & Technology SC Food Science & Technology GA BTP58 UT WOS:000287716900012 ER PT B AU Taylor, DR AF Taylor, Deborah R. BE Tan, SL He, YP TI Hepatitis C Virus: Public Resources SO HEPATITIS C: ANTIVIRAL DRUG DISCOVERY AND DEVELOPMENT LA English DT Article; Book Chapter ID HCV INTERNATIONAL STANDARD AB The tremendous progress in the field of HCV research has led to an explosion of resources, ranging from research tools and scientific reagents to information sources, including internet tools, meetings and conferences, and regulation policies. Access to such valuable HCV resources is important to facilitate HCV pathogenesis research as well as drug discovery and development. This chapter summarizes the current major resources that are publicly available for scientists, physicians, health professionals, educators, and patients. C1 US FDA, CBER,Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Chron Hepatitis & Innate Immun, Bethesda, MD 20014 USA. RP Taylor, DR (reprint author), US FDA, CBER,Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Lab Chron Hepatitis & Innate Immun, Bethesda, MD 20014 USA. EM Deborah.Taylor@FDA.HHS.gov NR 3 TC 0 Z9 0 U1 1 U2 2 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-78-3 PY 2011 BP 67 EP 73 PG 7 WC Immunology; Infectious Diseases; Pharmacology & Pharmacy SC Immunology; Infectious Diseases; Pharmacology & Pharmacy GA BUH82 UT WOS:000289380100004 ER PT B AU Farrell, AT Dagher, RN Pazdur, R AF Farrell, Ann T. Dagher, Ramzi N. Pazdur, Richard BE Hidalgo, M Eckhardt, SG GarrettMayer, E Clendeninn, NJ TI Role of the US Food and Drug Administration in Cancer Drug Development SO PRINCIPLES OF ANTICANCER DRUG DEVELOPMENT SE Cancer Drug Discovery and Development LA English DT Article; Book Chapter C1 [Farrell, Ann T.] US FDA, Div Hematol Prod, OODP, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Dagher, Ramzi N.] Pfizer Inc, Global Regulatory, Worldwide Regulatory Strategy, New London, CT 06320 USA. [Dagher, Ramzi N.] Pfizer Inc, Oncol Business Unit, New London, CT 06320 USA. RP Farrell, AT (reprint author), US FDA, Div Hematol Prod, OODP, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM ann.farrell@fda.hhs.gov; ramzi.dagher@pfizer.com; richard.pazdur@fda.hhs.gov NR 28 TC 0 Z9 0 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-4419-7357-3 J9 CANCER DRUG DISCOV D JI Canc. Drug. Disc. Dev. PY 2011 BP 305 EP 332 DI 10.1007/978-1-4419-7358-0_12 PG 28 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA BTC93 UT WOS:000286531700012 ER PT S AU Wang, QZ Le, D Ramella-Roman, J Pfefer, J AF Wang, Quanzeng Le, Du Ramella-Roman, Jessica Pfefer, Joshua BE Raghavachari, R Liang, R TI Broadband UV-Vis optical property measurement in layered turbid media SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES IV SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies IV CY JAN 23-25, 2011 CL San Francisco, CA SP SPIE DE optical property; mucosal tissue; Monte Carlo; neural network; reflectance; broadband; fiberoptic ID DIFFUSE-REFLECTANCE SPECTRA; EPITHELIAL TISSUE; MODEL; REFLECTOMETRY; SPECTROSCOPY; DIAGNOSIS; PROBE AB Quantitative data on the fundamental optical properties (OPs) of biological tissue, including absorption and reduced scattering coefficients are important for elucidating light propagation during optical spectroscopy and facilitating diagnostic device design and optimization, and may enable rapid detection of early neoplasia. However, systems for in situ broadband measurement of mucosal tissue OPs in the ultraviolet-visible range have not been realized. In this study, we evaluated a fiberoptic-based reflectance system, coupled with neural network inverse models (trained with Monte Carlo simulation data), for measuring OPs in highly attenuating, two-layer turbid media. The experimental system incorporated a broadband light source, a fiberoptic probe and a CCD camera. The calibration method involved a set of standard nigrosin-microsphere phantoms as well as a more permanent spectralon phantom for quality assurance testing and recalibration. The system was experimentally evaluated using two-layer hydrogel phantoms with hemoglobin and polystyrene microspheres. The effects of tissue top-layer thickness and fitting approaches based on known absorption and scattering distributions were discussed. With our method, measurements with error less than 28% were obtained in the wavelength range of 350-630 nm. C1 [Wang, Quanzeng; Pfefer, Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-428-4 J9 PROC SPIE PY 2011 VL 7891 AR 78910F DI 10.1117/12.879647 PG 10 WC Biophysics; Engineering, Biomedical; Optics SC Biophysics; Engineering; Optics GA BVL26 UT WOS:000291793300007 ER PT J AU Gilks, WR Wang, CY AF Gilks, Walter R. Wang, Chinying TI A Non-Parametric Method for Detecting Specificity Determining Sites in Protein Sequence Alignments SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE multiple sequence alignment; parsimony; phylogenetics; protein sequence; randomisation; specificity determining sites; subfamily ID FUNCTIONAL SPECIFICITY; DETERMINING RESIDUES; PREDICTION; EVOLUTION; FAMILIES; DIVERGENCE; POSITIONS AB Specificity determining sites (SDSs) in alignments of protein sequences are sites at which subfamilies of the aligned sequences have been under differential selective pressure. Identifying SDSs is important because they are key in understanding the functional specificity of each subfamily. Differential selection at an SDS will result in differences between subfamilies in the distribution of amino-acids at that site. However, statistical analysis of such differences is complicated by phylogenetic relationships within each subfamily, which profoundly influence these differences. We develop a non-parametric approach to evaluating purely statistical SDS evidence in a sequence alignment, taking account of phylogeny through a novel tree-respecting randomisation based on the principle of parsimony. Our approach does not exploit bioinformatic measures based on amino-acid properties or rates of evolution, as do other methods. Our intention is thereby to supplement and strengthen other methods of SDS prediction, not to compete with them. Our methodology is implemented in the R package called SDSparsimony, freely downloadable from http://www.maths.leeds.ac.uk/%7Ewally.gilks/SDSparsimonyPackage/Welcome.html. C1 [Gilks, Walter R.] Univ Leeds, Harpenden, Herts, England. [Gilks, Walter R.] Rothamsted Res, Harpenden, Herts, England. Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Gilks, WR (reprint author), Univ Leeds, Harpenden, Herts, England. EM wally.gilks@maths.leeds.ac.uk; Chinying.Wang@fda.hhs.gov NR 27 TC 0 Z9 0 U1 1 U2 3 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 EI 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2011 VL 10 IS 1 AR 20 DI 10.2202/1544-6115.1584 PG 32 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 759DO UT WOS:000290221100004 ER PT J AU Gnjidic, D Hilmer, SN Le Couteur, DG Abernethy, DR AF Gnjidic, Danijela Hilmer, Sarah N. Le Couteur, David G. Abernethy, Darrell R. TI Drug burden index (DBI) and Beers criteria: impact on function in older people SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 84th Annual Meeting of the Japanese-Pharmacological-Society/11th Southeast Asian Western Pacific Regional Meeting of Pharmacologists CY MAR 22-24, 2011 CL Yokohama, JAPAN SP Japanese Pharmacolog Soc C1 [Gnjidic, Danijela; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Clin Pharmacol & Aged Care, St Leonards, NSW 2065, Australia. [Gnjidic, Danijela; Hilmer, Sarah N.; Le Couteur, David G.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Le Couteur, David G.] Concord Hosp, Ctr Educ & Res Ageing, Sydney, NSW, Australia. [Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2011 VL 115 SU 1 BP 288P EP 288P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 743QU UT WOS:000289034601535 ER PT J AU Li, MJ Hanson, T AF Li, Meijuan Hanson, Timothy TI Bayesian non-parametric multivariate statistical models for testing association between quantitative traits and candidate genes in structured populations SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE Association mapping; Kinship; Linkage disequilibrium; Multivariate mixture of Polya trees; Population structure ID FLOWERING-LOCUS-C; LINKAGE DISEQUILIBRIUM; ARABIDOPSIS; INFERENCE; MIXTURES; VERNALIZATION; RELATEDNESS; REPRESSOR; VARIANTS; FRIGIDA AB Population-based linkage disequilibrium mapping permits finer scale mapping than linkage analysis. However, the population-based association mapping is subject to false positive results due to the population structure and the kinship between the samples. Although there is interest in simultaneously testing the association between a candidate gene and the multiple phenotypes of interest, the currently available association mapping methods are limited to univariate traits only. Here we present a new method for population-based multitrait candidate gene association mapping as a Bayesian semiparametric approach, where the error distribution is flexibly modelled via a multivariate mixture of Polya trees centred on the family of multivariate normal distributions. The method that we develop accounts for the population structure and the complex relatedness between the samples. We compare the new proposal in type I error rate and power with the existing multivariate version of the parametric model of Yu and co-workers and Li's univariate semiparametric model by using the previously published two type Arabidopsis thaliana flowering data sets of association mapping, as well as simulated data. C1 [Li, Meijuan] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Li, MJ (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Bldg 66,Room 2225,10903 New Hampshire Ave, Silver Spring, MD USA. EM meijuan.li@fda.hhs.gov RI Hanson, Timothy/A-9127-2016 NR 29 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0035-9254 J9 J R STAT SOC C-APPL JI J. R. Stat. Soc. Ser. C-Appl. Stat. PY 2011 VL 60 BP 207 EP 219 DI 10.1111/j.1467-9876.2010.00741.x PN 2 PG 13 WC Statistics & Probability SC Mathematics GA 730EX UT WOS:000288017300004 ER PT J AU Mossoba, MM Seiler, A Steinhart, H Kramer, JKG Rodrigues-Saona, L Griffith, AP Pierceall, R van de Voort, FR Sedman, J Ismail, AA Barr, D Da Costa, PA Li, H Zhang, Y Liu, X Bradley, M AF Mossoba, M. M. Seiler, A. Steinhart, H. Kramer, J. K. G. Rodrigues-Saona, L. Griffith, A. P. Pierceall, R. van de Voort, F. R. Sedman, J. Ismail, A. A. Barr, D. Da Costa Filho, P. A. Li, H. Zhang, Y. Liu, X. Bradley, M. TI Regulatory Infrared Spectroscopic Method for the Rapid Determination of Total Isolated Trans Fat: A Collaborative Study SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE Fats and oils; Infrared; Spectroscopy; Lipid chemistry; Lipid analysis ID ISOMERS AB Using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, collaborating scientists in ten different laboratories measured (in duplicate) the total trans fat content of ten fat or oil test samples, two of which were blind duplicates. The procedure used entailed measuring the height of the negative second derivative of the IR absorption band at 966 cm(-1). This absorption is attributed to the C-H deformation vibration that is characteristic of isolated (non-conjugated) double bonds with the trans configuration. The precision of ATR-FTIR results in this international collaborative study was satisfactory and led to the approval of this validated procedure as official method AOCS Cd 14e-09 in late 2009. This official method is also suitable for analysis of total isolated trans fat and oil products containing, or supplemented with, trans conjugated linoleic acid (CLA) isomers. Although this method does not require derivatization of the oil or fat test materials, as required for GC, fats and oils in foods must be extracted with organic solvents before analysis. This method is also rapid (5 min) and does not require any weighing or quantitative dilution of unknown neat fat or oil test samples in any solvent. The AOCS Cd 14e-09 method is suitable for determination of test samples with zero trans fat, which is defined according to the US labeling regulations as 0.5 g trans fat per serving or 1.8% trans fat, as a percentage of total fat. C1 [Mossoba, M. M.; Seiler, A.] Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Seiler, A.; Steinhart, H.] Univ Hamburg, Hamburg, Germany. [Kramer, J. K. G.] Agr & Agri Food Canada, Guelph, ON, Canada. [Rodrigues-Saona, L.] Ohio State Univ, Columbus, OH 43210 USA. [Griffith, A. P.; Pierceall, R.] Archer Daniels Midland Co, Decatur, IL USA. [van de Voort, F. R.; Sedman, J.; Ismail, A. A.] McGill Univ, Ste Anne De Bellevue, PQ, Canada. [Barr, D.] Deakin Univ, Burwood, Vic, Australia. [Da Costa Filho, P. A.] Nestle Res Ctr, CH-1000 Lausanne, Switzerland. [Li, H.] Bruker Opt, Billerica, MA USA. [Zhang, Y.; Liu, X.] Bruker Opt China, Beijing, Peoples R China. [Bradley, M.] Thermo Elect, Madison, WI USA. RP Mossoba, MM (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, Mail Stop HFS 717,Room BE 012,5100 Paint Branch P, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 15 TC 8 Z9 8 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD JAN PY 2011 VL 88 IS 1 BP 39 EP 46 DI 10.1007/s11746-010-1648-0 PG 8 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 721RJ UT WOS:000287372200005 ER PT J AU Vu, NT Rickard, JD Sullivan, MP Richfield-Fratz, N Weisz, A AF Vu, Nga T. Rickard, James D. Sullivan, Michael P. Richfield-Fratz, Naomi Weisz, Adrian TI DETERMINATION OF INTERMEDIATES AND SUBSIDIARY COLORS IN THE COLOR ADDITIVE FDC RED NO. 4 (PONCEAU SX) USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE 3-[(2; 4-dimethyl-6-sulfophenyl)azo]-4-hydroxy-1-naphthalenesulfonic acid; 4-hydroxy-1-naphthalenesulfonic acid; 5-amino-2; 4-dimethyl-1-benzenesulfonic acid; C; I; 14700; FDC Red No; 4; High-speed countercurrent chromatography (HSCCC); HPLC; Ponceau SX ID COUNTER-CURRENT CHROMATOGRAPHY AB Specifications in the U.S. Code of Federal Regulations for the color additive FDC Red No. 4 (Color Index 14700) limit the levels of the intermediates, 5-amino-2,4-dimethyl-1-benzenesulfonic acid (AMBSA) and 4-hydroxy-1-naphthalenesulfonic acid (HNSA), and of subsidiary colors. The present study reports the development of a high-performance liquid chromatography (HPLC) method for the quantitative determination of these intermediates and subsidiary colors in one analysis. The most commonly-found subsidiary color, 3-[(2,4-dimethyl-6-sulfophenyl)azo]-4-hydroxy-1-naphthalenesulfonic acid (6SSC), is determined and is used as a secondary reference material to determine the quantities of other subsidiary colors present. High-speed countercurrent chromatography was used to obtain purified HNSA and 6SSC for use as reference materials. AMBSA, HNSA, and 6SSC were quantified by using five-point calibration curves with data points that ranged from 0.028-0.234%, 0.031-0.252%, and 0.113-2.036% by weight, respectively. The HPLC method is rapid (50min for the total analysis cycle) and simple to implement. It was applied to the analysis of test portions from 23 lots of FDC Red No. 4 submitted to the U.S. Food and Drug Administration (FDA) for certification and was later implemented by the FDA for routine batch certification of FDC Red No. 4. C1 [Vu, Nga T.; Rickard, James D.; Sullivan, Michael P.; Richfield-Fratz, Naomi; Weisz, Adrian] US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, HFS 106,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 8 TC 5 Z9 5 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1082-6076 EI 1520-572X J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2011 VL 34 IS 2 BP 106 EP 115 AR PII 931975951 DI 10.1080/10826076.2010.526874 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 714NV UT WOS:000286817200003 ER PT J AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. TI Laser therapy: A review of its mechanism of action and potential medical applications SO LASER & PHOTONICS REVIEWS LA English DT Review DE Laser therapy; stimulation; inhibition; hydrogen peroxide; reactive oxygen species (ROS); metabolic activity; adenosine triphosphate (ATP); nuclear factor k beta photobiomodulation; LLLT (Low-Level Light Therapy) ID LOW-LEVEL LASER; HELIUM-NEON LASER; CARPAL-TUNNEL-SYNDROME; NEAR-IR RADIATION; HYDROGEN-PEROXIDE; REACTIVE OXYGEN; IN-VITRO; PHOTODYNAMIC THERAPY; NEUROLOGICAL DEFICITS; 670-NM PHOTOTHERAPY AB Civilizations in antiquity have endeavored to champion the use of light to treat illnesses in the human body. Although laser light has unique applications in medicine, its mechanism of action for low intensity exposures on cells, tissues, and the body continues to be controversial after nearly 50 years of investigations. This paper presents evidence for visible red and near infrared light to induce (indirect) generation of hydrogen peroxide as an important chemical messenger behind the stimulatory and inhibitory responses observed to low intensity light exposures. It is hypothesized that other ionizing or non-ionizing modalities can either directly or indirectly induce / or generate H2O2 in an aqueous environment and could also bring about similar stimulatory or inhibitory bio-effects. One salient parameter which governs the bio-response is the level of generated H2O2. The authors discuss the mechanism which enables a small amount of hydrogen peroxide generated by light to produce beneficial effects. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ronald.waynant@fda.hhs.gov NR 137 TC 9 Z9 11 U1 2 U2 28 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1863-8880 J9 LASER PHOTONICS REV JI Laser Photon. Rev. PD JAN PY 2011 VL 5 IS 1 BP 1 EP 12 DI 10.1002/lpor.200900032 PG 12 WC Optics; Physics, Applied; Physics, Condensed Matter SC Optics; Physics GA 712QV UT WOS:000286682200003 ER PT J AU Schlessinger, S Kokko, K Fratkin, J Butt, F Hawxby, A Todaro, M Henderson, H Seawright, A Parker, C Byers, P Gonzalez-Peralta, R Kayler, L Fauerbach, L Lawrence, R Haafi, A Stanek, D Hammond, R Thoroughman, D Pippen, T Johnson, S Mahle, W Lyon, G Laporte, K Kanter, K Ivey, M Arnold, K Lance, S Navarro-Almario, E Farnon, E Kuehnert, M Shieh, W Paddock, C Zaki, S Drew, C Schmitz, A Sejvar, J Sriram, R Visvesvara, G Beach, M Yoder, J Roy, S Qvarnstrom, Y Bandea, R daSilva, A Bosserman, E Budge, P Lutterloh, E AF Schlessinger, S. Kokko, K. Fratkin, J. Butt, F. Hawxby, A. Todaro, M. Henderson, H. Seawright, A. Parker, C. Byers, P. Gonzalez-Peralta, R. Kayler, L. Fauerbach, L. Lawrence, R. Haafi, A. Stanek, D. Hammond, R. Thoroughman, D. Pippen, T. Johnson, S. Mahle, W. Lyon, G., III Laporte, K. Kanter, K. Ivey, M. Arnold, K. Lance, S. Navarro-Almario, E. Farnon, E. Kuehnert, M. Shieh, W. Paddock, C. Zaki, S. Drew, C. Schmitz, A. Sejvar, J. Sriram, R. Visvesvara, G. Beach, M. Yoder, J. Roy, S. Qvarnstrom, Y. Bandea, R. daSilva, A. Bosserman, E. Budge, P. Lutterloh, E. TI Balamuthia mandrillaris Transmitted Through Organ Transplantation - Mississippi, 2009 SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID MENINGOENCEPHALITIS; PATIENT C1 [Schlessinger, S.] Mississippi Organ Recovery Agcy, Flowood, MS USA. [Kokko, K.; Fratkin, J.; Butt, F.; Hawxby, A.; Todaro, M.; Henderson, H.; Seawright, A.; Parker, C.] Univ Mississippi, Med Ctr, University, MS 38677 USA. [Gonzalez-Peralta, R.; Kayler, L.; Fauerbach, L.; Lawrence, R.; Haafi, A.] Univ Florida, Shands Hosp, Gainesville, FL 32611 USA. [Mahle, W.; Lyon, G., III; Laporte, K.; Kanter, K.] Emory Univ, Atlanta, GA 30322 USA. [Navarro-Almario, E.] US FDA, Rockville, MD 20857 USA. [Budge, P.; Lutterloh, E.] CDC, Atlanta, GA 30333 USA. RP Schlessinger, S (reprint author), Mississippi Organ Recovery Agcy, Flowood, MS USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JAN PY 2011 VL 11 IS 1 BP 173 EP 176 DI 10.1111/j.1600-6143.2010.03395_1.x PG 4 WC Surgery; Transplantation SC Surgery; Transplantation GA 700ZG UT WOS:000285783500026 ER PT J AU Ganesan, D Lindvall, M Cleaveland, R Jetley, R Jones, P Zhang, Y AF Ganesan, Dharmalingam Lindvall, Mikael Cleaveland, Rance Jetley, Raoul Jones, Paul Zhang, Yi GP IEEE TI Architecture Reconstruction and Analysis of Medical Device Software SO 2011 9TH WORKING IEEE/IFIP CONFERENCE ON SOFTWARE ARCHITECTURE (WICSA) LA English DT Proceedings Paper CT 9th Working IEEE/IFIP Conference on Software Architecture (WICSA) on Architecture Across Boundaries/CompArch Conference CY JUN 20-24, 2011 CL Boulder, CO SP IEEE, IFIP, IEEE Comp Soc, IBM, Siemens Corp Res, Carnegie Mellon Univ, Software Engn Inst DE Medical device safety; Testability; Verifiability; Static Analysis; Reverse Architecting ID MODEL AB New research is underway at the FDA to investigate the benefits of integrating architecture analysis into safety evaluations of medical-device software. Due to the complexity in setting up testing environments for such software, the FDA is unable to conduct large-scale safety testing; instead, it must rely on other techniques to build an argument for whether the software is safe or not. The architecture analysis approach, formalized using relational algebra, is based on reconstructing abstract, yet precise, architectural views from source code to help build such arguments about safety. This paper discusses the use of the formal approach to analyze the Computer-Assisted Resuscitation Algorithm (CARA) software, which controls an infusion pump designed to provide automated assistance for transfusing blood. The results suggest that a) architecture analysis offers many insights related to software quality in general and testability (i.e., the ease of testing) and its impact on safety in particular, and b) architectural analysis results can be used to help configure static analysis tools to improve their performance for verifying safety properties. C1 [Ganesan, Dharmalingam; Lindvall, Mikael; Cleaveland, Rance] Fraunhofer CESE, College Pk, MD USA. [Jetley, Raoul; Jones, Paul; Zhang, Yi] FDA, Silver Spring, MD USA. RP Ganesan, D (reprint author), Fraunhofer CESE, College Pk, MD USA. EM dganesan@fc-md.umd.edu; mlindvall@fc-md.umd.edu; rcleaveland@fc-md.umd.edu; raoul.jetley@fda.hhs.gov; paul.jones@fda.hhs.gov; yi.zhang2@fda.hhs.gov NR 28 TC 3 Z9 3 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 978-0-7695-4351-2 PY 2011 BP 194 EP 203 DI 10.1109/WICSA.2011.33 PG 10 WC Computer Science, Software Engineering; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BYL75 UT WOS:000299279500024 ER PT S AU Johannesen, L AF Johannesen, Lars BE Murray, A TI Assessment of ECG Quality on an Android Platform SO 2011 COMPUTING IN CARDIOLOGY SE Computing in Cardiology Series LA English DT Proceedings Paper CT Conference on Computing in Cardiology CY SEP 18-21, 2011 CL Hangzhou, PEOPLES R CHINA SP European Soc Cardiol, Zhejiang Univ, EMB, IEEE, Drager, Mortara, Philips, Univ Rochester, Telemetr & Holter ECG Warehouse, Physiol Measurement, Mindray, GE Healthcare, Zoll, Edan, GSMA AB An algorithm to determine quality of ECGs can enable inexperienced nurses and paramedics to record ECGs of sufficient diagnostic quality. We propose an algorithm that can assess the quality of an ECG designed for an Android-based platform. The algorithm is based on previously established ECG quality metrics for quantifying ECG quality but designed in a way to make it efficient to run on a mobile platform. Using the training data set the proposed algorithm obtained a sensitivity of 91% and a specificity of 85%. Testing against the test data sets, resulted in a score of 0.88 (events 1 and 2) and 0.79 (events 3). The proposed algorithm discriminates between ECGs of good and bad quality, which could help diagnose patients earlier and reduce associated treatment costs. C1 [Johannesen, Lars] US FDA, Div Pharmacometr, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Johannesen, L (reprint author), 10903 New Hampshire Ave,Bldg 51, Silver Spring, MD 20993 USA. EM lars.johannesen@fda.hhs.gov NR 7 TC 4 Z9 4 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4577-0611-0 J9 COMPUT CARDIOL PY 2011 VL 38 BP 433 EP 436 PG 4 WC Cardiac & Cardiovascular Systems; Computer Science, Interdisciplinary Applications SC Cardiovascular System & Cardiology; Computer Science GA BAP78 UT WOS:000305132500110 ER PT S AU Connors, M Agrawal, A Liang, CP Chen, Y Drezek, R Pfefer, J AF Connors, Megan Agrawal, Anant Liang, Chia-Pin Chen, Yu Drezek, Rebekah Pfefer, Joshua GP IEEE TI Characterizing the Point Spread Function of Retinal OCT Devices with a Model Eye-Based Phantom SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD ID OPTICAL COHERENCE TOMOGRAPHY AB We have designed, fabricated, and tested a nanoparticle-embedded phantom incorporated into a model eye for characterizing the point spread function of retinal OCT devices in three dimensions under realistic imaging conditions. C1 [Connors, Megan; Agrawal, Anant; Liang, Chia-Pin; Pfefer, Joshua] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20902 USA. [Connors, Megan] Univ Maryland, Dept Elect & Comp Engn, Coll Park, MD 21228 USA. [Liang, Chia-Pin; Chen, Yu] Univ Maryland, Dept Bioengn, Coll Park, MD 21228 USA. [Drezek, Rebekah] Rice Univ, Dept Elect & Comp Engn, Houston, TX 77251 USA. RP Connors, M (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20902 USA. EM Anant.Agrawal@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612400037 ER PT S AU Ilev, I AF Ilev, Ilko GP IEEE TI Beyond Diffraction Limited Imaging and Sensing in Nanobiophotonics SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD ID MICROSCOPY AB Based on simple fiber-optic approaches, we present some advanced nanobiophotonics methods for ultrahigh-resolution bioimaging and biosensing beyond the diffraction barrier in the subwavelength nanometric range at cellular, intracellular and bulk tissue level. (C) 2011 Optical Society of America C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Ilev, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM ilko.ilev@eob.cdrh.fda.gov NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612402236 ER PT S AU Le, D Wang, Q Ramella-Roman, J Pfefer, J AF Le, D. Wang, Q. Ramella-Roman, J. Pfefer, J. GP IEEE TI Theoretical Analysis of a Technique for Broadband Optical Property Estimation in Two-layer Tissue SO 2011 CONFERENCE ON LASERS AND ELECTRO-OPTICS (CLEO) SE Conference on Lasers and Electro-Optics LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 01-06, 2011 CL Baltimore, MD AB Our data processing algorithms for determination of optical properties in two-layer tissue from broadband reflectance are evaluated. By combining Monte Carlo, neural network and spectral fitting approaches, accurate estimates can be produced. C1 [Le, D.; Wang, Q.; Pfefer, J.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Le, D.; Ramella-Roman, J.] Catholic Univ Amer, Dept Biomed Engn, Washington, DC 20064 USA. RP Le, D (reprint author), Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng.wang@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 2160-9020 BN 978-1-55752-910-7 J9 CONF LASER ELECTR PY 2011 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BXB77 UT WOS:000295612400032 ER PT S AU Gala, HD Peng, R Zeng, RP Freed, M O'Bryan, E Jennings, RJ AF Gala, Hugo de las Heras Peng, Rui Zeng, Rongping Freed, Melanie O'Bryan, Eugene Jennings, Robert J. GP IEEE TI A versatile laboratory platform for studying x-ray 3D breast imaging SO 2011 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (NSS/MIC) SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference (NSS/MIC)/18th International Workshop on Room-Temperature Semiconductor X-Ray and Gamma-Ray Detectors CY OCT 23-29, 2011 CL Valencia, SPAIN SP IEEE, Inst Elect & Elect Engineers Nucl & Plasma Sci Soc (IEEE NPSS) AB Purpose: This paper presents the features of a new laboratory x-ray platform for 3D breast imaging at FDA and initial projection images and tomosynthesis reconstructions. Materials and methods: The laboratory consists of an x-ray generator, x-ray tube and detector, as well as seven stepper motors controlling four linear and three rotary stages. All components are currently being integrated using Lab View to allow for an automated operation of the lab. We used 3 different phantoms to obtain initial images. From all the possible geometry arrangements and techniques possible with the system, we selected a breast tomosynthesis acquisition protocol that is similar to those used by systems being investigated or developed by industry. The simultaneous algebraic reconstruction technique (SART) was used to obtain the reconstructions. Results and conclusion: The laboratory provides a flexible platform for performing studies in 3D breast x-ray imaging that can be used to study the effect of different system components on image quality and lead to a better understanding of the system performance. C1 [Gala, Hugo de las Heras] Quart GmbH, D-85604 Zorneding, Germany. [Gala, Hugo de las Heras; Peng, Rui; Zeng, Rongping; Freed, Melanie; O'Bryan, Eugene; Jennings, Robert J.] US FDA, Ctr Dev & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Pontificia Univ Catolica Chile, Santiago, Chile. RP Gala, HD (reprint author), Quart GmbH, D-85604 Zorneding, Germany. EM hugo.delasheras@daad-alumni.de; rui.peng@fda.hhs.gov; rongping.zeng@fda.hhs.gov; freed@fis.puc.cl; Eugene.OBryan@fda.hhs.gov; RobertJ.Jennings@fda.hhs.gov FU ORISE; Office of Women's Health. He now works part-time for Quart GmbH FX He was funded by an ORISE fellowship and supported in part by the Office of Women's Health. He now works part-time for Quart GmbH NR 13 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4673-0120-6 J9 IEEE NUCL SCI CONF R PY 2011 BP 2851 EP 2854 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Physics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAM64 UT WOS:000304755603015 ER PT J AU Samuelson, F Brown, DG AF Samuelson, Frank Brown, David G. GP IEEE TI Application of Cover's Theorem to the Evaluation of the Performance of CI Observers SO 2011 INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN) CY JUL 31-AUG 05, 2011 CL San Jose, CA SP Int Neural Network Soc (INNS), IEEE Computat Intelligence Soc (CIS), Natl Sci Fdn (NSF), Cognimem Technol, Inc, Univ Cincinnati Coll Engn & Appl Sci, Toyota Res Inst N Amer, Univ Cincinnati, Sch Elect & Compu Syst AB For any N points arbitrarily located in a d-dimensional space, Thomas Cover popularized and augmented a theorem that gives an expression for the number of the 2(N) possible two-class dichotomies of those points that are separable by a hyperplane. Since separation of two-class dichotomies in d dimensions is a common problem addressed by computational intelligence (CI) decision functions or "observers," Cover's theorem provides a benchmark against which CI observer performance can be measured. We demonstrate that the performance of a simple perceptron approaches the ideal performance and how a single layer MLP and an SVM fare in comparison. We show how Cover's theorem can be used to develop a procedure for CI parameter optimization and to serve as a descriptor of CI complexity. Both simulated and micro-array genomic data are used. C1 [Samuelson, Frank; Brown, David G.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Samuelson, F (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 3105, Silver Spring, MD 20993 USA. EM frank.samuelson@fda.hhs.gov; david.brown@fda.hhs.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-9636-5 PY 2011 BP 1020 EP 1026 PG 7 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BXX80 UT WOS:000297541201021 ER PT J AU Chen, WJ Brown, DG AF Chen, Weijie Brown, David G. GP IEEE TI Optimistic bias in the assessment of high dimensional classifiers with a limited dataset SO 2011 INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS (IJCNN) LA English DT Proceedings Paper CT International Joint Conference on Neural Networks (IJCNN) CY JUL 31-AUG 05, 2011 CL San Jose, CA SP Int Neural Network Soc (INNS), IEEE Computat Intelligence Soc (CIS), Natl Sci Fdn (NSF), Cognimem Technol, Inc, Univ Cincinnati Coll Engn & Appl Sci, Toyota Res Inst N Amer, Univ Cincinnati, Sch Elect & Compu Syst ID GENE-EXPRESSION DATA; MICROARRAY DATA; OVER-OPTIMISM; SELECTION; CLASSIFICATION; BIOINFORMATICS; VALIDATION; PITFALLS AB It is commonly recognized that using the same dataset for training and testing the classifier introduces optimistic bias in estimating classifier performance. However, bias of the same kind may still exist even when independent datasets are used for training and testing a classifier. This problem is especially important in the setting of high dimensional feature space and limited data. Bioinformatics data is typically characterized by a tremendous amount of data per patient but from a limited number of patients. Often the entire data set is utilized in a "pre-training" stage during which the feature set is winnowed to a manageable number, and the parameters of the training algorithm are established. Subsequently the data is bifurcated into training and test sets; however, bias has already been introduced into the classifier development process. We investigate the significance of this bias by performing simulated gene expression experiments. We find that, for data with moderate intrinsic separability and modest sample size, any observed separation is due to selection bias introduced in the aforementioned pre-training process. For greater intrinsic separability, correct data hygiene, i.e., complete separation of development and validation data yields a positive result, but one far less impressive than that mistakenly obtained using incomplete data separation. C1 [Chen, Weijie; Brown, David G.] US FDA, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, Silver Spring, MD 20993 USA. EM Weijie.chen@fda.hhs.gov; david.brown@fda.hhs.gov NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-9636-5 PY 2011 BP 2698 EP 2703 PG 6 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BXX80 UT WOS:000297541202121 ER PT J AU Boehmer, JL Olumee-Shabon, Z AF Boehmer, Jamie L. Olumee-Shabon, Zohra BE Veas, F TI Veterinary Biomarker Discovery: Proteomic Analysis of Acute Phase Proteins SO ACUTE PHASE PROTEINS AS EARLY NON-SPECIFIC BIOMARKERS OF HUMAN AND VETERINARY DISEASES LA English DT Article; Book Chapter ID C-REACTIVE PROTEIN; SERUM-AMYLOID-A; DISSOCIATION MASS-SPECTROMETRY; HEAVY-CHAIN 4; ALPHA(1)-ACID GLYCOPROTEIN; ALPHA-1-ACID GLYCOPROTEIN; DAIRY-COWS; EXPERIMENTAL-INFECTION; ESCHERICHIA-COLI; ACTINOBACILLUS-PLEUROPNEUMONIAE C1 [Boehmer, Jamie L.; Olumee-Shabon, Zohra] US FDA, Ctr Vet Med, Res Off, Rockville, MD 20857 USA. RP Boehmer, JL (reprint author), US FDA, Ctr Vet Med, Res Off, Rockville, MD 20857 USA. NR 95 TC 0 Z9 0 U1 0 U2 0 PU INTECH EUROPE PI RIJEKA PA JANEZA TRDINE9, RIJEKA, 51000, CROATIA BN 978-953-307-873-1 PY 2011 BP 189 EP 210 D2 10.5772/1045 PG 22 WC Immunology; Pathology SC Immunology; Pathology GA BE6CS UT WOS:000373891800010 ER PT J AU Wilcox, N Goldberg, A AF Wilcox, Neil Goldberg, Alan TI Food for Thought ... on Validation. A Puzzle or a Mystery: an Approach Founded on New Science SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE in vitro; 21(st) century toxicity testing; test method validation ID TOXICITY TEST PROCEDURES; RECOMMENDATIONS AB The notion of test method validation, when applied to in vitro models, has been subjected to standards, practices, and regulatory mandates that may represent significant barriers to the development of new methods based on target toxicological pathways, mode of action, and mechanistic endpoints. Currently, there is an expectation that toxicity test methods used for regulatory purposes must be formally validated by a legislated body. In this manuscript, we review the genesis of current formal validation programs, their purpose, their justification for future need, and an examination of the scientific process as the driving force. With the collision of three major international events in the scientific and regulatory communities (viz. EU Cosmetic Directive, EU REACH legislation, and the NRC publication, Toxicity Testing in the 21(st) Century: A Vision and a Strategy), there may be a need for a shift in the current validation paradigm. Further, test method validity may be recognized by the appropriate authorities when specific criteria and the fundamental precepts of reliability and reproducibility have been adequately met. C1 [Wilcox, Neil] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. [Goldberg, Alan] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. RP Wilcox, N (reprint author), US FDA, Off Cosmet & Colors, 5100 Paint Branch Pkwy,CPK2,HFS 125, College Pk, MD 20740 USA. EM Neil.wilcox@fda.hhs.gov NR 17 TC 5 Z9 5 U1 0 U2 0 PU SPEKTRUM AKAD VERLAG PI HEIDELBERG PA SLEVOGTSTRASSE 3-5, D-69126 HEIDELBERG, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2011 VL 28 IS 1 BP 3 EP 8 PG 6 WC Instruments & Instrumentation; Medicine, Research & Experimental SC Instruments & Instrumentation; Research & Experimental Medicine GA 734SQ UT WOS:000288358600002 PM 21311846 ER PT J AU Silbergeld, EK Contreras, EQ Hartung, T Hirsch, C Hogberg, H Jachak, AC Jordan, W Landsiedel, R Morris, J Patri, A Pounds, JG Ruiz, AD Shvedova, A Tanguay, R Tatarazako, N van Vliet, E Walker, NJ Wiesner, M Wilcox, N Zurlo, J AF Silbergeld, Ellen K. Contreras, Elizabeth Q. Hartung, Thomas Hirsch, Cordula Hogberg, Helena Jachak, Ashish C. Jordan, William Landsiedel, Robert Morris, Jeffery Patri, Anil Pounds, Joel G. de Vizcaya Ruiz, Andrea Shvedova, Anna Tanguay, Robert Tatarazako, Norihasa van Vliet, Erwin Walker, Nigel J. Wiesner, Mark Wilcox, Neil Zurlo, Joanne TI Nanotoxicology: "The End of the Beginning" - Signs on the Roadmap to a Strategy for Assuring the Safe Application and Use of Nanomaterials SO ALTEX-ALTERNATIVES TO ANIMAL EXPERIMENTATION LA English DT Article DE nanomaterials; nanotoxicology; alternative methods; 3Rs; Tox-21c AB In October 2010, a group of experts met as part of the transatlantic think tank for toxicology (t(4)) to exchange ideas about the current status and future of safety testing of nanomaterials. At present, there is no widely accepted path forward to assure appropriate and effective hazard identification for engineered nanomaterials. The group discussed needs for characterization of nanomaterials and identified testing protocols that incorporate the use of innovative alternative whole models such as zebrafish or C. elegans, as well as in vitro or alternative methods to examine specific functional pathways and modes of action. The group proposed elements of a potential testing scheme for nanomaterials that works towards an integrated testing strategy, incorporating the goals of the NRC report Toxicity Testing in the 21(st) Century: A Vision and a Strategy by focusing on pathways of toxic response, and utilizing an evidence-based strategy for developing the knowledge base for safety assessment. Finally, the group recommended that a reliable, open, curated database be developed that interfaces with existing databases to enable sharing of information. C1 [Silbergeld, Ellen K.; Jachak, Ashish C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. [Contreras, Elizabeth Q.] Rice Univ, Dept Chem, Houston, TX USA. [Hartung, Thomas; Hogberg, Helena; van Vliet, Erwin; Zurlo, Joanne] Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Alternat Anim Testing, Baltimore, MD USA. [Hirsch, Cordula] Empa Swiss Fed Labs Mat Sci & Technol, St Gallen, Switzerland. [Jordan, William; Morris, Jeffery] US EPA, Washington, DC 20460 USA. [Landsiedel, Robert] BASF, Ludwigshafen, Germany. [Patri, Anil] NCI, Nanotechnol Characterizat Lab, NIH, Frederick, MD 21701 USA. [Pounds, Joel G.] Pacific NW Natl Lab, Richland, WA 99352 USA. [de Vizcaya Ruiz, Andrea] CINVESTAV, Mexico City 14000, DF, Mexico. [Shvedova, Anna] CDC, Natl Inst Occupat Safety & Hlth, Morgantown, WV USA. [Tanguay, Robert] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. [Tatarazako, Norihasa] Natl Inst Environm Sci, Tsukuba, Ibaraki, Japan. [Walker, Nigel J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. [Walker, Nigel J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [Wiesner, Mark] Duke Univ, Dept Civil & Environm Engn, Durham, NC 27706 USA. [Wilcox, Neil] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Zurlo, J (reprint author), Johns Hopkins Ctr Alternat Anim Testing, 615 N Wolfe St,W7032, Baltimore, MD 21205 USA. EM jzurlo@jhsph.edu RI Landsiedel, Robert/D-1960-2012; Walker, Nigel/D-6583-2012; Nanotechnology Characterization Lab, NCL/K-8454-2012 OI Landsiedel, Robert/0000-0003-3756-1904; Walker, Nigel/0000-0002-9111-6855; FU Doerenkamp-Zbinden Foundation FX We thank the Doerenkamp-Zbinden Foundation for sponsoring this workshop as part of the t4 activities. NR 5 TC 10 Z9 10 U1 1 U2 11 PU SPEKTRUM AKAD VERLAG PI HEIDELBERG PA SLEVOGTSTRASSE 3-5, D-69126 HEIDELBERG, GERMANY SN 1868-596X J9 ALTEX-ALTERN ANIM EX JI ALTEX-Altern. Anim. Exp. PY 2011 VL 28 IS 3 BP 236 EP 241 PG 6 WC Instruments & Instrumentation; Medicine, Research & Experimental SC Instruments & Instrumentation; Research & Experimental Medicine GA 829IZ UT WOS:000295573100006 PM 21993959 ER PT J AU Nelson, RM Beauchamp, T Miller, VA Reynolds, W Ittenbach, RF Luce, MF AF Nelson, Robert M. Beauchamp, Tom Miller, Victoria A. Reynolds, William Ittenbach, Richard F. Luce, Mary Frances TI The Concept of Voluntary Consent SO AMERICAN JOURNAL OF BIOETHICS LA English DT Article DE authenticity; control; decision making; informed consent; intentionality; voluntariness ID CLINICAL-TRIALS; INFORMED-CONSENT; UNDUE INDUCEMENT; FOLLOW-UP; PARTICIPATION; RANDOMIZATION; COMMUNICATION; ATTRITION; AUTONOMY; ENTER AB Our primary focus is on analysis of the concept of voluntariness, with a secondary focus on the implications of our analysis for the concept and the requirements of voluntary informed consent. We propose that two necessary and jointly sufficient conditions must be satisfied for an action to be voluntary: intentionality, and substantial freedom from controlling influences. We reject authenticity as a necessary condition of voluntary action, and we note that constraining situations may or may not undermine voluntariness, depending on the circumstances and the psychological capacities of agents. We compare and evaluate several accounts of voluntariness and argue that our view, unlike other treatments in bioethics, is not a value-laden theory. We also discuss the empirical assessment of individuals' perceptions of the degrees of noncontrol and self-control. We propose use of a particular Decision Making Control Instrument. Empirical research using this instrument can provide data that will help establish appropriate policies and procedures for obtaining voluntary consent to research. C1 [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. [Beauchamp, Tom] Georgetown Univ, Washington, DC 20057 USA. [Miller, Victoria A.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Reynolds, William] Richard Stockton Coll New Jersey, Pomona, NJ USA. [Ittenbach, Richard F.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Luce, Mary Frances] Duke Univ, Durham, NC 27706 USA. RP Nelson, RM (reprint author), US FDA, Off Pediat Therapeut, 10903 New Hampshire Ave,WO32,Room 5126, Silver Spring, MD 20993 USA. EM robert.nelson@fda.hhs.gov RI Ittenbach, Richard/Q-1806-2015 FU National Science Foundation [SES-0527618]; National Institutes of Health, National Cancer Institute [R21CA118377-01A1]; Institutional Development Grant FX This research was supported in part by grants from the National Science Foundation (SES-0527618; Drs. Nelson, Luce, and Beauchamp); 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. Address correspondence to Dr. Robert M. Nelson, U. S. Food and Drug Administration, Office of Pediatric Therapeutics, 10903 New Hampshire Ave., WO32, Room 5126, Silver Spring, MD 20993, USA. E-mail: robert.nelson@fda.hhs.gov NR 60 TC 33 Z9 34 U1 6 U2 23 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 8 BP 6 EP 16 DI 10.1080/15265161.2011.583318 PG 11 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 806VO UT WOS:000293843800005 PM 21806428 ER PT J AU Nelson, RM AF Nelson, Robert M. TI A Relative Standard for Minimal Risk is Unnecessary and Potentially Harmful to Children: Lessons from the Phambili Trial SO AMERICAN JOURNAL OF BIOETHICS LA English DT Editorial Material C1 US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. RP Nelson, RM (reprint author), US FDA, Off Pediat Therapeut, 10903 New Hampshire Ave,WO32,Room 5126, Silver Spring, MD 20993 USA. EM robert.nelson@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 6 BP 14 EP 16 AR PII 938601501 DI 10.1080/15265161.2011.568588 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 779UV UT WOS:000291808600004 PM 21678206 ER PT J AU Nelson, RM Beauchamp, TL AF Nelson, Robert M. Beauchamp, Tom L. TI Response to Open Peer Commentaries on "The Concept of Voluntary Consent" SO AMERICAN JOURNAL OF BIOETHICS LA English DT Letter C1 [Nelson, Robert M.] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. [Beauchamp, Tom L.] Georgetown Univ, Washington, DC 20057 USA. RP Nelson, RM (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 10903 New Hampshire Ave,WO32-5126, Silver Spring, MD 20993 USA. EM Robert.nelson@fda.hhs.gov FU NCI NIH HHS [R21CA118377-01A1] NR 14 TC 0 Z9 0 U1 0 U2 5 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1526-5161 J9 AM J BIOETHICS JI Am. J. Bioeth. PY 2011 VL 11 IS 8 BP W1 EP W3 DI 10.1080/15265161.2011.600621 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 806VO UT WOS:000293843800001 PM 21806424 ER PT J AU Chan, PC Peckham, JC Malarkey, DE Kissling, GE Travlos, GS Fu, PP AF Chan, Po-Chuen Peckham, John C. Malarkey, David E. Kissling, Grace E. Travlos, Gregory S. Fu, Peter P. TI Two-Year Toxicity and Carcinogenicity Studies of Panax ginseng in Fischer 344 Rats and B6C3F1 Mice SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Panax ginseng; Toxicity; Carcinogenicity; Herbal Dietary Supplements ID ZERO-DOSE CONTROL; GENE-EXPRESSION CHANGES; EXTRACT; TESTS; KAVA; SUPPLEMENTS; METABOLISM; REGRESSION; MORTALITY; ANIMALS AB Ginseng is one of the most popular herbal supplements on the US market. Numerous reports of adverse effects from products containing ginseng have been filed with the US Food and Drug Administration (FDA) and the literature documents a "ginseng abuse syndrome" among regular users. However, the chronic toxic effects of ginseng are not well characterized. Because of its significant human exposure and the fact that little information on its toxicity is available, Panax ginseng was nominated by the US National Institutes of Health (NIH) to the US National Toxicology Program (NTP) to assess its carcinogenic potential. In this paper, we reported the results of NTP chronic toxicity and tumorigenicity bioassay. It shows that, under these experimental conditions, Panax ginseng is not toxic or tumorigenic. C1 [Chan, Po-Chuen; Peckham, John C.; Malarkey, David E.; Kissling, Grace E.; Travlos, Gregory S.] NIEHS, Res Triangle Pk, NC 27709 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chan, PC (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM chanp@niehs.nih.gov FU NIH, National Institute of Environmental Health Sciences FX We thank Drs. Frederick A. Beland, Rick Irwin, In Ok Surh and Charles Alden for critical review of this manuscript. This research was partly supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. NR 54 TC 15 Z9 18 U1 0 U2 9 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X EI 1793-6853 J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2011 VL 39 IS 4 BP 779 EP 788 DI 10.1142/S0192415X11009184 PG 10 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 785CP UT WOS:000292205300012 PM 21721156 ER PT J AU Rodriguez, JD Westenberger, BJ Buhse, LF Kauffman, JF AF Rodriguez, Jason D. Westenberger, Benjamin J. Buhse, Lucinda F. Kauffman, John F. TI Standardization of Raman spectra for transfer of spectral libraries across different instruments SO ANALYST LA English DT Article ID RELATIVE INTENSITY CORRECTION; RESPONSE FUNCTION; SPECTROSCOPY; CALIBRATION; SPECTROMETERS; IDENTIFICATION; SENSITIVITY; DATABASE AB In this paper we evaluate methods for standardization of Raman spectra that are required to improve spectral correlation computations between spectra measured on different instruments. Five commercially-available 785 nm Raman spectrometers from different vendors were included in the study. These spectrometers have diverse specifications and performance levels and range in size from laboratory-based instruments to field-deployable portable and handheld platforms. Since each Raman spectrometer has different characteristics, spectra obtained on one instrument cannot readily be compared to a library acquired on a different instrument without performing various types of spectral corrections (standardization). We outline a procedure that combines previously established Raman shift and intensity correction protocols with a resolution matching step to facilitate the comparison of a centralized master library with spectra acquired on different geographically distributed Raman spectrometers. The standardization procedure is effective in reducing the inherent instrument-to-instrument variability so that spectra from different spectrometers can be compared and reliable results obtained using library-based spectral correlation methods. The findings have important implications for the ability to transfer Raman spectral libraries between instruments. C1 [Rodriguez, Jason D.; Westenberger, Benjamin J.; Buhse, Lucinda F.; Kauffman, John F.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Kauffman, JF (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.kauffman@fda.hhs.gov FU FDA 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 the FDA Center for Drug Evaluation and Research Critical Path Program and by an appointment (J.D.R.) 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. NR 25 TC 23 Z9 23 U1 0 U2 32 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2011 VL 136 IS 20 BP 4232 EP 4240 DI 10.1039/c1an15636e PG 9 WC Chemistry, Analytical SC Chemistry GA 826EJ UT WOS:000295334000022 PM 21874199 ER PT J AU Keire, DA Ye, HP Trehy, ML Ye, W Kolinski, RE Westenberger, BJ Buhse, LF Nasr, M Al-Hakim, A AF Keire, David A. Ye, Hongping Trehy, Michael L. Ye, Wei Kolinski, Richard E. Westenberger, Benjamin J. Buhse, Lucinda F. Nasr, Moheb Al-Hakim, Ali TI Characterization of currently marketed heparin products: key tests for quality assurance SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Heparin; OSCS; SAX-HPLC; NMR; CE; Factor IIa/Xa ID MAGNETIC-RESONANCE-SPECTROSCOPY; OVERSULFATED CHONDROITIN SULFATE; ADVERSE CLINICAL EVENTS; ANTICOAGULANT ACTIVITY; DERMATAN SULFATE; GLYCOSAMINOGLYCANS; CONFORMATION; CONTAMINANTS; NMR AB During the 2007-2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz (1)H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007-2008 crisis. C1 [Keire, David A.; Ye, Hongping; Trehy, Michael L.; Ye, Wei; Kolinski, Richard E.; Westenberger, Benjamin J.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. [Nasr, Moheb; Al-Hakim, Ali] US FDA, Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA. RP Keire, DA (reprint author), US FDA, Div Pharmaceut Anal, CDER, 1114 Market St, St Louis, MO 63101 USA. EM David.Keire@fda.hhs.gov NR 34 TC 19 Z9 19 U1 0 U2 13 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JAN PY 2011 VL 399 IS 2 BP 581 EP 591 DI 10.1007/s00216-010-4023-y PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 700YQ UT WOS:000285781900006 PM 20680615 ER PT J AU Zang, QD Keire, DA Wood, RD Buhse, LF Moore, CMV Nasr, M Al-Hakim, A Trehy, ML Welsh, WJ AF Zang, Qingda Keire, David A. Wood, Richard D. Buhse, Lucinda F. Moore, Christine M. V. Nasr, Moheb Al-Hakim, Ali Trehy, Michael L. Welsh, William J. TI Determination of galactosamine impurities in heparin samples by multivariate regression analysis of their H-1 NMR spectra SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Heparin; Galactosamine impurities; Proton nuclear magnetic resonance (H-1 NMR); Multivariate regression (MVR); Variable selection ID NUCLEAR-MAGNETIC-RESONANCE; OVERSULFATED CHONDROITIN SULFATE; CAPILLARY-ZONE-ELECTROPHORESIS; SUPPORT VECTOR REGRESSION; GENETIC ALGORITHMS; DERMATAN SULFATE; CALIBRATION METHODS; ANTICOAGULANT ACTIVITY; VARIABLE SELECTION; SPECTROSCOPY AB Heparin, a widely used anticoagulant primarily extracted from animal sources, contains varying amounts of galactosamine impurities. Currently, the United States Pharmacopeia (USP) monograph for heparin purity specifies that the weight percent of galactosamine (%Gal) may not exceed 1%. In the present study, multivariate regression (MVR) analysis of H-1 NMR spectral data obtained from heparin samples was employed to build quantitative models for the prediction of %Gal. MVR analysis was conducted using four separate methods: multiple linear regression, ridge regression, partial least squares regression, and support vector regression (SVR). Genetic algorithms and stepwise selection methods were applied for variable selection. In each case, two separate prediction models were constructed: a global model based on dataset A which contained the full range (0-10%) of galactosamine in the samples and a local model based on the subset dataset B for which the galactosamine level (0-2%) spanned the 1% USP limit. All four regression methods performed equally well for dataset A with low prediction errors under optimal conditions, whereas SVR was clearly superior among the four methods for dataset B. The results from this study show that H-1 NMR spectroscopy, already a USP requirement for the screening of contaminants in heparin, may offer utility as a rapid method for quantitative determination of %Gal in heparin samples when used in conjunction with MVR approaches. 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] 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 52 TC 16 Z9 16 U1 0 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD JAN PY 2011 VL 399 IS 2 BP 635 EP 649 DI 10.1007/s00216-010-4268-5 PG 15 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 700YQ UT WOS:000285781900011 PM 20953772 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Summary SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 1 EP 5 PG 5 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700001 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS Introduction SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Editorial Material; Book Chapter ID YERSINIA-PESTIS; EVOLUTION; PLAGUE; TSG101 C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 7 EP 13 PG 7 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700002 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Evaluation of Current and Future TMT-Used Animal Models SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID EBOLA-VIRUS-INFECTION; MARBURG HEMORRHAGIC-FEVER; VERVET MONKEY DISEASE; HUMAN ANTHRAX VACCINE; GUINEA-PIGS; BACILLUS-ANTHRACIS; FRANCISELLA-TULARENSIS; DRUG DEVELOPMENT; CYNOMOLGUS MACAQUES; PRIMATE MODELS C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 15 EP 37 PG 23 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700003 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Ethical and Regulatory Challenges in the Development of Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID VACCINE; CONSENT; ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 39 EP 49 PG 11 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700004 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Developing New Animal Models for Biodefense Research SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID ANTHRAX C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 51 EP 59 PG 9 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700005 ER PT J AU Korch, GW Niemi, SM Bergman, NH Carucci, DJ Ehrlich, SA Gronvall, GK Hartung, T Heitman, E Kotb, M Kuhn, JH Lyons, CR Morse, SS Murphy, FA Patel, VS Swearengen, JR Bloom, F Bayne, KA Davis, MA Garnett, NL Clark, JAM Marsman, DS Neil, G Nevalainen, TO Niemi, SM Novak, MA Pangalos, M Rollin, BE Roth, JA Sharples, F Anestidou, L Fletcher, CH Worthy, J AF Korch, George W., Jr. Niemi, Steven M. Bergman, Nicholas H. Carucci, Daniel J. Ehrlich, Susan A. Gronvall, Gigi Kwik Hartung, Thomas Heitman, Elizabeth Kotb, Malak Kuhn, Jens H. Lyons, C. Rick Morse, Stephen S. Murphy, Frederick A. Patel, Vikram S. Swearengen, James R. Bloom, Floyd Bayne, Kathryn A. Davis, Myrtle A. Garnett, Nelson L. Clark, Judy A. Macarthur Marsman, Daniel S. Neil, Garry Nevalainen, Timo Olavi Niemi, Steven M. Novak, Melinda A. Pangalos, Menelas Rollin, Bernard E. Roth, James A. Sharples, Frances Anestidou, Lida Fletcher, Cameron H. Worthy, Jason CA Comm Anim Models Assessing Counter Inst Lab Anim Res GP Natl Res Council TI Alternative Approaches to Animal Testing for Biodefense Countermeasures SO ANIMAL MODELS FOR ASSESSING COUNTERMEASURES TO BIOTERRORISM AGENTS LA English DT Article; Book Chapter ID MONKEYPOX VIRUS; NONHUMAN-PRIMATES; GENE-EXPRESSION; COMPLEX; RESPONSES; SMALLPOX; DESIGN; TRAITS; CELLS; HEMAGGLUTININ C1 [Korch, George W., Jr.] Johns Hopkins Univ, Baltimore, MD 21205 USA. [Niemi, Steven M.; Niemi, Steven M.] Massachusetts Gen Hosp, Ctr Comparat Med, Charlestown, MA USA. [Bergman, Nicholas H.; Swearengen, James R.] Battelle Natl Biodef Inst, Frederick, MD USA. [Carucci, Daniel J.] Global Hlth Consulting, Washington, DC USA. [Ehrlich, Susan A.] Arizona Court Appeals, Phoenix, AZ USA. [Gronvall, Gigi Kwik] Univ Pittsburgh, Med Ctr, Ctr Biosecur, Baltimore, MD USA. [Hartung, Thomas] Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. [Heitman, Elizabeth] Vanderbilt Univ, Med Ctr, Ctr Biomed Eth & Soc, Clin & Res Eth, Nashville, TN USA. [Kotb, Malak] Univ Cincinnati, Coll Med, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. [Kuhn, Jens H.] NIAID, NIH, New Maximum Containment Facil, Integrated Res Facil Ft Detrick IRF Frederick, Frederick, MD USA. [Lyons, C. Rick] Colorado State Univ, Infect Dis Res Ctr, Ft Collins, CO 80523 USA. [Morse, Stephen S.] Columbia Univ, Sch Publ Hlth, New York, NY USA. [Murphy, Frederick A.] Univ Texas Med Branch, Dept Pathol, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Inst Human Infect & Immun, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Biodef & Emerging Infect Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Galveston Natl Lab, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, Ctr Trop Dis, Galveston, TX 77555 USA. [Murphy, Frederick A.] Univ Texas Med Branch, McLaughlin Endowment Infect & Immun, Galveston, TX 77555 USA. [Patel, Vikram S.] US FDA, Div Drug Safety Res, CDER, Silver Spring, MD USA. [Bloom, Floyd] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA. [Bayne, Kathryn A.] Assoc Assessment & Accreditat Lab Anim Care Int, Frederick, MD USA. [Davis, Myrtle A.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. [Garnett, Nelson L.] Lab Anim Care & Use Programs, Dickerson, MD USA. [Clark, Judy A. Macarthur] Anim Sci Procedures Inspectorate, Home Off, London, England. [Marsman, Daniel S.] Procter & Gamble Co, Mason, OH USA. [Neil, Garry] Johnson & Johnson, Corp Off Sci & Technol, New Brunswick, NJ USA. [Nevalainen, Timo Olavi] Univ Eastern Finland, Kuopio, Finland. [Novak, Melinda A.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. [Pangalos, Menelas] AstraZeneca, Innovat Med, Alderley Pk, England. [Rollin, Bernard E.] Colorado State Univ, Dept Philosophy, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Behav Sci, Ft Collins, CO 80523 USA. [Rollin, Bernard E.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Roth, James A.] Iowa State Univ, Coll Vet Med, Ctr Food Secur & Publ Hlth, Ames, IA USA. RP Korch, GW (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-21909-9 PY 2011 BP 61 EP 76 PG 16 WC Medical Ethics; Medicine, Research & Experimental SC Medical Ethics; Research & Experimental Medicine GA BC4IN UT WOS:000352547700006 ER PT J AU Couderc, JP Garnett, C Li, M Handzel, R McNitt, S Xia, XJ Polonsky, S Zareba, W AF Couderc, Jean-Philippe Garnett, Christine Li, Mike Handzel, Robert McNitt, Scott Xia, Xiajuan Polonsky, Slava Zareba, Wojciech TI Highly Automated QT Measurement Techniques in 7 Thorough QT Studies Implemented under ICH E14 Guidelines SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE thorough QT study; drug cardiotoxicity; moxifloxacin; QT interval; electrocardiogram; drug safety ID HEART-RATE CORRECTION; TORSADES-DE-POINTES; CARDIAC REPOLARIZATION; INTERVAL MEASUREMENT; HEALTHY-SUBJECTS; VENTRICULAR REPOLARIZATION; QT/QTC INTERVAL; PROLONGATION; MOXIFLOXACIN; ELECTROCARDIOGRAM AB Thorough QT (TQT) studies are designed to evaluate potential effect of a novel drug on the ventricular repolarization process of the heart using QTc prolongation as a surrogate marker for torsades de pointes. The current process to measure the QT intervals from the thousands of electrocardiograms is lengthy and expensive. In this study, we propose a validation of a highly automatic-QT interval measurement (HA-QT) method. We applied a HA-QT method to the data from 7 TQT studies. We investigated both the placebo and baseline-adjusted QTc interval prolongation induced by moxifloxacin (positive control drug) at the time of expected peak concentration. The comparative analysis evaluated the time course of moxifloxacin-induced QTc prolongation in one study as well. The absolute HA-QT data were longer than the FDA-approved QTc data. This trend was not different between ECGs from the moxifloxacin and placebo arms: 9.6 +/- 24 ms on drug and 9.8 +/- 25 ms on placebo. The difference between methods vanished when comparing the placebo-baseline-adjusted QTc prolongation (1.4 +/- 2.8 ms, P = 0.4). The differences in precision between the HA-QT and the FDA-approved measurements were not statistically different from zero: 0.1 +/- 0.1 ms (P = 0.7). Also, the time course of the moxifloxacin-induced QTc prolongation adjusted for placebo was not statistically different between measurements methods. Ann Noninvasive Electrocardiol 2011;16(1):13-24 C1 [Couderc, Jean-Philippe; McNitt, Scott; Xia, Xiajuan; Polonsky, Slava; Zareba, Wojciech] Univ Rochester, Med Ctr, Heart Res Follow Up Program, Dept Cardiol, Rochester, NY 14642 USA. [Garnett, Christine; Li, Mike] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Handzel, Robert] Univ Rochester, Sch Biomed Engn, Rochester, NY 14642 USA. RP Couderc, JP (reprint author), Univ Rochester, Med Ctr, Heart Res Follow Up Program, Dept Cardiol, Box 653, Rochester, NY 14642 USA. EM jean-philippe.couderc@heart.rochester.edu FU National Institute for Health [R01HL084402] FX This work was funded by the National Institute for Health through the R01HL084402 award. NR 45 TC 18 Z9 18 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD JAN PY 2011 VL 16 IS 1 BP 13 EP 24 DI 10.1111/j.1542-474X.2010.00402.x PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 709HF UT WOS:000286428400003 PM 21251129 ER PT S AU Woodcock, J Behrman, RE Dal Pan, GJ AF Woodcock, Janet Behrman, Rachel E. Dal Pan, Gerald J. BE Caskey, CT TI Role of Postmarketing Surveillance in Contemporary Medicine SO ANNUAL REVIEW OF MEDICINE, VOL 62, 2011 SE Annual Review of Medicine LA English DT Review; Book Chapter DE drug safety; safe use; Sentinel Initiative; Sentinel System; adverse event ID ADVERSE DRUG EVENTS; APLASTIC-ANEMIA; FELBAMATE AB Contemporary medicine is a large and complex system involving many participants, all of whom play a critical role in managing the risks intrinsic to medical product use. Despite the robust premarket review and approval process of the U.S. Food and Drug Administration (FDA), new information will inevitably be learned in the postmarketing period about the safety of medicines and how they are and should be used. For much of this information, FDA relies on public reports about possible adverse events. In turn, the public depends on FDA to communicate the most up-to-date safety information on medical products to better inform treatment decisions. Expanding the scope and strengthening the capabilities of the drug safety surveillance system are among key FDA projects designed to reduce avoidable injury and death from medication use. Although improving drug safety is our goal and obligation to the public, FDA cannot protect the public adequately without the active involvement of all participants in healthcare. C1 [Woodcock, Janet; Behrman, Rachel E.; Dal Pan, Gerald J.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM Janet.Woodcock@fda.hhs.gov; Rachel.Behrman@fda.hhs.gov; Gerald.DalPan@fda.hhs.gov NR 17 TC 18 Z9 18 U1 0 U2 1 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0897 USA SN 0066-4219 BN 978-0-8243-0562-8 J9 ANNU REV MED JI Annu. Rev. Med. PY 2011 VL 62 BP 1 EP 10 DI 10.1146/annurev-med-060309-164311 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BTS32 UT WOS:000287956900001 PM 20809798 ER PT J AU Boyd, SD Maldarelli, F Sereti, I Ouedraogo, GL Rehm, CA Boltz, V Shoemaker, D Pau, AK AF Boyd, Sarita D. Maldarelli, Frank Sereti, Irini Ouedraogo, G. Laissa Rehm, Catherine A. Boltz, Valerie Shoemaker, Diana Pau, Alice K. TI Transmitted raltegravir resistance in an HIV-1 CRF_AG-infected patient SO ANTIVIRAL THERAPY LA English DT Article ID ANTIRETROVIRAL DRUG-RESISTANCE; REVERSE-TRANSCRIPTASE; INTEGRASE INHIBITORS; MUTATIONS; NAIVE; THERAPY; SUSCEPTIBILITY; INDIVIDUALS; PREVALENCE; CITIES AB Here, we describe an HIV-infected patient with pretreatment resistance to raltegravir, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors, and the ultimate ability to achieve viral suppression. Pretreatment integrase resistance testing is not routinely performed because transmitted integrase mutations conferring resistance to raltegravir are currently thought to be negligible. We suggest obtaining a pretreatment integrase genotype in patients with transmitted multiclass drug resistance in order to create an optimal first regimen and increase the chance for virological suppression. C1 [Boyd, Sarita D.; Sereti, Irini; Ouedraogo, G. Laissa; Rehm, Catherine A.; Shoemaker, Diana; Pau, Alice K.] NIAID, NIH, Bethesda, MD 20892 USA. [Boyd, Sarita D.; Ouedraogo, G. Laissa] SAIC Frederick Inc, Frederick, MD USA. [Maldarelli, Frank; Boltz, Valerie] NCI, HIV Drug Resistance Program, NIH, Bethesda, MD 20892 USA. RP Boyd, SD (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM sarita.boyd@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX This work was supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. It is also funded, in part, with federal funds from the National Cancer Institute, National Institutes of Health, under contract number 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 United States Government. NR 22 TC 29 Z9 31 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 2 BP 257 EP 261 DI 10.3851/IMP1749 PG 5 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 813NZ UT WOS:000294375500017 PM 21447876 ER PT J AU Kouiavskaia, DV Dragunsky, EM Liu, HM Oberste, MS Collett, MS Chumakov, KM AF Kouiavskaia, Diana V. Dragunsky, Eugenia M. Liu, Hong-Mei Oberste, M. Steven Collett, Marc S. Chumakov, Konstantin M. TI Immunological and pathogenic properties of poliovirus variants selected for resistance to antiviral drug V-073 SO ANTIVIRAL THERAPY LA English DT Article AB Background: The National Research Council has recommended development of polio antiviral drugs to assist in management of outbreaks and to mitigate adverse consequences of vaccination. V-073 is a small molecule poliovirus capsid inhibitor that is being developed for these purposes. Antiviral use raises the potential of treatment-emergent resistance. Understanding virological consequences of resistance is important. Methods: Six independent laboratory-derived V-073-resistant poliovirus variants were characterized for their ability to be neutralized by conventional vaccine-induced immune sera, to elicit serum neutralizing antibodies upon CD-1 mouse immunization, and to replicate in and to cause paralysis of TgPVR21 mice. Results: V-073-resistant variants were effectively neutralized by oral perliovirus vaccine and inactivated poliovirus vaccine human immune sera. All variants elicited virus neutralizing antibody titres in CD-1 mice that were comparable to drug-susceptible parental and Sabin vaccine strain viruses. Infection efficiency of TgPVR21 mice by variants was comparable to (1 of 6 variants) or considerably lower than (5 of 6 variants) parental viruses. Drug-resistant variants replicated to levels comparable to (1 of 6 variants) or substantially less than (5 of 6 variants) their drug-susceptible parental viruses and were on average 1.4 log(10) (range 0.3 to >2.8 log(10)) less neurovirulent. Conclusions: Laboratory-derived V-073-resistant variants exhibit clear attenuation of pathogenic properties while maintaining immunological features of drug-susceptible viruses. C1 [Collett, Marc S.] ViroDefense Inc, Rockville, MD USA. [Kouiavskaia, Diana V.; Dragunsky, Eugenia M.; Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Liu, Hong-Mei; Oberste, M. Steven] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Collett, MS (reprint author), ViroDefense Inc, Rockville, MD USA. EM mscollett@aol.com 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; ViroDefense Inc. FX The work was supported by the Interagency Agreement number 224-06-1322 / Y1-AI-6153-01 between CBER/FDA and NIAID/NIH. ViroDefense Inc. received financial support from The Task Force for Global Health, Inc. through grants from the WHO and Rotary International. We thank Dr Walter Dowdle for his continued support.; MSC is a principal of ViroDefense Inc., the corporate sponsor of drug candidate V-073. All other authors declare no competing interests. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of Centers for Diseases Control and Prevention or Food and Drug Administration. NR 11 TC 14 Z9 14 U1 0 U2 2 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2011 VL 16 IS 7 BP 999 EP 1004 DI 10.3851/IMP1838 PG 6 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 846ZO UT WOS:000296941900008 PM 22024515 ER PT J AU Feng, PCH Councell, T Keys, C Monday, SR AF Feng, Peter C. H. Councell, Terry Keys, Christine Monday, Steven R. TI Virulence Characterization of Shiga-Toxigenic Escherichia coli Isolates from Wholesale Produce SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ENTEROCYTE EFFACEMENT; MULTIPLEX PCR; STRAINS; CATTLE; LOCUS; SEROTYPES; SAA; O113-H21; BRAZIL AB The 13 Shiga-toxigenic Escherichia coli (STEC) strains isolated from wholesale spinach and lettuce consisted mostly of serotypes that have not been implicated in illness. Among these strains, however, were two O113:H21 that carried virulence genes common to this pathogenic serotype (stx(2), ehxA, saa, and subAB), suggesting that their presence in ready-to-eat produce may be of health concern. C1 [Feng, Peter C. H.; Keys, Christine; Monday, Steven R.] US FDA, Div Microbiol, College Pk, MD 20740 USA. [Councell, Terry] Agr Mkt Serv, USDA, Manassas, VA USA. 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 NR 21 TC 11 Z9 11 U1 0 U2 4 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 JAN PY 2011 VL 77 IS 1 BP 343 EP 345 DI 10.1128/AEM.01872-10 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 697WK UT WOS:000285550300040 PM 21057025 ER PT B AU Ali, AA Salminen, W Leakey, JE AF Ali, Akhtar Afshan Salminen, William Leakey, Julian E. BE Bagchi, D Moriyama, H Raychaudhuri, SP TI Hexosamine Flux and the Efficacy and Safety of Glucosamine in the Treatment of Osteoarthritis SO ARTHRITIS: PATHOPHYSIOLOGY, PREVENTION, AND THERAPEUTICS LA English DT Article; Book Chapter ID GROWTH-FACTOR-BETA; PERFORMANCE LIQUID-CHROMATOGRAPHY; HUMAN ARTICULAR CHONDROCYTES; ORAL CHONDROITIN SULFATE; INSULIN-RESISTANCE; KNEE OSTEOARTHRITIS; TGF-BETA; MESANGIAL CELLS; GENE-EXPRESSION; DOUBLE-BLIND C1 [Ali, Akhtar Afshan; Salminen, William] Natl Ctr Toxicol Res, Dept Syst Biol, Div Hepatotox, Jefferson, AR 72079 USA. [Leakey, Julian E.] Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. RP Ali, AA (reprint author), Natl Ctr Toxicol Res, Dept Syst Biol, Div Hepatotox, Jefferson, AR 72079 USA. NR 133 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1687-5; 978-1-4398-1686-8 PY 2011 BP 261 EP 282 PG 22 WC Rheumatology SC Rheumatology GA BC4XP UT WOS:000352993600021 ER PT B AU O'May, GA Brady, RA Prabhakara, R Leid, JG Calhoun, JH Shirtliff, ME AF O'May, Graeme A. Brady, Rebecca A. Prabhakara, Ranjani Leid, Jeff G. Calhoun, Jason H. Shirtliff, Mark E. BE Bjarnsholt, T Moser, C Jensen, PO Hoiby, N TI Osteomyelitis SO BIOFILM INFECTIONS LA English DT Article; Book Chapter ID RESISTANT STAPHYLOCOCCUS-AUREUS; ACUTE HEMATOGENOUS OSTEOMYELITIS; BACTERIAL BIOFILM FORMATION; FIBRINOGEN-BINDING PROTEIN; DIABETIC FOOT INFECTIONS; QUORUM-SENSING CONTROL; PSEUDOMONAS-AERUGINOSA; SEPTIC ARTHRITIS; CYSTIC-FIBROSIS; DNA RELEASE C1 [O'May, Graeme A.; Prabhakara, Ranjani; Shirtliff, Mark E.] Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, Baltimore, MD 21201 USA. [Brady, Rebecca A.] CBER FDA, Bethesda, MD 20892 USA. [Leid, Jeff G.] No Arizona Univ, Ctr Microbial Genet & Genom, Flagstaff, AZ 86011 USA. [Calhoun, Jason H.] Ohio State Univ, Med Ctr, Dept Orthoped, Columbus, OH 43210 USA. RP Shirtliff, ME (reprint author), Univ Maryland, Sch Dent, Dept Microbial Pathogenesis, 650 W Baltimore St, Baltimore, MD 21201 USA. EM jeff.leid@nau.edu; mshirtliff@umaryland.edu OI Shirtliff, Mark/0000-0002-8913-3445 NR 126 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-6083-2 PY 2011 BP 111 EP 137 DI 10.1007/978-1-4419-6084-9_7 D2 10.1007/978-1-4419-6084-9 PG 27 WC Microbiology SC Microbiology GA BSC47 UT WOS:000284120900007 ER PT S AU Volokhov, DV Kong, H Herold, K Chizhikov, VE Rasooly, A AF Volokhov, Dmitriy V. Kong, Hyesuk Herold, Keith Chizhikov, Vladimir E. Rasooly, Avraham BE Khademhosseini, A Suh, KY Zourob, M TI Oligonucleotide Microarrays for Identification of Microbial Pathogens and Detection of Their Virulence-Associated or Drug-Resistance Determinants SO BIOLOGICAL MICROARRAYS: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Microarray; Microbial pathogens; Virulence factors; Food safety ID ESCHERICHIA-COLI O157-H7; BACTERIAL PHYLOGENY; SIGNATURE SEQUENCES; QUANTITATIVE ASSAY; DNA PROBES; HYBRIDIZATION; GENE; MULTIANALYTE; IMMUNOASSAY; STABILITY AB Microarrays are spatially ordered arrays with ligands chemically immobilized in discrete spots on a solid matrix, usually a microscope slide. Microarrays are a high-throughput large-scale screening system enabling simultaneous identification fa large number of labeled target molecules (up to several hundred thousand) that bind specifically to the immobilized ligands of the array. DNA microarrays represent a promising tool for clinical, environmental, and industrial microbiology since the technology allows relatively rapid identification of large number of genetic determinants simultaneously, providing detailed genomic level information regarding the pathogen species, including identification of their virulence-associated factors and the presence of antibiotic resistance genes. In this chapter, we describe key aspects and methodologies important for the development and use of DNA microarrays for microbial diagnostics. C1 [Volokhov, Dmitriy V.; Kong, Hyesuk; Chizhikov, Vladimir E.] US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. [Herold, Keith] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Rasooly, Avraham] NCI, NIH, US FDA, Bethesda, MD 20892 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. NR 60 TC 3 Z9 3 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-934115-95-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 671 BP 55 EP 94 DI 10.1007/978-1-59745-551-0_3 D2 10.1007/978-1-59745-551-0 PG 40 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSA51 UT WOS:000284031200003 PM 20967623 ER PT S AU Chen, T Li, ZG AF Chen, Tao Li, Zhiguang BE Tarasenko, O TI "Transcriptome Analysis Gene Expression Profiles in Kidneys of Rats Treated with Aristolochic" Acid" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Chen, Tao; Li, Zhiguang] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 34 EP 35 PG 2 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100013 ER PT S AU Li, ZG Chen, T AF Li, Zhiguang Chen, Tao BE Tarasenko, O TI "Human Carcinogen Atristolochic Acid Induces Dysregulated microRNA Expression in Rat Kidneys" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Li, Zhiguang; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 37 EP 38 PG 2 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100019 ER PT S AU Paule, MG AF Paule, Merle G. BE Tarasenko, O TI "The Biology of Neurotoxicity: using Technology to Advance Discovery" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Paule, Merle G.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 39 EP 39 PG 1 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100023 ER PT S AU Chidambaram, M Trbojevich, R Woodling, K Heinze, T Siitonen, P AF Chidambaram, Mani Trbojevich, Raul Woodling, Kellie Heinze, Thomas Siitonen, Paul BE Tarasenko, O TI "Optmization of the Analytical Method for Measuring Low Levels of Bisphenol A (BPA) and Ethinylestradiol (Ee2) by Liquid Chromatography/Electron Spray Ionization Mass Spectrometry (LC/ESI/MS)" SO BIOLOGY, NANOTECHNOLOGY, TOXICOLOGY, AND APPLICATIONS: PROCEEDINGS OF THE 5TH BIONANOTOX AND APPLICATIONS INTERNATIONAL RESEARCH CONFERENCE SE AIP Conference Proceedings LA English DT Meeting Abstract CT 5th BioNanoTox and Applications International Research Conference CY NOV 04-05, 2010 CL Little Rock, AR SP U S Food & Drug Adm, Arkansas Sci & Technol Author, Winthrop Rockefeller Fdn, Coll Sci & Math, Univ Arkansas, Grad Sch (UALR), Univ Arkansas, Med Sci (UAMS), Arkansas Biosci Inst, BioNanoTox Intl (BNT), UALRs Grad Sch, Dept Biol, Biol Club C1 [Chidambaram, Mani; Trbojevich, Raul; Woodling, Kellie; Heinze, Thomas; Siitonen, Paul] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0910-1 J9 AIP CONF PROC PY 2011 VL 1326 BP 52 EP 52 PG 1 WC Biology; Nanoscience & Nanotechnology; Toxicology SC Life Sciences & Biomedicine - Other Topics; Science & Technology - Other Topics; Toxicology GA BZT53 UT WOS:000302909100047 ER PT B AU Rubin, S Vandermeulen, C AF Rubin, Steven Vandermeulen, Corinne BE Samal, SK TI Mumps Virus SO BIOLOGY OF PARAMYXOVIRUSES LA English DT Article; Book Chapter ID VESICULAR STOMATITIS-VIRUS; NEWCASTLE-DISEASE VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; NUCLEOTIDE-SEQUENCE ANALYSIS; RESPIRATORY SYNCYTIAL VIRUS; LINKED IMMUNOSORBENT-ASSAY; RECOMBINANT VACCINIA VIRUS; NEUROVIRULENCE SAFETY TEST; CENTRAL NERVOUS-SYSTEM; REPLICATION IN-VITRO AB Mumps virus, a member of the Rubulavirus genus in the Paramyxoviridae family, causes a communicable illness characterized by a wide array of acute inflammatory reactions. Mumps outbreaks were common in the pre-vaccine era, with nearly everyone having been exposed by adolescence based on the presence of virus-specific antibody. The hallmark of infection is the painful enlargement of the parotid gland, and, although perceived as a benign childhood disease, mumps was the leading cause of aseptic meningitis and sensorineural deafness prior to the adoption of widespread vaccine use. The changing epidemiology of mumps in the post-vaccine era has renewed interest in the virus, specifically in regards to the biology of the virus, development of new diagnostic tools, investigation of immune responses following vaccination and the epidemiological effects of mumps vaccination in large populations. This chapter reviews the current knowledge of mumps virus as an infectious agent, the immune response to infection and its epidemiology, prevention and control measures. C1 [Vandermeulen, Corinne] Ctr Youth Hlth Care KU Leuven, Louvain, Belgium. [Rubin, Steven] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Vandermeulen, C (reprint author), Ctr Youth Hlth Care KU Leuven, Louvain, Belgium. EM Steven.Rubin@fda.hhs.gov; corinne.vandermeulen@uzleuven.be NR 358 TC 2 Z9 2 U1 0 U2 1 PU CAISTER ACADEMIC PRESS PI WYMONDHAM PA 32 HEWITTS LANE, WYMONDHAM NR 18 0JA, ENGLAND BN 978-1-904455-85-1 PY 2011 BP 5 EP 36 PG 32 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA BVP39 UT WOS:000292216900002 ER PT J AU Soon, GG Nie, L Hammerstrom, T Zeng, W Chu, HT AF Soon, Guoxing G. Nie, Lei Hammerstrom, Thomas Zeng, Wen Chu, Haitao TI Meeting the demand for more sophisticated study designs. A proposal for a new type of clinical trial: the hybrid design SO BMJ OPEN LA English DT Article AB Background: Treatment effect is traditionally assessed through either superiority or non-inferiority clinical trials. Investigators may find that because of safety concerns and/or wide variability across strata of the superiority margin of active controls over placebo, neither a superiority nor a non-inferiority trial design is ethical or practical in some disease populations. Prior knowledge may allow and drive study designers to consider more sophisticated designs for a clinical trial. Design: In this paper, the authors propose hybrid designs which may combine a superiority design in one subgroup with a non-inferiority design in another subgroup or combine designs with different control regimens in different subgroups in one trial when a uniform design is unethical or impractical. The authors show how the hybrid design can be planned and how inferences can be made. Through two examples, the authors illustrate the scenarios where hybrid designs are useful while the conventional designs are not preferable. Conclusion: The hybrid design is a useful alternative to current superiority and non-inferiority designs. C1 [Soon, Guoxing G.; Nie, Lei; Hammerstrom, Thomas; Zeng, Wen] US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD USA. [Chu, Haitao] Univ Minnesota Twin Cities, Div Biostat, Minneapolis, MN USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD USA. EM lei.nie@fda.hhs.gov OI Chu, Haitao/0000-0003-0932-598X NR 22 TC 2 Z9 2 U1 0 U2 2 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 2044-6055 J9 BMJ OPEN JI BMJ Open PY 2011 VL 1 IS 2 AR e000156 DI 10.1136/bmjopen-2011-000156 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA V27UQ UT WOS:000208638500014 PM 22021876 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Evaluation of a morphine maturation model for the prediction of morphine clearance in children: how accurate is the predictive performance of the model? SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE allometric scaling; clearance; maturation model; paediatric population ID INTRAVENOUS MORPHINE; NEWBORN-INFANTS; DRUG CLEARANCE; PHARMACOKINETICS; KINETICS; PREMATURE; ONTOGENY; PATHWAYS; INFUSION; ADULTS AB The pharmacokinetics of morphine are well known in pre-term and term neonates, infants, younger and older children, as well as in adults. There are circumstances when a pharmacokinetic study may not be possible in children (especially neonates and infants), and as a result one would like to predict drug clearance in children. Several methods, such as allometric scaling and prediction based on incorporation of physiological parameters, have been suggested. Recently a morphine maturation model has been proposed to predict morphine clearance in the paediatric population. WHAT THIS STUDY ADDS The current study evaluates the predictive performance of the morphine maturation model for the prediction of morphine clearance in pre-term, term, infants and children up to 5 years of age. The results of the study highlight the shortcomings of the model to predict morphine clearance in children in aforementioned age groups. AIMS Recently, a maturation model that incorporates a sigmoidal E(max) type model has been proposed for the estimation of morphine clearance in paediatric patients. The primary objective of this report is to evaluate the predictive performance of the morphine maturation model for the prediction of morphine clearance in children of different ages. The secondary objective of this report is to evaluate the predictive performance of exponent 0.75 on bodyweight in the absence of the sigmoidal part of the morphine maturation model. METHODS In order to evaluate the predictive performance of the morphine maturation model, the clearance values of morphine for individual children (preterm neonates to 5-year-old children; n = 147) were obtained from the literature. The predicted clearance of morphine in an individual child, obtained from the maturation model as well as from the fixed exponent 0.75 was compared with the observed clearance in that individual child. RESULTS The morphine maturation model's predictive power in neonates, infants and younger children is poor and the inclusion of the sigmoidal part in the model only helps in reducing the substantial error introduced in the prediction due to the application of exponent 0.75 on bodyweight. Furthermore, the real benefit of the sigmoidal E(max) part of the model disappears by 1 year of age. CONCLUSIONS The morphine maturation model has a poor predictive power of morphine clearance in preterm and term neonates, infants and very young children and may not be of any practical value for the prediction of morphine clearance in this age group. C1 US FDA, OBRR, Ctr Biol Evaluat & Research, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, OBRR, Ctr Biol Evaluat & Research, 1451 Rockville Pike, Rockville, MD 20852 USA. EM Iftekhar.mahmood@fda.hhs.gov NR 22 TC 15 Z9 16 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC 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 JAN PY 2011 VL 71 IS 1 BP 88 EP 94 DI 10.1111/j.1365-2125.2010.03802.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 692KR UT WOS:000285152200011 PM 21143504 ER PT J AU Rosado, LAR Rodriguez-Canales, J Zhang, BL AF Rosado, Leslie A. Rivera Rodriguez-Canales, Jaime Zhang, Baolin TI Association of D4-GDI expression with breast cancer progression SO CANCER BIOMARKERS LA English DT Article DE D4-GDI; breast cancer; progression; immunohistochemistry ID GDP-DISSOCIATION INHIBITOR; DRUG-INDUCED APOPTOSIS; CELL-LINES; RHO-GTPASES; GENE-EXPRESSION; METASTASIS; TUMOR; INVASIVENESS; PROTEINS; RHOGDI2 AB D4-GDI is a key regulator of Rho GTPases that have been implicated in several aspects of breast tumorigenesis. We have previously found that D4-GDI was selectively expressed in breast cancer cell lines over normal mammary epithelial cells [45]. In this study, we investigated the expression level of D4-GDI in breast tumor specimens (n = 165) by immunohistochemistry using a validated antibody that specifically recognizes the full-length D4-GDI protein. D4-GDI was predominantly expressed in the luminal cells of the duct in contrast to the myoepithelial cells of the outer layer. The percentage of D4-GDI positive samples were found to be higher in the early stages of breast cancers followed by a significant decrease in malignant tumors and metastatic lesions when compared to normal breast tissues (p < 0.01). Analysis of matched samples confirmed the lower expression of D4-GDI in malignant tumors than normal adjacent tissues, while there was no further decrease in metastatic lesions. These results suggest that D4-GDI may function as a biphasic regulator of breast cancer progression and metastasis. C1 [Rosado, Leslie A. Rivera; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Rodriguez-Canales, Jaime] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), 29 Lincoln Dr,Bldg 29A,Rm 2A01,HFD 122, Bethesda, MD 20892 USA. EM Baolin.Zhang@fda.hhs.gov OI Rodriguez-Canales, Jaime/0000-0002-0885-2377 FU FDA FX We thank Dr. John Gillespie from Pathology Consultant Services for tissue microarray analysis and scoring and helpful discussions on the pathology of breast tissues. This research was supported by the FDA Critical Path funding. NR 46 TC 3 Z9 3 U1 0 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1574-0153 J9 CANCER BIOMARK JI Cancer Biomark. PY 2011 VL 10 IS 3-4 BP 163 EP 173 DI 10.3233/CBM-2012-0240 PG 11 WC Oncology SC Oncology GA 957JK UT WOS:000305157500006 ER PT J AU Glasser, SP Willard, J Defelice, A Lawrence, J Hung, J Obot, E Girton, J Targum, S Throckmorton, D Mangano, D Lipicky, RJ AF Glasser, Stephen P. Willard, James Defelice, Albert Lawrence, John Hung, James Obot, Evelyn Girton, John Targum, Shari Throckmorton, Douglas Mangano, Dennis Lipicky, Raymond J. TI Is Randomization to Placebo Safe? Risk in Placebo-Controlled Angina Trials: Angina Risk Meta-Analysis SO CARDIOLOGY LA English DT Article DE Angina; Arrhythmia; Congestive heart failure; Placebo; Stroke; Transient ischemic attack; Ventricular tachycardia ID CLINICAL-TRIALS; HYPERTENSION AB Objective: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. Patients and Methods: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. Results: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. Conclusions:For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing. Copyright (C) 2012 S. Karger AG, Basel C1 [Glasser, Stephen P.] Univ Alabama, Birmingham, AL 35202 USA. [Willard, James; Defelice, Albert; Lawrence, John; Hung, James; Targum, Shari; Throckmorton, Douglas] US FDA, Rockville, MD 20857 USA. [Obot, Evelyn] NIH, Bethesda, MD 20892 USA. [Mangano, Dennis] Ischemia Res & Educ Fdn, San Francisco, CA USA. [Lipicky, Raymond J.] Lipicky LLC, N Potomac, MD USA. RP Glasser, SP (reprint author), Univ Alabama, 1717 11th Ave S, Birmingham, AL 35202 USA. EM sglasser@uab.edu OI Glasser, Stephen/0000-0001-9620-6406 NR 17 TC 0 Z9 0 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0008-6312 J9 CARDIOLOGY JI Cardiology PY 2011 VL 120 IS 3 BP 174 EP 181 DI 10.1159/000335522 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 888AM UT WOS:000299976200012 PM 22261892 ER PT S AU Tyner, K Sadrieh, N AF Tyner, Katherine Sadrieh, Nakissa BE McNeil, SE TI Considerations When Submitting Nanotherapeutics to FDA/CDER for Regulatory Review SO CHARACTERIZATION OF NANOPARTICLES INTENDED FOR DRUG DELIVERY SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Nano-therapeutic; nano-pharmaceutics; characterization; regulatory; safety assessment ID DYNAMIC LIGHT-SCATTERING; DRUG-DELIVERY; NANOPARTICLES AB The Food and Drug Administration (FDA) does not, as yet, have specific guidances for products containing nanoscale materials. As announced in the report issued by the FDA Nanotechnology Task Force (July 2007), however, there are recommendations to various centers within the FDA to develop guidances for industry. Regardless of the lack of explicit FDA guidances, there are therapeutics currently on the market containing nanoscale materials, and additional novel nanomaterial-containing therapeutics arc being developed with the hopes of being submitted for regulatory review and approval. While, for the most part, these novel nanomaterial-containing products are being evaluated using the same regulatory requirements as products that do not contain nanomaterials, it is increasingly evident that at least in the area of characterization of nanomaterials used in drug products, there may be areas where special focus is needed. Specific areas include the validity of applying small molecule principles and methodologies to nanomaterial-containing products, the effects the nanomaterial will impart to the rest of the formulation (or vice versa), and how the physicochemical properties may be impacted by biological settings. Similarly, for safety evaluation, biodistribution studies will be at the core of any evaluation of products containing nanomaterials. These biodistribution studies will, in effect, be indicative of where the nanoparticles are traveling and possibly accumulating, therefore subjecting those sites to increased likelihood of toxicological effects. This chapter focuses on questions and considerations that may arise for sponsors during product characterization, as well as considerations for the appropriate design and conduct of in vivo toxicology studies. This chapter will also review how current FDA guidances apply to nanotherapeutics. This chapter reflects the current thinking and experience of the authors. However, this is not a policy document and should not be used in lieu of regulations, published FDA guidances, or direct discussions with the agency. C1 [Tyner, Katherine; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Tyner, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 20 TC 28 Z9 28 U1 1 U2 14 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-197-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 697 BP 17 EP 31 DI 10.1007/978-1-60327-198-1_3 D2 10.1007/978-1-60327-198-1 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA BSU98 UT WOS:000285851400003 PM 21116951 ER PT B AU Buehler, PW D'Agnillo, F AF Buehler, Paul W. D'Agnillo, Felice BE Mozzarelli, A Bettati, S TI Animal Models and Oxidative Biomarkers to Evaluate Preclinical Safety of Extracellular Hemoglobins SO CHEMISTRY AND BIOCHEMISTRY OF OXYGEN THERAPEUTICS: FROM TRANSFUSION TO ARTIFICIAL BLOOD LA English DT Article; Book Chapter ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; SEVERE UNCONTROLLED HEMORRHAGE; SMALL-VOLUME RESUSCITATION; OXYGEN CARRIER HBOC-201; FOCAL CEREBRAL-ISCHEMIA; TRANSGENIC SICKLE MICE; INDUCED RENAL-FAILURE; ENDOTHELIAL-CELLS; NITRIC-OXIDE C1 [Buehler, Paul W.; D'Agnillo, Felice] US FDA, Ctr Biol Evaluat & Res CBER, Div Hematol, Lab Biochem & Vasc Biol, Rockville, MD 20857 USA. RP Buehler, PW (reprint author), US FDA, Ctr Biol Evaluat & Res CBER, Div Hematol, Lab Biochem & Vasc Biol, Rockville, MD 20857 USA. NR 106 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-1-119-97543-4; 978-0-470-68668-3 PY 2011 BP 391 EP 411 D2 10.1002/9781119975427 PG 21 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BA5XQ UT WOS:000337054800029 ER PT J AU Fisher, RW Reed, JL Snoy, PJ Mikolajczyk, MG Bray, M Scott, DE Kennedy, MC AF Fisher, R. W. Reed, J. L. Snoy, P. J. Mikolajczyk, M. G. Bray, M. Scott, D. E. Kennedy, M. C. TI Postexposure Prevention of Progressive Vaccinia in SCID Mice Treated with Vaccinia Immune Globulin SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID VIRUS-INFECTION; ECZEMA VACCINATUM; SMALLPOX VACCINEE; MAST-CELLS; CIDOFOVIR; PROTECTION; EFFICACY; RECEPTOR; MODEL; IGG AB A recently reported case of progressive vaccinia (PV) in an immunocompromised patient has refocused attention on this condition. Uniformly fatal prior to the licensure of vaccinia immune globulin (VIG) in 1978, PV was still fatal in about half of VIG-treated patients overall, with a greater mortality rate in infants and children. Additional therapies would be needed in the setting of a smallpox bioterror event, since mass vaccination following any variola virus release would inevitably result in exposure of immunocompromised people through vaccination or contact with vaccinees. Well-characterized animal models of disease can support the licensure of new products when human studies are not ethical or feasible, as in the case of PV. We chose vaccinia virus-scarified SCID mice to model PV. As in immunocompromised humans, vaccinia virus-scarified SCID animals develop enlarging primary lesions with minimal or no inflammation, eventual distal virus spread, and lethal outcomes if left untreated. Postexposure treatment with VIG slowed disease progression, caused local lesion regression, and resulted in the healthy survival of most of the mice for more than 120 days. Combination treatment with VIG and topical cidofovir also resulted in long-term disease-free survival of most of the animals, even when initiated 7 days postinfection. These results support the possibility that combination treatments may be effective in humans and support using this SCID model of PV to test new antibody therapies and combination therapies and to provide further insights into the pathogenesis and treatment of PV. C1 [Fisher, R. W.; Reed, J. L.; Mikolajczyk, M. G.; Scott, D. E.; Kennedy, M. C.] US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Snoy, P. J.] US FDA, Div Vet Serv, Off Management, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Bray, M.] NIAID, Integrated Res Facil, NIH, Ft Detrick, MD USA. RP Fisher, RW (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, HFM-345,1401 Rockville Pike, Rockville, MD 20852 USA. EM Robert.Fisher@fda.hhs.gov FU NIAID for biodefense research FX This work was supported in part by an interagency agreement with NIAID for biodefense research. NR 42 TC 9 Z9 9 U1 0 U2 3 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 JAN PY 2011 VL 18 IS 1 BP 67 EP 74 DI 10.1128/CVI.00280-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 702BK UT WOS:000285869400006 PM 21106779 ER PT J AU Rose, CE Romero-Steiner, S Burton, RL Carlone, GM Goldblatt, D Nahm, MH Ashton, L Haston, M Ekstrom, N Haikala, R Kayhty, H Henckaerts, I Durant, N Poolman, JT Fernsten, P Yu, XH Hu, BT Jansen, KU Blake, M Simonetti, ER Hermans, PWM Plikaytis, BD AF Rose, Charles E. Romero-Steiner, Sandra Burton, Robert L. Carlone, George M. Goldblatt, David Nahm, Moon H. Ashton, Lindsey Haston, Mitch Ekstrom, Nina Haikala, Raili Kayhty, Helena Henckaerts, Isabelle Durant, Nathalie Poolman, Jan T. Fernsten, Phil Yu, Xinhong Hu, Branda T. Jansen, Kathrin U. Blake, Milan Simonetti, Elles R. Hermans, Peter W. M. Plikaytis, Brian D. TI Multilaboratory Comparison of Streptococcus pneumoniae Opsonophagocytic Killing Assays and Their Level of Agreement for the Determination of Functional Antibody Activity in Human Reference Sera SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PNEUMOCOCCAL ANTIBODIES AB Antibody-mediated killing of Streptococcus pneumoniae (pneumococcus) by phagocytes is an important mechanism of protection of the human host against pneumococcal infections. Measurement of opsonophagocytic antibodies by use of a standardized opsonophagocytic assay (OPA) is important for the evaluation of candidate vaccines and required for the licensure of new pneumococcal conjugate vaccine formulations. We assessed agreement among six laboratories that used their own optimized OPAs on a panel of 16 human reference sera for 13 pneumococcal serotypes. Consensus titers, estimated using an analysis-of-variance (ANOVA) mixed-effects model, provided a common reference for assessing agreement among these laboratories. Agreement was evaluated in terms of assay accuracy, reproducibility, repeatability, precision, and bias. We also reviewed four acceptance criterion intervals for assessing the comparability of protocols when assaying the same reference sera. The precision, accuracy, and concordance results among laboratories and the consensus titers revealed acceptable agreement. The results of this study indicate that the bioassays evaluated in this study are robust, and the resultant OPA values are reproducible for the determination of functional antibody titers specific to 13 pneumococcal serotypes when performed by laboratories using highly standardized but not identical assays. The statistical methodologies employed in this study may serve as a template for evaluating future multilaboratory studies. C1 [Rose, Charles E.; Plikaytis, Brian D.] Ctr Dis Control & Prevent, Biostat Off, Div Bacterial Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Romero-Steiner, Sandra; Carlone, George M.] Ctr Dis Control & Prevent, Meningitis & Vaccine Preventable Dis Branch, Div Bacterial Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. [Burton, Robert L.; Nahm, Moon H.] Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. [Goldblatt, David; Ashton, Lindsey; Haston, Mitch] UCL, Immunobiol Unit, Inst Child Hlth, London, England. [Ekstrom, Nina; Haikala, Raili; Kayhty, Helena] Natl Inst Hlth & Welf, Dept Vaccinat & Immune Protect, Helsinki, Finland. [Henckaerts, Isabelle; Durant, Nathalie; Poolman, Jan T.] GlaxoSmithKline Biol, Bacterial Vaccines Program, R&D, B-1330 Rixensart, Belgium. [Fernsten, Phil; Yu, Xinhong; Hu, Branda T.; Jansen, Kathrin U.] Pfizer Vaccine Res, Pearl River, NY 10965 USA. [Blake, Milan] US FDA, Div Bacterial Parasit & Allergenic Prod, Ctr Biol Evaluat & Res, Rockville, MD 20851 USA. [Simonetti, Elles R.; Hermans, Peter W. M.] Radboud Univ Nijmegen, Med Ctr, Dept Pediat, NL-6525 ED Nijmegen, Netherlands. RP Rose, CE (reprint author), Ctr Dis Control & Prevent, Biostat Off, Div Bacterial Dis, Natl Ctr Immunizat & Resp Dis, Bldg 1,Room 5044,MS C-09,1600 Clifton Rd, Atlanta, GA 30333 USA. EM CRose@cdc.gov RI Goldblatt, David/C-5972-2008; Hermans, Peter/H-8042-2014; Simonetti, Elles/N-2966-2016; OI Goldblatt, David/0000-0002-0769-5242; Romero-Steiner, Sandra/0000-0003-4128-7768; Nahm, Moon/0000-0002-6922-1042 FU NIH [AI-30021 (NIH/NIAID/DMID)] FX This project was funded in part by NIH contract AI-30021 (NIH/NIAID/DMID) to the University of Alabama at Birmingham (M.H.N.). NR 25 TC 24 Z9 27 U1 0 U2 3 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 JAN PY 2011 VL 18 IS 1 BP 135 EP 142 DI 10.1128/CVI.00370-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 702BK UT WOS:000285869400015 PM 21084458 ER PT J AU Kutanzi, KR Yurchenko, OV Beland, FA Checkhun, VF Pogribny, IP AF Kutanzi, Kristy R. Yurchenko, Olga V. Beland, Frederick A. Checkhun, Vasyl' F. Pogribny, Igor P. TI MicroRNA-mediated drug resistance in breast cancer SO CLINICAL EPIGENETICS LA English DT Review DE microRNA; Drug resistance; Breast cancer AB Chemoresistance is one of the major hurdles to overcome for the successful treatment of breast cancer. At present, there are several mechanisms proposed to explain drug resistance to chemotherapeutic agents, including decreased intracellular drug concentrations, mediated by drug transporters and metabolic enzymes; impaired cellular responses that affect cell cycle arrest, apoptosis, and DNA repair; the induction of signaling pathways that promote the progression of cancer cell populations; perturbations in DNA methylation and histone modifications; and alterations in the availability of drug targets. Both genetic and epigenetic theories have been put forward to explain the mechanisms of drug resistance. Recently, a small non-coding class of RNAs, known as microRNAs, has been identified as master regulators of key genes implicated in mechanisms of chemoresistance. This article reviews the role of microRNAs in regulating chemoresistance and highlights potential therapeutic targets for reversing miRNA-mediated drug resistance. In the future, microRNA-based treatments, in combination with traditional chemotherapy, may be a new strategy for the clinical management of drug-resistant breast cancers. C1 [Kutanzi, Kristy R.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. [Yurchenko, Olga V.; Checkhun, Vasyl' F.] RE Kavetsky Inst Expt Pathol Oncol & Radiobiol, Dept Mech Anticanc Therapy, Kiev, Ukraine. RP Kutanzi, KR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM kristy.kutanzi@fda.hhs.gov; igor.pogribny@fda.hhs.gov NR 140 TC 63 Z9 67 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1868-7083 J9 CLIN EPIGENETICS JI Clin. Epigenetics PY 2011 VL 2 BP 171 EP 185 DI 10.1007/s13148-011-0040-8 PG 15 WC Oncology SC Oncology GA V42ST UT WOS:000209634200028 ER PT J AU Lee, JY Garnett, CE Gobburu, JVS Bhattaram, VA Brar, S Earp, JC Jadhav, PR Krudys, K Lesko, LJ Li, F Liu, J Madabushi, R Marathe, A Mehrotra, N Tornoe, C Wang, Y Zhu, H AF Lee, Joo Yeon Garnett, Christine E. Gobburu, Jogarao V. S. Bhattaram, Venkatesh A. Brar, Satjit Earp, Justin C. Jadhav, Pravin R. Krudys, Kevin Lesko, Lawrence J. Li, Fang Liu, Jiang Madabushi, Rajnikanth Marathe, Anshu Mehrotra, Nitin Tornoe, Christoffer Wang, Yaning Zhu, Hao TI Impact of Pharmacometric Analyses on New Drug Approval and Labelling Decisions A Review of 198 Submissions Between 2000 and 2008 SO CLINICAL PHARMACOKINETICS LA English DT Article ID PEDIATRICS AB Pharmacometric analyses have become an increasingly important component of New Drug Application (NDA) and Biological License Application (BLA) submissions to the US FDA to support drug approval, labelling and trial design decisions. Pharmacometrics is defined as a science that quantifies drug, disease and trial information to aid drug development, therapeutic decisions and/or regulatory decisions. In this report, we present the results of a survey evaluating the impact of pharmacometric analyses on regulatory decisions for 198 submissions during the period from 2000 to 2008. Pharmacometric review of NDAs included independent, quantitative analyses by FDA pharmacometricians, even when such analysis was not conducted by the sponsor, as well as evaluation of the sponsor's report. During 2000-2008, the number of reviews with pharmacometric analyses increased dramatically and the number of reviews with an impact on approval and labelling also increased in a similar fashion. We also present the impact of pharmacometric analyses on selection of paediatric dosing regimens, approval of regimens that had not been directly studied in clinical trials and provision of evidence of effectiveness to support a single pivotal trial. Case studies are presented to better illustrate the role of pharmacometric analyses in regulatory decision making. C1 [Lee, Joo Yeon; Garnett, Christine E.; Gobburu, Jogarao V. S.; Bhattaram, Venkatesh A.; Brar, Satjit; Earp, Justin C.; Jadhav, Pravin R.; Krudys, Kevin; Lesko, Lawrence J.; Li, Fang; Liu, Jiang; Madabushi, Rajnikanth; Marathe, Anshu; Mehrotra, Nitin; Tornoe, Christoffer; Wang, Yaning; Zhu, Hao] US FDA, Div Pharmacometr, Off Clin Pharmacol, Silver Spring, MD USA. RP Lee, JY (reprint author), 10903 New Hampshire Ave,Room 3198,Bldg 51, Silver Spring, MD 20993 USA. EM jooyeon2.lee@fda.hhs.gov NR 11 TC 44 Z9 46 U1 1 U2 10 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2011 VL 50 IS 10 BP 627 EP 635 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 832ND UT WOS:000295810800002 PM 21895036 ER PT S AU Garnett, CE Lee, JY Gobburu, JVS AF Garnett, Christine E. Lee, Joo Yeon Gobburu, Jogarao V. S. BE Kimko, HHC Peck, CC TI Contribution of Modeling and Simulation in the Regulatory Review and Decision-Making: US FDA Perspective SO CLINICAL TRIAL SIMULATIONS: APPLICATIONS AND TRENDS SE AAPS Advances in the Pharmaceutical Sciences Series LA English DT Article; Book Chapter ID CLINICAL DRUG DEVELOPMENT; LABELING DECISIONS; IMPACT; PHARMACOKINETICS; PHARMACODYNAMICS; PHARMACOMETRICS; INTEGRATION; EXPERIENCE; APPROVAL AB The Division of Pharmacometrics at the U.S. FDA engages in regulatory reviews, research and policy development. During 2000-2008, over 50% of pharmacometric reviews of 198 NDA and BLA applications influenced approval and safety decisions. During this time, pharmacometric analyses were used in pediatric dose selection, and approval of doses not directly studied in effectiveness trials. Additionally, pharmacometrics has been used in FDA advice on protocol design to optimize dosing regimens based on benefit-risk for clinical testing, and to provide confirmatory evidence of effectiveness. Current research projects aim to solve drug development challenges and develop policies grounded in pharmacometric principles and methodologies. C1 [Garnett, Christine E.; Lee, Joo Yeon; Gobburu, Jogarao V. S.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Garnett, CE (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Christine.Garnett@fda.gov NR 49 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 2210-7371 BN 978-1-4419-7414-3 J9 AAPS ADV PHARM SCI PY 2011 VL 1 BP 37 EP 57 DI 10.1007/978-1-4419-7415-0_3 D2 10.1007/978-1-4419-7415-0 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BSY60 UT WOS:000286132800003 ER PT J AU Rellahan, BL Graham, L Hirsch, D Kennett, S Rawat, R Brorson, K Swisher, J AF Rellahan, B. L. Graham, L. Hirsch, D. Kennett, S. Rawat, R. Brorson, K. Swisher, J. BE MooYoung, M TI Recent and Emerging Trends and Concerns Related to the Manufacturing and Testing of Monoclonal Antibodies Intended for Clinical Use SO COMPREHENSIVE BIOTECHNOLOGY, VOL 3: INDUSTRIAL BIOTECHNOLOGY AND COMMODITY PRODUCTS, 2ND EDITION LA English DT Article; Book Chapter ID CELL-CULTURE; IN-VIVO; DESIGN; CLEARANCE; THERAPEUTICS; QUALITY; ENGAGE; FUTURE C1 [Rellahan, B. L.; Graham, L.; Hirsch, D.; Kennett, S.; Rawat, R.] US FDA, Bethesda, MD 20014 USA. [Brorson, K.; Swisher, J.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Rellahan, BL (reprint author), US FDA, Bethesda, MD 20014 USA. NR 40 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 363 EP 375 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3VS UT WOS:000334940100032 ER PT J AU Kaiser, AD AF Kaiser, A. D. BE MooYoung, M TI Combination Products Are Not Solely Biological Products, Drugs, or Devices: A Regulatory Perspective SO COMPREHENSIVE BIOTECHNOLOGY, VOL 3: INDUSTRIAL BIOTECHNOLOGY AND COMMODITY PRODUCTS, 2ND EDITION LA English DT Article; Book Chapter C1 US FDA, Silver Spring, MD 20993 USA. RP Kaiser, AD (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 399 EP 409 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3VS UT WOS:000334940100035 ER PT J AU Lee, K AF Lee, K. BE MooYoung, M TI Regulatory Aspects of Chemistry Manufacturing and Controls for Investigational New Drug Applications and Biologic License Applications to the United States Food and Drug Administration SO COMPREHENSIVE BIOTECHNOLOGY, VOL 3: INDUSTRIAL BIOTECHNOLOGY AND COMMODITY PRODUCTS, 2ND EDITION LA English DT Article; Book Chapter ID QUALITY; DESIGN; BIOPHARMACEUTICALS; RECOMMENDATIONS; OPTIMIZATION; THERAPEUTICS; PERSPECTIVE; ANTIBODIES; PRODUCTS C1 US FDA, Bethesda, MD 20014 USA. RP Lee, K (reprint author), US FDA, Bethesda, MD 20014 USA. NR 43 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 439 EP 452 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3VS UT WOS:000334940100038 ER PT J AU Cordoba-Rodriguez, R AF Cordoba-Rodriguez, R. BE MooYoung, M TI Raw Materials in the Manufacture of Biotechnology Products SO COMPREHENSIVE BIOTECHNOLOGY, VOL 3: INDUSTRIAL BIOTECHNOLOGY AND COMMODITY PRODUCTS, 2ND EDITION LA English DT Article; Book Chapter ID CONTAMINATION; CELLS C1 US FDA, Bethesda, MD 20014 USA. RP Cordoba-Rodriguez, R (reprint author), US FDA, Bethesda, MD 20014 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 453 EP 458 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3VS UT WOS:000334940100039 ER PT J AU Vallejos, JR Moreira, A Rao, G Brorson, K AF Vallejos, J. R. Moreira, A. Rao, G. Brorson, K. BE MooYoung, M TI Integrating Process Scouting Devices (PSDs) With Bench-Scale Devices: Challenges and Opportunities for Mammalian Cell Culture SO COMPREHENSIVE BIOTECHNOLOGY, VOL 3: INDUSTRIAL BIOTECHNOLOGY AND COMMODITY PRODUCTS, 2ND EDITION LA English DT Article; Book Chapter ID GLUTAMINE-BINDING-PROTEIN; MINIATURE BIOREACTOR; SHAKEN BIOREACTORS; OXYGEN-TRANSFER; MASS-TRANSFER; MICROBIOREACTOR; FERMENTATION; BIOSENSORS; GROWTH; SYSTEM C1 [Vallejos, J. R.; Moreira, A.; Rao, G.] Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. [Brorson, K.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Vallejos, JR (reprint author), Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. NR 36 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 659 EP 667 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA BA3VS UT WOS:000334940100056 ER PT J AU Kim, SJ Kweon, O Cerniglia, CE AF Kim, S-J Kweon, O. Cerniglia, C. E. BE MooYoung, M Agathos, S TI Proteomic Applications to Elucidate Bacterial Aromatic Hydrocarbon Metabolic Pathways SO COMPREHENSIVE BIOTECHNOLOGY, VOL 6: ENVIRONMENTAL BIOTECHNOLOGY AND SAFETY, 2ND EDITION LA English DT Article; Book Chapter ID MYCOBACTERIUM-VANBAALENII PYR-1; BURKHOLDERIA-XENOVORANS LB400; RING-HYDROXYLATING DIOXYGENASES; ACINETOBACTER-LWOFFII K24; BETA-KETOADIPATE PATHWAY; SP STRAIN PYR-1; PSEUDOMONAS-PUTIDA; GEL-ELECTROPHORESIS; CATABOLIC PATHWAYS; MASS-SPECTROMETRY C1 [Kim, S-J; Kweon, O.; Cerniglia, C. E.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kim, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 56 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088504-9 PY 2011 BP 105 EP 114 PG 10 WC Biotechnology & Applied Microbiology; Engineering, Environmental SC Biotechnology & Applied Microbiology; Engineering GA BA3WV UT WOS:000335042600011 ER PT J AU Wang, L Abbasi, F Jasper, GA Kreitman, RJ Liewehr, DJ Marti, GE Stetler-Stevenson, M AF Wang, Lili Abbasi, Fatima Jasper, Gregory A. Kreitman, Robert J. Liewehr, David J. Marti, Gerald E. Stetler-Stevenson, Maryalice TI Variables in the Quantification of CD4 in Normals and Hairy Cell Leukemia Patients SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE quantitative flow cytometry; CD4 quantification; anti-CD4 PE unimolar conjugate; sample preparation method ID FLOW CYTOMETRIC ANALYSIS; T-LYMPHOCYTES; EXPRESSION; QUANTITATION; SPECIMENS; BEADS AB Background: Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory. Quantitative normal T-cell CD4 expression represents a biologic standard and quality control agent. However, low levels of CD4 expression were detected in normal T-cells in Hairy Cell Leukemia (HCL) samples. Methods: The QuantiBrite System (R) was used to determine the level of CD4 expression (mean antibody bound per cell, ABC) in fresh and shipped HCL blood and fresh normal donor blood (NDB). The effects of shipping, lysing reagent, cell preparation method, and antibody lot were evaluated. Results: Shipped HCL specimens (n = 69) had a significantly lower mean CD4 ABC of 38,788 (CV = 9.1%) compared to fresh specimens (n = 105) CD4 value of 40,330 (CV = 8.4%) (P < 0.05). In NDB, significant differences were seen for fresh versus shipped specimens using the stain/lyse method but not for lyse/stain method. Consistent differences in CD4 ABC based upon antibody lot were observed in fresh HCL and NDB samples. Stain/lyse and lyse/stain methods using NH(4)Cl lyse were compared in NDB using identical samples and antibodies. The NDB CD4 ABC values obtained with the lyse (NH(4)Cl)/stain method (45,562, 3.7% CV) were lower than those obtained with the stain/lyse (NH(4)Cl) method (49,955, 3.3% CV) with P < 0.001. Conclusions: CD4 expression in HCL patient samples is not inherently different from that observed in NDB and therefore may serve as a biological control in clinical QFCM. Technical variables impact significantly on QFCM of CD4. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Jasper, Gregory A.; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Wang, Lili] NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. [Abbasi, Fatima] CBER FDA, Div Cell & Gene Therapies, Lab Stem Cell Biol, Cellular & Tissue Therapy Branch,Off Cellular Tis, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, NIH, Bethesda, MD 20892 USA. [Liewehr, David J.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov FU NIH; NCI; CBER; FDA FX Grant sponsors: NIH, NCI, CBER, FDA. NR 20 TC 7 Z9 7 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD JAN PY 2011 VL 80B IS 1 BP 51 EP 56 DI 10.1002/cyto.b.20541 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 703MC UT WOS:000285981000008 PM 20687201 ER PT B AU Braddy, AC Conner, DP AF Braddy, April C. Conner, Dale P. BE Murthy, SN TI Regulatory Perspective of Dermatokinetic Studies SO Dermatokinetics of Therapeutic Agents LA English DT Article; Book Chapter ID DOSE-RESPONSE; BIOEQUIVALENCE C1 [Conner, Dale P.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Conner, Dale P.] Scios Nova Inc, Pharmacokinet, Sunnyvale, CA USA. RP Braddy, AC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-0478-0; 978-1-4398-0477-3 PY 2011 BP 193 EP 201 D2 10.1201/b10845 PG 9 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA BC5NJ UT WOS:000353399200008 ER PT J AU Heemstra, HE Leufkens, HGM Rodgers, RPC Xu, K Voordouw, BCG Braun, MM AF Heemstra, Harald E. Leufkens, Hubert G. M. Rodgers, R. P. Channing Xu, Kui Voordouw, Bettie C. G. Braun, M. Miles TI Characteristics of orphan drug applications that fail to achieve marketing approval in the USA SO DRUG DISCOVERY TODAY LA English DT Review ID PULMONARY ARTERIAL-HYPERTENSION; 6-MINUTE WALK DISTANCE; RARE DISEASES; END-POINTS; INVESTIGATIONAL DRUGS; CYSTIC-FIBROSIS; CLINICAL-TRIALS; SUCCESS RATES; MEDICINES; ACCESS AB The US Orphan Drug Act has fostered the development of drugs for patients with rare diseases by granting 'orphan designations', although several orphan drugs for which a marketing application has been submitted to the FDA have failed to obtain approval. This study identified the clinical trial design, the level of experience of the sponsor and the level of interaction with the FDA to be associated with non-approval. Sponsors, therefore, should engage in dialogue with the FDA and thoughtfully design pivotal clinical trials in accordance with FDA guidance documents. C1 [Heemstra, Harald E.; Leufkens, Hubert G. M.; Voordouw, Bettie C. G.] Med Evaluat Board, NL-2500 BE The Hague, Netherlands. [Rodgers, R. P. Channing; Xu, Kui; Braun, M. Miles] US FDA, FDA Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Heemstra, Harald E.; Voordouw, Bettie C. G.] Steering Comm Orphan Drugs, NL-2509 AE The Hague, Netherlands. RP Leufkens, HGM (reprint author), Med Evaluat Board, POB 16229, NL-2500 BE The Hague, Netherlands. EM hg.leufkens@cbg-meb.nl NR 36 TC 23 Z9 23 U1 1 U2 15 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 JAN PY 2011 VL 16 IS 1-2 BP 73 EP 80 DI 10.1016/j.drudis.2010.11.006 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 712TO UT WOS:000286689300010 PM 21094692 ER PT B AU Reynolds, KS AF Reynolds, Kellie Schoolar BE Piscitelli, SC Rodvold, KA Pai, MP TI Drug Interaction Considerations Throughout Drug Development SO DRUG INTERACTIONS IN INFECTIOUS DISEASES, THIRD EDITION SE Infectious Disease LA English DT Article; Book Chapter ID METABOLIZING-ENZYMES; NUCLEAR RECEPTORS; IN-VITRO; COCKTAIL; TRANSPORTERS; INDUCTION; CYP3A4; EFFICACY; 2C9; 3A4 AB The objectives of a drug interaction program are to determine whether there are interactions with an NME (new molecular entity) that necessitate a dose adjustment of the NME or other drugs that it might be used with, or whether an interaction requires a contraindication or special precautions. The program should begin early in drug development so the clinical implications of interactions can be assessed adequately in clinical studies. It is important that all studies are conducted using rigorous scientific procedures. The clinical significance of interactions should be assessed based on exposure-response knowledge of the affected drug.. Drug labels need to include complete information about the potential for drug interactions, including instructions for dose adjustments and special monitoring or precautions. C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Reynolds, KS (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Kellie.Reynolds@fda.hhs.gov NR 41 TC 0 Z9 0 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-61779-212-0 J9 INFECT DIS PY 2011 BP 613 EP 630 DI 10.1007/978-1-61779-213-7_18 D2 10.1007/978-1-61779-213-7 PG 18 WC Infectious Diseases; Medicine, General & Internal; Pharmacology & Pharmacy SC Infectious Diseases; General & Internal Medicine; Pharmacology & Pharmacy GA BYU08 UT WOS:000300328700018 ER PT J AU Jones, SC Sorbello, A Boucher, RM AF Jones, S. Christopher Sorbello, Alfred Boucher, Robert M. TI Fluoroquinolone-Associated Myasthenia Gravis Exacerbation Evaluation of Postmarketing Reports from the US FDA Adverse Event Reporting System and a Literature Review SO DRUG SAFETY LA English DT Article ID NEUROMUSCULAR-TRANSMISSION; CIPROFLOXACIN; ANTIBIOTICS; CHLOROQUINE; OFLOXACIN AB Background: Exacerbations of myasthenia gravis have been reported in antibacterial-treated patients. In animal and in vitro models of experimentally-induced myasthenia gravis, fluoroquinolones exhibit neuromuscular blockade. Objective: The aim of this retrospective study was to evaluate postmarketing adverse event reports submitted to the US FDA and case reports published in the scientific literature for a potential association between fluoroquinolone exposure and acute exacerbations of myasthenia gravis. Methods: On 1 March 2011, we searched the FDA Adverse Event Reporting System (AERS) database to retrieve all reports of myasthenia gravis exacerbation as a serious adverse event in patients treated with fluoroquinolones. We also conducted an Internet-based search using EMBASE for additional English-language cases in the scientific literature. Results: We identified a total of 37 unique cases describing myasthenia gravis exacerbation following fluoroquinolone systemic exposure. We retrieved AERS reports for 27 non-ventilated patients administered the following fluoroquinolones: levofloxacin (n=9), moxifloxacin (n=6), ciprofloxacin (n=6), ofloxacin (n=2), gatifloxacin (n=2), norfloxacin (n=1) and trovafloxacin (n=1). Additionally, we retrieved ten case reports published in the literature involving non-ventilated patients administered ciprofloxacin (n=4), levofloxacin (n=2) and ofloxacin, norfloxacin, pefloxacin and prulifloxacin (1 patient each). Myasthenia gravis exacerbations developed a median of 1 day following fluoroquinolone exposure. The 37 cases describe dyspnoea (n=19; 51%), myasthenic crisis requiring ventilatory support (n=11; 30%) and death (n=2; 5%). Additional exacerbation-related adverse events were generalized muscle weakness (n=20; 54%), dysphagia (n=9; 24%), diplopia (n=6; 16%) and ptosis (n=6; 16%). Six patients (16%) experienced a positive rechallenge, with recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction. Conclusions: Fluoroquinolone exposure may result in potentially life-threatening myasthenia gravis exacerbations in patients with underlying disease. Healthcare professionals should be aware of this serious drug-disease association and carefully weigh the benefit-risks of fluoroquinolones when treating infections in non-ventilated myasthenic patients. C1 [Jones, S. Christopher; Sorbello, Alfred; Boucher, Robert M.] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Pharmacovigilance 2, Silver Spring, MD 20993 USA. RP Jones, SC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Pharmacovigilance 2, 10903 New Hampshire Ave,Bldg 22,Rm 3464, Silver Spring, MD 20993 USA. NR 25 TC 8 Z9 13 U1 0 U2 2 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2011 VL 34 IS 10 BP 839 EP 847 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 827QR UT WOS:000295443500004 PM 21879778 ER PT J AU Hillebrenner, MG Swain, JA Zuckerman, B AF Hillebrenner, Matthew G. Swain, Julie A. Zuckerman, Bram TI VARC consensus report: the FDA perspective SO EUROPEAN HEART JOURNAL LA English DT Editorial Material C1 [Hillebrenner, Matthew G.; Swain, Julie A.; Zuckerman, Bram] US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Hillebrenner, MG (reprint author), US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-1232, Silver Spring, MD 20993 USA. EM matthew.hillebrenner@fda.hhs.gov NR 2 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JAN PY 2011 VL 32 IS 2 BP 138 EP 139 DI 10.1093/eurheartj/ehq414 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 706JU UT WOS:000286215500006 PM 21216740 ER PT J AU Ostera, G Tokumasu, F Teixeira, C Collin, N Sa, J Hume, J Kumar, S Ribeiro, J Lukat-Rodgers, GS Rodgers, KR AF Ostera, Graciela Tokumasu, Fuyuki Teixeira, Clarissa Collin, Nicolas Sa, Juliana Hume, Jennifer Kumar, Sanjai Ribeiro, Jose Lukat-Rodgers, Gudrun S. Rodgers, Kenton R. TI Plasmodium falciparum: Nitric oxide modulates heme speciation in isolated food vacuoles SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Protozoa; Plasmodium falciparum; Malaria; Nitric oxide; Heme; Hemozoin; Antimalarials; Food vacuole ID REDUCTIVE NITROSYLATION; SCHISTOSOMA-MANSONI; MALARIA PARASITE; BETA-HEMATIN; HEMOZOIN; COMPLEXES; CRYSTALLIZATION; ADDUCTS; INSECT; NO AB Nitric oxide (NO) and NO-derived reactive nitrogen species (RNS) are present in the food vacuole (FV) of Plasmodium falciparum trophozoites. The product of PFL1555w, a putative cytochrome 65, localizes in the FV membrane, similar to what was previously observed for the product of PF13_0353, a putative cytochrome 65 reductase. These two gene products may contribute to NO generation by denitrification chemistry from nitrate and/or nitrite present in the erythrocyte cytosol. The possible coordination of NO to heme species present in the food vacuole was probed by resonance Raman spectroscopy. The spectroscopic data revealed that in situ generated NO interacts with heme inside the intact FVs to form ferrous heme nitrosyl complexes that influence intra-vacuolar heme solubility. The formation of heme nitrosyl complexes within the FV is a previously unrecognized factor that could affect the equilibrium between soluble and crystallized heme within the FV in vivo. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ostera, Graciela; Tokumasu, Fuyuki; Teixeira, Clarissa; Sa, Juliana; Hume, Jennifer; Ribeiro, Jose] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. [Collin, Nicolas] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Kumar, Sanjai] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lukat-Rodgers, Gudrun S.; Rodgers, Kenton R.] N Dakota State U, Dept Chem & Biochem, Fargo, ND 58108 USA. RP Ostera, G (reprint author), Georgetown Univ, Dept Biochem, Washington, DC 20057 USA. EM osterag@georgetown.edu; kent.rodgers@ndsu.edu OI Tokumasu, Fuyuki/0000-0003-2790-1071; Ribeiro, Jose/0000-0002-9107-0818 FU NIH-NIAID [AI072719] FX The authors would like to thank Drs. Thomas Wellems, Jesus Valenzuela, Alan Schechter and F. Ann Walker for their helpful discussions and contributions to this project. This research was supported by the Intramural Research Program of the NIAID, NIH and by NIH-NIAID (AI072719 to K.R.R.). NR 31 TC 8 Z9 8 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JAN PY 2011 VL 127 IS 1 BP 1 EP 8 DI 10.1016/j.exppara.2010.05.006 PG 8 WC Parasitology SC Parasitology GA 710BV UT WOS:000286486800001 PM 20493843 ER PT J AU Brekhman, V Lugassie, J Zaffryar-Eilot, S Sabo, E Kessler, O Smith, V Golding, H Neufeld, G AF Brekhman, Vera Lugassie, Jennie Zaffryar-Eilot, Shelly Sabo, Edmond Kessler, Ofra Smith, Victoria Golding, Hana Neufeld, Gera TI Receptor activity modifying protein-3 mediates the protumorigenic activity of lysyl oxidase-like protein-2 SO FASEB JOURNAL LA English DT Article DE LOXL2; RAMP3; invasion; tumor progression ID TUMOR PROGRESSION; CANCER-CELLS; CALCITONIN RECEPTOR; MOLECULAR ROLE; IN-VIVO; ADRENOMEDULLIN; AMYLIN; GROWTH; INVASION; ANGIOGENESIS AB Lysyl oxidase-like protein-2 (LOXL2) induces epithelial to mesenchymal transition and promotes invasiveness. To understand the mechanisms involved, we examined the effect of LOXL2 overexpression in MCF-7 cells on gene expression. We found that LOXL2 up-regulated the expression of receptor activity modifying protein-3 (RAMP3). Expression of RAMP3 in MDA-MB-231 cells in which LOXL2 expression was inhibited restored vimentin expression, invasiveness, and tumor development. Inhibition of RAMP3 expression in MDA-MB-231 cells mimicked the effects produced by inhibition of LOXL2 expression and was accompanied by inhibition of p38 phosphorylation. LOXL2 overexpression in these cells did not restore invasiveness, suggesting that RAMP3 functions downstream to LOXL2. LOXL2 and RAMP3 are strongly coexpressed in human colon, breast, and gastric carcinomas but not in normal colon or gastric epithelial cells. RAMP3 associates with several G-protein-coupled receptors forming receptors for peptides, such as adrenomedullin and amylin. We hypothesized that RAMP3 could function as a transducer of autocrine signals induced by such peptides. However, the proinvasive effects of RAMP3 could not be abrogated following inhibition of the expression or activity of these peptides. Our experiments suggest that the protumorigenic effects of LOXL2 are partially mediated by RAMP3 and that RAMP3 inhibitors may function as antitumorigenic agents.-Brekhman, V., Lugassie, J., Zaffryar-Eilot, S., Sabo, E., Kessler, O., Smith, V., Golding, H., Neufeld, G. Receptor activity modifying protein-3 mediates the protumorigenic activity of lysyl oxidase-like protein-2. FASEB J. 25, 55-65 (2011). www.fasebj.org C1 [Brekhman, Vera; Lugassie, Jennie; Zaffryar-Eilot, Shelly; Sabo, Edmond; Kessler, Ofra; Neufeld, Gera] Technion Israel Inst Technol, Canc Res & Vasc Biol Ctr, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel. [Sabo, Edmond] Rambam Med Ctr, Haifa, Israel. [Smith, Victoria] Arresto Biosci Inc, Palo Alto, CA USA. [Golding, Hana] Food & Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Neufeld, G (reprint author), Technion Israel Inst Technol, Canc Res & Vasc Biol Ctr, Bruce Rappaport Fac Med, POB 9679,1 Efron St, IL-31096 Haifa, Israel. EM gera@tx.technion.ac.il FU Arresto Biosciences Inc. (Palo Alto, CA, USA); U.S. Army [W81XWH-04-1-0430] FX This work was funded, in part, by a grant from Arresto Biosciences Inc. (Palo Alto, CA, USA; G.N.) and in part by a grant from the U.S. Army (W81XWH-04-1-0430; G.N. and H. G.). The authors thank Dr. Scott Ogg for critically reading the manuscript. The authors thank Dr. Robert Kerbel (Women's College Health Sciences Centre, Toronto, ON, Canada) and Dr. Israel Vlodavsky (Faculty of Medicine, Technion, Haifa, Israel) for gifts of cells. NR 43 TC 18 Z9 18 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2011 VL 25 IS 1 BP 55 EP 65 DI 10.1096/fj.10-162677 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 702BL UT WOS:000285869500006 PM 20802105 ER PT J AU Chen, ST AF Chen, Shaw T. TI Regulation of research: Is it a drug trial or a supplement trial? SO FITOTERAPIA LA English DT Article DE Regulatory requirements; Clinical studies; Dietary supplements AB Investigators and sponsors of dietary supplement research need to know the relevant regulatory requirements and how to comply with them. This brief review describes how research on dietary supplements is regulated by FDA. In general, whether an FDA sanctioned Investigational New Drug (IND) application is required for a human research project on dietary supplement depends on the intended use and clinical setting of the clinical study, and not on the supplement's physical or chemical properties. Even if the study product is already available on the market as a dietary supplement, an IND will be required for products that will be used as a drug to treat, mitigate or prevent a disease or its related conditions in the proposed clinical study. On the other hand, for studies on structure and function endpoints, and not on drug use, no IND will be required. The paper also discusses the principles FDA uses to determine whether an IND is needed for clinical studies of surrogate endpoints that do not lead to approvable drug claims. Useful FDA contact information is also provided. (C) 2010 Published by Elsevier B.V. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chen, ST (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Rm 22-5306, Silver Spring, MD 20993 USA. EM shaw.chen@fda.hhs.gov 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 0367-326X J9 FITOTERAPIA JI Fitoterapia PD JAN PY 2011 VL 82 IS 1 SI SI BP 14 EP 16 DI 10.1016/j.fitote.2010.11.011 PG 3 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 724HS UT WOS:000287567300004 PM 21073930 ER PT J AU Edison, SE Lin, LA Parrales, L AF Edison, S. E. Lin, L. A. Parrales, L. TI Practical considerations for the rapid screening for pesticides using ambient pressure desorption ionisation with high-resolution mass spectrometry SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE LC/MS; pesticide residues ID REAL-TIME; VEGETABLES; FRUIT; AIR AB A rapid screening method for pesticides has been developed to streamline the processing of produce entering the United States. Foam swabs were used to recover multi-class mixtures of 240, 140, 132 and 60 pesticides from the surfaces of apples, kiwis, peaches and tomatoes. The mixtures were selected to span a large range of chemical classes, polarities, solubilities and sizes to provide a broad look at how this technique will perform for a variety of analytes. The swabs were analysed using direct analysis in real-time (DART) ionisation coupled with a high-resolution Exactive Orbitrap (TM) mass spectrometer. This study expands the types of commodities analysed using this method and explores the feasibility of compositing multiple units of produce per batch to analyse a representative sample. It was established that whilst smooth-skinned produce, such as apples, maintained a high detection rate for the pesticide mixtures even when ten apples are swabbed with one foam disk, commodities with rougher surfaces, such as peaches, suffered a decrease in detection rate when ten peaches are swabbed with one foam disk. In order to maintain some consistency across the sample preparation process, a composite size of three units was selected. The varying topography of the commodities necessitated minor modifications to the method; for example, analysis of kiwi required that the hair on the surface be shaved prior to swabbing to achieve good recovery. Additionally, the effect of storage conditions on detection rate was analysed by spiking the surface of tomatoes at levels of 5 and 10 ng g(-1) for each pesticide, storing them under refrigeration and ambient conditions for 3 and 8 days, and then analysing the surface using this method. After 8 days of storage under both conditions more than 80% of the pesticides in the mixture were detected. Also, analysis of the multi-class mixtures was performed in both positive-and negative-ion mode and many classes were detected in both modes. Some classes, such thiocarbamates, phenylamides and organochlorine pesticides, were only observed in the positive-ion mode, whilst benzoylphenylurea pesticides were only detected in the negative-ion mode. C1 [Edison, S. E.; Lin, L. A.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. [Parrales, L.] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. RP Edison, SE (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM Sara.edison@fda.hhs.gov NR 14 TC 27 Z9 27 U1 3 U2 38 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. PY 2011 VL 28 IS 10 SI SI BP 1393 EP 1404 DI 10.1080/19440049.2011.596165 PG 12 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 848CW UT WOS:000297027500010 PM 21838598 ER PT J AU Cowley, SC Elkins, KL AF Cowley, Siobhan C. Elkins, Karen L. TI Immunity to Francisella SO FRONTIERS IN MICROBIOLOGY LA English DT Review DE Francisella; immunity; innate; adaptive; lymphocyte; cytokine AB In recent years, studies on the intracellular pathogen Francisella tularensis have greatly intensified, generating a wealth of new information on the interaction of this organism with the immune system. Here we review the basic elements of the innate and adaptive immune responses that contribute to protective immunity against Francisella species, with special emphasis on new data that has emerged in the last 5 years. Most studies have utilized the mouse model of infection, although there has been an expansion of work on human cells and other new animal models. In mice, basic immune parameters that operate in defense against other intracellular pathogen infections, such as interferon gamma, TNF-alpha, and reactive nitrogen intermediates, are central for control of Francisella infection. However, new important immune mediators have been revealed, including IL-17A, Toll-like receptor 2, and the inflammasome. Further, a variety of cell types in addition to macrophages are now recognized to support Francisella growth, including epithelial cells and dendritic cells. CD4+ and CD8+T cells are clearly important for control of primary infection and vaccine-induced protection, but new T cell subpopulations and the mechanisms employed by T cells are only beginning to be defined. A significant role for B cells and specific antibodies has been established, although their contribution varies greatly between bacterial strains of lower and higher virulence. Overall, recent data profile a pathogen that is adept at subverting host immune responses, but susceptible to many elements of the immune system's antimicrobial arsenal. C1 [Cowley, Siobhan C.; Elkins, Karen L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cowley, SC (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Div Bacterial Parasit & Allergen Prod,Off Vaccine, HFM 431,29 Lincoln Dr,Room 516, Bethesda, MD 20892 USA. EM siobhan.cowley@fda.hhs.gov NR 197 TC 49 Z9 50 U1 1 U2 4 PU FRONTIERS RESEARCH FOUNDATION PI LAUSANNE PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND SN 1664-302X J9 FRONT MICROBIOL JI Front. Microbiol. PY 2011 VL 2 AR 26 DI 10.3389/fmicb.2011.00026 PG 21 WC Microbiology SC Microbiology GA V31DE UT WOS:000208863500036 PM 21687418 ER PT B AU Patterson, TA Paule, MG AF Patterson, Tucker A. Paule, Merle G. BE Bolon, B Butt, MT TI COGNITIVE ASSESSMENTS IN NONHUMAN PRIMATES SO FUNDAMENTAL NEUROPATHOLOGY FOR PATHOLOGISTS AND TOXICOLOGISTS: PRINCIPLES AND TECHNIQUES LA English DT Article; Book Chapter ID OPERANT TEST BATTERY; BEHAVIORAL-TEST BATTERY; RHESUS-MONKEY PERFORMANCE; COMPLEX BRAIN-FUNCTION; WORKING-MEMORY; METHYLENEDIOXYMETHAMPHETAMINE MDMA; PROGRESSIVE RATIO; PREFRONTAL CORTEX; MARIJUANA SMOKE; ACQUISITION C1 [Patterson, Tucker A.; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Patterson, TA (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 47 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-93994-9; 978-0-470-22733-6 PY 2011 BP 115 EP 123 D2 10.1002/9780470939956 PG 9 WC Clinical Neurology; Toxicology SC Neurosciences & Neurology; Toxicology GA BA6JJ UT WOS:000337159300010 ER PT B AU Sarkar, S Schmued, L AF Sarkar, Sumit Schmued, Larry BE Bolon, B Butt, MT TI FLUORO-JADE DYES: FLUOROCHROMES FOR THE HISTOCHEMICAL LOCALIZATION OF DEGENERATING NEURONS SO FUNDAMENTAL NEUROPATHOLOGY FOR PATHOLOGISTS AND TOXICOLOGISTS: PRINCIPLES AND TECHNIQUES LA English DT Article; Book Chapter ID RAT FOREBRAIN; EXPOSURE; PROGRESSION; CORTEX; MARKER; MYELIN; NERVE; BRAIN C1 [Sarkar, Sumit; Schmued, Larry] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sarkar, S (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 22 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-93994-9; 978-0-470-22733-6 PY 2011 BP 171 EP 179 D2 10.1002/9780470939956 PG 9 WC Clinical Neurology; Toxicology SC Neurosciences & Neurology; Toxicology GA BA6JJ UT WOS:000337159300014 ER PT J AU Shields, JM AF Shields, Joan M. BE Fratamico, P Liu, Y Kathariou, S TI Cyclospora cayetanensis: a Review of the Genome SO GENOMES OF FOODBORNE AND WATERBORNE PATHOGENS LA English DT Review; Book Chapter ID COCCIDIAN PARASITES APICOMPLEXA; MOLECULAR PHYLOGENETIC ANALYSIS; TRANSCRIBED SPACER REGION; RIBOSOMAL-RNA GENE; REAL-TIME PCR; CRYPTOSPORIDIUM-PARVUM; CONTROLLED-TRIAL; EIMERIA-TENELLA; INFECTION; OUTBREAK C1 US FDA, Div Virulence Assessment, Virulence Mech Branch, Laurel, MD 20708 USA. RP Shields, JM (reprint author), US FDA, Div Virulence Assessment, Virulence Mech Branch, Laurel, MD 20708 USA. NR 78 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-457-1 PY 2011 BP 299 EP 308 PG 10 WC Food Science & Technology; Genetics & Heredity; Microbiology SC Food Science & Technology; Genetics & Heredity; Microbiology GA BTZ28 UT WOS:000288488300022 ER PT J AU Strauss, DG Poole, JE Wagner, GS Selvester, RH Miller, JM Rn, JA Johnson, G McNulty, SE Mark, DB Lee, KL Bardy, GH Wu, KC AF Strauss, David G. Poole, Jeanne E. Wagner, Galen S. Selvester, Ronald H. Miller, Julie M. Rn, Jill Anderson Johnson, George McNulty, Steven E. Mark, Daniel B. Lee, Kerry L. Bardy, Gust H. Wu, Katherine C. TI An ECG index of myocardial scar enhances prediction of defibrillator shocks: An analysis of the Sudden Cardiac Death in Heart Failure Trial SO HEART RHYTHM LA English DT Article DE Sudden death; Defibrillation; Electrocardiography; Electrophysiology; Tachyarrhythmias ID QRS SCORING SYSTEM; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; CARDIOVASCULAR MAGNETIC-RESONANCE; INFARCT TISSUE HETEROGENEITY; LEFT-VENTRICULAR DYSFUNCTION; ISCHEMIC CARDIOMYOPATHY; EJECTION FRACTION; SIZE; PERFORMANCE; VALIDATION AB BACKGROUND Only a minority of patients receiving implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden death receive appropriate shocks, yet almost as many are subjected to inappropriate shocks and device complications. Identifying and quantifying myocardial scar, which forms the substrate for ventricular tachyarrhythmias, may improve risk stratification. OBJECTIVE This study sought to determine whether the absence of myocardial scar detected by novel 12-lead electrocardiographic (ECG) Selvester QRS scoring criteria identifies patients with low risk for appropriate ICD shocks. METHODS We applied QRS scoring to 797 patients from the ICD arm of the Sudden Cardiac Death in Heart Failure Trial. Patients were followed up for a median of 45.5 months for ventricular tachycardia/fibrillation treated by the ICD or sudden tachyarrhythmic death (combined group referred to as VT/VF). RESULTS Increasing QRS score scar size predicted higher rates of VT/VF. Patients with no scar (QRS score = 0) represented a particularly low-risk cohort with 48% fewer VT/VF events than the rest of the population (absolute difference 11%; hazard ratio 0.52, 95% confidence interval 0.31 to 0.88). QRS score scar absence versus presence remained a significant prognostic factor after controlling for 10 clinically relevant variables. Combining QRS score (scar absence versus presence) with ejection fraction (>= 25% versus <25%) distinguished low-, middle-, and high-risk subgroups with 73% fewer VT/VF events in the low-risk versus high-risk group (absolute difference 22%; hazard ratio = 0.27, 95% confidence interval 0.12 to 0.62). CONCLUSION Patients with no scar by QRS scoring have significantly fewer VT/VF events. This inexpensive 12-lead ECG tool provides unique, incremental prognostic information and should be considered in risk-stratifying algorithms for selecting patients for ICDs. C1 [Strauss, David G.; Miller, Julie M.; Wu, Katherine C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Poole, Jeanne E.; Rn, Jill Anderson; Bardy, Gust H.] Seattle Inst Cardiac Res, Seattle, WA USA. [Wagner, Galen S.; Johnson, George; McNulty, Steven E.; Mark, Daniel B.; Lee, Kerry L.] Duke Clin Res Inst, Durham, NC USA. [Selvester, Ronald H.] Mem Hosp, Res Ctr, Long Beach, CA USA. RP Wu, KC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. EM kwu@jhmi.edu RI Strauss, David/A-9211-2012; OI Mark, Daniel/0000-0001-6340-8087 FU Sarnoff Cardiovascular Research Foundation (Great Falls, VA); Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University (Baltimore, MD); Doris Duke Charitable Foundation (New York, NY); NHLBI, National Institutes of Health [UO1 HL55766, UO1 HL55297, UO1 HL55496]; Medtronic; Wyeth-Ayerst Laboratories; Knoll Pharmaceuticals; Biotronik; Physio-Control; Welch-Allyn; Abbott Laboratories; Abbott Vascular Business; Abiomed; Acorn Cardiovascular; St. Jude Medical FX Dr. Strauss was supported by the Sarnoff Cardiovascular Research Foundation (Great Falls, VA) for work at Johns Hopkins, and has subsequently moved to the U.S. Food and Drug Administration. Views expressed do not represent those of the FDA. Dr. Wu and Dr. Miller were supported by the Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University (Baltimore, MD), and Dr. Miller was supported by the Doris Duke Charitable Foundation (New York, NY). The main SCD-HeFT study was supported by grants (UO1 HL55766, UO1 HL55297, and UO1 HL55496) from the NHLBI, National Institutes of Health, and by Medtronic, Wyeth-Ayerst Laboratories, and Knoll Pharmaceuticals. Dr. Poole has received speaking fees from Medtronic, Boston Scientific and St. Jude Medical, and a research grant from Biotronik. Dr. Wagner has received research support from Physio-Control and Welch-Allyn. Dr. Mark has received research support from Abbott Laboratories, Abbott Vascular Business, Abiomed, and Acorn Cardiovascular. Dr. Bardy has received research grants from St. Jude Medical, is a consultant for Phillips Medical and Cardiac Sciences, and is a board member and has equity and intellectual property in Cameron Health Inc. This study is registered at http://www.clinicaltrials.gov - identifier NCT00000609. Address reprint requests and correspondence: Dr. Katherine C. Wu, Division of Cardiology, Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 568, Baltimore, MD 21287. E-mail address: kwu@jhmi.edu. (Received August 19, 2010; accepted September 22, 2010.) NR 35 TC 28 Z9 30 U1 0 U2 6 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 JAN PY 2011 VL 8 IS 1 BP 38 EP 45 DI 10.1016/j.hrthm.2010.09.071 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 698VW UT WOS:000285622700010 PM 20884379 ER PT J AU Afdhal, NH McHutchison, JG Zeuzem, S Mangia, A Pawlotsky, JM Murray, JS Shianna, KV Tanaka, Y Thomas, DL Booth, DR Goldstein, DB AF Afdhal, Nezam H. McHutchison, John G. Zeuzem, Stefan Mangia, Alessandra Pawlotsky, Jean-Michel Murray, Jeffrey S. Shianna, Kevin V. Tanaka, Yasuhito Thomas, David L. Booth, David R. Goldstein, David B. CA Pharmacogenetics Hepatitis C TI Hepatitis C Pharmacogenetics: State of the Art in 2010 SO HEPATOLOGY LA English DT Review ID PEGYLATED INTERFERON-ALPHA; GENETIC-VARIATION; IL28B POLYMORPHISM; ANTIVIRAL ACTIVITY; RIBAVIRIN THERAPY; VIRUS-REPLICATION; IFN-LAMBDA; GENOTYPE 1; INFECTION; KINETICS AB In 2009, a correlated set of polymorphisms in the region of the interleukin-28B (IL28B) gene were associated with clearance of genotype 1 hepatitis C virus (HCV) in patients treated with pegylated interferon-alfa and ribavirin. The same polymorphisms were subsequently associated with spontaneous clearance of HCV in untreated patients. The link between IL28B genotype and HCV clearance may impact decisions regarding initiation of current therapy, the design and interpretation of clinical studies, the economics of treatment, and the process of regulatory approval for new anti-HCV therapeutic agents. (HEPATOLOGY 2011;53:336-345) C1 [Afdhal, Nezam H.] Beth Israel Deaconess Med Ctr, Div Gastroenterol & Hepatol, Boston, MA 02215 USA. [Afdhal, Nezam H.] Harvard Univ, Sch Med, Boston, MA 02215 USA. [McHutchison, John G.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Shianna, Kevin V.; Goldstein, David B.] Duke Univ, Med Ctr, Ctr Human Genome Variat, Durham, NC USA. [Zeuzem, Stefan] JW Goethe Univ Hosp, Dept Internal Med, Frankfurt, Germany. [Mangia, Alessandra] IRCCS Casa Sollievo Sofferenza, Div Gastroenterol, San Giovanni Rotondo, Italy. [Pawlotsky, Jean-Michel] Univ Paris EST, Hop Henri Mondor, Dept Virol, Creteil, France. [Murray, Jeffrey S.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Tanaka, Yasuhito] Nagoya City Univ, Dept Virol, Nagoya, Aichi, Japan. [Tanaka, Yasuhito] Nagoya City Univ, Liver Unit, Nagoya, Aichi, Japan. [Thomas, David L.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Booth, David R.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW, Australia. RP Afdhal, NH (reprint author), Beth Israel Deaconess Med Ctr, Div Gastroenterol & Hepatol, 110 Francis St, Boston, MA 02215 USA. EM nafdhal@caregroup.harvard.edu RI Fellay, Jacques/A-6681-2009 OI Fellay, Jacques/0000-0002-8240-939X FU Abbott Laboratories, Abbott Park, IL; Anadys Pharmaceuticals, Inc., San Diego, CA; Bristol-Myers Squibb, Princeton, NJ; Genentech, Inc., Hoboken, NJ; Gilead Sciences, Inc., Foster City, CA; Globe-Immune, Inc., Louisville, CO; Human Genome Sciences, Inc., Rockville, MD; Idera Pharmaceuticals, Inc., Cambridge, MA; LabCorp, Burlington, NC; Liver Institute for Education and Research, NJ; Medtronic, Inc., Minneapolis, MN; Merck & Co., Inc., Kenilworth, NJ; Monogram Business Sciences, Inc., South San Francisco, CA; Pharmasset, Inc., Princeton, NJ; Roche Laboratories, South San Francisco, CA; Roche Molecular Diagnostics, Pleasanton, CA; Roche Pharmaceuticals, Palo Alto, CA; Scynexis, Inc., Durham, NC; Tibotec BVBA, Beerse, Belgium; Tibotec, Inc., Titusville, NJ; Vertex Pharmaceuticals, Inc., Cambridge, MA; Virco BVBA, Beerse, Belgium; Abbott Laboratories; Anadys Pharmaceuticals; Bristol-Myers Squibb; Gilead Sciences, Inc.; Human Genome Sciences, Inc.; Idera Pharmaceuticals, Inc.; Liver Institute for Education and Research; Merck Co., Inc.; Pharmasset, Inc.; Scynexis, Inc.; Tibotec BVBA; Tibotec, Inc.; Vertex Pharmaceuticals, Inc.; Globe Immune, Inc.; Lab Corp; Medtronic, Inc.; Monogram Business Sciences, Inc.; Roche Laboratories; Roche Pharmaceuticals FX The costs of this meeting were sponsored by Abbott Laboratories, Abbott Park, IL; Anadys Pharmaceuticals, Inc., San Diego, CA; Bristol-Myers Squibb, Princeton, NJ; Genentech, Inc., Hoboken, NJ; Gilead Sciences, Inc., Foster City, CA; Globe-Immune, Inc., Louisville, CO; Human Genome Sciences, Inc., Rockville, MD; Idera Pharmaceuticals, Inc., Cambridge, MA; LabCorp, Burlington, NC; Liver Institute for Education and Research, NJ; Medtronic, Inc., Minneapolis, MN; Merck & Co., Inc., Kenilworth, NJ; Monogram Business Sciences, Inc., South San Francisco, CA; Pharmasset, Inc., Princeton, NJ; Roche Laboratories, South San Francisco, CA; Roche Molecular Diagnostics, Pleasanton, CA; Roche Pharmaceuticals, Palo Alto, CA; Scynexis, Inc., Durham, NC; Tibotec BVBA, Beerse, Belgium; Tibotec, Inc., Titusville, NJ; Vertex Pharmaceuticals, Inc., Cambridge, MA; and Virco BVBA, Beerse, Belgium.; John G. McHutchison, Kevin V. Shianna, and David B. Goldstein are coinventors of patents commercially protecting the use of IL28B and ITPA genetic variation to predict treatment response and anemia for patients undergoing treatment for chronic hepatitis C infection. Nezam H. Afdhal reports the following financial relationships: Abbott Laboratories (consulting, advisory arrangements), Anadys Pharmaceuticals (consulting, advisory arrangements), Bristol-Myers Squibb (consulting, speakers' bureau, research grants), Gilead Sciences, Inc. (consulting, speakers' bureau, research grants), Human Genome Sciences, Inc. (consulting, advisory arrangements, research grants), Idera Pharmaceuticals, Inc. (consulting), Liver Institute for Education and Research (director), Merck & Co., Inc. (consulting, advisory arrangements, speakers' bureau, research grants), Pharmasset, Inc. (consulting), Scynexis, Inc. (consulting), Tibotec BVBA (advisory arrangements), Tibotec, Inc. (consulting, advisory arrangements, research grants), Vertex Pharmaceuticals, Inc. (consulting, advisory arrangements, research grants). John G. McHutchison reports the following financial relationships: Abbott Laboratories (research grants), Anadys Pharmaceuticals (advisory arrangements, research grants), Bristol-Myers Squibb (advisory arrangements, research grants), Gilead Sciences, Inc. (stock ownership or equity, employment), Globe Immune, Inc. (advisory arrangements, research grants), Human Genome Sciences, Inc. (advisory arrangements, research grants), Idera Pharmaceuticals, Inc. (advisory arrangements, research grants), Lab Corp (consulting), Liver Institute for Education and Research (unrestricted grants), Medtronic, Inc. (research grants), Merck & Co., Inc. (advisory arrangements, research grants, intellectual property), Monogram Business Sciences, Inc. (advisory arrangements), Pharmasset, Inc. (consulting, research grants), Roche Laboratories (research grants), Roche Pharmaceuticals (research grants), Scynexis, Inc. (consulting, research grants), Tibotec BVBA (research grants), Tibotec, Inc. (research grants), Vertex Pharmaceuticals, Inc. (consulting, advisory arrangements, research grants). Stefan Zeuzem reports the following financial relationships: Abbott Laboratories (consulting), Anadys Pharmaceuticals (consulting), Bristol-Myers Squibb (consulting, speakers' bureau), Genentech (consulting, speakers' bureau), Gilead Sciences, Inc. (consulting, speakers' bureau), Human Genome Sciences, Inc. (consulting), Idera Pharmaceuticals, Inc. (consulting), Merck & Co., Inc. (consulting, speakers' bureau), Pharmasset, Inc. (consulting), Roche Molecular Diagnostics (speakers' bureau), Roche Pharmaceuticals (consulting, speakers' bureau), Tibotec BVBA (consulting), Vertex Pharmaceuticals, Inc. (consulting). Alessandra Mangia reports the following financial relationships: Merck & Co., Inc. (research grants), Roche Pharmaceuticals (advisory arrangements), Tibotec, Inc. (advisory arrangements). Jean-Michel Pawlotsky reports the following NR 26 TC 95 Z9 101 U1 1 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2011 VL 53 IS 1 BP 336 EP 345 DI 10.1002/hep.24052 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 709AB UT WOS:000286406300035 PM 21254181 ER PT S AU Singh, P Nayak, R Kwon, YM AF Singh, Pallavi Nayak, Rajesh Kwon, Young Min BE Kwon, YM Ricke, SC TI Target-Enrichment Through Amplification of Hairpin-Ligated Universal Targets for Next-Generation Sequencing Analysis SO HIGH-THROUGHPUT NEXT GENERATION SEQUENCING: METHODS AND APPLICATION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Target-enrichment; Multiple targets; Next-generation sequencing; Hairpin selector; PCR amplification ID MUTATION DISCOVERY; GENES AB With rapid development of next-generation sequencing (NGS) technologies, it is becoming increasingly feasible to sequence entire genomes of various organisms from virus to human. However, in many occasions, it is still more practical to sequence and analyze only small regions of the entire genome that arc informative for the purpose of the experiment. Although many target-enrichment or target capture methods exist, each method has its own strength and weakness in terms of the number of enriched targets, specificity, drop-off rate, and uniformity in capturing target DNA sequences. Many applications require a consistently low drop-off rate and high uniformity of enriched targets for routine collection of meaningful data. Here, we describe a simple and robust PCR-based protocol that can allow simultaneous amplification of numerous target regions. This method employs target-specific hairpin selectors to create DNA templates that contain target regions flanked by common universal priming sequences. We demonstrated the utility of this method by applying it for simultaneous amplification of 21 targets in the range of 191-604 bp from 41 different Salmonella strains using bar-coded universal primers. Analysis of 454 FLX pyrosequencing data demonstrated the promising performance of this method in terms of specificity and uniformity. This method, with great potential for robust amplification of hundreds of targets, should find broad applications for efficient analysis of multiple genomic targets for various experimental goals. C1 [Singh, Pallavi; Kwon, Young Min] Univ Arkansas, Cell & Mol Biol Program, Fayetteville, AR 72701 USA. [Nayak, Rajesh] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kwon, Young Min] Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. RP Singh, P (reprint author), Univ Arkansas, Cell & Mol Biol Program, Fayetteville, AR 72701 USA. OI Singh, Pallavi/0000-0002-0283-7459 NR 7 TC 5 Z9 5 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-088-1 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 733 BP 267 EP 278 DI 10.1007/978-1-61779-089-8_19 D2 10.1007/978-1-61779-089-8 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BUI26 UT WOS:000289444000019 PM 21431777 ER PT J AU Dormitzer, PR Galli, G Castellino, F Golding, H Khurana, S Del Giudice, G Rappuoli, R AF Dormitzer, Philip R. Galli, Grazia Castellino, Flora Golding, Hana Khurana, Surender Del Giudice, Giuseppe Rappuoli, Rino TI Influenza vaccine immunology SO IMMUNOLOGICAL REVIEWS LA English DT Review DE influenza; vaccine; immunology; pandemic; immunization; memory ID LIVE ATTENUATED INFLUENZA; A/DUCK/SINGAPORE/97 H5N3 VACCINE; HONG-KONG INFLUENZA; A VIRUS-VACCINES; MF59-ADJUVANTED INFLUENZA; ANTIBODY-RESPONSES; WHOLE-VIRUS; T-CELLS; B-CELLS; NEURAMINIDASE ANTIBODY AB Studying the spread of influenza in human populations and protection by influenza vaccines provides important insights into immunity against influenza. The 2009 H1N1 pandemic has taught the most recent lessons. Neutralizing and receptor-blocking antibodies against hemagglutinin are the primary means of protection from the spread of pandemic and seasonal strains. Anti-neuraminidase antibodies seem to play a secondary role. More broadly cross-reactive forms of immunity may lessen disease severity but are insufficient to prevent epidemic spread. Priming by prior exposure to related influenza strains through infection or immunization permits rapid, potent antibody responses to immunization. Priming is of greater importance to the design of immunization strategies than the immunologically fascinating phenomenon of dominant recall responses to previously encountered strains (original antigenic sin). Comparisons between non-adjuvanted inactivated vaccines and live attenuated vaccines demonstrate that both can protect, with some advantage of live attenuated vaccines in children and some advantage of inactivated vaccines in those with multiple prior exposures to influenza antigens. The addition of oil-in-water emulsion adjuvants to inactivated vaccines provides enhanced functional antibody titers, greater breadth of antibody cross-reactivity, and antigen dose sparing. The MF59 adjuvant broadens the distribution of B-cell epitopes recognized on HA and NA following immunization. C1 [Dormitzer, Philip R.; Galli, Grazia; Castellino, Flora; Del Giudice, Giuseppe; Rappuoli, Rino] Novartis Vaccines & Diagnost, Cambridge, MA 02139 USA. [Dormitzer, Philip R.; Galli, Grazia; Castellino, Flora; Del Giudice, Giuseppe; Rappuoli, Rino] Novartis Vaccines & Diagnost, Siena, Italy. [Golding, Hana; Khurana, Surender] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Dormitzer, PR (reprint author), Novartis Vaccines & Diagnost, 350 Massachusetts Ave, Cambridge, MA 02139 USA. EM philip.dormitzer@novartis.com RI Chiang, Vincent, Ming-Hsien/D-4312-2016 OI Chiang, Vincent, Ming-Hsien/0000-0002-2029-7863 NR 93 TC 86 Z9 88 U1 2 U2 26 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JAN PY 2011 VL 239 BP 167 EP 177 DI 10.1111/j.1600-065X.2010.00974.x PG 11 WC Immunology SC Immunology GA 700TE UT WOS:000285766400011 PM 21198671 ER PT J AU Jenkins, A Cote, C Twenhafel, N Merkel, T Bozue, J Welkos, S AF Jenkins, Amy Cote, Christopher Twenhafel, Nancy Merkel, Tod Bozue, Joel Welkos, Susan TI Role of Purine Biosynthesis in Bacillus anthracis Pathogenesis and Virulence SO INFECTION AND IMMUNITY LA English DT Article ID GUINEA-PIGS; PROTECTIVE ANTIGEN; ESCHERICHIA-COLI; MURINE MODEL; SALMONELLA-TYPHIMURIUM; NUCLEOSIDE TRANSPORT; SPORE GERMINATION; FULLY VIRULENT; MOUSE MODEL; SUBTILIS AB Bacillus anthracis, the etiological agent of anthrax, is a spore-forming, Gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon-mutagenized B. anthracis spores identified a mutant displaying an altered phenotype that harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine IMP. We constructed and characterized defined purH mutants of the virulent B. anthracis Ames strain. The virulence of the purH mutants was assessed in guinea pigs, mice, and rabbits. The spores of the purH mutants were as virulent as wild-type spores in mouse intranasal and rabbit subcutaneous infection models but were partially attenuated in a mouse intraperitoneal model. In contrast, the purH mutant spores were highly attenuated in guinea pigs regardless of the administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, since both bacilli and toxins were detected in vivo, suggesting that the significant attenuation was associated with a growth defect in vivo. We hypothesize that an intact purine biosynthetic pathway is required for the virulence of B. anthracis in guinea pigs. C1 [Jenkins, Amy; Cote, Christopher; Bozue, Joel; Welkos, Susan] USAMRIID, Bacteriol Div, Frederick, MD 21702 USA. [Twenhafel, Nancy] USAMRIID, Div Pathol, Frederick, MD 21702 USA. [Merkel, Tod] US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20014 USA. RP Welkos, S (reprint author), USAMRIID, Bacteriol Div, 1425 Porter St, Frederick, MD 21702 USA. EM Susan.welkos@us.army.mil FU Defense Threat Reduction Agency JSTO-CBD [02-4-5C-023] FX The research described here was sponsored by the Defense Threat Reduction Agency JSTO-CBD as 02-4-5C-023 (to S. W.)/Medical Research/Material Command Research Plan. NR 72 TC 23 Z9 23 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2011 VL 79 IS 1 BP 153 EP 166 DI 10.1128/IAI.00925-10 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 697WJ UT WOS:000285550200014 PM 21041498 ER PT J AU Bell, RL Gonzalez-Escalona, N Stones, R Brown, EW AF Bell, Rebecca L. Gonzalez-Escalona, Narjol Stones, Robert Brown, Eric W. TI Phylogenetic evaluation of the 'Typhimurium' complex of Salmonella strains using a seven-gene multi-locus sequence analysis SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Salmonella enterica; Phylogenetics; Multi-locus sequence analysis; Reference collection; Genetic diversity ID FIELD GEL-ELECTROPHORESIS; ENTERICA SEROVAR TYPHIMURIUM; ESCHERICHIA-COLI; POPULATION-STRUCTURE; TYPING DATA; EVOLUTIONARY; RECOMBINATION; PATHOGENS; INCONGRUENCE; CLONES AB Salmonella enterica comprises over 2500 serovars, many of which are significant foodborne pathogens in humans. The ability to subtype these microbes is difficult due to the highly clonal nature of many Salmonella strains and a lack of congruence among traditional typing approaches. This work examines the phylogenetic utility of a multi-locus sequence typing (MIST) approach to discriminate between members of a closely related collection of salmonellae, the Salmonella reference collection A (SARA). This 72 strain collection, referred to as the 'Typhimurium' complex, consists of S. Typhimurium and its four closest serological relatives. In this analysis, nucleotide sequences from seven housekeeping genes (aroC, dnaN, hemD, hisD, purE, sucA, and thrA) were PCR amplified, sequenced, and combined into a single concatenated character matrix providing 3360 bp for cladistic analysis. The resultant most parsimonious tree yielded seven clades of Salmonella strains that partitioned largely along serovar divisions within the collection except for five 'Paratyphi B' strains, two 'Saintpaul' strains, and two 'Typhimurium' strains. Convergence in the SARA tree was approximately 20% indicating that the vast majority of sequence changes were phylogenetically informative. Despite a high consistency among nucleotide substitutions, analysis of congruence identified several SARA strains with recombinant alleles in the concatenated matrix. These findings point to important differences among phylogenetic contributions made by the individual genes comprising this MLST dataset. Published by Elsevier B.V. C1 [Bell, Rebecca L.; Gonzalez-Escalona, Narjol; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Stones, Robert] Food & Environm Res Agcy, York YO41 1LZ, N Yorkshire, England. RP Bell, RL (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Mailstop HFS-712, College Pk, MD 20740 USA. EM rebecca.bell@fda.hhs.gov RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU Center for Food Safety and Applied Nutrition FX We are very grateful to E. Strain, M. Naum, J. Zheng, and M. Allard, for insightful comments and to E.F. Boyd for kindly contributing strains. R. Bell was supported in part by an appointment with the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by Oak Ridge Institute for Science and Education through and interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration NR 40 TC 11 Z9 11 U1 0 U2 6 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 JAN PY 2011 VL 11 IS 1 BP 83 EP 91 DI 10.1016/j.meegid.2010.10.005 PG 9 WC Infectious Diseases SC Infectious Diseases GA 711AT UT WOS:000286558800012 PM 20970525 ER PT J AU Trujillo, S Keys, CE Brown, EW AF Trujillo, Socrates Keys, Christine E. Brown, Eric W. TI Evaluation of the taxonomic utility of six-enzyme pulsed-field gel electrophoresis in reconstructing Salmonella subspecies phylogeny SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE Salmonella enterica; PFGE; Taxonomy; Phylogenetic analysis; Serovar; Subspecies; Cladistics; Congruence ID ESCHERICHIA-COLI O157-H7; HORIZONTAL GENE-TRANSFER; LENGTH DIFFERENCE TEST; REFERENCE COLLECTION; MOLECULAR PHYLOGENY; UNITED-STATES; STRAINS; RECOMBINATION; INCONGRUENCE; RELATEDNESS AB Pulsed-field gel electrophoresis (PFGE) remains an important tool in the molecular epidemiological evaluation of strains emerging from disease outbreak clusters. Recent studies of Escherichia coli O157:H7 and Salmonella Enteritidis have noted marked improvements in the discriminatory power of PFGE when combining band profiles from up to six restriction enzyme datasets into a single concatenated analysis. This approach has provided more accurate assignments of genetic relationships among closely related strains and allowed effective phylogenetic inference of host and geographical reservoirs. Although this approach enhances epidemiological congruence among closely related strains, it remains unclear to what extent six-enzyme PFGE pattern similarity reiterates evolutionary relatedness among more distantly related Salmonella strains (i.e., serovar or subspecies levels). Here, taxonomic accuracy of six-enzyme PFGE is tested phylogenetically across two distinct Salmonella enterica populations-Salmonella reference collection B (SARB), representing the breadth of taxonomic diversity of S. enterica subspecies I only, and Salmonella reference collection C (SARC), comprising the seven disparate subspecies of S. enterica plus S. bongori. Cladistic analysis of SAR strains revealed substantial polyphyly between the two strain collections such that numerous SARB strains clustered more closely with diverged SARC subspecies rather than with other members of subspecies I. Also, in several cases, SARC sibling strains from the same subspecies were evolutionary obscured-broken into distant locales on the most parsimonious six-enzyme trees. Genetic diversity among SARB and SARC strains was comparable at 45% and 47%, respectively, while congruence testing revealed discordance among individual enzyme datasets. While six-enzyme PFGE is effective in ascertaining accurate genetic relationships for more closely related strains (e.g, strains within the same serovar), reconstitution of evolutionarily meaningful strain groupings may be elusive for Salmonella at the serovar level and above. Thus, caution is warranted when applying PFGE with a limited number of enzymes as the primary phylogenetic marker in these instances. Published by Elsevier B.V. C1 [Trujillo, Socrates; Keys, Christine E.; Brown, Eric W.] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trujillo, S (reprint author), US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,Mailstop HFS-712, College Pk, MD 20740 USA. EM socrates.trujillo@gmail.com NR 44 TC 6 Z9 6 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 EI 1567-7257 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JAN PY 2011 VL 11 IS 1 BP 92 EP 102 DI 10.1016/j.meegid.2010.10.004 PG 11 WC Infectious Diseases SC Infectious Diseases GA 711AT UT WOS:000286558800013 PM 20959148 ER PT S AU Graff, CG Myers, KJ AF Graff, Christian G. Myers, Kyle J. BE Szekely, G Hahn, HK TI The Ideal Observer Objective Assessment Metric for Magnetic Resonance Imaging Application to Signal Detection Tasks SO INFORMATION PROCESSING IN MEDICAL IMAGING SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 22nd International Conference on Information Processing in Medical Imaging (IPMI) CY JUL 03-08, 2011 CL GERMANY SP Swiss Natl Ctr Competence Res Comp-Aided & Image-Guided Med Intervent (NCCR Co-Me), Bayer HealthCare, Diagnost Imaging, MeVis Med Solut AG, Siemens AG, HealthCare Sect, Zurich Ctr Imaging Sci & Technol (CIMST) ID NOISE MEASUREMENTS; SNR; PERFORMANCE AB The ideal Bayesian observer is a mathematical construct which makes optimal use of all statistical information about the object and imaging system to perform a task. Its performance serves as an upper bound on any observer's task performance. In this paper a methodology based on the ideal observer for assessing magnetic resonance (MR) acquisition sequences and reconstruction algorithms is developed. The ideal observer in the context of MR imaging is defined and expressions for ideal observer performance metrics are derived. Comparisons are made between the raw-data ideal observer and image-based ideal observer to elucidate the effect of image reconstruction on task performance. Lesion detection tasks are studied in detail via analytical expressions and simulations. The effect of imaging sequence parameters on lesion detectability is shown and the advantages of this methodology over image quality metrics currently in use in MR imaging is demonstrated. C1 [Graff, Christian G.; Myers, Kyle J.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD USA. RP Graff, CG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD USA. EM christian.graff@fda.hhs.gov NR 10 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-642-22091-3 J9 LECT NOTES COMPUT SC PY 2011 VL 6801 BP 760 EP 771 PG 12 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Radiology, Nuclear Medicine & Medical Imaging GA BAW91 UT WOS:000305885000062 ER PT J AU Fischhoff, B AF Fischhoff, Baruch BE Fischhoff, B Chauvin, C TI Communicating About Analysis SO INTELLIGENCE ANALYSIS: BEHAVIORAL AND SOCIAL SCIENTIFIC FOUNDATIONS LA English DT Article; Book Chapter ID DECISION-MAKING; PROBABILITY; FORECASTS; MODELS; RISK C1 [Fischhoff, Baruch] Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. [Fischhoff, Baruch] Carnegie Mellon Univ, Dept Engn & Publ Policy, Pittsburgh, PA 15213 USA. [Fischhoff, Baruch] Soc Risk Anal, New York, NY USA. [Fischhoff, Baruch] Soc Judgment & Decis Making, Washington, DC USA. [Fischhoff, Baruch] Amer Psychol Soc, Washington, DC USA. [Fischhoff, Baruch] Amer Psychol Assoc, Washington, DC USA. [Fischhoff, Baruch] US FDA, Risk Commun Advisory Comm, Rockville, MD 20857 USA. [Fischhoff, Baruch] US EPA, Sci Advisory Board, Homeland Secur Advisory Comm, Washington, DC USA. RP Fischhoff, B (reprint author), Carnegie Mellon Univ, Dept Social & Decis Sci, Pittsburgh, PA 15213 USA. NR 54 TC 1 Z9 1 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 978-0-309-17698-9 PY 2011 BP 227 EP 248 PG 22 WC Multidisciplinary Sciences; Social Sciences, Interdisciplinary SC Science & Technology - Other Topics; Social Sciences - Other Topics GA BC4IE UT WOS:000352541500015 ER PT S AU Stokes, WS Kulpa-Eddy, J McFarland, R AF Stokes, William S. Kulpa-Eddy, Jodie McFarland, Richard BE KulpaEddy, J McFarland, R Stokes, WS TI The International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing: introduction and summary SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE veterinary vaccines; human vaccines; ICCVAM; potency testing; safety testing; alternatives ID INACTIVATED RABIES VACCINES; QUALITY-CONTROL; RECOMMENDATIONS; CHALLENGE AB Vaccines contribute to improved animal and human health and welfare by preventing diseases and deaths from infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of available alternative methods and approaches that can further reduce, refine, and replace the use of animals for human and veterinary vaccine potency and safety testing, and to identify research, development, and validation efforts necessary to further advance new and improved alternative methods. Workshop participants identified human and veterinary vaccines that should have the highest priority for future efforts. Prioritization criteria included testing that involves significant pain and distress, large numbers of animals, and pathogens that are dangerous to people and animals. Participants noted that in vitro antigen quantification assays have replaced animals for potency testing for some killed vaccines, and recommended that this approach be expanded to other vaccines. Recommendations to support more humane animal use included development and use of humane endpoints for all challenge tests, development of serologic assays to replace challenge tests, and development of in vitro toxin neutralization tests (TNT) to replace in vivo TNTs. Workshop participants recommended several approaches that might further reduce the number of animals required for specific potency tests. Participants also recommended priority vaccines for which alternative safety testing methods should be pursed and that would have the greatest impact on avoiding pain and distress and reducing animal numbers. Finally, workshop participants recommended enhanced international harmonization and cooperation efforts and closer collaborations between human and veterinary researchers to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will reduce animal use, benefit animal welfare, and ensure continued and improved protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Stokes, William S.] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. [Kulpa-Eddy, Jodie] US Dept, Agr Anim & Plant Hlth Inspect Serv Vet Serv, Riverdale, MD USA. [McFarland, Richard] US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM stokes@niehs.nih.gov NR 58 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 1 EP 15 DI 10.1016/j.provac.2011.10.001 PG 15 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900001 ER PT S AU McFarland, R Verthelyi, D Casey, W Arciniega, J Isbrucker, R Schmitt, M Finn, T Descamps, J Horiuchi, Y Sesardic, D Stickings, P Johnson, NW Lipscomb, E Allen, D AF McFarland, Richard Verthelyi, Daniela Casey, Warren Arciniega, Juan Isbrucker, Richard Schmitt, Michael Finn, Theresa Descamps, Johan Horiuchi, Yoshinobu Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Lipscomb, Elizabeth Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Non-animal replacement methods for human vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine potency testing; vaccine safety testing; replacement alternatives; ICCVAM ID RABIES VACCINES; ANIMAL-MODELS; UNITED-STATES; COMBINATION; ELISA AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. This report addresses methods and strategies identified by workshop participants for replacement of animals used for potency testing of human vaccines. Vaccines considered to have the highest priority for future efforts were (1) vaccines for which antigen quantification methods are already developed but not validated, (2) vaccines/components that require the largest number of animals, (3) vaccines that require an in vivo challenge test, and (4) vaccines with in vivo tests that are highly variable and cause a significant number of invalid tests. Vaccine potency tests identified as the highest priorities for replacement were those for diphtheria and tetanus, pertussis (whole cell and acellular), rabies, anthrax, polio vaccine (inactivated) and complex combination vaccines based on DT or DTwP/aP. Research into understanding the precise mechanism of protection afforded by vaccines and the identification of clinically relevant immunological markers are needed to facilitate the successful implementation of in vitro testing alternatives. This report also identifies several priority human vaccines and associated research objectives that are necessary to successfully implement in vitro vaccine potency testing alternatives. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [McFarland, Richard; Casey, Warren] NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [McFarland, Richard; Arciniega, Juan; Schmitt, Michael; Finn, Theresa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Casey, Warren] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Ctr Evaluat Alternat Toxicol Methods, Natl Toxicol Program Interagency, Morrisville, NC USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON, Canada. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy Japan, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Standards & Control, Hlth Protect Agcy, Ridge, England. [Johnson, Nelson W.; Lipscomb, Elizabeth; Allen, David] Integrated Lab Syst Inc, Morrisville, NC USA. RP Casey, W (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM warren.casey@nih.gov NR 70 TC 9 Z9 9 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 16 EP 32 DI 10.1016/j.provac.2011.10.002 PG 17 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900002 ER PT S AU Casey, W Schmitt, M McFarland, R Isbrucker, R Levis, R Arciniega, J Descamps, J Finn, T Hendriksen, C Horiuchi, Y Keller, J Kojima, H Sesardic, D Stickings, P Johnson, NW Lipscomb, E Allen, D AF Casey, Warren Schmitt, Michael McFarland, Richard Isbrucker, Richard Levis, Robin Arciniega, Juan Descamps, Johan Finn, Theresa Hendriksen, Coenraad Horiuchi, Yoshinobu Keller, James Kojima, Hajime Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Lipscomb, Elizabeth Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Improving animal welfare and reducing animal use for human vaccine potency testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine potency testing; vaccine safety testing; refinement alternatives; reduction alternatives; ICCVAM ID QUALITY-CONTROL; VALIDATION AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use. Topics were addressed in detail by speakers and workshop participants and are reported in a series of six reports. This workshop report, the third in the series, addresses methods and strategies for human vaccine potency testing that can refine animal use to lessen pain and distress, improve animal welfare, and reduce animal use. Workshop participants agreed that the following potency tests for human vaccines should have the highest priority for development of reduction and/or refinement methods: (1) potency tests for vaccines that are most commonly used, (2) potency tests that require the largest number of animals, (3) potency tests that cause severe animal pain and distress, (4) potency tests where the knowledge base of each antigen is advanced, and (5) potency tests for which alternative methods already exist or are in development. Based on these criteria, the highest-priority human vaccines were identified as diphtheria and tetanus vaccines, pertussis vaccines (whole cell and acellular), rabies vaccine, anthrax vaccine, and complex combination vaccines (containing diphtheria, tetanus, and pertussis together with other antigens such as IPV, Hib, and HepB). For successful implementation of reduction and refinement alternatives, further research is required into the development and broader use of humane endpoints, serological potency methods, and approaches that would reduce the number of animals used in currently approved potency assays. Because the workshop focused on both human and veterinary vaccines, workshop participants also recommended that human vaccine potency testing methods for rabies and tetanus be reviewed for their potential application to the corresponding veterinary vaccines. Participants agreed that achieving broader acceptance and use of alternative methods, requires that the general principles and procedures for the validation of alternative methods for vaccines be standardized/harmonized internationally. The research, development, validation, and harmonization activities recommended at this workshop are expected to lead to new reduction and/or refinement of animal use in human vaccine potency testing methods and more widespread adoption of existing methods that can reduce animal use and improve animal welfare while ensuring the continued safety and efficacy of human vaccines. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Casey, Warren] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. [Schmitt, Michael; McFarland, Richard; Levis, Robin; Arciniega, Juan; Finn, Theresa; Keller, James] United States Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evalut, Ottawa, ON, Canada. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Hendriksen, Coenraad] Netherlands Vaccine Inst, Bilthoven, Netherlands. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy, Tokyo, Japan. [Kojima, Hajime] Japanese Ctr Validat Alternat Methods, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Hertford, England. [Johnson, Nelson W.; Lipscomb, Elizabeth; Allen, David] Integrated Syst Lab Inc, Res Triangle Pk, NC USA. RP Casey, W (reprint author), Natl Inst Environm Hlth Sci, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, POB 12233, Res Triangle Pk, NC 27709 USA. EM warren.casey@nih.gov NR 66 TC 11 Z9 11 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 33 EP 46 DI 10.1016/j.provac.2011.10.003 PG 14 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900003 ER PT S AU Isbrucker, R Levis, R Casey, W McFarland, R Schmitt, M Arciniega, J Descamps, J Finn, T Hendriksen, C Horiuchi, Y Keller, J Kojima, H Sesardic, D Stickings, P Johnson, NW Allen, D AF Isbrucker, Richard Levis, Robin Casey, Warren McFarland, Richard Schmitt, Michael Arciniega, Juan Descamps, Johan Finn, Theresa Hendriksen, Coenraad Horiuchi, Yoshinobu Keller, James Kojima, Hajime Sesardic, Dorothea Stickings, Paul Johnson, Nelson W. Allen, David BE KulpaEddy, J McFarland, R Stokes, WS TI Alternative methods and strategies to reduce, refine, and replace animal use for human vaccine post-licensing safety testing: state of the science and future directions SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine safety testing; vaccine potency testing; 3Rs alternatives; ICCVAM ID QUALITY-CONTROL; PERTUSSIS TOXIN; POLIOVIRUS; ENDOTOXIN; ASSAY AB NICEATM and ICCVAM convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing methods, and to identify opportunities to advance new and improved methods that can further reduce, refine, and replace animal use (the 3Rs). Six topics were addressed in detail by speakers and workshop participants and are reported in a series of reports. This workshop report, the fifth in the series, addresses methods and strategies for human vaccine post-licensing safety testing that can reduce, refine, and replace animal use. It also provides recommendations for priority research and other activities necessary to advance the development and/or implementation of 3Rs methods for human vaccine post-licensing safety testing. Workshop participants agreed that future 3Rs activities should give highest priority to vaccine safety tests that (1) use the most animals per test and for which many vaccine lots are tested annually, (2) produce high variability and/or require frequent repeat tests, (3) are associated with severe animal pain and distress, and/or (4) involve nonhuman primates. Based on these criteria, safety tests for diphtheria, pertussis, oral polio, and tetanus vaccines were identified as the highest priorities. Recommended priority research, development, and validation activities included (1) expanding use of the transgenic mouse model for oral polio vaccine, and (2) developing alternatives to the monkey neurovirulence test for preclinical safety and lot release neurovirulence testing of mumps vaccines. Implementation of the workshop recommendations is expected to advance alternative in vitro methods for human vaccine post-licensing safety testing that will benefit animal welfare while ensuring continued production of safe human vaccines and protection of human and animal health. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of the National Toxicology Program Interagency for the Evaluation of Alternative Toxicological Methods (NICEATM). C1 [Casey, Warren] NIEHS, Natl Toxicol Program Interagency Ctr, Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, Res Triangle Pk, NC USA. [Isbrucker, Richard] Hlth Canada, Ctr Vaccine Evaluat, Ottawa, ON, Canada. [Levis, Robin; McFarland, Richard; Schmitt, Michael; Arciniega, Juan; Finn, Theresa; Keller, James] US FDA, Ctr Biol Evaluat & Res, Rockville, MD USA. [Descamps, Johan] GlaxoSmithKline Biol, Rixensart, Belgium. [Hendriksen, Coenraad] Netherlands Vaccine Inst, Bilthoven, Netherlands. [Horiuchi, Yoshinobu] Pharmaceut & Med Devices Agcy Japan, Tokyo, Japan. [Kojima, Hajime] Japanese Ctr Validat Alternat Methods, Tokyo, Japan. [Sesardic, Dorothea; Stickings, Paul] Natl Inst Biol Stand & Controls, Hlth Protect Agcy, Hertford, England. [Johnson, Nelson W.; Allen, David] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Casey, W (reprint author), NIEHS, Natl Toxicol Program Interagency Ctr, Evaluat Alternat Toxicol Methods, Div Natl Toxicol Program, Res Triangle Pk, NC USA. EM warren.casey@nih.gov NR 66 TC 9 Z9 9 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 106 EP 119 DI 10.1016/j.provac.2011.10.004 PG 14 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900007 ER PT S AU Finn, TM AF Finn, Theresa M. BE KulpaEddy, J McFarland, R Stokes, WS TI US FDA requirements for human vaccine product safety and potency testing SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE human vaccines; vaccine potency testing; vaccine safety testing; FDA requirements; alternative methods AB The Office of Vaccines Research and Review (OVRR) at the Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA) regulates preventative and therapeutic vaccines for infectious disease indications for use in humans. The framework for regulation of biological products includes Statutes (e.g. The U. S. Food, Drug and Cosmetic Act and the Public Health Service Act), regulations as defined in the Code of Federal Regulations (CFR) and guidance documents. Approval of a biologics license for a product, including vaccines, is based on a demonstration of safety, purity, and potency and assurance that the facility for manufacture, processing, and packaging meets standards to ensure that product released for distribution is safe, pure and potent. The regulatory definitions of safety, purity and potency are detailed in Title 21 of the Code of Federal regulations (CFR) Part 600. All manufacturing information including tests for safety, purity, and potency for a particular product must be documented in the Biologics License Application (BLA). Potency testing may be performed on the final bulk sample or final container sample and may consist of either in vivo or in vitro tests or both. To change a potency or safety test post-licensure requires a Supplement to the License and data to support a modified or alternative test. CBER encourages the development and use of appropriate alternative methods for vaccine safety and potency testing. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Integrated Laboratory Systems, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Finn, TM (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM theresa.finn@fda.hhs.gov NR 0 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 137 EP 140 DI 10.1016/j.provac.2011.10.010 PG 4 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900010 ER PT S AU Keller, JE AF Keller, James E. BE KulpaEddy, J McFarland, R Stokes, WS TI Overview of currently approved serological methods with a focus on diphtheria and tetanus toxoid potency testing SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE tetanus; diphtheria; toxoid; potency ID INHIBITION TOBI TEST; CELL-CULTURE METHOD; TOXIN NEUTRALIZATION; ANTITOXIN TITRATION; CLOSTRIDIAL TOXINS; GUINEA-PIGS; VERO CELLS; HUMAN-SERA; VACCINES; ALUM AB Vaccines are biological products made from living organisms. The natural complexity of biological molecules along with the inherent uncertainties of product manufacturing introduces the likelihood that random alterations can impact the quality of the vaccine each time it is made. The factors that can affect the final product are often unknown. Testing for potency of vaccine bulk or product dispensed into final containers was designed with the hope of ensuring that a vaccine is effective when used during its approved dating period and that its protective activity was not inadvertently altered during any phase of production. Ideally, potency testing measures a biological or biochemical property of the vaccine that is related to its ability to elicit protective immunity in the target population and provide some assurance that consistent clinical benefit is derived from each lot of product. Potency methods vary depending on the nature and composition of the vaccine. In vivo potency testing might entail immunizing groups of laboratory animals and then challenging them directly to measure survival, or involve serological potency assays in which sera from immunized laboratory animals are tested for the ability to neutralize pathogens or toxins. In the U.S., diphtheria toxoid and tetanus toxoid potency tests have customarily involved a serological method. This approach uses fewer animals than would have been required using a direct challenge method, while providing satisfactory evidence that each toxoid lot could induce protective immunity. This paper will discuss the details of the original U. S. test method for diphtheria and tetanus toxoid potency and present issues that must be considered when developing and validating non-animal-based approaches to refine or replace these tests. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Integrated Laboratory Systems, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM james.keller@fda.hhs.gov NR 49 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 192 EP 199 DI 10.1016/j.provac.2011.10.019 PG 8 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900019 ER PT S AU Arciniega, JL Dominguez-Castillo, RI AF Arciniega, Juan L. Dominguez-Castillo, Rocio I. BE KulpaEddy, J McFarland, R Stokes, WS TI Development and validation of serological methods for human vaccine potency testing: case study of an anthrax vaccine SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE potency testing; anthrax; TNA ID PROTECTIVE ANTIGEN; TOXIN NEUTRALIZATION; BACILLUS-ANTHRACIS; LETHAL TOXIN; BINDING; ELISA; MICE AB Only one anthrax vaccine (Anthrax Vaccine Adsorbed, AVA) is licensed in the US to date, although new vaccines are under development. Logistic difficulties with the potency testing of AVA, plus humane considerations, have prompted the development of an alternative test method that can be used as a potency test not only for AVA, but also for newer vaccines. A potency test is not limited to measuring the concentration and quality of the antigen in the final formulation at the time of vaccine release, but should also detect changes in these characteristics during the dating period of the product, to ensure that the vaccine has retained its potency. We have developed a mouse immunogenicity test with potential for use as a potency test for anthrax vaccines. This model is based on the measurement of antibodies induced by a fixed dose of antigen. The test consists of two stages: a) the induction of antibodies in mice with one pre-selected test dose of vaccine; and b) the measurement of the response. We have established the test dose for AVA and experimental vaccines based on the use of anthrax Protective Antigen (PA). Two types of assays, an ELISA and a toxin neutralization assay (TNA) have been employed to measure antibodies to PA. TNA may be more useful in predicting vaccine efficacy, since it measures the neutralizing activity of sera against the cytotoxic effect of the toxin formed by PA when associated with Lethal Factor. However, anti-PA ELISA is less demanding from a technical point of view. Therefore, if ELISA were capable of detecting accurately changes in antigen quantity and quality, then it could be selected as the antibody-measuring test. Studies in our laboratory suggest that even though ELISA and TNA results are correlated, they may not be strictly interchangeable for quantification of anti-PA antibodies after a single immunization of mice with a test dose of anthrax vaccine. We have also found that TNA is better suited than ELISA to detect changes in immunogenicity caused by vaccine exposure to high temperature for very short periods (two minutes). These results open the possibility that an immunogenicity test in which TNA is used to quantify the anti-PA antibody responses can be used to measure vaccine potency of anthrax vaccines at the end of the manufacturing process and periodically after the finished product has been placed in storage, instead of an active protection test that requires lethal challenge. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Integrated Laboratory Systems, Inc. C1 [Arciniega, Juan L.; Dominguez-Castillo, Rocio I.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Arciniega, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM juan.arciniega@fda.hhs.gov NR 18 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 213 EP 220 DI 10.1016/j.provac.2011.10.021 PG 8 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900021 ER PT S AU Arciniega, JL Corvette, L Hsu, H Lynn, F Romani, T Dobbelaer, R AF Arciniega, Juan L. Corvette, Laura Hsu, Henry Lynn, Freyja Romani, Theresa Dobbelaer, Roland BE KulpaEddy, J McFarland, R Stokes, WS TI Target alternative vaccine safety testing strategies for pertussis toxin SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE pertussis; vaccine; testing ID HISTAMINE-SENSITIZATION TEST; ADP-RIBOSYLATION ACTIVITY; BORDETELLA-PERTUSSIS; RESIDUAL ACTIVITY; QUALITY-CONTROL; ASSAY; CELL; LOCUS; BPHS; RESPONSIVENESS AB All acellular pertussis (aP) vaccines in use contain chemically inactivated pertussis toxin (PT). The finding that mice, naturally resistant to the effects of histamine, become sensitive upon injection of minute amounts of PT, led to the development of the test for residual PT known as the histamine sensitization assay (HSA). The HSA used by U. S.-licensed manufacturers is a limit test that shows that the residual bioactivity of PT in a single human dose of vaccine is below a threshold. Limit tests do not allow quantitative measurement. When the method is newly established at the point of use, three or more dilutions of pure PT are used to verify that mice injected with the vaccine came from a shipment that have sensitivity consistent with historical values. Sensitizability is expressed as an HSD50 (the dose that sensitizes 50% of a group of mice). However, once linearity of the dose response has been demonstrated, the assay may be simplified so as to include in each test only a single control group injected with PT. This assay simplification constitutes an example of the so-called "consistency approach." A Japanese variant of the HSA uses a drop in body temperature as a nonlethal alternative index of PT-mediated sensitization and can provide a quantitative estimate of the residual PT activity of a vaccine. However, the advantage of a quantitative method is not obvious, because the amount of PT that is unsafe for humans is unknown. In addition, although the use of a nonlethal endpoint constitutes an important refinement, the need for a reference group in the test to obtain a quantitative estimate increases the number of animals required, relative to the number used in a simplified limit test. Moreover, the nonlethal endpoint might be adapted to the limit test format, and important steps have been taken in this regard. Finally, one option under early evaluation is the possibility of using the results from two in vitro assays, an enzymatic activity assay and a binding assay, to replace the HSA. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Integrated Laboratory Systems, Inc. C1 [Arciniega, Juan L.; Corvette, Laura; Hsu, Henry; Lynn, Freyja; Romani, Theresa] US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. [Dobbelaer, Roland] Inst Scientigique Sante Publique, Brussels, Belgium. RP Arciniega, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM juan.arciniega@fda.hhs.gov NR 42 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 248 EP 260 DI 10.1016/j.provac.2011.10.026 PG 13 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900026 ER PT S AU Rubin, SA AF Rubin, Steven A. BE KulpaEddy, J McFarland, R Stokes, WS TI Toward replacement of the monkey neurovirulence test in vaccine safety testing SO INTERNATIONAL WORKSHOP ON ALTERNATIVE METHODS TO REDUCE, REFINE, AND REPLACE THE USE OF ANIMALS IN VACCINE POTENCY AND SAFETY TESTING: STATE OF THE SCIENCE AND FUTURE DIRECTIONS SE Procedia in Vaccinology LA English DT Proceedings Paper CT International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing - State of the Science and Future Directions CY SEP 14-16, 2010 CL Bethesda, MD DE vaccine; neurovirulence safety testing; monkey; MAPREC; MPS ID ORAL POLIOVIRUS VACCINE; MUMPS-VIRUS NEUROVIRULENCE; RHESUS-MONKEYS; RAT-BRAIN; MICE; LIVE AB For live, attenuated vaccines derived from neurotropic wild-type viruses, regulatory authorities require neurovirulence safety testing, typically using monkeys, to assure the absence of residual neurotoxicity. Ethical concerns surrounding the use of nonhuman primates in product testing, coupled with questions over its predictive value, has resulted in a concerted effort to replace monkey-based neurovirulence safety testing with more informative, validated alternative methods that include the use of lower animal species (e.g., mice and rats) and/or in vitro assays such as mutation analysis by PCR and restriction enzyme cleavage (MAPREC). MAPREC is a WHO-approved screening tool to assess reversion to neurovirulence of oral poliovirus vaccine (OPV). Monitoring the genetic consistency of OPV lots by identification and quantification of the mutational profile using the recently developed technology of massively parallel sequencing (MPS) also holds promise not only as a replacement for nonhuman primate testing of OPV lots but for other vaccines for which animal-based tests are currently performed as a measure of manufacturing consistency and freedom of adventitious virus contamination. In many cases, the greatest hurdle to availability of such alternative methods has been the process rather than the science. This report summarizes the current status of alternative methods of neurovirulence safety testing, both those validated and those currently in development. (C) 2011 Published by Elsevier Ltd. Selection and/or peer-review under responsibility of Integrated Laboratory Systems, Inc. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Steven.rubin@fda.hhs.gov NR 24 TC 7 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2011 VL 5 BP 261 EP 265 DI 10.1016/j.provac.2011.10.027 PG 5 WC Public, Environmental & Occupational Health; Immunology; Medicine, Research & Experimental SC Public, Environmental & Occupational Health; Immunology; Research & Experimental Medicine GA BYU28 UT WOS:000300380900027 ER PT J AU Handy, SM Deeds, JR Ivanova, NV Hebert, PDN Hanner, RH Ormos, A Weigt, LA Moore, MM Yancy, HF AF Handy, Sara M. Deeds, Jonathan R. Ivanova, Natalia V. Hebert, Paul D. N. Hanner, Robert H. Ormos, Andrea Weigt, Lee A. Moore, Michelle M. Yancy, Haile F. TI A Single-Laboratory Validated Method for the Generation of DNA Barcodes for the Identification of Fish for Regulatory Compliance SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHYLOGENETIC TREES; SEAFOOD; LIFE AB The U.S. Food and Drug Administration is responsible for ensuring that the nation's food supply is safe and accurately labeled. This task is particularly challenging in the case of seafood where a large variety of species are marketed, most of this commodity is imported, and processed product is difficult to identify using traditional morphological methods. Reliable species identification is critical for both foodborne illness investigations and for prevention of deceptive practices, such as those where species are intentionally mislabeled to circumvent import restrictions or for resale as species of higher value. New methods that allow accurate and rapid species identifications are needed, but any new methods to be used for regulatory compliance must be both standardized and adequately validated. "DNA barcoding" is a process by which species discriminations are achieved through the use of short, standardized gene fragments. For animals, a fragment (655 base pairs starting near the 5' end) of the cytochrome c oxidase subunit 1 mitochondrial gene has been shown to provide reliable species level discrimination in most cases. We provide here a protocol with single-laboratory validation for the generation of DNA barcodes suitable for the identification of seafood products, specifically fish, in a manner that is suitable for FDA regulatory use. C1 [Handy, Sara M.; Deeds, Jonathan R.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ivanova, Natalia V.; Hebert, Paul D. N.] Univ Guelph, Biodivers Inst Ontario, Canadian Ctr DNA Barcoding, Guelph, ON N1G 2W1, Canada. [Hanner, Robert H.] Univ Guelph, Dept Integrat Biol, Guelph, ON N1G 2W1, Canada. [Ormos, Andrea; Weigt, Lee A.] Smithsonian Inst, Natl Museum Nat Hist, Labs Analyt Biol, Washington, DC 20013 USA. [Moore, Michelle M.] US FDA, Off Regulatory Affairs, Pacific Reg Lab NW, Appl Technol Ctr, Bothell, WA 98021 USA. [Yancy, Haile F.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP Handy, SM (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Sara.Handy@fda.hhs.gov RI Handy, Sara/C-6195-2008; Hebert, Paul/C-4161-2013 OI Hebert, Paul/0000-0002-3081-6700 FU Genome Canada through the Ontario Genomics Institute; Natural Sciences and Engineering Research Council of Canada; Advanced Foods and Materials Network FX We would like to thank Karen Blickenstaff (FDA Center for Veterinary Medicine) for instruction and support on the ABI 3730 sequencer; Jeff Williams and Jerry Finan (Fish Division of NMNH) for fish authentication; Errol Strain (FDA Center for Food Safety and Applied Nutrition) for his help with data analysis; and Yolanda Jones (FDA Center for Veterinary Medicine) for sample preparation. The pilot studies carried out at CCDB were supported by grants to P.D.N.H. from Genome Canada through the Ontario Genomics Institute, and Natural Sciences and Engineering Research Council of Canada. We also acknowledge the laboratory assistance of Heather Braid during pilot studies conducted in the Department of Integrative Biology at the University of Guelph, with grant support to R.H.H. from Advanced Foods and Materials Network. NR 32 TC 55 Z9 59 U1 3 U2 33 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 JAN-FEB PY 2011 VL 94 IS 1 BP 201 EP 210 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 719QA UT WOS:000287222000024 PM 21391497 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung K. TI Determination of Operating Characteristic, Retesting, and Testing Amount Probabilities Associated with Testing for the Presence of Salmonella in Foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The relatively small perceived probability associated with retesting a food for the presence of Salmonella at low levels is often considered as one of the reasons that a confirmatory or check-analysis tends to disagree in practice with the results of an original test. Given a retesting process where a retest is only performed to confirm an original positive Salmonella test, the probability that both the original and retest will test positive for Salmonella has been traditionally determined by some as the product of the probabilities of a positive Salmonella test for the original and retest samples. When examining the probabilities associated with the retesting process, we found that our results disagreed with those based on intuitions apparently held by others concerning how these probabilities should be calculated. For Salmonella testing, operating characteristic values were computed to demonstrate the protections afforded by the Salmonella sampling plans presented in the U.S. Food and Drug Administration's Bacteriological Analytical Manual and to obtain the probability of a positive Salmonella test. The geometric distribution was examined for possible utility in determining the probabilities associated with testing amounts, i.e., the number of Salmonella tests needed to obtain a positive test. C1 [McClure, Foster D.; Lee, Jung K.] US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. RP McClure, FD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Def Commun & Emergency Response, Div Publ Hlth & Biostat, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM fdmc5100@yahoo.com NR 8 TC 1 Z9 1 U1 1 U2 2 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 JAN-FEB PY 2011 VL 94 IS 1 BP 327 EP 334 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 719QA UT WOS:000287222000038 PM 21391511 ER PT J AU Peredeltchouk, M David, SAW Bhattacharya, B Volokhov, DV Chizhikov, V AF Peredeltchouk, M. David, S. A. Wilson Bhattacharya, B. Volokhov, D. V. Chizhikov, V. TI Detection of mycoplasma contamination in cell substrates using reverse transcription-PCR assays SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE 16S rRNA; detection; mycoplasma; PCR; reverse transcription ID RIBOSOMAL-RNA; NUCLEIC-ACIDS; BACTERIA; AMPLIFICATION; TECHNOLOGY; DIAGNOSIS; BLOOD AB Aims: To assess the limit of detection (LOD) and the feasibility of 16S rRNA-based reverse transcription-PCR (RT-PCR) assays for advanced detection of mycoplasma contamination in cell substrates. Materials and Methods: The RT-PCR approach is based on detecting the 16S rRNA molecules that, in contrast to genomic bacterial DNA, are represented by multiple copies in mycoplasma cell. The number of 16S rRNA molecules in mycoplasma cells of five species i.e. Mycoplasma arginini, Myc. fermentans, Myc. hyorhinis, Myc. orale and Acholeplasma laidlawii, all known to be frequent cell line contaminants in industrial and research laboratories, was measured using molecular methods. The results of two independently prepared mycoplasma cultures harvested at the stationary phase of their growth showed that the 16S rRNA copy number per cell varied in the range from about 400 to 2000 copies, depending on species, but stayed close between different preparations of one species. The assessment of the LOD of the in-house 16S rRNA-based RT-PCR was performed using samples of MDCK cell culture spiked with different amounts of five aforementioned mycoplasma species. To minimize the bias in methods comparison, the LOD of the RT-PCR assay was expressed in terms of genome equivalents (GEs) and compared with that determined for highly optimized 16S rDNA-based mycoplasma testing methods previously described in scientific literature. Conclusions: The results of the study showed that the in-house 16S rRNA-based RT-PCR assay was able to reliably detect the presence of less than one mycoplasma GE that is at least 10-fold higher of the LOD previously determined for well-optimized 16S rDNA-based assays developed and described by other researchers. Significance and Impact of the Study: The results of the study showed that rapid RT-PCR methods based on the detection of bacterial 16S rRNA are able to expedite mycoplasma testing of cell cultures (1-2 days vs 28 days) and to ensure the limits of detection comparable to that of currently used culture-based mycoplasma testing methods. C1 [Chizhikov, V.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, Rockville, MD 20852 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM vladimir.chizhikov@fda.hhs.gov NR 17 TC 5 Z9 6 U1 0 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD JAN PY 2011 VL 110 IS 1 BP 54 EP 60 DI 10.1111/j.1365-2672.2010.04853.x PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 693EO UT WOS:000285207600006 PM 20854458 ER PT J AU Li, Q Zheng, G Tiwari, R AF Li, Q. Zheng, G. Tiwari, R. TI Analysis of ordered categorical data with score averaging: with applications to case-control genetic associations SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE case-control genetic associations; MAX; ordered categorical data; robustness; score averaging tests; trend tests ID GENOME-WIDE ASSOCIATION; NUISANCE PARAMETER; STATISTICAL-METHODS; CONTINGENCY-TABLES; TREND TESTS; RISK; DRAWBACKS; MAXIMUM; CANCER; CHOICE AB The trend test is often used for the analysis of 2 x K ordered categorical data, in which K pre-specified increasing scores are used. There have been discussions on how to assign these scores and the impact of the outcomes on different scores. The scores are often assigned based on the data-generating model. When this model is unknown, using the trend test is not robust. We discuss the weighted average of a trend test over all scientifically plausible choices of scores or models. This approach is more computationally efficient than a commonly used robust test MAX when K is large. Our discussion is for any ordered 2 x K table, but simulation and applications to real data are focused on case-control genetic association studies. Although there is no single test optimal for all choices of scores, our numerical results show that some score averaging tests can achieve the performance of MAX. C1 [Li, Q.] Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. [Zheng, G.] US Natl Heart Lung & Blood Inst, Off Biostat Res, Bethesda, MD 20892 USA. [Tiwari, R.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. RP Li, Q (reprint author), Chinese Acad Sci, Acad Math & Syst Sci, Beijing 100190, Peoples R China. EM liqz@amss.ac.cn FU National Young Science Foundation of China [10901155] FX The work of Q. Li was supported in part by the National Young Science Foundation of China (grant 10901155). NR 24 TC 1 Z9 1 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2011 VL 38 IS 9 BP 1833 EP 1843 DI 10.1080/02664763.2010.529881 PG 11 WC Statistics & Probability SC Mathematics GA 873YF UT WOS:000298921300006 ER PT J AU Goodman, MS Li, Y Tiwari, RC AF Goodman, Melody S. Li, Yi Tiwari, Ram C. TI Detecting multiple change points in piecewise constant hazard functions SO JOURNAL OF APPLIED STATISTICS LA English DT Article DE survival analysis; change points; piecewise constant; hazard function; cancer ID 2-PHASE REGRESSION; RATE MODEL; INFERENCE; LIKELIHOOD; CANCER AB The National Cancer Institute (NCI) suggests a sudden reduction in prostate cancer mortality rates, likely due to highly successful treatments and screening methods for early diagnosis. We are interested in understanding the impact of medical breakthroughs, treatments, or interventions, on the survival experience for a population. For this purpose, estimating the underlying hazard function, with possible time change points, would be of substantial interest, as it will provide a general picture of the survival trend and when this trend is disrupted. Increasing attention has been given to testing the assumption of a constant failure rate against a failure rate that changes at a single point in time. We expand the set of alternatives to allow for the consideration of multiple change-points, and propose a model selection algorithm using sequential testing for the piecewise constant hazard model. These methods are data driven and allow us to estimate not only the number of change points in the hazard function but where those changes occur. Such an analysis allows for better understanding of how changing medical practice affects the survival experience for a patient population. We test for change points in prostate cancer mortality rates using the NCI Surveillance, Epidemiology, and End Results dataset. C1 [Goodman, Melody S.] SUNY Stony Brook, Grad Program Publ Hlth, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA. [Li, Yi] Harvard Univ, Dept Biostat, Boston, MA 02115 USA. [Li, Yi] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Goodman, MS (reprint author), Washington Univ, Sch Med, Dept Surg, Div Publ Hlth Sci, St Louis, MO 63110 USA. EM goodmanm@wudosis.wustl.edu RI Goodman, Melody/F-6768-2011 OI Goodman, Melody/0000-0001-8932-624X FU National Institute of Child Health and Human Development [5 F31 HD043695]; National Institute of Health [R01CA95747] FX The research of M. S. G. was supported by National Institute of Child Health and Human Development grant 5 F31 HD043695. The research of Y.L. was supported by National Institute of Health grant R01CA95747. Views expressed by R. C. T. here are his own and do not necessarily represent those of Food and Drug Administration. NR 17 TC 13 Z9 13 U1 2 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0266-4763 J9 J APPL STAT JI J. Appl. Stat. PY 2011 VL 38 IS 11 BP 2523 EP 2532 DI 10.1080/02664763.2011.559209 PG 10 WC Statistics & Probability SC Mathematics GA 873YY UT WOS:000298923300010 PM 22707842 ER PT J AU Soon, GX AF Soon, Guoxing (Greg) TI Missing Data-Moving Forward SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clinical trial; External data; Missing data; Prevention; Treatment C1 US FDA, Div Biometr 4, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Soon, GX (reprint author), US FDA, Div Biometr 4, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,WO21-3606, Silver Spring, MD 20993 USA. EM Guoxing.Soon@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 177 EP 179 AR PII 934433288 DI 10.1080/10543406.2011.550093 PG 3 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800001 PM 21390994 ER PT J AU Campbell, G Pennello, G Yue, L AF Campbell, Gregory Pennello, Gene Yue, Lilly TI Missing Data in the Regulation of Medical Devices SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian statistics; Diagnostic medical tests; Nonrandomized studies; Propensity scores; Sensitivity analysis; Verification bias ID DIAGNOSTIC-TESTS; CLINICAL-TRIALS; GOLD STANDARD; VERIFICATION; IMPUTATION; CANCER; ISSUES; BIAS AB Handling missing data is an important consideration in the analysis of data from all kinds of medical device studies. Missing data in medical device studies can arise for all the reasons one might expect in pharmaceutical clinical trials. In addition, they occur by design, in nonrandomized device studies, and in evaluations of diagnostic tests. For dichotomous endpoints, a tipping point analysis can be used to examine nonparametrically the sensitivity of conclusions to missing data. In general, sensitivity analysis is an important tool to study deviations from simple assumptions about missing data, such as the data being missing at random. Approaches to missing data in Bayesian trials are discussed, including sensitivity analysis. Many types of missing data that can occur with diagnostic test evaluations are surveyed. Careful planning and conduct are recommended to minimize missing data. Although difficult, the prespecification of all missing data analysis strategies is encouraged before any data are collected. C1 [Campbell, Gregory; Pennello, Gene; Yue, Lilly] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Campbell, G (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM greg.campbell@fda.hhs.gov NR 26 TC 12 Z9 13 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 180 EP 195 AR PII 934436658 DI 10.1080/10543406.2011.550094 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800002 PM 21390995 ER PT J AU Scott, JA Hsu, H AF Scott, John A. Hsu, Henry TI Missing Data Issues at the FDA Center for Biologics Evaluation and Research SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Biologics; Blood; FDA guidance; Missing data; Vaccines AB Missing data in clinical trials pose a tremendous problem in the regulatory setting. The U.S. Food and Drug Administration relies on statistically rigorous evidence of safety and efficacy as a precondition for granting marketing approval for drugs, biologics, and many devices. The presence of missing data can compromise the integrity of any statistical analysis, further complicating a regulatory decision-making process with significant public health, legal, and financial implications. We review the unique missing data challenges faced by the Center for Biologics Evaluation and Research and discuss limitations in our current approach to these issues and potential directions for improvement. C1 [Scott, John A.; Hsu, Henry] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Scott, JA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-219, Rockville, MD 20852 USA. EM John.Scott@fda.hhs.gov OI Scott, John/0000-0002-9116-948X NR 3 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 196 EP 201 AR PII 934435323 DI 10.1080/10543406.2011.550095 PG 6 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800003 PM 21390996 ER PT J AU Berger, VW Vali, B AF Berger, Vance W. Vali, Behrang TI Intent-to-Randomize Corrections for Missing Data Resulting from Run-In Selection Bias in Clinical Trials for Chronic Conditions SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Enrichment; Intent-to-Randomize; Missing Completely at Random; Run-in ID PHYSICIANS-HEALTH; ENRICHMENT; PERIOD; EFFICIENCY; VALIDITY; DESIGNS AB In many clinical trials for chronic conditions a run-in period is used prior to randomization. Often, only those participants who meet certain criteria during the run-in phase go on to get randomized. The others, along with the information that they might have provided, are excluded from the study. This exclusion of the relevant response data from any subsequent study analysis can be considered as resulting in missing data; although quite common in practice, this approach has expectedly been shown to create a bias in favor of the active treatment when this active treatment is used during the run-in. Hence, many randomized clinical trials report overly optimistic results, with the extent of the bias depending in large part on how many otherwise eligible subjects were excluded due to the use of the run-in. If these biased trials are to contribute valid information to medical decision making, then the biases need to be corrected, and this involves accounting for all participants who were intended to be randomized. We propose specific imputation methods for doing so. C1 [Berger, Vance W.] NCI, EPN, Bethesda, MD 20892 USA. [Vali, Behrang] US FDA, Div Biometr 3, OB OTS CDER, Silver Spring, MD USA. RP Berger, VW (reprint author), NCI, EPN, Suite 3131,6130 Execut Blvd, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 25 TC 5 Z9 5 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 263 EP 270 AR PII 934436828 DI 10.1080/10543406.2011.550107 PG 8 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800007 PM 21391000 ER PT J AU Li, XB Caffo, BS AF Li, Xianbin Caffo, Brian S. TI Comparison of Proportions for Composite Endpoints with Missing Components SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Comparison of proportions; Maximum likelihood estimator; Missing data; Three-component composite endpoint ID CROSS-CLASSIFIED DATA; CONTINGENCY-TABLES AB Composite endpoints are commonly used in clinical trials. When there are missing values in their individual components, inappropriate handling of the missingness may create inefficient or even biased estimates of the proportions of successes in composite endpoints. Assuming missingness is completely at random or dependent on baseline covariates, we derived a maximum likelihood estimator of the proportion of successes in a three-component composite endpoint and closed-form variance for the proportion, and compared two groups in the difference in proportions and in the logarithm of a relative risk. Sample size and statistical power were studied. Simulation studies were used to evaluate the performance of the developed methods. With a moderate sample size the developed methods works satisfactorily. C1 [Li, Xianbin] US FDA, Silver Spring, MD USA. [Caffo, Brian S.] Johns Hopkins Univ, Baltimore, MD USA. RP Li, XB (reprint author), CDER OTS OB OBIV, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM xianbin.li@fda.hhs.gov FU FDA/CDER [08-42] FX The research is supported by the FDA/CDER Regulatory Science and Review Enhancement program (RSR #08-42). The authors would like to thank the anonymous referees for their thoughtful suggestions, which greatly improved the paper. NR 6 TC 0 Z9 0 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 271 EP 281 AR PII 934436775 DI 10.1080/10543406.2011.550109 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800008 PM 21391001 ER PT J AU Kim, Y AF Kim, Yongman TI Missing Data Handling in Chronic Pain Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE BOCF; Chronic pain trial; Continuous responder analysis; LOCF; Missing data; Two-part model analysis ID LONGITUDINAL CLINICAL-TRIALS AB In chronic pain trials, proper handling of missing data due to dropout is an important issue because the dropout rate is high and the study conclusion may depend on the method chosen. The intent-to-treat (ITT) principle usually requires imputations for missing data to include the dropouts as well as completers in the statistical analysis. However, a statistical analysis with imputation might lead to a misinterpretation of clinical data. In chronic pain trials, treatment-related dropouts are clinical outcomes themselves. For example, an early dropout due to toxicity usually indicates a treatment failure, as does a dropout due to lack of efficacy. Problems with traditional methods such as last observation carried forward (LOCF) or baseline observation carried forward (BOCF) are identified especially in the chronic pain setting. Alternative methods, such as continuous responder analysis and two-part model analysis, treating dropouts as clinical events, are introduced with an example of osteoarthritis clinical trial data. C1 US FDA, Silver Spring, MD 20993 USA. RP Kim, Y (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yongman.kim@fda.hhs.gov NR 9 TC 15 Z9 15 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 311 EP 325 AR PII 934434071 DI 10.1080/10543406.2011.550112 PG 15 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800011 PM 21391004 ER PT J AU Dinh, P Yang, PL AF Dinh, Phillip Yang, Peiling TI Handling Baselines in Repeated Measures Analyses with Missing Data at Random SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Baseline; Longitudinal data; Missing at random; MMRM ID CLINICAL-TRIALS; COVARIANCE; LIKELIHOOD; INFERENCE; MODELS AB In longitudinal clinical studies, after randomization at baseline, subjects are followed for a period of time for development of symptoms. A mixed model for repeated measures (MMRM) can be used to analyze data from such studies. Fitzmaurice et al. (2004) outlined five approaches for handling baseline responses in an MMRM analysis. They are: (1) Retain the baselines as part of the outcome vector and make no assumptions about group differences in the mean response at baseline. (2) Retain the baselines as part of the outcome vector and assume the group means are equal at baseline. (3) Subtract the baselines from all of the remaining post-baseline responses, and analyze the differences from baseline. (4) Use the baselines as a covariate in the analysis of the post-baseline responses, assuming homogeneous regression slopes. (5) Use the baselines as a covariate in the analysis of the post-baseline responses, allowing different regression slopes. In this paper, we evaluate these five approaches in the presence of data missing at random. We evaluate the approaches based on the bias of the estimate and the coverage accuracy of the confidence interval. The results suggest that strategies 2 and 5 are recommended. C1 [Dinh, Phillip; Yang, Peiling] US FDA, Div Biometr 1, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Dinh, P (reprint author), US FDA, Div Biometr 1, Off Biostat Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 21,Room 4633, Silver Spring, MD 20993 USA. EM Phillip.Dinh@fda.hhs.gov NR 24 TC 1 Z9 1 U1 1 U2 8 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 2 SI SI BP 326 EP 341 AR PII 934432268 DI 10.1080/10543406.2011.550113 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 733RZ UT WOS:000288281800012 PM 21391005 ER PT J AU Siddiqui, O AF Siddiqui, Ohidul TI MMRM versus MI in Dealing with Missing DataA Comparison Based on 25 NDA Data Sets SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE LOCF; MAR; Missing data; MMRM analysis; Multiple imputation ID CLINICAL-TRIALS; MULTIPLE IMPUTATION; LONGITUDINAL DATA; DROP-OUT; SPECIFICATION; MODELS; ERROR; LOCF AB Both multiple imputation (MI) and mixed-effects model repeated measures (MMRM) approaches appear to be better choices than the traditional last-observation-carried-forward (LOCF) approach in analyzing incomplete clinical trial data sets in drug development research. However, relative performances of these two approaches are unknown in controlling type I error rate and statistical power in the hypothesis testing of determining the efficacy of an investigational drug. Little research has been done in comparing robustness of the two approaches in analyzing ignorable missing data of clinical trials. In this research, a comparison between the MI and MMRM approaches is made in analyzing the simulated incomplete data sets and 25 New Drug Application (NDA) data sets of neuropsychiatric drug products. The MMRM approach appears to be a better choice in maintaining statistical properties of a test as compared to the MI approach in dealing with ignorable missing data of clinical trials. C1 US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Siddiqui, O (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Av,Rm 4606, Silver Spring, MD 20993 USA. EM ohidul.siddiqui@fda.hhs.gov NR 32 TC 10 Z9 11 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 3 BP 423 EP 436 AR PII 935354193 DI 10.1080/10543401003777995 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 742QA UT WOS:000288958200004 PM 21442517 ER PT J AU Huque, MF Alosh, M Bhore, R AF Huque, Mohammad F. Alosh, Mohamed Bhore, Rafia TI Addressing Multiplicity Issues of a Composite Endpoint and Its Components in Clinical Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Composite endpoint; Component endpoints; Multiple testing ID STRATEGY AB Randomized controlled clinical trials often use a composite endpoint as a primary endpoint especially when treatment effects or frequency of individual components of the composite are likely to be small and combining them makes clinical sense for the disease under study. An advantage of the composite endpoint is that, as it combines multiple endpoints to a single endpoint, it reduces or eliminates the multiplicity problem of testing multiple endpoints. In addition, accumulating evidence from individual endpoints into the composite endpoint can lead to better study power and reduce the study size and the duration of the trial. However, composite endpoints can also lead to ambiguous findings and consequently cause difficulty in interpreting study results, for example, when individual component endpoints of a composite show treatment effects in different directions. Also, multiplicity issues will arise if a study sponsor seeks efficacy claims for specific components of the composite or for a targeted subgroup of patients. This paper visits some of these issues and presents some solutions through applications of multiple testing strategies. C1 [Huque, Mohammad F.] US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Alosh, Mohamed] US FDA, Div Biometr 3, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Bhore, Rafia] Univ Texas SW Med Ctr Dallas, Div Biostat, Dept Clin Sci, Dallas, TX 75390 USA. RP Huque, MF (reprint author), US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Bldg 21,Room 3510,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mohammad.huque@fda.hhs.gov NR 22 TC 24 Z9 24 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 4 SI SI BP 610 EP 634 AR PII 936782823 DI 10.1080/10543406.2011.551327 PG 25 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 754GA UT WOS:000289841700004 PM 21516560 ER PT J AU Dmitrienko, A Kordzakhia, G Tamhane, AC AF Dmitrienko, Alex Kordzakhia, George Tamhane, Ajit C. TI Multistage and Mixture Parallel Gatekeeping Procedures in Clinical Trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Closure principle; Familywise error rate; Multiple comparisons; Mixture procedure; Parallel gatekeeping ID MULTIPLE TESTS AB Gatekeeping procedures have been developed to solve multiplicity problems arising in clinical trials with hierarchical objectives where the null hypotheses that address these objectives are grouped into ordered families. A general method for constructing multistage parallel gatekeeping procedures was proposed by Dmitrienko et al. (2008). The objective of this paper is to study two related classes of parallel gatekeeping procedures. Restricting to two-family hypothesis testing problems, we first use the mixture method developed in Dmitrienko and Tamhane (2011) to define a class of parallel gatekeeping procedures derived using the closure principle that can be more powerful than multistage gatekeeping procedures. Second, we show that power of multistage gatekeeping procedures can also be improved by using -exhaustive tests for the component procedures. Extensions of these results for multiple families are stated. Illustrative examples from clinical trials are given. C1 [Dmitrienko, Alex] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Kordzakhia, George] US FDA, Silver Spring, MD USA. [Tamhane, Ajit C.] Northwestern Univ, Evanston, IL USA. RP Dmitrienko, A (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM dmitrienko_alex@lilly.com RI Tamhane, Ajit/B-7495-2009 NR 20 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 4 SI SI BP 726 EP 747 AR PII 936782666 DI 10.1080/10543406.2011.551333 PG 22 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 754GA UT WOS:000289841700010 PM 21516566 ER PT J AU Wang, SJ Hung, HMJ O'Neill, R AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert TI Regulatory Perspectives on Multiplicity in Adaptive Design Clinical Trials throughout a Drug Development Program SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Confirmatory; Exploratory; Learn and confirm; Probability of correct decision; Probability of correct selection; Probability of success ID GROUP-SEQUENTIAL TRIALS; STATISTICAL CONSIDERATIONS; HYPOTHESES SELECTION; 2-STAGE DESIGN; SAMPLE-SIZE; END-POINTS; INTERIM; BOUNDARIES; PATIENT; WIZARD AB A clinical research program for drug development often consists of a sequence of clinical trials that may begin with uncontrolled and nonrandomized trials, followed by randomized trials or randomized controlled trials. Adaptive designs are not infrequently proposed for use. In the regulatory setting, the success of a drug development program can be defined to be that the experimental treatment at a specific dose level including regimen and frequency is approved based on replicated evidence from at least two confirmatory trials. In the early stage of clinical research, multiplicity issues are very broad. What is the maximum tolerable dose in an adaptive dose escalation trial? What should the dose range be to consider in an adaptive dose-ranging trial? What is the minimum effective dose in an adaptive dose-response study given the tolerability and the toxicity observable in short term or premarketing trials? Is establishing the dose-response relationship important or the ability to select a superior treatment with high probability more important? In the later stage of clinical research, multiplicity problems can be formulated with better focus, depending on whether the study is for exploration to estimate or select design elements or for labeling consideration. What is the study objective for an early-phase versus a later phase adaptive clinical trial? How many doses are to be studied in the early exploratory adaptive trial versus in the confirmatory adaptive trial? Is the intended patient population well defined or is the applicable patient population yet to be adaptively selected in the trial due to the potential patient and/or disease heterogeneity? Is the primary efficacy endpoint well defined or still under discussion providing room for adaptation? What are the potential treatment indications that may adaptively lead to an intended-to-treat patient population and the primary efficacy endpoint? In this work we stipulate the multiplicity issues with adaptive designs encountered in regulatory applications. For confirmatory adaptive design clinical trials, controlling studywise type I error and type II error is of paramount importance. For exploratory adaptive trials, we define the probability of correct selection of design features, e.g., dose, effect size, and the probability of correct decision for drug development. We assert that maximizing these probabilities would be critical to determine whether the drug development program continues or how to plan the confirmatory trials if the development continues. C1 [Wang, Sue-Jane; O'Neill, Robert] US FDA, Off Biostat, OTS, CDER, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, OB, OTS,CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS, CDER, 10903 New Hampshire Ave,Bldg 21,HFD-710,Mail Stop, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU Center for Drug Evaluation and Research of the U.S. Food and Drug Administration [05-02, 05-14] FX The regulatory research work presented here was supported by the RSR funds, number 05-02, 05-14, provided by Center for Drug Evaluation and Research of the U.S. Food and Drug Administration. The authors thank Dr. Martin Posch, the guest editor for this special issue, for the kind invitation for publication. The research views expressed in this paper are the authors' professional views and not necessarily those of the U.S. Food and Drug Administration. NR 43 TC 2 Z9 2 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 4 SI SI BP 846 EP 859 AR PII 936782866 DI 10.1080/10543406.2011.552878 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 754GA UT WOS:000289841700017 PM 21516573 ER PT J AU Li, XF Xu, YL AF Li, Xuefeng Xu, Yunling TI BAYESIAN APPROACHES FOR MEDICAL PRODUCT EVALUATION-TODAY AND TOMORROW SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 [Li, Xuefeng; Xu, Yunling] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Li, XF (reprint author), US FDA, Div Biostat, OSB CDRH, 10903 New Hamsphire Ave, Silver Spring, MD 20993 USA. EM xuefeng.li@fda.hhs.gov; yun-ling.xu@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 869 EP 870 DI 10.1080/10543406.2012.589291 PG 2 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900001 PM 21830919 ER PT J AU Campbell, G AF Campbell, Gregory TI BAYESIAN STATISTICS IN MEDICAL DEVICES: INNOVATION SPARKED BY THE FDA SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adaptive designs; Bayesian hierarchical models; Implants; Noninferiority; Software ID CLINICAL-TRIALS; ATRIAL-FIBRILLATION; DIAGNOSTIC-TESTS; GOLD STANDARD; PREVALENCE; EXPERIENCE; OUTCOMES; THERAPY; ABSENCE; DESIGN AB Bayesian statistical methodology has been used for more than 10 years in medical device premarket submissions to the U.S. Food and Drug Administration (FDA). A complete list of the publicly available information associated with these FDA applications is presented. In addition to the increasing number of Bayesian methodological papers in the statistical journals, a number of successful Bayesian clinical trials in the biomedical journals have been recently reported. Some challenges that require more methodological development are discussed. The promise of using Bayesian methods for incorporation of prior information as well as for conducting adaptive trials is great. C1 US FDA, Div Biostat, Silver Spring, MD 20993 USA. RP Campbell, G (reprint author), US FDA, Div Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Greg.campbell@fda.hhs.gov NR 35 TC 11 Z9 12 U1 0 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 871 EP 887 DI 10.1080/10543406.2011.589638 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900002 PM 21830920 ER PT J AU Gamalo, MA Wu, R Tiwari, RC AF Gamalo, Mark A. Wu, Rui Tiwari, Ram C. TI BAYESIAN APPROACH TO NONINFERIORITY TRIALS FOR PROPORTIONS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian criterion; Bayesian paradigm; Beta-binomial; Noninferiority margin; Normal approximation ID NON-INFERIORITY TRIALS; ACTIVE-CONTROL TRIALS; STATISTICAL-METHODS; PLACEBO; ISSUES AB Noninferiority trials are unique because they are dependent upon historical information in order to make meaningful interpretation of their results. Hence, a direct application of the Bayesian paradigm in sequential learning becomes apparently useful in the analysis. This paper describes a Bayesian procedure for testing noninferiority in two-arm studies with a binary primary endpoint that allows the incorporation of historical data on an active control via the use of informative priors. In particular, the posteriors of the response in historical trials are assumed as priors for its corresponding parameters in the current trial, where that treatment serves as the active control. The Bayesian procedure includes a fully Bayesian method and two normal approximation methods on the prior and/or on the posterior distributions. Then a common Bayesian decision criterion is used but with two prespecified cutoff levels, one for the approximation methods and the other for the fully Bayesian method, to determine whether the experimental treatment is noninferior to the active control. This criterion is evaluated and compared with the frequentist method using simulation studies in keeping with regulatory framework that new methods must protect type I error and arrive at a similar conclusion with existing standard strategies. Results show that both methods arrive at comparable conclusions of noninferiority when applied to a modified real data set. The advantage of the proposed Bayesian approach lies in its ability to provide posterior probabilities for effect sizes of the experimental treatment over the active control. C1 [Gamalo, Mark A.; Tiwari, Ram C.] US FDA, Off Biostat, Silver Spring, MD 20993 USA. [Wu, Rui] Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. RP Gamalo, MA (reprint author), US FDA, Off Biostat, Silver Spring, MD 20993 USA. EM Mark.Gamalo@fda.hhs.gov NR 15 TC 8 Z9 8 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 902 EP 919 DI 10.1080/10543406.2011.589646 PG 18 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900004 PM 21830922 ER PT J AU Bonangelino, P Irony, T Liang, SD Li, XF Mukhi, V Ruan, SL Xu, YL Yang, XT Wang, CG AF Bonangelino, Pablo Irony, Telba Liang, Shengde Li, Xuefeng Mukhi, Vandana Ruan, Shiling Xu, Yunling Yang, Xiting Wang, Chenguang TI BAYESIAN APPROACHES IN MEDICAL DEVICE CLINICAL TRIALS: A DISCUSSION WITH EXAMPLES IN THE REGULATORY SETTING SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian adaptive designs; Bayesian hierarchical models; Clinical significance; Multiregional clinical trial; Prior distribution; Regulatory agency; Subgroup analysis ID MULTIREGIONAL TRIAL; SAMPLE-SIZE; REGIONS AB Challenging statistical issues often arise in the design and analysis of clinical trials to assess safety and effectiveness of medical devices in the regulatory setting. The use of Bayesian methods in the design and analysis of medical device clinical trials has been increasing significantly in the past decade, not only due to the availability of prior information, but mainly due to the appealing nature of Bayesian clinical trial designs. The Center for Devices and Radiological Health at the Food and Drug Administration (FDA) has gained extensive experience with the use of Bayesian statistical methods and has identified some important issues that need further exploration. In this article, we discuss several topics relating to the use of Bayesian statistical methods in medical device trials, based on our experience and real applications. We illustrate the benefits and challenges of Bayesian approaches when incorporating prior information to evaluate the effectiveness and safety of a medical device. We further present an example of a Bayesian adaptive clinical trial and compare it to a traditional frequentist design. Finally, we discuss the use of Bayesian hierarchical models for multiregional trials and highlight the advantages of the Bayesian approach when specifying clinically relevant study hypotheses. C1 [Bonangelino, Pablo; Irony, Telba; Liang, Shengde; Li, Xuefeng; Mukhi, Vandana; Ruan, Shiling; Xu, Yunling; Yang, Xiting; Wang, Chenguang] US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Irony, T (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Telba.irony@fda.hhs.gov NR 18 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 938 EP 953 DI 10.1080/10543406.2011.589650 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900006 PM 21830924 ER PT J AU Pennello, GA AF Pennello, Gene A. TI BAYESIAN ANALYSIS OF DIAGNOSTIC TEST ACCURACY WHEN DISEASE STATE IS UNVERIFIED FOR SOME SUBJECTS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Data augmentation; Gibbs sampling; Missing at random; Nonignorable missing data mechanism; Selection model; Sensitivity analysis ID GOLD STANDARD; SENSITIVITY-ANALYSIS; VERIFICATION; PREVALENCE; ABSENCE; MODELS; BIAS AB Studies of the accuracy of medical tests to diagnose the presence or absence of disease can suffer from an inability to verify the true disease state in everyone. When verification is missing at random (MAR), the missing data mechanism can be ignored in likelihood-based inference. However, this assumption may not hold even approximately. When verification is nonignorably missing, the most general model of the distribution of disease state, test result, and verification indicator is overparameterized. Parameters are only partially identified, creating regions of ignorance for maximum likelihood estimators. For studies of a single test, we use Bayesian analysis to implement the most general nonignorable model, a reduced nonignorable model with identifiable parameters, and the MAR model. Simple Gibbs sampling algorithms are derived that enable computation of the posterior distribution of test accuracy parameters. In particular, the posterior distribution is easily obtained for the most general nonignorable model, which makes relatively weak assumptions about the missing data mechanism. For this model, the posterior distribution combines two sources of uncertainty: ignorance in the estimation of partially identified parameters, and imprecision due to finite sampling variability. We compare the three models on data from a study of the accuracy of scintigraphy to diagnose liver disease. C1 US FDA, Div Biostat, Silver Spring, MD 20993 USA. RP Pennello, GA (reprint author), US FDA, Div Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM gene.pennello@fda.hhs.gov NR 19 TC 6 Z9 7 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 954 EP 970 DI 10.1080/10543406.2011.590921 PG 17 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900007 PM 21830925 ER PT J AU Scott, JA Hand, AL Sian, LS AF Scott, John A. Hand, Austin L. Sian, Layla S. TI BayesWeb: A USER-FRIENDLY PLATFORM FOR EXPLORATORY BAYESIAN ANALYSIS OF SAFETY SIGNALS FROM SMALL CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Bayesian analysis; Exploratory; Phase I; Phase II; Safety; Statistical software ID DESIGN AB Safety signals observed in early-phase clinical trials can have profound implications for the development of new medical products. It is difficult to interpret the occurrence of safety signals in small clinical trials, where formal inferential procedures may be impractical. We advocate wider use of simple Bayesian methods to explore and understand safety signals from small clinical trials. We describe a new web-based application, BayesWeb.com, that makes such exploratory Bayesian methods accessible to subject-matter experts. We illustrate the use of this software with an example from a hypothetical phase I trial for a Factor VIII product for patients with hemophilia A. C1 [Scott, John A.; Hand, Austin L.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Hand, Austin L.] Baylor Univ, Dept Stat, Waco, TX 76798 USA. [Sian, Layla S.] Univ Pittsburgh, Ctr Res Hlth Care Data Ctr, Pittsburgh, PA USA. RP Scott, JA (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM John.Scott@fda.hhs.gov OI Scott, John/0000-0002-9116-948X NR 19 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2011 VL 21 IS 5 SI SI BP 1030 EP 1041 DI 10.1080/10543406.2011.590924 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 882PJ UT WOS:000299575900011 PM 21830929 ER PT J AU Zheng, J Keys, CE Zhao, SH Ahmed, R Meng, JH Brown, EW AF Zheng, Jie Keys, Christine E. Zhao, Shaohua Ahmed, Rafiq Meng, Jianghong Brown, Eric W. TI Simultaneous Analysis of Multiple Enzymes Increases Accuracy of Pulsed-Field Gel Electrophoresis in Assigning Genetic Relationships among Homogeneous Salmonella Strains SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ENTERICA SEROTYPE ENTERITIDIS; ESCHERICHIA-COLI O157-H7; TANDEM REPEAT ANALYSIS; TYPHIMURIUM DT104; HOST ADAPTATION; UNITED-STATES; PHAGE TYPES; SEQUENCE; RECOMBINATION; EVOLUTION AB Due to a highly homogeneous genetic composition, the subtyping of Salmonella enterica serovar Enteritidis strains to an epidemiologically relevant level remains intangible for pulsed-field gel electrophoresis (PFGE). We reported previously on a highly discriminatory PFGE-based subtyping scheme for S. enterica serovar Enteritidis that relies on a single combined cluster analysis of multiple restriction enzymes. However, the ability of a subtyping method to correctly infer genetic relatedness among outbreak strains is also essential for effective molecular epidemiological traceback. In this study, genetic and phylogenetic analyses were performed to assess whether concatenated enzyme methods can cluster closely related salmonellae into epidemiologically relevant hierarchies. PFGE profiles were generated by use of six restriction enzymes (XbaI, BlnI, SpeI, SfiI, PacI, and NotI) for 74 strains each of S. enterica serovar Enteritidis and S. enterica serovar Typhimurium. Correlation analysis of Dice similarity coefficients for all pairwise strain comparisons underscored the importance of combining multiple enzymes for the accurate assignment of genetic relatedness among Salmonella strains. The mean correlation increased from 81% and 41% for single-enzyme PFGE up to 99% and 96% for five-enzyme combined PFGE for S. enterica serovar Enteritidis and S. enterica serovar Typhimurium strains, respectively. Data regressions approached 100% correlation among Dice similarities for S. enterica serovar Enteritidis and S. enterica serovar Typhimurium strains when a minimum of six enzymes were concatenated. Phylogenetic congruence measures singled out XbaI, BlnI, SfiI, and PacI as most concordant for S. enterica serovar Enteritidis, while XbaI, BlnI, and SpeI were most concordant among S. enterica serovar Typhimurium strains. Together, these data indicate that PFGE coupled with sufficient enzyme numbers and combinations is capable of discerning accurate genetic relationships among Salmonella serovars comprising highly homogeneous strain complexes. C1 [Zheng, Jie; Keys, Christine E.; Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Ahmed, Rafiq] Canadian Sci Ctr Human & Anim Hlth, Natl Microbiol Lab, Winnipeg, MB, Canada. [Zheng, Jie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Brown, EW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM eric.brown@fda.hhs.gov NR 41 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 EI 1098-660X J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2011 VL 49 IS 1 BP 85 EP 94 DI 10.1128/JCM.00120-10 PG 10 WC Microbiology SC Microbiology GA 701AQ UT WOS:000285787100011 PM 20980570 ER PT J AU Madabushi, R Cox, DS Hossain, M Boyle, DA Patel, BR Young, G Choi, YM Gobburu, JVS AF Madabushi, Rajanikanth Cox, Donna S. Hossain, Mohammad Boyle, Duane A. Patel, Bela R. Young, Guy Choi, Young-Moon Gobburu, Jogarao V. S. TI Pharmacokinetic and Pharmacodynamic Basis for Effective Argatroban Dosing in Pediatrics SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Heparin-induced thrombocytopenia; argatroban; pediatrics; pharmacokinetics; pharmacodynamics; activated plasma thromboplastin time (aPTT); simulation ID HEPARIN-INDUCED THROMBOCYTOPENIA; LABELING DECISIONS; DRUG APPLICATIONS; CHILDREN; THERAPY; IMPACT; PHARMACOMETRICS; APPROVAL AB The objective was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of argatroban in pediatric patients and derive dosing recommendations. An open-label multicenter trial was conducted in pediatric patients (n = 18 from birth to 16 years). A population modeling approach was used to characterize pharmacokinetics and pharmacodynamics of argatroban in pediatric patients. Simulations were performed to derive a dosing regimen for pediatric patients. The estimated clearance of argatroban in pediatric patients was 2-fold lower than that in healthy adults. Body weight was significant predictor of argatroban clearance. The clearance in a typical 20-kg pediatric patient was 3.1 L/h. In 4 patients with elevated serum bilirubin levels, the estimated clearance was 0.6 L/h. Effect on activated plasma thromboplastin time (aPTT) was found to be concentration dependent. Simulations suggested that a starting dose of 0.75 mu g/kg/min in pediatric patients was comparable in performance to 2.0 mu g/kg/min approved in adults for attaining target aPTT and risk for bleeding. A dose increment step size of 0.25 mu g/kg/min was suitable for titration. The PK/PD of argatroban was reasonably characterized in pediatrics. Plasma concentration-aPTT relationship was used to derive a safe starting dose and titration scheme for the first time in pediatric patients and was incorporated into the US prescribing information for argatroban. C1 [Madabushi, Rajanikanth; Choi, Young-Moon; Gobburu, Jogarao V. S.] FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. [Cox, Donna S.; Hossain, Mohammad; Boyle, Duane A.; Patel, Bela R.] GlaxoSmithKline Inc, Clin Pharmacol Modeling & Simulat, King Of Prussia, PA USA. [Young, Guy] Childrens Hosp Los Angeles, Ctr Thrombosis & Hemostasis, Los Angeles, CA 90027 USA. RP Madabushi, R (reprint author), FDA, Off Clin Pharmacol, Off Translat Sci, CDER, 10903 New Hampshire Ave,Bldg 21,Rm 2172, Silver Spring, MD 20993 USA. EM Rajnikanth.Madabushi@fda.hhs.gov FU GlaxoSmithKline; Encysive Pharmaceuticals, Inc FX GlaxoSmithKline and Encysive Pharmaceuticals, Inc, provided study support. Donna S. Cox, Mohammad Hossain, Duane A. Boyle, and Bela R. Patel are employees of GlaxoSmithKline. The study sponsors (specifically, the authors employed by GlaxoSmithKline) were involved in study design; data collection, analysis, or data interpretation. NR 27 TC 26 Z9 26 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 JAN PY 2011 VL 51 IS 1 BP 19 EP 28 DI 10.1177/0091270010365550 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 694ZS UT WOS:000285341000003 PM 20421511 ER PT J AU Sanetti, LMH Fallon, LM AF Sanetti, Lisa M. Hagermoser Fallon, Lindsay M. TI Treatment Integrity Assessment: How Estimates of Adherence, Quality, and Exposure Influence Interpretation of Implementation SO JOURNAL OF EDUCATIONAL AND PSYCHOLOGICAL CONSULTATION LA English DT Article ID GOOD BEHAVIOR GAME; PREVENTIVE INTERVENTIONS; SCHOOL; CLASSROOM; OUTCOMES; PROGRAM; IMPACT; CONSULTATION; 1ST-GRADE; ISSUES AB The assessment of treatment integrity is important for determining the effectiveness of an intervention. Treatment integrity, a multidimensional construct, can be evaluated in two ways: by session or component. In this study, adherence, quality, and exposure data are estimated using permanent product data from implementation of the PAX Good Behavior Game to demonstrate how varied assessment of treatment integrity can influence interpretation of implementation. Implications for implementers and school-based decisions are discussed. C1 [Sanetti, Lisa M. Hagermoser] Univ Connecticut, Neag Sch Educ, Storrs, CT 06269 USA. [Sanetti, Lisa M. Hagermoser] Univ Connecticut, CBER, Storrs, CT 06269 USA. [Fallon, Lindsay M.] Univ Connecticut, Sch Psychol, Storrs, CT 06269 USA. RP Sanetti, LMH (reprint author), Univ Connecticut, Neag Sch Educ, 249 Glenbrook Rd,Unit 2064, Storrs, CT 06269 USA. EM lisa.sanetti@uconn.edu NR 34 TC 9 Z9 9 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1047-4412 J9 J EDUC PSYCHOL CONS JI J. Educ. Psychol. Consult. PY 2011 VL 21 IS 3 BP 209 EP 232 DI 10.1080/10474412.2011.595163 PG 24 WC Psychology, Educational SC Psychology GA 885AW UT WOS:000299751100003 ER PT J AU Mollenhauer, MAM Bradshaw, SG Fair, PA Mcguinn, WD Peden-Adams, MM AF Mollenhauer, Meagan A. M. Bradshaw, Sarah G. Fair, Patricia A. Mcguinn, W. David Peden-Adams, Margie M. TI Effects of perfluorooctane sulfonate (PFOS) exposure on markers of inflammation in female B6C3F1 mice SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART A-TOXIC/HAZARDOUS SUBSTANCES & ENVIRONMENTAL ENGINEERING LA English DT Article DE PFOS; inflammation; IL-6; TNF; cytokines; immune; macrophages ID ACTIVATED-RECEPTOR-ALPHA; TUMOR-NECROSIS-FACTOR; PEROXISOME-PROLIFERATOR; PERFLUORINATED COMPOUNDS; PERFLUOROALKYL ACIDS; GENE-EXPRESSION; TURSIOPS-TRUNCATUS; NUCLEAR RECEPTORS; HUMORAL IMMUNITY; FATTY-ACIDS AB Perfluorooctane sulfonate (PFOS; 1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-heptadecafluoro-1-octanesulfonic acid) has been reported to alter humoral immune functions, but inflammatory processes following PFOS exposure have not been fully characterized. Therefore, the current study, assessed TNF- and IL-6 concentrations in serum and peritoneal lavage fluid, numbers of splenoctyes expressing intracellular TNF-, IL-6, IL-10 or IL-1, and ex vivo TNF- and IL-6 production by peritoneal macrophages following either in vivo or in vitro LPS exposure. Adult female B6C3F1 mice were exposed orally for 28 days to 0, 1, 3, or 300 mg PFOS/kg total administered dose [TAD] (e.g., 0, 0.0331, 0.0993 or 9.93 mg/kg/day). Body and spleen masses were significantly reduced in the highest PFOS treatment group compared to the control group, whereas liver mass was significantly increased. Serum TNF- levels were significantly decreased following exposure to 1 mg PFOS/kg TAD as compared to controls, while serum IL-6 levels were increased. IL-6 concentrations in peritoneal lavage fluid decreased with increasing dose. PFOS treatment did not alter numbers of splenocytes expressing intracellular levels of TNF-, IL-10 or IL-1. Numbers of splenocytes expressing intracellular levels of IL-6 were significantly decreased in the 3 mg/kg treatment as compared to controls. Overall, these data suggest that PFOS exposure can alter some inflammatory processes, which could potentially lead to misdirected inflammatory responses. C1 [Peden-Adams, Margie M.] Univ Nevada, Harry Reid Ctr Environm Studies, Las Vegas, NV 89154 USA. [Bradshaw, Sarah G.] Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. [Peden-Adams, Margie M.] Univ Nevada, Harry Reid Ctr Environm Studies, NOAA NOS CCEHBR, Charleston, SC 29412 USA. [Mcguinn, W. David] US FDA, Silver Spring, MD USA. RP Peden-Adams, MM (reprint author), Univ Nevada, Harry Reid Ctr Environm Studies, NOAA NOS CCEHBR, Rm 248,219 Ft Johnson Rd, Charleston, SC 29412 USA. EM pedenadams@gmail.com FU National Oceanic and Atmospheric Administration/National Ocean Service/Center for Coastal Environmental Health and Biomolecular Research FX This publication does not constitute an endorsement of any commercial product or intend to be an opinion beyond scientific or other results obtained by the National Oceanic and Atmospheric Administration (NOAA). No reference shall be made to NOAA, or this publication furnished by NOAA, to any advertising or sales promotion which would indicate or imply that NOAA recommends or endorses any proprietary product mentioned herein, or which has as its purpose an interest to cause the advertised product to be used or purchased because of this publication. The project was funded in part by the National Oceanic and Atmospheric Administration/National Ocean Service/Center for Coastal Environmental Health and Biomolecular Research and internal university funding. The authors have no conflict of interest to declare. NR 68 TC 15 Z9 15 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-4529 J9 J ENVIRON SCI HEAL A JI J. Environ. Sci. Health Part A-Toxic/Hazard. Subst. Environ. Eng. PY 2011 VL 46 IS 2 BP 97 EP 108 AR PII 931349041 DI 10.1080/10934529.2011.532418 PG 12 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 696AQ UT WOS:000285414700001 PM 21170772 ER PT J AU Ray, PC Yu, HT Fu, PP AF Ray, Paresh Chandra Yu, Hongtao Fu, Peter P. TI Nanogold-Based Sensing of Environmental Toxins: Excitement and Challenges SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Gold nanoparticle; sensing; bacteria; metals; nitroaromatics ID ENHANCED RAMAN-SCATTERING; HYPER-RAYLEIGH SCATTERING; NONLINEAR-OPTICAL PROPERTIES; ESCHERICHIA-COLI O157-H7; GOLD NANOPARTICLE PROBES; TARGETED PHOTOTHERMAL LYSIS; DYNAMIC LIGHT-SCATTERING; HUMAN SKIN KERATINOCYTES; SINGLE-MOLECULE; ENERGY-TRANSFER AB There have been tremendous advances in the past ten years on the development of various nanomaterials-based sensors for detection of environmental toxins. Nanogold is of special interest because of its unique shape- and size-dependent optical properties, hyper-quenching ability, super surface-enhanced Raman and dynamic light scattering, and surface-modifiability by small organic molecules and biomolecules. These unique optical properties of nanogold have been explored for ultra-sensitive detection, while its surface-modifiability has been explored for selectivity. In general, the nanogold-based sensors are highly selective and sensitive along with simple sample preparation and sensor design. In this review article, we intend to capture some of the recent advances in nanogold-based sensor development and mechanistic studies, especially for bacteria, heavy metals, and nitroaromatic compounds. Undoubtedly, these developments will generate a lot of excitement for environmental scientists and toxicologists as well as the general public. C1 [Ray, Paresh Chandra; Yu, Hongtao] Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ray, PC (reprint author), Jackson State Univ, Dept Chem & Biochem, Jackson, MS 39217 USA. EM paresh.c.ray@jsums.edu FU NSF-PREM [DMR-0611539]; ARO through ERDC [W911NF-06-1-0512]; NIH/NCRR RCMI [G12RR013459] FX The authors wish to thank various sources for financial support for some part of this research: NSF-PREM grant #DMR-0611539, ARO grant #W911NF-06-1-0512 through ERDC, and NIH/NCRR RCMI Grant #G12RR013459. NR 207 TC 16 Z9 16 U1 1 U2 50 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2011 VL 29 IS 1 BP 52 EP 89 AR PII 935125366 DI 10.1080/10590501.2011.551315 PG 38 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 738XY UT WOS:000288677100003 PM 21424976 ER PT J AU Zhang, YT Lee, GR AF Zhang, Yuanting Lee, Gary R. TI Intercountry Versus Transracial Adoption: Analysis of Adoptive Parents' Motivations and Preferences in Adoption SO JOURNAL OF FAMILY ISSUES LA English DT Article DE adoption; intercountry; transracial; motivations ID INTERNATIONAL ADOPTION; UNITED-STATES; CHILDREN; PERSPECTIVE; IMMIGRATION; FAMILIES; AMERICA AB The United States is one of the major baby-receiving countries in the world. Relatively little research has focused on why there is such a high demand for intercountry adoption. Using in-depth qualitative interviews with adoptive parents, the authors explored the reasons why Americans prefer to adopt foreign-born children instead of adopting minority children domestically. Other than infertility reasons, concerns about domestic adoption, and the uneven domestic supply and demand of "desirable" children, the authors' findings suggested that there was a perception that American children available for adoption presented difficult problems whereas foreign children presented interesting challenges. The "problems" inherent in children from American foster care were confounded with race differences. Studying adoption motivations will not only help us better understand the domestic adoption situation, especially why so many Black children are left behind in foster care, it may also reveal important insights into current race relations and distances between groups in the United States. C1 [Lee, Gary R.] Bowling Green State Univ, Dept Sociol, Bowling Green, OH 43403 USA. [Zhang, Yuanting] US FDA, College Pk, MD USA. RP Lee, GR (reprint author), Bowling Green State Univ, Dept Sociol, 219 Williams Hall, Bowling Green, OH 43403 USA. EM grlee@bgnet.bgsu.edu NR 50 TC 19 Z9 19 U1 1 U2 19 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-513X J9 J FAM ISSUES JI J. Fam. Issues PD JAN PY 2011 VL 32 IS 1 BP 75 EP 98 DI 10.1177/0192513X10375410 PG 24 WC Family Studies SC Family Studies GA 694IV UT WOS:000285290800004 ER PT J AU Savoye, F Feng, P Rozand, C Bouvier, M Gleizal, A Thevenot, D AF Savoye, F. Feng, P. Rozand, C. Bouvier, M. Gleizal, A. Thevenot, D. TI Comparative Evaluation of a Phage Protein Ligand Assay with Real-Time PCR and a Reference Method for the Detection of Escherichia coli O157:H7 in Raw Ground Beef and Trimmings SO JOURNAL OF FOOD PROTECTION LA English DT Article ID IMMUNOMAGNETIC SEPARATION; MULTIPLEX PCR; O157-H7; GROWTH; CATTLE; MEDIA; PREVALENCE; OUTBREAK; STRAINS; O157H7 AB Enterohemorrhagic Escherichia coli O157:H7 is an important pathogen associated with infections caused by consumption of undercooked raw meat. Sensitive and rapid detection methods for E. coli O157:H7 are essential for the meat industry to ensure a safe meat supply. This study was conducted to compare the sensitivity of the VIDAS ultraperformance E. coli test (ECPT UP) with a noncommercial real-time (RT) PCR method and the U.S. Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS) reference method for detecting E. coli O157:H7 in raw ground beef. Optimal enrichment times and the efficacy of testing different types of raw meat, either as individual samples (25 g) or as composites (375 g), were examined. For 25-g samples of each type of raw ground beef tested, 6 h of enrichment was sufficient for both the VIDAS ECPT UP and RT-PCR methods, but for 375-g samples, 24 h of enrichment was required. Both the VIDAS ECPT UP and RT-PCR methods produced results similar to those obtained with the USDA-FSIS reference method after 18 to 24 h of enrichment. The primer specificity of the RT-PCR assay and the highly specific phage ligand used in the VIDAS ECPT UP for target recognition enabled the detection of low levels of E. coli O157:H7 in 25 g of various types of raw ground beef. The tests also allowed the detection of E. coli O157:H7 in composite raw ground beef and trimmings in samples of up to 375 g. C1 [Savoye, F.; Rozand, C.; Bouvier, M.; Gleizal, A.; Thevenot, D.] Vetagro Sup Lyon, Unite Microbiol Alimentaire & Previs, F-69280 Marcy Letoile, France. [Feng, P.] US FDA, Div Microbiol, College Pk, MD 20740 USA. RP Savoye, F (reprint author), Vetagro Sup Lyon, Unite Microbiol Alimentaire & Previs, 1 Av Bourgelat, F-69280 Marcy Letoile, France. EM f.savoye@vetagro-sup.fr NR 41 TC 13 Z9 14 U1 0 U2 8 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 JAN PY 2011 VL 74 IS 1 BP 6 EP 12 DI 10.4315/0362-028X.JFP-10-271 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 704EC UT WOS:000286032900001 PM 21219756 ER PT J AU Xia, XD Meng, JH Zhao, SH Bodeis-Jones, S Gaines, SA Ayers, SL McDermott, PF AF Xia, Xiaodong Meng, Jianghong Zhao, Shaohua Bodeis-Jones, Sonya Gaines, Stuart A. Ayers, Sherry L. McDermott, Patrick F. TI Identification and Antimicrobial Resistance of Extraintestinal Pathogenic Escherichia coli from Retail Meats SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MULTIDRUG-RESISTANT; PHYLOGENETIC GROUP; COLI STRAINS; VIRULENCE; PRODUCTS; FOODS; ACQUISITION; INFECTIONS; MINNESOTA; ORIGIN AB Extraintestinal pathogenic Escherichia coli (ExPEC) causes a variety of infections outside the gastrointestinal tract. Retail meats are frequently contaminated with E. coli strains, and they might serve as a vehicle for transmitting ExPEC. A total of 1,275 E. coli isolates recovered from ground beef, ground turkey, chicken breasts, and pork chops obtained in Georgia, Maryland, Oregon, and Tennessee in 2006 were investigated for the presence of ExPEC by using multiplex PCR. Identified ExPEC isolates were assigned to serogroups and phylogenetic groups and then analyzed for antimicrobial susceptibility. Approximately 16% (200 of 1,275) of the E. coli isolates were identified as ExPEC, based on defined genetic criteria. The occurrence of ExPEC was highest in E. coli isolated from ground turkey (23.5%) and chicken breasts (20.2%), and less frequent in isolates from pork chops (8.3%) and ground beef (3.4%). Phylogenetic grouping revealed that most (66.5%) ExPEC isolates fell into the same phylogenetic groups (B2 and D) as did virulent human ExPEC strains. Among the 15 antimicrobial agents tested, resistance to tetracycline (67.0%), sulfisoxazole (59.5%), and streptomycin (46.0%) was most frequent. Most ExPEC isolates (n = 163 [81.5%]) were resistant to at least one antimicrobial agent, and more than half (n = 114 [57%]) exhibited resistance to at least three drugs. This study found that ExPEC strains, including antimicrobial-resistant strains, were frequent among E. coli recovered from retail meats, especially those from chicken and turkey products. These findings indicate a need to better understand the role of certain meat types as potential sources of human ExPEC infection. C1 [Zhao, Shaohua; Bodeis-Jones, Sonya; Gaines, Stuart A.; Ayers, Sherry L.; McDermott, Patrick F.] USDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Xia, Xiaodong; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP McDermott, PF (reprint author), USDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. EM Patrick.McDermott@fda.hhs.gov FU Joint Institute for Food Safety and Applied Nutrition of the University of Maryland; U.S. Food and Drug Administration FX This study was supported in part by the Joint Institute for Food Safety and Applied Nutrition of the University of Maryland and the U.S. Food and Drug Administration. We are grateful to Dr. James R. Johnson of the University of Minnesota for providing clinical E. coli strains. NR 35 TC 15 Z9 16 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 EI 1944-9097 J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2011 VL 74 IS 1 BP 38 EP 44 DI 10.4315/0362-028X.JFP-10-251 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 704EC UT WOS:000286032900006 PM 21219761 ER PT J AU Rummel, N Chung, I Shaikh, B AF Rummel, Nathan Chung, Ivy Shaikh, Badar TI DETERMINATION OF ALBENDAZOLE, FENBENDAZOLE, AND THEIR METABOLITES IN MOUSE PLASMA BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY USING FLUORESCENCE AND ULTRAVIOLET DETECTION SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article DE albendazole; albendazole metabolites; fenbendazole; fenbendazole metabolites; high performance liquid chromatography; mouse plasma ID SHEEP PLASMA; IN-VITRO; SULFOXIDE; SULFONE; MICE; RICOBENDAZOLE; OXFENDAZOLE; DISPOSITION; GROWTH; CATTLE AB A rapid and reliable high performance liquid chromatographic (HPLC) method has been developed and validated for the determination of albendazole (ABZ), albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO(2)); fenbendazole (FBZ), fenbendazole sulfoxide (FBZSO), and fenbendazole sulfone (FBZSO(2)) in mouse plasma. The mouse plasma was made alkaline with potassium carbonate and extracted with ethylacetate. The extracts were evaporated, reconstituted in mobile phase, and analyzed by HPLC. The chromatography was carried out on a reversed-phase column using acetonitrile-methanol-buffer as the mobile phase. The fenbendazole and its metabolites were detected by using UV detector set at the wavelength of 290 nm. The albendazole and its metabolites were detected by a fluorescence detector with excitation and emission wavelengths of 290 and 330 nm, respectively. The average recoveries of ABZ, ABZSO, and ABZSO(2) from fortified control plasma samples were 95, 82, and 92%, respectively. Similarly, the average recoveries of FBZ, FBZSO, and FBZSO(2) were 64, 90, and 94%, respectively. The average CVs were <= 15% for all of the compounds. The method was applied to incurred mouse plasma samples to determine ABZ, FBZ, and their metabolites. C1 [Rummel, Nathan; Shaikh, Badar] US FDA, Ctr Vet Med Off Res, Laurel, MD 20708 USA. [Chung, Ivy] Harvard Univ, Sch Med, Vasc Biol Program, Boston, MA USA. [Chung, Ivy] Childrens Hosp, Karp Family Res Labs, Boston, MA 02115 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med Off Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM shaikh@fda.hhs.gov RI Chung, Ivy/C-3804-2012 NR 20 TC 2 Z9 3 U1 0 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 2011 VL 34 IS 18 BP 2211 EP 2223 DI 10.1080/10826076.2011.587219 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 880AF UT WOS:000299375600014 ER PT J AU Gnjidic, D Hilmer, SN Roughead, EE Gilbert, AL Le Couteur, DG Abernethy, DR AF Gnjidic, Danijela Hilmer, Sarah N. Roughead, Elizabeth E. Gilbert, Andrew L. Le Couteur, David G. Abernethy, Darrell R. TI Drug burden index (DBI) and mortality in Australian veteran population SO JOURNAL OF PHARMACOLOGICAL SCIENCES LA English DT Meeting Abstract CT 84th Annual Meeting of the Japanese-Pharmacological-Society/11th Southeast Asian Western Pacific Regional Meeting of Pharmacologists CY MAR 22-24, 2011 CL Yokohama, JAPAN SP Japanese Pharmacolog Soc C1 [Gnjidic, Danijela; Hilmer, Sarah N.] Royal N Shore Hosp, Dept Clin Pharmacol & Aged Care, St Leonards, NSW 2065, Australia. [Gnjidic, Danijela; Hilmer, Sarah N.; Le Couteur, David G.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia. [Le Couteur, David G.] Concord Hosp, Ctr Educ & Res Ageing, Sydney, NSW, Australia. [Roughead, Elizabeth E.; Gilbert, Andrew L.] Univ S Australia, Qual Use Meds & Pharm Res Ctr, Adelaide, SA 5001, Australia. [Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RI Gilbert, Andrew/C-6892-2009; Roughead, Elizabeth/G-4431-2010 OI Roughead, Elizabeth/0000-0002-6811-8991 NR 0 TC 0 Z9 0 U1 0 U2 2 PU JAPANESE PHARMACOLOGICAL SOC PI KYOTO PA EDITORIAL OFF, KANTOHYA BLDG GOKOMACHI-EBISUGAWA NAKAGYO-KU, KYOTO, 604, JAPAN SN 1347-8613 J9 J PHARMACOL SCI JI J. Pharmacol. Sci. PY 2011 VL 115 SU 1 BP 288P EP 288P PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 743QU UT WOS:000289034601536 ER PT J AU Taylor, AD Vaisocherova, H Deeds, J DeGrasse, S Jiang, SY AF Taylor, Allen D. Vaisocherova, Hana Deeds, Jonathan DeGrasse, Stacey Jiang, Shaoyi TI Tetrodotoxin Detection by a Surface Plasmon Resonance Sensor in Pufferfish Matrices and Urine SO JOURNAL OF SENSORS LA English DT Article AB Tetrodotoxin (TTX) poisoning is most commonly associated with consumption of pufferfish. TTX is a low molecular weight (similar to 319 Da) neurotoxin that selectively blocks voltage-sensitive Na+-gated ion channels. The standard method accepted worldwide for monitoring TTX toxicity in food matrices is the mouse bioassay. Ethical concerns from live animal testing, low sample throughput, and analytical inaccuracies have led to the need for an alternative method. We have previously established that surface plasmon resonance (SPR) sensors can quantify TTX in aqueous buffer samples by an antibody-based inhibition assay. In this paper, we report the extension of the assay for the detection of TTX in both clinical- and food-relevant matrices. The assay was optimized for application to three relevant complex matrices: pufferfish liver extract, pufferfish muscle extract, and human urine. Matrix effects are discussed and calibration curves are presented. Naturally contaminated pufferfish liver and muscle extracts were analyzed by the SPR method, and the data is compared to liquid-chromatography electrospray-ionization multiple reactions monitoring mass spectrometry (LC/ESI/MRM/MS) data. Ten samples, including three from a poisoning incident, two control monkfish samples, and five toxic pufferfish samples, were analyzed using this method, and the data is compared to LC/ESI/MRM/MS analysis of the samples. C1 [Taylor, Allen D.; Vaisocherova, Hana; Jiang, Shaoyi] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. [Deeds, Jonathan; DeGrasse, Stacey] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP DeGrasse, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM stacy.degrasse@fda.hhs.gov; sjiang@uw.edu RI Evans, David/H-6325-2013; Lisalova, Hana/H-4706-2014; OI Lisalova, Hana/0000-0002-8755-2398; DeGrasse, Stacey/0000-0001-7808-4193 FU National Research Initiative of the USDA Cooperative State Research, Education and Extension Service [2005-35201-16321]; United States Food and Drug Administration [HHSF223200610011]; Intel Foundation Ph.D. Fellowship Award; Kaiser Aluminum Fellowship Award at the University of Washington FX The authors are grateful to Betsy Yakes for her comments and revision of this paper prior to submission. This project was supported by the National Research Initiative of the USDA Cooperative State Research, Education and Extension Service, Grant no. 2005-35201-16321 and the United States Food and Drug Administration, Grant no. HHSF223200610011. Allen D. Taylor was partially supported by the Intel Foundation Ph.D. Fellowship Award and the Kaiser Aluminum Fellowship Award at the University of Washington. NR 32 TC 7 Z9 7 U1 2 U2 23 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1687-725X EI 1687-7268 J9 J SENSORS JI J. Sens. PY 2011 AR 601704 DI 10.1155/2011/601704 PG 10 WC Engineering, Electrical & Electronic; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA V31DS UT WOS:000208864900016 ER PT J AU Gardner, JY Brillhart, DE Benjamin, MM Dixon, LG Mitchell, LM Dimandja, JMD AF Gardner, J. Yvette Brillhart, Darcy E. Benjamin, Melissa M. Dixon, Lurlene G. Mitchell, LaTonya M. Dimandja, Jean-Marie D. TI The use of GC x GC/TOF MS with multivariate analysis for the characterization of foodborne pathogen bacteria profiles SO JOURNAL OF SEPARATION SCIENCE LA English DT Article DE Bacterial fatty acid methyl esters; Chemical index template; GC x GC/TOF MS; Multidimensional scaling; Principal component analysis ID 2-DIMENSIONAL GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; FATTY-ACIDS; RETENTION INDEXES; MICROORGANISMS; IDENTIFICATION; DIFFERENTIATION; CLASSIFICATION; HYDROCARBONS; COMMUNITIES AB The cellular fatty acid profiles of eight strains of Bacillus, Staphylococcus, and Enterobacteriacae (Escherichia coli and Salmonella) were analyzed by comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry. A novel template method was developed to standardize the raw two-dimensional gas chromatography retention data through the use of a chemical indexing mixture. Analyte retention coordinates were normalized in the primary dimension with respect to a series of n-alkanes (Kovats index) and in the secondary dimension with respect to a series of aromatic hydrocarbons (Lee index). Fatty acid profiles extracted from the templates were compared by multidimensional scaling and principal component analysis. Differences in the profiles of Gram-positive and Gram-negative bacteria were observed, and a series of heterogeneous mixtures comprising different fractions (containing one Gram-positive and one Gram-negative bacteria strain) were also distinguished from their homogeneous constituents. C1 [Dimandja, Jean-Marie D.] Spelman Coll, Dept Chem, Atlanta, GA 30314 USA. [Dimandja, Jean-Marie D.] Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. [Gardner, J. Yvette] Clayton State Univ, Dept Nat Sci, Morrow, GA USA. [Brillhart, Darcy E.; Benjamin, Melissa M.; Dixon, Lurlene G.; Mitchell, LaTonya M.] US FDA, SE Reg Lab, Atlanta, GA USA. RP Dimandja, JMD (reprint author), Spelman Coll, Dept Chem, 350 Spelman Lane SW,Box 279, Atlanta, GA 30314 USA. EM jdimandja@spelman.edu FU NSF [0923295]; NASA under NSF Center for Chemical Evolution [CHE-1004570] FX This work was jointly supported by NSF and the NASA Astrobiology Program, under the NSF Center for Chemical Evolution, CHE-1004570. Financial support from NSF grant 0923295 (NSF/MRI) is also gratefully acknowledged. NR 48 TC 17 Z9 17 U1 1 U2 21 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD JAN PY 2011 VL 34 IS 2 BP 176 EP 185 DI 10.1002/jssc.201000612 PG 10 WC Chemistry, Analytical SC Chemistry GA 724VD UT WOS:000287603400008 PM 21246723 ER PT J AU Gwise, TE Zhou, JH Hu, FF AF Gwise, Thomas E. Zhou, Jianhui Hu, Feifang TI An optimal response adaptive biased coin design with k heteroscedastic treatments SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Heteroscedasticity; k treatments; Response adaptive design ID SEQUENTIAL CLINICAL-TRIALS; PLAY-WINNER RULE; RANDOMIZATION PROCEDURES; ASYMPTOTIC PROPERTIES; PROGNOSTIC FACTORS AB For comparing treatments in clinical trials, Atkinson (1982) introduced optimal biased coins for balancing patients across treatment assignments by using D-optimality under the assumption of homoscedastic responses of different treatments. However, this assumption can be violated in many real applications. In this paper, we relax the homoscedasticity assumption in the k treatments setting with k>2. A general family of optimal response adaptive biased coin designs are proposed following Atkinson's procedure. Asymptotic properties of the proposed designs are obtained. Some advantages of the proposed design are discussed. (C) 2010 Elsevier B.V. All rights reserved. C1 [Zhou, Jianhui; Hu, Feifang] Univ Virginia, Dept Stat, Charlottesville, VA 22904 USA. [Gwise, Thomas E.] US FDA, Rockville, MD 20857 USA. RP Zhou, JH (reprint author), Univ Virginia, Dept Stat, POB 400135,Kerchof Hall, Charlottesville, VA 22904 USA. EM jz9p@virginia.edu NR 17 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 EI 1873-1171 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN PY 2011 VL 141 IS 1 BP 235 EP 242 DI 10.1016/j.jspi.2010.06.013 PG 8 WC Statistics & Probability SC Mathematics GA 660UA UT WOS:000282670100018 ER PT J AU Nie, L Chen, Y Chu, HT AF Nie, Lei Chen, Yong Chu, Haitao TI Asymptotic variances of maximum likelihood estimator for the correlation coefficient from a BVN distribution with one variable subject to censoring SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE Censoring; Limit of detection; Maximum likelihood estimator ID DETECTION LIMITS; VIRAL LOAD; POPULATIONS; SAMPLES AB This paper deals with the problem of estimating the Pearson correlation coefficient when one variable is subject to left or right censoring. In parallel to the classical results on the Pearson correlation coefficient, we derive a workable formula, through tedious computation and intensive simplification, of the asymptotic variances of the maximum likelihood estimators in two cases: (1) known means and variances and (2) unknown means and variances. We illustrate the usefulness of the asymptotic results in experimental designs. Published by Elsevier B.V. C1 [Chu, Haitao] Univ Minnesota Twin Cities, Div Biostat, Minneapolis, MN 55455 USA. [Nie, Lei] US FDA, Div 4, Off Biometr, OTS,CDER, Silver Spring, MD 20993 USA. [Chen, Yong] Univ Texas Hlth Sci Ctr, Div Biostat, Houston, TX 77030 USA. RP Chu, HT (reprint author), Univ Minnesota Twin Cities, Div Biostat, Minneapolis, MN 55455 USA. EM chux0051@umn.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X NR 15 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN PY 2011 VL 141 IS 1 BP 392 EP 401 DI 10.1016/j.jspi.2010.06.021 PG 10 WC Statistics & Probability SC Mathematics GA 660UA UT WOS:000282670100032 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB This document is a summary report of the Guidelines for the Diagnosis and Management of Food Allergy in the United States. The full guidelines can be found online at http://www.jacionline.org C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Rheumatol Immunol & Allergy, Cambridge, MA 02138 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Emergency Med, Dept Med,Div Rheumatol Allergy & Immunol, Cambridge, MA 02138 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Pulm & Crit Med Div, Boston, MA 02115 USA. [Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH 45221 USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Dept Pediat, Div Allergy & Immunol, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton SO9 5NH, Hants, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Baton Rouge, LA 70803 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Coll Med, Div Allergy & Immunol, Dept Med, Knoxville, TN 37996 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB R3T 2N2, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB R3T 2N2, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institutes of Health and the National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; not-for-profit research foundations; Dey; Novartis; variety of not-for-profit foundations; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; variety of not-for-profit research foundations; AllerGen; Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX J.A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S.M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network.She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H.A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R.A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S.H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S.L. Bahna has received funding/grant support from Genentech.; L.A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C.A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G.T. Furuta has served as a consultant and/or speaker to Ception Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J.M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc, Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sepracor. She has received funding/grant support from Genentech, GlaxoSmithKline, the National Institutes of Health and Novartis.; L.C. Schneider has served as a consultant/clinical advisor for the Food Allergy Initiative. She has received funding/grant support from a variety of not-for-profit research foundations, as well as Novartis and the National Institutes of Health.; F.E.R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma, and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health Research.; S.J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 0 TC 13 Z9 13 U1 0 U2 4 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 JAN PY 2011 VL 64 IS 1 BP 175 EP 192 DI 10.1016/j.jaad.2010.11.020 PG 18 WC Dermatology SC Dermatology GA 701XF UT WOS:000285857800021 PM 21167411 ER PT J AU Lee, S Poet, TS Smith, JN Hjerpe, AL Gunawan, R Timchalk, C AF Lee, S. Poet, T. S. Smith, J. N. Hjerpe, A. L. Gunawan, R. Timchalk, C. TI IMPACT OF REPEATED NICOTINE AND ALCOHOL COEXPOSURE ON IN VITRO AND IN VIVO CHLORPYRIFOS DOSIMETRY AND CHOLINESTERASE INHIBITION SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID PHARMACODYNAMIC PBPK/PD MODEL; ETHANOL-METABOLIZING CYP2E1; HUMAN LIVER-MICROSOMES; ORGANOPHOSPHORUS PESTICIDES; CHEMICAL-MIXTURES; RAT-LIVER; INSECTICIDE CHLORPYRIFOS; CYTOCHROMES P450; INDUCTION; EXPOSURE AB Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos-oxon. Routine consumption of alcohol and tobacco modifies metabolic and physiological processes impacting the metabolism and pharmacokinetics of other xenobiotics, including pesticides. This study evaluated the influence of repeated ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE) response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po), and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro metabolism of CPF was evaluated. For in vivo studies, rats were treated with saline or ethanol (1 g/kg/d, po)+ nicotine (1 mg/kg/d, sc) in addition to CPF (1 or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase (AChE) activities were measured in rats. There were differences in pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8-fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol + nicotine treatments showed significantly less inhibition following repeated 5 mg CPF/kg dosing compared to CPF only (96 +/- 13 and 66 +/- 7% of naive at 4 h post last CPF dosing, respectively). Although brain AChE activity was minimal inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment resulted in a similar trend (i.e., slightly less inhibition). No marked differences were observed in plasma ChE activities due to the alcohol + nicotine treatments. In vitro, CPF metabolism was not markedly affected by repeated ethanol or both ethanol + nicotine exposures. Compared with a previous study of nicotine and CPF exposure, there were no apparent additional exacerbating effects due to ethanol coexposure. C1 [Poet, T. S.; Smith, J. N.; Hjerpe, A. L.; Gunawan, R.; Timchalk, C.] Pacific NW Natl Lab, Ctr Biol Monitoring & Modeling, Richland, WA 99352 USA. [Lee, S.] US FDA, Atlanta, GA USA. RP Timchalk, C (reprint author), Pacific NW Natl Lab, Ctr Biol Monitoring & Modeling, 902 Battelle Blvd,POB 999,MSIN P7-59, Richland, WA 99352 USA. EM Charles.timchalk@pnl.gov FU Dow Chemical Company; Centers for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health (NIOSH) [CDC/NIOSH] [R01-OH003629] FX Although Drs. Timchalk and Poet have received funding from the Dow Chemical Company, the manufacturer of chlorpyrifos, to conduct research, the Dow Chemical Company did not have any involvement in the study design, analysis, and interpretation of data, in the writing of the report, or in the decision to submit this paper for publication. We gratefully acknowledge Dr. J. Campbell for valuable discussions. Although the research described in this article has been funded by the Centers for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health (NIOSH) [CDC/NIOSH grant (R01-OH003629) to Dr. Timchalk], it has not been subject to any CDC/NIOSH review and therefore does not necessarily reflect the official views of the agencies; its contents are solely the responsibility of the authors and no public endorsement should be inferred. NR 70 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2011 VL 74 IS 20 BP 1334 EP 1350 DI 10.1080/15287394.2011.567958 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 865PD UT WOS:000298321900003 PM 21899407 ER PT J AU Balsam, J Ossandon, M Kostov, Y Bruck, HA Rasooly, A AF Balsam, Joshua Ossandon, Miguel Kostov, Yordan Bruck, Hugh Alan Rasooly, Avraham TI Lensless CCD-based fluorometer using a micromachined optical Soller collimator SO LAB ON A CHIP LA English DT Article ID STAPHYLOCOCCAL-ENTEROTOXIN-B; ON-CHIP MICROSCOPY; BOTULINUM NEUROTOXIN; NEUROTRANSMITTER RELEASE; OPTOFLUIDIC MICROSCOPY; CAENORHABDITIS-ELEGANS; PROTEOLYTIC CLEAVAGE; CARBON NANOTUBES; ARRAY BIOSENSOR; PROTEIN AB In this paper, we describe a simple charge-coupled device (CCD) based lensless fluorometer with sensitivity in the range of current ELISA plate readers. In our lensfree fluorometer, a multi-wavelength LED light source was used for fluorophore excitation. To collimate the light, we developed a simple optical Soller collimator based on a "stack of pinholes'' (a stack of black PMMA with array of pinholes machined with laser) enabling the light to be collimated from the LED through the filters and the assay's microfluidics directly onto the CCD without a lens. The elimination of the lens that is used in almost all other current CCD based detection systems has four major advantages: (1) It simplifies the device design and fabrication while reducing cost. (2) It reduces the distance between the sample and the measuring device (without a lens the distance needed to focus the image on the CCD is reduced and the fluorometer can be more compact). (3) It couples the CCD and the detected surface by using an optical Soller Collimator which allows the use of filters for fluorescence detection. (4) It also uncouples the CCD and the microfluidics to enable the use of interchangeable fluidics while protecting the delicate CCD. The lensless CCD-based fluorometer is capable of detecting 16 samples simultaneously, and was used for in vitro detection of botulinum neurotoxin serotype A (BoNT-A) activity with a FRET assay that measures cleavage of a fluorophore-tagged peptide substrate specific for BoNT-A (SNAP-25) by the toxin light chain (LcA). The limit of detection (LOD) of our lensless fluorometer is 1.25 nM, which is similar to the LOD of a modern ELISA plate reader. Combined with microfluidics, this simple low cost point-of-care (POC) medical diagnostic system may be useful for the performance of many other complex medical diagnostic assays without a laboratory and thus potentially enhancing the accessibility and the quality of health care delivery in underserved populations. C1 [Balsam, Joshua; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Balsam, Joshua; Bruck, Hugh Alan] UMCP, College Pk, MD 20742 USA. [Ossandon, Miguel; Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. [Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] NCI, NIH, Rockville, MD 20852 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov NR 52 TC 22 Z9 22 U1 3 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2011 VL 11 IS 5 BP 941 EP 949 DI 10.1039/c0lc00431f PG 9 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 722CW UT WOS:000287409600023 PM 21243150 ER PT S AU Yin, JJ Xia, Q Lutterodt, H Wamer, W Fu, PP AF Yin, J. J. Xia, Q. Lutterodt, H. Wamer, W. Fu, P. P. BE Renou, JP Belton, PS Webb, GA TI APPLICATION OF ELECTRON SPIN RESONANCE SPECTROSCOPY TO STUDY DIETARY INGREDIENTS AND SUPPLEMENTS - DUAL ANTIOXIDANT AND PROOXIDANT FUNCTIONS OF RETINYL PALMITATE SO MAGNETIC RESONANCE IN FOOD SCIENCE: AN EXCITING FUTURE SE Royal Society of Chemistry Special Publications LA English DT Proceedings Paper CT 10th International Conference on the Applications of Magnetic Resonance in Food Science CY SEP 13-15, 2010 CL Clermont Ferrand, FRANCE SP Clermont Ferrand Theix Inst Natl Rech Agronomique ID CONJUGATED LINOLEIC-ACID; LIPID-PEROXIDATION; UVA PHOTOIRRADIATION; OXYGEN DIFFUSION; SINGLET OXYGEN; FUMONISIN B-1; MEMBRANES; PHOTODECOMPOSITION; CARDIOMYOCYTES; SUPEROXIDE C1 [Yin, J. J.; Wamer, W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Xia, Q.; Fu, P. P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lutterodt, H.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov NR 22 TC 2 Z9 2 U1 0 U2 0 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND SN 0260-6291 BN 978-1-84973-299-4 J9 ROY SOC CH PY 2011 IS 332 BP 126 EP 135 DI 10.1039/9781849732994-00126 PG 10 WC Food Science & Technology SC Food Science & Technology GA BA5CZ UT WOS:000336552200018 ER PT S AU Wong, JW Zhang, K Hayward, DG Kai-Meng, C AF Wong, Jon W. Zhang, Kai Hayward, Douglas G. Kai-Meng, Chin BE Zweigenbaum, J TI Multiresidue Pesticide Analysis by Capillary Gas Chromatography-Mass Spectrometry SO MASS SPECTROMETRY IN FOOD SAFETY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Gas chromatography-mass spectrometry; QuEChERS; Targeted analysis; Non-targeted data acquisition; Multiresidue methods ID FLAME PHOTOMETRIC DETECTION; SOLID-PHASE EXTRACTION; ORGANOPHOSPHORUS PESTICIDES; LIQUID-CHROMATOGRAPHY; QUECHERS METHOD; GINSENG ROOT; RESIDUES; PRODUCE; VEGETABLES; CONTAMINANTS AB A multiresidue pesticide method using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure and capillary gas chromatography-mass spectrometry (GC-MS) is described for the determination of 166 organochlorine, organophosphorus, and pyrethroid pesticides, metabolites, and isomers in spinach. The pesticides from spinach were extracted using acetonitrile saturated with magnesium sulfate and sodium chloride, followed by solid-phase dispersive cleanup using primary-secondary amine and graphitized carbon black sorbents and toluene. Analysis is performed using different GC-MS techniques emphasizing the benefits of non-targeted acquisition and targeted screening procedures. Non-targeted data acquisition of pesticides in the spinach was demonstrated using GC coupled to a single quadrupole mass spectrometery (GC-MS) in full scan mode or multidimensional GC-time-of-flight mass spectrometery (GC x GC-TOF/MS), along with deconvolution software and libraries. Targeted screening was achieved using GC-single quadrupole mass spectrometry in selective ion monitoring (GC-MS/SIM) mode or -tandem mass spectrometry (GC-MS/MS) in multiple reaction monitoring mode. The development of these techniques demonstrates the powerful use of GC-MS for the screening, identification, and quantitation of pesticide residues in foods. C1 [Wong, Jon W.; Zhang, Kai; Hayward, Douglas G.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Kai-Meng, Chin] Agilent Technol, Wilmington, DE USA. RP Wong, JW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 22 TC 5 Z9 5 U1 2 U2 9 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-61779-135-2 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 747 BP 131 EP 172 DI 10.1007/978-1-61779-136-9_6 D2 10.1007/978-1-61779-136-9 PG 42 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Food Science & Technology SC Biochemistry & Molecular Biology; Food Science & Technology GA BVP44 UT WOS:000292219300006 PM 21643907 ER PT S AU Paquerault, S Sahiner, B Kettermann, A Yarusso, LM Hadjiiski, LM Chan, HP AF Paquerault, Sophie Sahiner, Berkman Kettermann, Anna Yarusso, Laura M. Hadjiiski, Lubomir M. Chan, Heang-Ping BE Manning, DJ Abbey, CK TI Analysis of the number of distinct findings obtained by multiple readers in an MRMC study: When do findings obtained from the addition of new readers become redundant, or otherwise negligible? SO MEDICAL IMAGING 2011: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 16-17, 2011 CL Lake Buena Vista, FL SP SPIE, Dynasil Corp/RMD Res, AAPM - Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc DE MRMC observer study; computer-aided diagnosis (CAD) system; prediction model; reader performance ID COMPUTER-AIDED DIAGNOSIS; RADIOLOGISTS DETECTION; PERFORMANCE; SYSTEMS; SIZE AB The ultimate goal of this project is to investigate whether the effect of a computer-aided detection (CAD) system on readers' performance (especially, in situation of an upgrade of the CAD system, or between two different CAD systems with similar design) can be accurately predicted without having to perform a multi-reader multi-case (MRMC) observer study and, if such prediction is possible, to establish the underlying methodology. Our current study is intended to provide evidence that would substantiate efforts toward such investigation. The objectives of this study were 1) to investigate the relationship between the number of radiologists reading a dataset of thoracic computed tomography (CT) images to identify lung nodules and the number of distinct findings and 2) to determine the number of readers needed to identify almost all clinically distinct findings in a dataset. We used data from a multi-reader multi-case (MRMC) observer study that consisted of six radiologists interpreting 85 thoracic CT examinations. To further illustrate our approach, we also utilized simulated data consisting of twelve readers interpreting 198 samples equally distributed between three levels of detection difficulty. For each possible reader grouping, the number of distinct findings identified by the readers in the group was calculated. Five types of regression models used to describe the relationship between the average number of distinct findings per case and the number of readers needed were compared. The result showed that the logistic model best fitted both the thoracic CT data and the simulated data. Our assumption is that adding more readers after a certain reader set size would mostly add redundant findings and, therefore, the benefit would be negligible. Using this model, the predicted number of readers was found to depend on the type of findings considered. Our study showed that the number of clinically distinct findings that can be identified by radiologists on CT lung examinations without the use of a CAD system may be limited and that identifying almost all of these findings may only require a limited number of readers. C1 [Paquerault, Sophie; Sahiner, Berkman; Kettermann, Anna] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Paquerault, S (reprint author), US FDA, CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sophie.paquerault@telecom-paristech.org NR 8 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-81948-508-3 J9 PROC SPIE PY 2011 VL 7966 AR 79661M DI 10.1117/12.878103 PG 10 WC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BXL76 UT WOS:000296320800053 ER PT S AU Abboud, S Lee, K Vinehout, K Paquerault, S Kyprianou, IS AF Abboud, Samir Lee, Kristina Vinehout, Kaleb Paquerault, Sophie Kyprianou, Iacovos S. BE Pelc, NJ Samei, E Nishikawa, RM TI A comparison of methods for estimating the line spread function of a CT imaging system SO MEDICAL IMAGING 2011: PHYSICS OF MEDICAL IMAGING SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging 2011 - Physics of Medical Imaging CY FEB 13-17, 2011 CL Lake Buena Vista, FL SP Dynasil Corp/RMD Res, Amer Assoc Physicists Med, DQE Instruments, Inc, Ocean Thin Films, Inc, Univ Cent Florida, CREOL - Coll Opt & Photon, VIDA Diagnost, Inc, SPIE ID MODULATION TRANSFER-FUNCTION; DIGITAL RADIOGRAPHY; WIRE AB A quantitative description of the deterministic properties of a CT system is necessary when evaluating image quality. The most common such metric is the modulation transfer function (MTF), usually calculated from a line spread function (LSF) or point spread function (PSF). Currently, there exist many test objects used to measure the LSF or PSF. In this paper we report on a comparison of these measures using: a thin foil slit test object, a teflon cube edge test object and a novel "negative" cube test object. Images were acquired using a custom-built bench-top flat-panel-based cone-beam CT scanner and a cylindrical water-filled PMMA phantom with the test objects embedded in the middle. From the 3-dimensional reconstructed volumes, we estimated the LSF either directly or as estimated from the edge spread function. From these, a modulation transfer function can be estimated, and the frequency dependent image transfer of each object can be reported. C1 [Abboud, Samir; Paquerault, Sophie; Kyprianou, Iacovos S.] US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, Silver Spring, MD 20993 USA. RP Abboud, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math, 10903 New Hampshire Ave,W062-3109, Silver Spring, MD 20993 USA. EM samir.abboud@fda.hhs.gov NR 12 TC 1 Z9 1 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8503-8 J9 PROC SPIE PY 2011 VL 7961 AR 79615V DI 10.1117/12.877665 PG 10 WC Engineering, Electrical & Electronic; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BWL08 UT WOS:000294178500198 ER PT J AU Nada, A Krishnaiah, YSR Zaghloul, AA Khattab, I AF Nada, Aly Krishnaiah, Yellela S. R. Zaghloul, Abdel-Azim Khattab, Ibrahim TI In vitro and in vivo Permeation of Vitamin E and Vitamin E Acetate from Cosmetic Formulations SO MEDICAL PRINCIPLES AND PRACTICE LA English DT Article DE Vitamin E; Vitamin E acetate; Cosmetics; Permeation; Neonatal rats ID STRATUM-CORNEUM; PERCUTANEOUS-ABSORPTION; ALPHA-TOCOPHEROL; HAIRLESS MOUSE; SKIN; ANTIOXIDANTS; INHIBITION; SUNSCREENS; METABOLISM; EPIDERMIS AB Objective: To investigate the ability of alpha-tocopherol acetate (TA) and alpha-tocopherol (T), widely used ingredients in cosmetics, to cross the epidermal barrier using the neonatal rat as a model. Materials and Methods: The content of T and TA in four marketed products (A-D) and two experimental formulations (F1, F2) was investigated by HPLC. An in vitro permeation study was performed in neonatal rat epidermis using diffusion cells. In vivo permeation was studied in neonatal rats after repeated application of the products and analysis of T and TA in the stratum corneum/deeper skin layers. Results: Variable contents of TA were found in the marketed products (0.12-0.53%). No vitamin permeation was detected through the stratum corneum as in vitro biological barrier after 4 h. No detectable T and TA were seen in the in vivo permeation study in the epidermis. Variable degrees of drug penetration (4.3-12.6%) of the applied dose into the deeper skin layers were observed, depending on the formulation. In vivo application of TA-containing preparations did not result in any transformation of TA into T under the described experimental conditions. Conclusion: TA and T exhibited variable skin penetration and TA did not transform into T under the experimental conditions. The data underscored the need for further studies to optimize such formulations to improve vitamin E transdermal permeation and eventually achieve the expected cosmetic/therapeutic outcome. Copyright (C) 2011 S. Karger AG, Basel C1 [Nada, Aly; Krishnaiah, Yellela S. R.; Zaghloul, Abdel-Azim; Khattab, Ibrahim] Kuwait Univ, Dept Pharmaceut, Fac Pharm, Jabriya, Kuwait. [Krishnaiah, Yellela S. R.] US FDA, Silver Spring, MD USA. RP Nada, A (reprint author), Kuwait Univ, Dept Pharmaceut, Fac Pharm, POB 24923, Safat 13110, Kuwait. EM alynada@hsc.edu.kw FU Kuwait University [PP01/05] FX This work was supported by Kuwait University Research Grant No. PP01/05. The authors appreciate the technical help of Dr. F. Bandarkar, Mrs. E. Abraham, Mr. S. Abraham, Mrs. D. Nabil as well as Mrs. L. Varghese and Mrs. A. Thomas. NR 20 TC 1 Z9 2 U1 2 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1011-7571 J9 MED PRIN PRACT JI Med. Princ. Pract. PY 2011 VL 20 IS 6 BP 509 EP 513 DI 10.1159/000329883 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 832ZO UT WOS:000295850400004 PM 21986007 ER PT B AU Cole, M Kasuga, F Farber, JM Anderson, W Anelich, L Buchanan, RL Cordier, JL Dahms, S Dewanti-Hariyadi, R Flowers, RS Franco, BDGM Gorris, LGM Gram, L Lammerding, AM Liu, XM Potter, M Ross, T Swanson, KMJ Taniwaki, M Teufel, P Zwietering, M AF Cole, Martin Kasuga, Fumiko Farber, Jeffrey M. Anderson, Wayne Anelich, Lucia Buchanan, Robert L. Cordier, Jean-Louis Dahms, Susanne Dewanti-Hariyadi, Ratih Flowers, Russ S. Franco, Bernadette D. G. M. Gorris, Leon G. M. Gram, Lone Lammerding, Anna M. Liu, Xiumei Potter, Morris Ross, Tom Swanson, Katherine M. J. Taniwaki, Marta Teufel, Paul Zwietering, Marcel CA ICMSF GP ICMSF TI Nonalcoholic Beverages SO MICROORGANISMS IN FOODS 8: USE OF DATA FOR ASSESSING PROCESS CONTROL AND PRODUCT ACCEPTANCE LA English DT Article; Book Chapter ID ALICYCLOBACILLUS-ACIDOTERRESTRIS; HEAT-RESISTANCE; BYSSOCHLAMYS; PERFORMANCE; TEA C1 [Cole, Martin] CSIRO, N Ryde, NSW 2113, Australia. [Kasuga, Fumiko] Natl Inst Hlth Sci, Tokyo, Japan. [Buchanan, Robert L.] Univ Maryland, College Pk, MD 20742 USA. [Dahms, Susanne] Freie Univ, Berlin, Germany. [Dewanti-Hariyadi, Ratih] Bogor Agr Univ, Bogor, Indonesia. [Flowers, Russ S.] Silliker Grp Corp, Homewood, IL USA. [Franco, Bernadette D. G. M.] Univ Sao Paulo, Sao Paulo, SP, Brazil. [Gram, Lone] Tech Univ Denmark, DK-2800 Lyngby, Denmark. [Lammerding, Anna M.] Publ Hlth Agcy Canada, Guelph, ON, Canada. [Liu, Xiumei] Minist Hlth, China CDC, Beijing, Peoples R China. [Potter, Morris] US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. [Ross, Tom] Univ Tasmania, Hobart, Tas, Australia. [Swanson, Katherine M. J.] Ecolab, Eagan, MN USA. [Taniwaki, Marta] Inst Tecnol Alimentos, Campinas, SP, Brazil. [Teufel, Paul] Fed Dairy Res Ctr, Kiel, Germany. [Zwietering, Marcel] Wageningen Univ, Wageningen, Netherlands. RP Cole, M (reprint author), CSIRO, N Ryde, NSW 2113, Australia. NR 27 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-9373-1 PY 2011 BP 269 EP 280 DI 10.1007/978-1-4419-9374-8_20 PG 12 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BVN85 UT WOS:000292008500020 ER PT J AU Hunt, RC Geetha, S Allen, CE Hershko, K Fathke, R Kong, PL Plum, E Struble, EB Soejima, K Friedman, S Garfield, S Balaji, S Kimchi-Sarfaty, C AF Hunt, Ryan C. Geetha, S. Allen, Courtni E. Hershko, Klilah Fathke, Robert Kong, Philip L. Plum, Elizabeth Struble, Evi Budo Soejima, Kenji Friedman, Scott Garfield, Susan Balaji, S. Kimchi-Sarfaty, Chava TI Detection of a secreted metalloprotease within the nuclei of liver cells SO MOLECULAR BIOSYSTEMS LA English DT Article ID VON-WILLEBRAND-FACTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; LOCALIZATION SIGNALS; PROSTATE-CANCER; STELLATE CELLS; CUB DOMAINS; ADAMTS13; PROTEIN; TRANSLOCATION; IDENTIFICATION AB ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver cell lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the cellular secretory system, we detected an appreciable level of endogenous ADAMTS13 within the nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present in the ADAMTS13 propeptide may act as a nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly potentiated its nuclear localization. Bioinformatics analysis suggests that the ADAMTS13 CUB-2 domain has a double-stranded beta helix (DSBH) structural architecture characteristic of various protein-protein interaction modules like nucleoplasmins, class I collagenase, tumor necrosis factor ligand superfamily, supernatant protein factor (SPF) and the B1 domain of neuropilin-2. Based on this contextual evidence and that largely conserved polar residues could be mapped on to a template CUB domain homolog, we hypothesize that a region in the ADAMTS13 CUB-2 domain with conserved polar residues might be involved in protein-protein interaction within the nucleus. C1 [Garfield, Susan] NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Hunt, Ryan C.; Geetha, S.; Allen, Courtni E.; Hershko, Klilah; Fathke, Robert; Kong, Philip L.; Plum, Elizabeth; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol, Bethesda, MD 20892 USA. [Struble, Evi Budo] US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol, Bethesda, MD 20892 USA. [Soejima, Kenji] Chemoserotherapeut Res Inst, Res Dept 1, Kumamoto, Japan. [Friedman, Scott] Mt Sinai Sch Med, Div Liver Dis, New York, NY 10029 USA. [Balaji, S.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Garfield, S (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM Susan.Garfield@nih.hhs.gov; Balaji_Santhanam@DFCI.HARVARD.EDU; Chava.kimchi-sarfaty@fda.hhs.gov FU Intramural NIH HHS [Z01 BC010858-01] NR 34 TC 4 Z9 4 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PY 2011 VL 7 IS 6 BP 2012 EP 2018 DI 10.1039/c0mb00303d PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 763PR UT WOS:000290572700023 PM 21479334 ER PT B AU Schneider, KR Strawn, LK Lampel, KA Warren, BR AF Schneider, K. R. Strawn, L. K. Lampel, K. A. Warren, B. R. BE Liu, D TI Shigella SO MOLECULAR DETECTION OF HUMAN BACTERIAL PATHOGENS LA English DT Article; Book Chapter ID ACTIN-BASED MOTILITY; ENTEROINVASIVE ESCHERICHIA-COLI; POLYMERASE-CHAIN-REACTION; SHIGA TOXIN; FLEXNERI 2A; UNIPOLAR LOCALIZATION; SONNEI INFECTION; DYSENTERIAE TYPE-1; AEROBACTIN GENES; ICEBERG LETTUCE C1 [Schneider, K. R.] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Strawn, L. K.] Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. [Lampel, K. A.] US FDA, Div Microbiol, College Pk, MD USA. [Warren, B. R.] ConAgra Foods Inc, Res Qual & Innovat, Omaha, NE USA. RP Schneider, KR (reprint author), Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. NR 129 TC 0 Z9 0 U1 1 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-1239-6; 978-1-4398-1238-9 PY 2011 BP 1049 EP 1062 D2 10.1201/b10848 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BC7QK UT WOS:000355145400090 ER PT J AU Li, YH Sosnik, J Brassard, L Reese, M Spiridonov, NA Bates, TC Johnson, GR Anguita, J Visconti, PE Salicioni, AM AF Li, Yahui Sosnik, Julian Brassard, Laura Reese, Michael Spiridonov, Nikolay A. Bates, Tonya C. Johnson, Gibbes R. Anguita, Juan Visconti, Pablo E. Salicioni, Ana M. TI Expression and localization of five members of the testis-specific serine kinase (Tssk) family in mouse and human sperm and testis SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE Tssk kinases; testis-specific; signal transduction; contraception; sperm function ID SERINE/THREONINE KINASE; SPERMATOGENIC CELLS; CAPACITATION; PROTEINS; PHOSPHORYLATION; IDENTIFICATION; CLEAVAGE; FUSION; IZUMO AB Members of the testis-specific serine/threonine kinases (Tssk) family may have a role in sperm differentiation in the testis and/or fertilization. To gain insight into the functional relevance of these kinases, their expression was examined both at the mRNA and protein levels. Quantitative PCR analysis confirmed that all five Tssk mRNAs are almost exclusively expressed postmeiotically in the testis. Recombinant mouse and human Tssks were cloned and used for validation of an array of commercial and custom-made antibodies against Tssks. Immunolocalization in mouse testis, and in mouse and human sperm, showed that Tssk1, Tssk2, Tssk4 and Tssk6, but not Tssk3, were present in mouse sperm and in germ cells from mouse testis. TSSK1, TSSK2 and TSSK6 were also detected in human sperm, while TSSK3 was absent. In both mouse and human sperm, Tssk1 was partially soluble, while Tssk2, Tssk4 and Tssk6 were insoluble in non-ionic detergents. In vitro recombinant TSSK2 activity assays showed maximum enzymatic activity at 5 mM Mg(2+) and a Km for ATP of similar to 10 mu M. These, observations together with findings that the Tssk1/Tssk2 double knock-out as well as the Tssk6 null mice are sterile without presenting other detectable defects, suggest that these kinases could be used as targets for male contraception. C1 [Li, Yahui; Sosnik, Julian; Brassard, Laura; Reese, Michael; Bates, Tonya C.; Anguita, Juan; Visconti, Pablo E.; Salicioni, Ana M.] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Salicioni, AM (reprint author), Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. EM asalicioni@vasci.umass.edu RI Sosnik, Julian/A-8310-2010; Anguita, Juan/D-5432-2011; Spiridonov, Nikolay/B-6287-2014 OI Sosnik, Julian/0000-0002-0528-9929; Anguita, Juan/0000-0003-2061-7182; FU NIH [HD038082, HD044044, HD050341, F31HD049324]; University of Massachusetts; Baystate Medical Center; Gustavus and Louise Pfeiffer Research Foundation FX This study was supported by grants NIH HD038082, NIH HD044044 and NIH HD050341 (to P.E.V.), by the Collaborative Biomedical Research (CBR) Program between the University of Massachusetts and Baystate Medical Center (to A.M.S.), and by NIH F31HD049324 (to J.S.). Characterization of Tssks in human subjects was supported in part by the Gustavus and Louise Pfeiffer Research Foundation. NR 32 TC 26 Z9 31 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JAN PY 2011 VL 17 IS 1 BP 42 EP 56 DI 10.1093/molehr/gaq071 PG 15 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 696CL UT WOS:000285419400005 PM 20729278 ER PT B AU Whelton, AJ Duncan, TV Koontz, JL Nguyen, T AF Whelton, A. J. Duncan, T. V. Koontz, J. L. Nguyen, T. BE Laudon, M Romanowicz, B TI Nanoparticle Release from Polymer Nanocomposites Used for Potable Water Infrastructure and Food Packaging: Current Progress & Beyond SO NANOTECHNOLOGY 2011: BIO SENSORS, INSTRUMENTS, MEDICAL, ENVIRONMENT AND ENERGY, NSTI-NANOTECH 2011, VOL 3 LA English DT Proceedings Paper CT NSTI Nanotechnology Conference and Expo CY JUN 13-16, 2011 CL Boston, MA SP Clean Technol & Sustainable Ind Org, European Patent Off, Greenberg Traurig, Innovat & Mat Sci Inst, Jackson Walker LLP, Linde Nanomaterials, Lockheed Martin, Nano Sci & Technol Inst, Nano Tech Japan, NanoEurope Fair & Conf, Nanpolis Suzhou, Suzhou Nanotech Co Ltd, Natl Inst Standards & Technol, Ctr Nanoscale Sci & Technol, Fraunhofer, Res Germany, TechConnect, Technol Innovat Program, Canadian Trade Commiss Serv, Italian Trade Commiss DE nanoparticle; water; food; release; infrastructure AB Nanoparticle (NP) enhanced polymers have the potential to revolutionize food packaging and water pipe performance, though release of NPs from these materials has gone relatively unstudied. A literature review was conducted to identify potential NP release pathways from nanomposite materials into food and water. Results show little is known, and this lack of knowledge prevents responsible commercialization of safe and innovative nano enhanced products, development of predictive health risk models, and generation of science based environmental, health, and safety focused regulation. Common limitations of past studies are that quantitative results were not described, NP detection methods were lacking, and metal ions were not differentiated from NPs. Science has not quantitatively determined if and under what conditions nanocomposites release NPs into food and water matrices. Future research needs are also identified. C1 [Whelton, A. J.] Univ S Alabama, Mobile, AL 36688 USA. [Duncan, T. V.; Koontz, J. L.] FDA, Bedford Pk, IL USA. [Nguyen, T.] NIST, Gaithersburg, MD 20899 USA. RP Whelton, AJ (reprint author), Univ S Alabama, Mobile, AL 36688 USA. EM ajwhelton@usouthal.edu; Timothy.Duncan@fda.hhs.gov; John.Koontz@fda.hhs.gov; Tinh.Nguyen@nist.gov NR 39 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4398-7138-6 PY 2011 BP 505 EP 508 PG 4 WC Energy & Fuels; Engineering, Environmental; Nanoscience & Nanotechnology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Energy & Fuels; Engineering; Science & Technology - Other Topics; Research & Experimental Medicine; Materials Science GA BG9XC UT WOS:000394061000133 ER PT J AU Lee, CA Hillgren, KM Zhang, L Polli, JW AF Lee, Caroline A. Hillgren, Kathleen M. Zhang, Lei Polli, Joseph W. CA Int Transporter Consortium TI Response from the International Transporter Consortium SO NATURE REVIEWS DRUG DISCOVERY LA English DT Letter ID INTESTINAL P-GLYCOPROTEIN; DRUG INTERACTIONS; GRAPEFRUIT JUICE; CACO-2 CELLS; DIGOXIN; TALINOLOL; INCREASES; HUMANS; BIOAVAILABILITY; KETOCONAZOLE C1 [Polli, Joseph W.] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. [Lee, Caroline A.] Pfizer Global Res & Dev, La Jolla Labs, San Diego, CA 92121 USA. [Hillgren, Kathleen M.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [Zhang, Lei] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Polli, JW (reprint author), GlaxoSmithKline Inc, POB 13398, Res Triangle Pk, NC 27709 USA. EM caroline.lee01@pfizer.com; leik.zhang@fda.hhs.gov; joseph.w.polli@gsk.com NR 21 TC 3 Z9 3 U1 0 U2 2 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 JAN PY 2011 VL 10 IS 1 DI 10.1038/nrd3028-c2 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 700YV UT WOS:000285782400019 ER PT J AU Mays, J Butts, CL AF Mays, Jacqueline Butts, Cherie L. TI Intercommunication between the Neuroendocrine and Immune Systems: Focus on Myasthenia Gravis SO NEUROIMMUNOMODULATION LA English DT Article DE Autoimmunity; Thymoma; Acetylcholine receptor; Steroid hormones; Immune system ID RECEPTOR ALPHA-SUBUNIT; ACETYLCHOLINE-RECEPTOR; NEUROMUSCULAR-JUNCTION; CLASS-II; T-CELLS; ANTIBODIES; ESTROGEN; EXPRESSION; PREGNANCY; THYMOMA AB Crosstalk exists between the nervous, endocrine, and immune systems, and perturbations in these interactions have been associated with disease. This includes production of neuroendocrine factors that alter immune system activity and increase susceptibility to or severity of immune-related conditions, such as myasthenia gravis (MG) - a T-cell-dependent, B-cell-mediated autoimmune disorder. MG results from impairment of transmission to the neuromuscular junction and involves the thymus - especially in early-onset disease, but the exact mechanism by which the thymus impacts disease is unclear. MG afflicts millions of individuals worldwide each year, and both men and women can develop symptoms. However, prevalence and age of onset differs between men and women. Women exhibit higher incidence and earlier age of onset compared to men, and disease fluctuates during pregnancy. This suggests that sex hormones play a role in influencing disease outcome. In this review, we will consider what is known about the manifestation of MG, theories on how different forms of MG are influenced or alleviated by steroid hormones, current treatment options, and what measures could be important to consider in the future. Copyright (C) 2011 S. Karger AG, Basel C1 [Butts, Cherie L.] US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Mays, Jacqueline] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Butts, CL (reprint author), US FDA, Immunol Lab, Div Therapeut Prot, Off Biotechnol Prod,Ctr Drug Evaluat & Res, 8800 Rockville Pike,HFD 122,Bldg 29A,Room 3B19, Bethesda, MD 20892 USA. EM cherie.butts@fda.hhs.gov NR 57 TC 3 Z9 3 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7401 J9 NEUROIMMUNOMODULAT JI Neuroimmunomodulation PY 2011 VL 18 IS 5 BP 320 EP 327 DI 10.1159/000329491 PG 8 WC Endocrinology & Metabolism; Immunology; Neurosciences SC Endocrinology & Metabolism; Immunology; Neurosciences & Neurology GA 823XT UT WOS:000295162000008 PM 21952684 ER PT J AU Pereira, FC Gough, B Macedo, TR Ribeiro, CF Ali, SF Binienda, ZK AF Pereira, Frederico C. Gough, Bobby Macedo, Tice R. Ribeiro, Carlos F. Ali, Syed F. Binienda, Zbigniew K. TI Buprenorphine Modulates Methamphetamine-Induced Dopamine Dynamics in the Rat Caudate Nucleus SO NEUROTOXICITY RESEARCH LA English DT Article DE In vivo microdialysis; Dopamine; Opioids/methamphetamine combination; Caudate nucleus ID NOCICEPTIN/ORPHANIN FQ; RHESUS-MONKEYS; COCAINE ABUSE; MORPHINE; DEPENDENCE; RECEPTOR; MECHANISMS; ACCUMBENS; TURNOVER; RELEASE AB Methamphetamine (METH) abuse and addiction present a major problem in the United States and globally. Oxidative stress associated with exposure to METH mediates to the large extent METH-evoked neurotoxicity. While there are currently no medications approved for treating METH addiction, its pharmacology provides opportunities for potential pharmacotherapeutic adjuncts to behavioral therapy in the treatment of METH addiction. Opioid receptor agonists can modulate the activity of dopamine neurons and could, therefore, modify the pharmacodynamic effects of METH in the dopaminergic system. Efficacy of the adjunctive medication with buprenorphine has been demonstrated in the treatment of cocaine addiction extending beyond opiate addiction. We investigated the interactions of morphine (10 mg/kg) and buprenorphine (0.01 and 10 mg/kg) with METH (2 mg/kg) affecting striatal dopaminergic transmission. The extracellular concentration of dopamine (DA) and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were determined using brain microdialysis coupled with high performance liquid chromatography with electrochemical detection (HPLC-ED) in the caudate nucleus of adult, awake, male Sprague-Dawley rats. Compared to METH alone, extracellular DA release was prolonged for 140 min without changes in DA peak-effect by combined treatment with morphine/METH. Morphine did not change DOPAC efflux evoked by METH. On the other hand, both buprenorphine doses attenuated the METH-induced DA peak-effect. However, whereas high buprenorphine dose extended DA outflow for 190 min, the low-dose abbreviated DA release. High buprenorphine dose also shortened METH-induced decrease in DOPAC efflux. Data confirm that opiates modulate dopaminergic neurotransmission evoked by METH. Alteration of dopaminergic response to METH challenge under buprenorphine may suggest effectiveness of buprenorphine treatment in METH addiction. C1 [Pereira, Frederico C.; Macedo, Tice R.; Ribeiro, Carlos F.] Univ Coimbra, Inst Pharmacol & Therapeut, Biomed Inst Res Light & Image, Fac Med, P-3000354 Coimbra, Portugal. [Gough, Bobby; Ali, Syed F.; Binienda, Zbigniew K.] FDA NCTR, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Pereira, FC (reprint author), Univ Coimbra, Inst Pharmacol & Therapeut, Biomed Inst Res Light & Image, Fac Med, Subunit 1 Polo 3, P-3000354 Coimbra, Portugal. EM fredcp@ci.uc.pt; zbigniew.binienda@fda.hhs.gov OI Pereira, Frederico/0000-0002-9381-3320 NR 38 TC 6 Z9 6 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD JAN PY 2011 VL 19 IS 1 BP 94 EP 101 DI 10.1007/s12640-009-9143-9 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 721QB UT WOS:000287368600010 PM 20033362 ER PT J AU Croft, D O'Kelly, G Wu, GM Haw, R Gillespie, M Matthews, L Caudy, M Garapati, P Gopinath, G Jassal, B Jupe, S Kalatskaya, I Mahajan, S May, B Ndegwa, N Schmidt, E Shamovsky, V Yung, C Birney, E Hermjakob, H D'Eustachio, P Stein, L AF Croft, David O'Kelly, Gavin Wu, Guanming Haw, Robin Gillespie, Marc Matthews, Lisa Caudy, Michael Garapati, Phani Gopinath, Gopal Jassal, Bijay Jupe, Steven Kalatskaya, Irina Mahajan, Shahana May, Bruce Ndegwa, Nelson Schmidt, Esther Shamovsky, Veronica Yung, Christina Birney, Ewan Hermjakob, Henning D'Eustachio, Peter Stein, Lincoln TI Reactome: a database of reactions, pathways and biological processes SO NUCLEIC ACIDS RESEARCH LA English DT Article ID COMMUNITY STANDARD; PHYLOGENETIC TREES; REPRESENTATION; COLLECTION; UPDATE AB Reactome (http://www.reactome.org) is a collaboration among groups at the Ontario Institute for Cancer Research, Cold Spring Harbor Laboratory, New York University School of Medicine and The European Bioinformatics Institute, to develop an open source curated bioinformatics database of human pathways and reactions. Recently, we developed a new web site with improved tools for pathway browsing and data analysis. The Pathway Browser is an Systems Biology Graphical Notation (SBGN)-based visualization system that supports zooming, scrolling and event highlighting. It exploits PSIQUIC web services to overlay our curated pathways with molecular interaction data from the Reactome Functional Interaction Network and external interaction databases such as IntAct, BioGRID, ChEMBL, iRefIndex, MINT and STRING. Our Pathway and Expression Analysis tools enable ID mapping, pathway assignment and overrepresentation analysis of user-supplied data sets. To support pathway annotation and analysis in other species, we continue to make orthology-based inferences of pathways in non-human species, applying Ensembl Compara to identify orthologs of curated human proteins in each of 20 other species. The resulting inferred pathway sets can be browsed and analyzed with our Species Comparison tool. Collaborations are also underway to create manually curated data sets on the Reactome framework for chicken, Drosophila and rice. C1 [Wu, Guanming; Haw, Robin; Caudy, Michael; Kalatskaya, Irina; May, Bruce; Yung, Christina; Stein, Lincoln] Ontario Inst Canc Res Informat & Biocomp, Toronto, ON M5G 0A3, Canada. [Croft, David; O'Kelly, Gavin; Garapati, Phani; Jassal, Bijay; Jupe, Steven; Ndegwa, Nelson; Schmidt, Esther; Birney, Ewan; Hermjakob, Henning] Wellcome Trust Genome Campus, European Bioinformat Inst, Cambridge CB10 1SD, England. [Gillespie, Marc] St Johns Univ, Coll Pharm & Allied Hlth Profess, Queens, NY 11439 USA. [Matthews, Lisa; Mahajan, Shahana; Shamovsky, Veronica; D'Eustachio, Peter] NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. [Gopinath, Gopal] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Mahajan, Shahana] CUNY Hunter Coll, Sch Hlth Sci, New York, NY 10010 USA. [Stein, Lincoln] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. [Stein, Lincoln] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada. RP Stein, L (reprint author), Ontario Inst Canc Res Informat & Biocomp, Toronto, ON M5G 0A3, Canada. EM Peter.D'Eustachio@nyumc.org; lincoln.stein@gmail.com RI Gichora, Nelson /E-1749-2015; Haw, Robin/D-1393-2009; OI Kalatskaya, Irina/0000-0002-1663-859X; Hermjakob, Henning/0000-0001-8479-0262; Gichora, Nelson /0000-0002-5853-879X; Jupe, Steven/0000-0001-5807-0069; Croft, David/0000-0001-6363-8595; Garapati, Phani Vijay/0000-0003-0941-2207; Gillespie, Marc/0000-0002-5766-1702; Matthews, Lisa/0000-0001-5707-3065; Haw, Robin/0000-0002-2013-7835; D'Eustachio, Peter/0000-0002-5494-626X; Yung, Christina/0000-0003-2958-150X; Birney, Ewan/0000-0001-8314-8497 FU National Human Genome Research Institute at the National Institutes of Health [P41 HG003751]; European Union [LSHG-CT-2005-518254]; Ontario Institute for Cancer Research FX National Human Genome Research Institute at the National Institutes of Health (grant number P41 HG003751); European Union 6th Framework Programme 'ENFIN' (grant number LSHG-CT-2005-518254). Funding for open access charge: Ontario Institute for Cancer Research. NR 38 TC 499 Z9 508 U1 3 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JAN PY 2011 VL 39 SU 1 BP D691 EP D697 DI 10.1093/nar/gkq1018 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 701PA UT WOS:000285831700110 PM 21067998 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO NUTRITION RESEARCH LA English DT Article C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Massachusetts Gen Hosp, Dept Med,Sch Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Dept Emergency Med, Massachusetts Gen Hosp, Dept Med,Div Rheumatol Allergy & Immunol,Sch Med, Boston, MA 02115 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Pulm & Crit Med Div, Partners Asthma Ctr, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Cincinnati, OH USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Div Allergy & Immunol, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Dept Pediat, Div Allergy & Immunol, Elliot & Roslyn Jaffe Food Allergy Inst, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD 21205 USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Furuta, Glenn T.] Childrens Hosp Denver, Digest Hlth Inst, Sect Pediat Gastroenterol Hepatol & Nutr, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Furuta, Glenn T.] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Lieberman, Phil] Univ Tennessee, Dept Med, Coll Med, Div Allergy & Immunol, Memphis, TN 38104 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network; Gerber; Mead Johnson; Dyax Corp; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; variety of government agencies; Dey; Novartis; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc FX J. A. Boyce has served on the Advisory Board of GlaxoStmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoStmithKline and as a speaker for the American College of Allergy, Asthma, and Immunology, the North East Allergy Society, the Virginia Allergy Society, the New England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Daimon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S. M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network. She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S. L. Bahna has received funding/grant support from Genentech.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc. NR 1 TC 33 Z9 39 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD JAN PY 2011 VL 31 IS 1 BP 61 EP 75 DI 10.1016/j.nutres.2011.01.001 PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 724ZB UT WOS:000287613900010 PM 21310308 ER PT J AU Casak, SJ Lemery, SJ Shen, YL Rothmann, MD Khandelwal, A Zhao, H Davis, G Jarral, V Keegan, P Pazdur, R AF Casak, Sandra J. Lemery, Steven J. Shen, Yuan Li Rothmann, Mark D. Khandelwal, Aakanksha Zhao, Hong Davis, Gina Jarral, Vaishali Keegan, Patricia Pazdur, Richard TI US Food and Drug Administration Approval: Rituximab in Combination with Fludarabine and Cyclophosphamide for the Treatment of Patients with Chronic Lymphocytic Leukemia SO ONCOLOGIST LA English DT Article DE FDA; Rituximab; Chronic lymphocytic leukemia; Fludarabine; Cyclophosphamide ID PROGRESSION-FREE SURVIVAL AB Purpose. To describe the clinical studies that led to the FDA approval of rituximab in combination with fludarabine and cyclophosphamide (FC) for the treatment of patients with chronic lymphocytic leukemia (CLL). Materials and Methods. The results of two multinational, randomized trials in CLL patients comparing rituximab combined with fludarabine and cyclophosphamide versus FC were reviewed. The primary endpoint of both studies was progression-free survival (PFS). Results. The addition of rituximab to FC decreased the risk of a PFS event by 44% in 817 previously untreated patients and by 24% in 552 previously treated patients. Median survival times could not be estimated. Exploratory analysis in patients older than 70 suggested that there was no benefit to patients when rituximab was added to FC. The safety profile observed in both trials was consistent with the known toxicity profile of rituximab, FC, or CLL. Conclusions. On the basis of the demonstration of clinically meaningful prolongation of PFS, the FDA granted regular approval to rituximab in combination with FC for the treatment of patients with CLL. The magnitude of the treatment effect in patients 70 years and older is uncertain. The Oncologist 2011; 16: 97-104 C1 [Casak, Sandra J.] US FDA, Div Biol Oncol Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Oncol Drug Prod, Silver Spring, MD 20993 USA. [Shen, Yuan Li; Rothmann, Mark D.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. [Khandelwal, Aakanksha; Zhao, Hong] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Casak, SJ (reprint author), US FDA, Div Biol Oncol Prod, Ctr Drug Evaluat & Res, Off New Drugs,Off Oncol Drug Prod, 10903 New Hampshire Ave,Bldg 22,Room 5223, Silver Spring, MD 20993 USA. EM Sandra.Casak@fda.hhs.gov NR 8 TC 13 Z9 16 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2011 VL 16 IS 1 BP 97 EP 104 DI 10.1634/theoncologist.2010-0306 PG 8 WC Oncology SC Oncology GA 710JB UT WOS:000286506600011 PM 21212432 ER PT S AU Agrawal, A Chang, R Connors, M Stafford, C Hwang, J Pfefer, TJ AF Agrawal, Anant Chang, Robert Connors, Megan Stafford, Christopher Hwang, Jeeseong Pfefer, T. Joshua BE Nordstrom, RJ Cote, GL TI System-independent assessment of OCT axial resolution with a "bar chart" phantom SO OPTICAL DIAGNOSTICS AND SENSING XI: TOWARD POINT-OF-CARE DIAGNOSTICS AND DESIGN AND PERFORMANCE VALIDATION OF PHANTOMS USED IN CONJUNCTION WITH OPTICAL MEASUREMENT OF TISSUE III SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Diagnostics and Sensing XI - Toward Point-of-Care Diagnostics and Design and Performance Validation of Phantoms Used in Conjunction with Optical Measurement of Tissue III CY JAN 22-26, 2011 CL San Francisco, CA SP SPIE DE phantoms; optical coherence tomography; resolution ID OPTICAL COHERENCE TOMOGRAPHY; SCATTERING AB We present a optical phantom approach for the characterization of OCT axial resolution and contrast via multilayered "bar charts." We explored two methods to fabricate these phantoms: the first is based on monolayers of light-scattering microspheres with an intervening layer of transparent silicone, and the second involves alternating layers of scattering-enhanced silicone and transparent silicone. Varying the diameter of the microspheres and the thickness of the silicone layers permits different spatial frequencies to be realized in the axial dimension of the phantoms. Because the phantom's dimensions are accurately known independent of the OCT system, no information about the system's spatial calibration is required. We quantified the degree to which the bars in each phantom could be resolved with OCT, which provides insights into the axial contrast transfer function. Initial testing of these phantoms on time-resolved and Fourier-domain OCT platforms indicated that our approach can provide accurate, system-independent estimates of resolution. C1 [Agrawal, Anant; Connors, Megan; Pfefer, T. Joshua] US FDA, Opt Diagnost Devices Lab, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Agrawal, A (reprint author), US FDA, Opt Diagnost Devices Lab, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM anant.agrawal@fda.hhs.gov NR 11 TC 4 Z9 4 U1 1 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8443-7 J9 PROC SPIE PY 2011 VL 7906 AR 79060R DI 10.1117/12.880958 PG 7 WC Optics; Radiology, Nuclear Medicine & Medical Imaging SC Optics; Radiology, Nuclear Medicine & Medical Imaging GA BZS23 UT WOS:000302694400019 ER PT S AU Kim, DH Ilev, IK Han, YG AF Kim, Do-Hyun Ilev, Ilko K. Han, Young-Geun BE Gannot, I TI A Thickness Measurement Method for Biological Samples using Lensed-Fiber Sensors SO OPTICAL FIBERS, SENSORS, AND DEVICES FOR BIOMEDICAL DIAGNOSTICS AND TREATMENT XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Fibers, Sensors, and Devices for Biomedical Diagnostics and Treatment XI CY JAN 22-23, 2011 CL San Francisco, CA SP SPIE DE confocal microscopy; fiber sensor; thickness measurement ID DIFFERENTIAL CONFOCAL MICROSCOPY; OPTICAL COHERENCE TOMOGRAPHY; REFRACTIVE-INDEX; INTERFEROMETRY; TISSUE AB We present a simple fiber-optic confocal method for high-precision thickness measurement of optically transparent and non-transparent objects that require noncontact measurement. The method is based on measurement of confocal back-reflection responses from the opposite surfaces of objects, which imposes inessential limitations on the shape, thickness, and transparency of testing objects. A novel reference comparison method to eliminate additional errors existing commonly in confocal microscope designs is adapted. The measurement error highly depends on the axial response of confocal microscope, and was measured to be 5.0 mu m using a single-mode optical fiber construction, 60x objective lenses, and a 658-nm-wavelength laser source. We demonstrate the method using lensed-fiber sensors, which reduces the size of the experimental setup so that the method can be utilized for smaller samples at in-vivo situation. We demonstrate the proof-of-concept measurement using biological samples. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8431-4 J9 PROC SPIE PY 2011 VL 7894 AR 789416 DI 10.1117/12.881640 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BXY47 UT WOS:000297622000029 ER PT S AU Kim, DH AF Kim, Do-Hyun BE Gannot, I TI Evaluation of Phototoxicity from Scanning Biophotonic Devices SO OPTICAL FIBERS, SENSORS, AND DEVICES FOR BIOMEDICAL DIAGNOSTICS AND TREATMENT XI SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Fibers, Sensors, and Devices for Biomedical Diagnostics and Treatment XI CY JAN 22-23, 2011 CL San Francisco, CA SP SPIE DE phototoxicity; scanning devices; optical radiation hazard ID LASER; EXPOSURE; BEAM AB Scanning light sources in biophotonic devices are considered as either extended or pulsed sources when their potential optical hazard is evaluated. While the existing evaluation criteria are directly applicable to scanning light sources in most cases, different dwell-time and overlap between the beams need to be taken into account to obtain maximum irradiation. The effect of dwell-time and overlap of scanning light source on the irradiation of lights to skin was theoretically and experimentally analyzed in this report. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov NR 4 TC 2 Z9 2 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-8431-4 J9 PROC SPIE PY 2011 VL 7894 AR 78940H DI 10.1117/12.882004 PG 10 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BXY47 UT WOS:000297622000013 ER PT J AU Antunes, AMM Novais, DA da Silva, JLF Santos, PP Oliveira, MC Beland, FA Marques, MM AF Antunes, Alexandra M. M. Novais, David A. Ferreira da Silva, J. L. Santos, Pedro P. Conceicao Oliveira, M. Beland, Frederick A. Matilde Marques, M. TI Synthesis and oxidation of 2-hydroxynevirapine, a metabolite of the HIV reverse transcriptase inhibitor nevirapine SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID TO-CHILD TRANSMISSION; INDUCED SKIN RASH; DOSE NEVIRAPINE; QUINONE IMINE; ANTIRETROVIRAL THERAPY; PERIODATE OXIDATION; ACETYL HYPOFLUORITE; PREVOST REACTION; LACTOPEROXIDASE; SINGLE AB Nevirapine (11-cyclopropyl-5,11-dihydro-4-methyl-6H-dipyrido[3,2-b:2'3'e][1,4]diazepin-6-one, NVP) is a non-nucleoside HIV-1 reverse transcriptase inhibitor used to prevent mother-to-child transmission of the virus. However, severe hepatotoxicity and serious adverse cutaneous effects have raised concerns about the safety of NVP administration. NVP metabolism yields several phenol-type derivatives conceivably capable of undergoing further metabolic oxidation to electrophilic quinoid species that could react with bionucleophiles. The covalent adducts thus formed might be at the genesis of toxic responses. As an initial step to test this hypothesis, we synthesized the phenolic metabolite, 2-hydroxy-NVP, and investigated its oxidation in vitro. Using potassium nitrosodisulfonate and sodium periodate as model oxidants, we obtained evidence for fast generation of an electrophilic quinone-imine, which readily underwent hydrolytic conversion to fully characterized spiro derivatives, 1'-cyclopropyl-4-methyl-1H,1'H-spiro[pyridine-2,2'-pyrido[2,3-d]pyrimidine]-3,4',6(3'H)-trione in aqueous media and 1'-cyclopropyl-4-methyl-1'H,2H-spiro[pyridine-3,2'-pyrido[2,3-d]pyrimidine]2,4',6(1H,3'H)-trione in non-aqueous media. The spiro compound generated in aqueous solution underwent subsequent hydrolytic degradation of the NVP ring system, whereas the one formed in non-aqueous media was stable to hydrolysis. The product profile observed with the chemical oxidants in aqueous solution was replicated using lactoperoxidase-mediated oxidation of 2-hydroxy-NVP. These observations suggest that metabolic activation of NVP, via Phase I oxidation to 2-hydroxy-NVP and subsequent generation of a quinone-imine, could occur in vivo and play a role in NVP-induced toxicity. C1 [Antunes, Alexandra M. M.; Novais, David A.; Ferreira da Silva, J. L.; Santos, Pedro P.; Conceicao Oliveira, M.; Matilde Marques, M.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrut, P-1049001 Lisbon, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Antunes, AMM (reprint author), Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrut, P-1049001 Lisbon, Portugal. EM alexandra.antunes@ist.utl.pt; matilde.marques@ist.utl.pt RI Silva, Joao/H-7770-2012; Oliveira, Maria Conceicao/H-8263-2012; Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; Santos, Pedro Paulo/P-1769-2016; OI Silva, Joao/0000-0002-9751-9268; Oliveira, Maria Conceicao/0000-0002-3068-4920; Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Santos, Pedro Paulo/0000-0003-3045-4591; Ferreira da Silva, Joao/0000-0003-2797-5206 FU Fundacao para a Ciencia e a Tecnologia (FCT), Portugal [PEst-OE/QUI/UI0100/2011, PPCDT/QUI/56582/2004, PTDC/QUI-QUI/113910/2009]; National Center for Toxicological Research/Food and Drug Administration [Y1ES1027]; National Institute of Environmental Health Sciences [Y1ES1027] FX We thank the Portuguese NMR Network (IST-UTL Center) and the Portuguese MS Network (IST-UTL Center) for providing access to the facilities. This work was supported in part by Fundacao para a Ciencia e a Tecnologia (FCT), Portugal, through pluriannual funds to Centro de Quimica Estrutural (PEst-OE/QUI/UI0100/2011) and research grants PPCDT/QUI/56582/2004 and PTDC/QUI-QUI/113910/2009, and by Interagency Agreement Y1ES1027 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute of Environmental Health Sciences/National Toxicology Program. The opinions expressed in this paper do not necessarily represent those of the U. S. Food and Drug Administration. NR 81 TC 15 Z9 15 U1 0 U2 16 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PY 2011 VL 9 IS 22 BP 7822 EP 7835 DI 10.1039/c1ob06052j PG 14 WC Chemistry, Organic SC Chemistry GA 837LE UT WOS:000296203700033 PM 21969039 ER PT J AU Kerlikowske, G Jones, CM LaBelle, RM Condon, TP AF Kerlikowske, Gil Jones, Christopher M. LaBelle, Regina M. Condon, Timothy P. TI Prescription Drug Monitoring Programs-Lack of Effectiveness or a Call to Action? SO PAIN MEDICINE LA English DT Editorial Material ID NONMEDICAL USE C1 [Jones, Christopher M.] US Dept HHS, US FDA, Washington, DC 20201 USA. [Condon, Timothy P.] US Dept HHS, NIDA, Washington, DC 20201 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 5 BP 687 EP 689 DI 10.1111/j.1526-4637.2011.01108.x PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 762OM UT WOS:000290489300001 PM 21481174 ER PT J AU Reid, MC Bennett, DA Chen, WG Eldadah, BA Farrar, JT Ferrell, B Gallagher, RM Hanlon, JT Herr, K Horn, SD Inturrisi, CE Lemtouni, S Lin, YW Michaud, K Morrison, RS Neogi, T Porter, LL Solomon, DH Von Korff, M Weiss, K Witter, J Zacharoff, KL AF Reid, M. Cary Bennett, David A. Chen, Wen G. Eldadah, Basil A. Farrar, John T. Ferrell, Bruce Gallagher, Rollin M. Hanlon, Joseph T. Herr, Keela Horn, Susan D. Inturrisi, Charles E. Lemtouni, Salma Lin, Yu Woody Michaud, Kaleb Morrison, R. Sean Neogi, Tuhina Porter, Linda L. Solomon, Daniel H. Von Korff, Michael Weiss, Karen Witter, James Zacharoff, Kevin L. TI Improving the Pharmacologic Management of Pain in Older Adults: Identifying the Research Gaps and Methods to Address Them SO PAIN MEDICINE LA English DT Review DE Analgesic Use; Chronic Noncancer Pain; Older Adults ID CHRONIC NONCANCER PAIN; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; OBSTRUCTIVE PULMONARY-DISEASE; PERSISTENT NONMALIGNANT PAIN; NURSING-HOME RESIDENTS; NATIONAL-DATA-BANK; MUSCULOSKELETAL PAIN; UNITED-STATES; COGNITIVE IMPAIRMENT; RHEUMATIC-DISEASES AB Objective. There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an "Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults" conference in September 2010 to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and nonsteroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits. Design. Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists' slide presentations were reviewed to identify the gaps and the types of studies and research methods panelists suggested could best address them. Results. Fifteen gaps were identified in the areas of treatment (e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation (e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life. Conclusion. Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and wellbeing of older adults with chronic pain. C1 [Reid, M. Cary] Weill Cornell Med Ctr, Div Geriatr & Gerontol, New York, NY 10065 USA. [Bennett, David A.] Rush Univ, Med Ctr, Dept Neurol Sci, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. [Chen, Wen G.] NIA, Behav & Syst Neurosci Branch, Div Neurosci, Bethesda, MD 20892 USA. [Eldadah, Basil A.] NIA, Div Geriatr & Clin Gerontol, Bethesda, MD 20892 USA. [Farrar, John T.] Univ Penn, Dept Epidemiol, Philadelphia, PA 19104 USA. [Farrar, John T.] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. [Ferrell, Bruce] UCLA Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Penn, Sch Med, Philadelphia VA Med Ctr, Penn Pain Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA. [Gallagher, Rollin M.] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA USA. [Hanlon, Joseph T.] VA Pittsburgh Hlth Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Herr, Keela] Univ Iowa, Coll Nursing, John A Hartford Ctr Geriatr Nursing Excellence, Iowa City, IA 52242 USA. [Horn, Susan D.] Inst Clin Outcomes Res, Salt Lake City, UT USA. [Inturrisi, Charles E.] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA. [Lemtouni, Salma; Weiss, Karen] US FDA, Ctr Drug Evaluat & Res, Washington, DC 20204 USA. [Lin, Yu Woody] Natl Inst Drug Abuse, Div Clin Neurosci & Behav Res, Bethesda, MD USA. [Michaud, Kaleb] Univ Nebraska Med Ctr, Omaha, NE USA. [Michaud, Kaleb] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Morrison, R. Sean] Mt Sinai Sch Med, Brookdale Dept Geriatr & Palliat Med, New York, NY USA. [Neogi, Tuhina] Boston Univ, Sch Med, Sect Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. [Neogi, Tuhina] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Porter, Linda L.] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. [Solomon, Daniel H.] Harvard Univ, Brigham & Womens Hosp, Div Pharmacoepidemiol & Pharmacoecon, Sch Med, Boston, MA 02115 USA. [Solomon, Daniel H.] Brigham & Womens Hosp, Div Rheumatol, Boston, MA 02115 USA. [Von Korff, Michael] Ctr Hlth Studies Grp Hlth Cooperat, Seattle, WA USA. [Witter, James] NIAMSD, Div Skin & Rheumat Dis, Bethesda, MD 20892 USA. [Zacharoff, Kevin L.] Inflexxion Inc, Newton, MA USA. RP Reid, MC (reprint author), Weill Cornell Med Ctr, Div Geriatr & Gerontol, 525 E 68th St,Box 39, New York, NY 10065 USA. EM mcr2004@med.cornell.edu RI Inturrisi, Charles/E-7365-2013; OI Reid, Cary/0000-0001-8117-662X; Neogi, Tuhina/0000-0002-9515-1711 FU Edward R. Roybal Center for Translational Research on Aging, NIA [P30 AG22845]; NIA [P30AG10161, R01AG15819, R01AG17917, P30AG028741, K24AG022345, R01AG030141, R01AG034181]; National Center for Research Resources [UL1RR024134]; National Institute of Aging [P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553]; National Institute of Mental Health [R34MH082682]; National Institute of Nursing [R01NR010135]; AHRQ [R01HS017695, R01HS018721, K12HS019461]; VA Health Services [IIR-06-062]; National Cancer Institute [R01CA115363]; National Institute of Nursing Research [T32NR011147]; NIDA [RC2DA028928, R01DA022557]; National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) [RC1AR058601, K23AR055127, K24AR055989] FX The authors would like to acknowledge the participation of all the conference attendees, who are listed in Appendix A. Dr. Reid was supported by an Edward R. Roybal Center for Translational Research on Aging Award (P30 AG22845) provided by the NIA. Dr. Bennett was supported by NIA grants P30AG10161, R01AG15819, and R01AG17917. Dr. Farrar was supported by a grant from the National Center for Research Resources (UL1RR024134). Dr. Hanlon was supported by National Institute of Aging grants (P30AG024827, T32AG021885, K07AG033174, R01AG034056, R56AG027017, U01AG012553), a National Institute of Mental Health grant (R34MH082682), a National Institute of Nursing Research grant (R01NR010135), AHRQ grants (R01HS017695, R01HS018721, K12HS019461), and a VA Health Services Research grant (IIR-06-062). Dr. Herr was supported by grants from the National Cancer Institute (R01CA115363) and National Institute of Nursing Research (T32NR011147). Drs. Horn and Inturrisi were supported by American Recovery and Reinvestment Act (ARRA) grant RC2DA028928 from NIDA. Dr. Michaud was supported by an ARRA grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (RC1AR058601). Dr. Neogi was supported by a grant from the NIAMS (K23AR055127). Dr. Morrison was supported by grants from the NIA (P30AG028741, K24AG022345, and R01AG030141). Dr. Solomon was supported by a grant from the NIAMS (K24AR055989). Dr. Von Korff was supported by grants from the NIDA (R01DA022557) and the NIA (R01AG034181). NR 106 TC 37 Z9 38 U1 7 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1526-2375 J9 PAIN MED JI Pain Med. PY 2011 VL 12 IS 9 BP 1336 EP 1357 DI 10.1111/j.1526-4637.2011.01211.x PG 22 WC Medicine, General & Internal SC General & Internal Medicine GA 822MJ UT WOS:000295051500009 PM 21834914 ER PT J AU Muhammad, RD Haber, P Broder, KR Leroy, Z Ball, R Braun, MM Davis, RL McMahon, AW AF Muhammad, Riyadh D. Haber, Penina Broder, Karen R. Leroy, Zanie Ball, Robert Braun, M. Miles Davis, Robert L. McMahon, Ann W. TI Adverse Events Following Trivalent Inactivated Influenza Vaccination in Children Analysis of the Vaccine Adverse Event Reporting System SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE influenza vaccine; vaccine safety; adverse event ID GUILLAIN-BARRE-SYNDROME; IMMUNIZATION PRACTICES ACIP; SAFETY DATALINK PROJECT; UNITED-STATES; ROTAVIRUS VACCINATION; ADVISORY-COMMITTEE; VIRUS-VACCINE; VAERS; ADULTS; INTUSSUSCEPTION AB Background: The Advisory Committee on Immunization Practices' recommendations for influenza vaccination of children have expanded from the long-standing recommendation to vaccinate high-risk children aged >= 6 months, to vaccinating all 6- to 23-month-olds (2004), 2- to 4-year-olds (2006), and 5- to 18-year-olds (2008). Objective: To identify new or unexpected adverse events (AEs) after trivalent inactivated vaccine (TIV) in children. Methods: We analyzed reports after TIV to the Vaccine Adverse Event Reporting System from 1990-2006 in children aged 2 to 17 years, and from the 2008-2009 influenza season in children aged 5 to 17 years. Empiric Bayesian data mining techniques were used to identify new or unexpected AEs during 1990-2006. Results: During 1990-2006, the Vaccine Adverse Event Reporting System received 2054 reports of children aged 2 to 17 years with a peak in the 2003-2004 influenza season. In 2008-2009, 506 reports describing 5 to 17 year olds were received. The serious reports of tests performed after TIV were approximately 10% of all reports from 2001-2006, and 6% of the reports in the 2008-2009 season. Data mining showed an increased proportion of medication errors and Guillain Barre Syndrome (GBS). The findings of GBS could not be interpreted as causally related to vaccination. Among 201 reports of medication error, 94% had no AE reported other than the medication error itself. Conclusion: In this analysis, we found no unexpected AEs. Our review of medication error and GBS reports suggests that ongoing monitoring in these areas is appropriate. C1 [Muhammad, Riyadh D.; Ball, Robert; Braun, M. Miles; McMahon, Ann W.] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. [Haber, Penina; Broder, Karen R.; Leroy, Zanie; Davis, Robert L.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Immunizat Safety Off, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA. RP McMahon, AW (reprint author), 10903 New Hampshire Ave,WO 22,Room 3474, Silver Spring, MD 20993 USA. EM ann.mcmahon@fda.hhs.gov NR 56 TC 4 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JAN PY 2011 VL 30 IS 1 BP E1 EP E8 DI 10.1097/INF.0b013e3181ff9795 PG 8 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 697FU UT WOS:000285498800001 PM 21042229 ER PT J AU Dunne, J Murphy, D Wharton, G AF Dunne, Julia Murphy, Dianne Wharton, Gerold TI The Globalization of Pediatric Trials: Should We be Worried? SO PEDIATRICS LA English DT Letter C1 [Dunne, Julia; Murphy, Dianne; Wharton, Gerold] US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. RP Dunne, J (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, Silver Spring, MD 20993 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 2011 VL 127 IS 1 BP E252 EP E253 DI 10.1542/peds.2010-3381A PG 5 WC Pediatrics SC Pediatrics GA 700YT UT WOS:000285782200035 PM 21196576 ER PT J AU Lacher, DW AF Lacher, David W. BE Walk, ST Feng, PCH TI The Evolutionary Model of Escherichia coli O157:H7 SO POPULATION GENETICS OF BACTERIA: A TRIBUTE TO THOMAS S. WHITTAM LA English DT Article; Book Chapter ID HEMOLYTIC-UREMIC SYNDROME; O157-H7; VIRULENCE; O157H7; GENE; DIVERSITY; EMERGENCE; SEROTYPES; OUTBREAK; STRAINS C1 US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Lacher, DW (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-711-4 PY 2011 BP 227 EP 239 PG 13 WC Evolutionary Biology; Microbiology SC Evolutionary Biology; Microbiology GA BYN76 UT WOS:000299463700015 ER PT J AU Feng, PCH Monday, SR AF Feng, Peter C. H. Monday, Steven R. BE Walk, ST Feng, PCH TI Evolutionary Emergence and Impact of Atypical Escherichia coli O157:H7 Strains SO POPULATION GENETICS OF BACTERIA: A TRIBUTE TO THOMAS S. WHITTAM LA English DT Article; Book Chapter ID HEMOLYTIC UREMIC SYNDROME; HEMORRHAGIC COLITIS; SEROTYPE O157-H7; GENETIC-ANALYSIS; TOXIN-2 GENES; IDENTIFICATION; ANTIGEN; EXPRESSION; INFECTION; VARIANTS C1 [Feng, Peter C. H.; Monday, Steven R.] US FDA, Div Microbiol, College Pk, MD 20740 USA. RP Feng, PCH (reprint author), US FDA, Div Microbiol, College Pk, MD 20740 USA. NR 36 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-711-4 PY 2011 BP 241 EP 255 PG 15 WC Evolutionary Biology; Microbiology SC Evolutionary Biology; Microbiology GA BYN76 UT WOS:000299463700016 ER PT S AU Croley, TR AF Croley, Timothy R. BE Walls, D Loughran, ST TI Ultra-Performance Liquid Chromatography-Mass Spectrometry of Proteins SO PROTEIN CHROMATOGRAPHY: METHODS AND PROTOCOLS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE UPLC; Intact proteins; Mass spectrometry; Protein identification; Chromatography ID STATIONARY-PHASE; TOP-DOWN; STABILITY; SILICA AB The commercialization of ultra-performance liquid chromatography (UPLC) has allowed more researchers to take advantage of the benefits of this work. Many researchers are exploring this technique to reduce analytical throughput and to increase resolution. The majority of this work has focused on small molecule analysis; however, this technique can provide the same advantages for the analysis of proteins. Traditionally, protein chromatography has suffered from a number of issues such as carryover, peak splitting, peak broadening, and poor peak shape. Because UPLC utilizes a smaller particle at a higher pressure and flow rate, many of these issues are remedied. When used in combination with mass spectrometry, UPLC becomes a powerful tool for protein identification, characterization, and quantitation. In this work we show how UPLC/MS can be used to separate and identify intact proteins. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Croley, TR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD USA. FU PHS HHS [U90/CCU317014] NR 14 TC 1 Z9 1 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-912-3 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2011 VL 681 BP 419 EP 429 DI 10.1007/978-1-60761-913-0_23 D2 10.1007/978-1-60761-913-0 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BSD42 UT WOS:000284201200023 PM 20978979 ER PT B AU Hoorfar, J Cahill, S Clarke, R Barker, GC Fazil, A Wong, DLF Feng, PCH AF Hoorfar, J. Cahill, S. Clarke, R. Barker, G. C. Fazil, A. Wong, D. L. F. Feng, P. C. H. BE Hoorfar, J TI THE PUBLIC HEALTH, INDUSTRIAL, AND GLOBAL SIGNIFICANCE OF RAPID MICROBIOLOGICAL FOOD TESTING SO RAPID DETECTION, CHARACTERIZATION, AND ENUMERATION OF FOODBORNE PATHOGENS LA English DT Article; Book Chapter ID QUANTITATIVE RISK-ASSESSMENT; PCR; PATHOGENS; TOOL C1 [Hoorfar, J.] Tech Univ Denmark DTU, Natl Food Inst, DK-2860 Soborg, Denmark. [Cahill, S.; Clarke, R.] Food & Agr Org United Nations, Nutr & Consumer Protect Div, I-00183 Rome, Italy. [Barker, G. C.] Inst Food Res, Norwich NR4 7UA, Norfolk, England. [Fazil, A.] Publ Hlth Agcy Canada, Guelph, ON N1G 5B2, Canada. [Wong, D. L. F.] World Hlth Org, Sustainable Dev & Healthy Environm, Food Safety Zoonoses & Foodborne Dis, CH-1211 Geneva 27, Switzerland. [Feng, P. C. H.] US FDA, College Pk, MD 20740 USA. RP Hoorfar, J (reprint author), Tech Univ Denmark DTU, Natl Food Inst, Morkhoj Bygade 28, DK-2860 Soborg, Denmark. RI Barker, Gary /B-5429-2013 OI Barker, Gary /0000-0003-1844-6257 NR 32 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-712-1; 978-1-55581-542-4 PY 2011 BP 1 EP 12 D2 10.1128/9781555817121 PG 12 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BC6EK UT WOS:000353832700002 ER PT B AU Reynisson, E Rudi, K Marteinsson, VP Nakayama, J Sakamoto, N Rasooly, A Hoorfar, J AF Reynisson, E. Rudi, K. Marteinsson, V. P. Nakayama, J. Sakamoto, N. Rasooly, A. Hoorfar, J. BE Hoorfar, J TI AUTOMATED AND LARGE-SCALE CHARACTERIZATION OF MICROBIAL COMMUNITIES IN FOOD PRODUCTION SO RAPID DETECTION, CHARACTERIZATION, AND ENUMERATION OF FOODBORNE PATHOGENS LA English DT Article; Book Chapter ID 16S RIBOSOMAL-RNA; COD GADUS-MORHUA; GRADIENT GEL-ELECTROPHORESIS; NUCLEOTIDE PRIMER EXTENSION; PURE CULTURE TECHNIQUE; MODIFIED-ATMOSPHERE; FLOW-CYTOMETRY; OLIGONUCLEOTIDE MICROARRAY; DNA MICROARRAY; GENE ANALYSIS C1 [Reynisson, E.; Marteinsson, V. P.] Matis Iceland Food Res & Biothech R&D, IS-113 Reykjavik, Iceland. [Rudi, K.] Nofima Food, N-1430 As, Norway. [Rudi, K.] Hedmark Univ Coll, N-2318 Hamar, Norway. [Nakayama, J.; Sakamoto, N.] Kyushu Univ, Fac Agr, Grad Sch, Dept Biosci & Biotechnol,Higashi Ku, Fukuoka 812, Japan. [Rasooly, A.] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Rasooly, A.] NCI, Canc Diag Program, Rockville, MD 20852 USA. [Hoorfar, J.] Tech Univ Denmark, Natl Food Inst, DK-2860 Soborg, Denmark. RP Reynisson, E (reprint author), Matis Iceland Food Res & Biothech R&D, Vinlandsleio 12, IS-113 Reykjavik, Iceland. NR 104 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-712-1; 978-1-55581-542-4 PY 2011 BP 63 EP 79 D2 10.1128/9781555817121 PG 17 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BC6EK UT WOS:000353832700005 ER PT B AU Hitchins, AD Jordan, KN Sanaa, M Wagner, M AF Hitchins, A. D. Jordan, K. N. Sanaa, M. Wagner, M. BE Hoorfar, J TI LISTERIA MONOCYTOGENES IN MILK, CHEESE, AND THE DAIRY ENVIRONMENT SO RAPID DETECTION, CHARACTERIZATION, AND ENUMERATION OF FOODBORNE PATHOGENS LA English DT Article; Book Chapter ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; TANDEM-REPEAT ANALYSIS; LOCUS VARIABLE-NUMBER; MULTIPLEX PCR; IMMUNOMAGNETIC CAPTURE; MOLECULAR EPIDEMIOLOGY; QUANTITATIVE DETECTION; COUNT METHOD; WHOLE MILK C1 [Hitchins, A. D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Jordan, K. N.] TEAGASC, Moorepk Food Res Ctr, Fermoy, Cork, Ireland. [Sanaa, M.] Directorate Risk Assessment, Agence Francaise Securite Sanit Aliments, F-94701 Maisons Alfort, France. [Wagner, M.] Univ Vet Med, Inst Milk Hyg Milk Technol & Food Sci, A-1210 Vienna, Austria. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 64 TC 1 Z9 1 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-712-1; 978-1-55581-542-4 PY 2011 BP 257 EP 274 D2 10.1128/9781555817121 PG 18 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA BC6EK UT WOS:000353832700019 ER PT B AU Bright, S AF Bright, Susan BE Gupta, RC TI Postmarket surveillance and regulatory considerations in reproductive and developmental toxicology: an FDA perspective SO REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY LA English DT Article; Book Chapter ID VACCINE; PREGNANCY C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. RP Bright, S (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20857 USA. NR 30 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382033-4 PY 2011 BP 75 EP 88 DI 10.1016/B978-0-12-382032-7.10007-4 PG 14 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA BEX82 UT WOS:000318575300008 ER PT J AU Hansen, DK Inselman, AL AF Hansen, Deborah K. Inselman, Amy L. BE Gupta, RC TI Applications of stem cells in developmental toxicology SO REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY LA English DT Article; Book Chapter ID HUMAN EMBRYONIC STEM; VITRO EMBRYOTOXICITY TEST; FIBROBLAST-GROWTH-FACTOR; TOXICITY TEST PROCEDURES; HUMAN SOMATIC-CELLS; IN-VITRO; SELF-RENEWAL; MAINTAINS PLURIPOTENCY; DEFINED FACTORS; MOUSE EMBRYOS C1 [Hansen, Deborah K.; Inselman, Amy L.] FDA Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR USA. RP Hansen, DK (reprint author), FDA Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR USA. NR 99 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382033-4 PY 2011 BP 783 EP 792 DI 10.1016/B978-0-12-382032-7.10058-X PG 10 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA BEX82 UT WOS:000318575300059 ER PT J AU Choudhuri, S AF Choudhuri, Supratim BE Gupta, RC TI Epigenetic regulation of gene and genome expression SO REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY LA English DT Article; Book Chapter ID DIETARY-PROTEIN RESTRICTION; CAENORHABDITIS-ELEGANS; DNA METHYLATION; SMALL RNAS; PREGNANT RATS; CHROMATIN; MECP2; CANCER; ROLES; NUCLEOSOMES C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Notice Review, College Pk, MD USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Notice Review, College Pk, MD USA. NR 60 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-382033-4 PY 2011 BP 801 EP 813 DI 10.1016/B978-0-12-382032-7.10060-8 PG 13 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA BEX82 UT WOS:000318575300061 ER PT B AU Getie-Kebtie, M Alterman, MA AF Getie-Kebtie, Melkamu Alterman, Michail A. BE Ivanov, AR Lazarev, AV TI Exploring the Capabilities of the Protein Identification by Unconventional Sample Preparation Approaches: LC/MALDI/On-Target Digestion Approach and High Pressure-Assisted In-Gel Tryptic Digestion SO SAMPLE PREPARATION IN BIOLOGICAL MASS SPECTROMETRY LA English DT Article; Book Chapter DE LC; MALDI; PCT; Tryptic Digestion; On-target ID PROTEOMICS AB The rapid and comprehensive separation, identification, and characterization of proteins from complex biological samples are formidable challenges that the growing field of proteomics faces. A robust and efficient digest of separated proteins is central to the development of any quantitative and/or qualitative proteomic approach. We describe here two unconventional approaches to a trypsin digestion of biological samples. One of those approaches integrates separation of proteins using RP-HPLC with on-target proteolytic digestion of the proteins for subsequent MALD1-MS analysis. This approach allows the combined information from peptide mass fingerprinting (PMF), MS/MS peptide fragment fingerprinting (PPF) and whole protein MS to increase confidence in protein identification and structural analysis of proteins. The other approach is based on the application of high-pressure cycling technology (PCT) for in-gel trypsin digest of 1D electrophoretically separated proteins. That approach was used in our laboratory to develop a label-free mass spectrometry based method for a relative quantification of proteins after SDS PAGE separation, including co-migrating proteins. C1 [Getie-Kebtie, Melkamu; Alterman, Michail A.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alterman, MA (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Melkamu.Getiekebtie@fda.hhs.gov; michail.alterman@fda.hhs.gov NR 4 TC 0 Z9 1 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-94-007-0758-0 PY 2011 BP 141 EP 155 DI 10.1007/978-94-007-0828-0_9 D2 10.1007/978-94-007-0828-0 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BVY63 UT WOS:000293148700010 ER PT J AU Ortiz, PG Hansen, SH Shah, VP Sonne, J Benfeldt, E AF Ortiz, P. Garcia Hansen, S. H. Shah, V. P. Sonne, J. Benfeldt, E. TI Are Marketed Topical Metronidazole Creams Bioequivalent? Evaluation by in vivo Microdialysis Sampling and Tape Stripping Methodology SO SKIN PHARMACOLOGY AND PHYSIOLOGY LA English DT Article DE Bioequivalence; Cutaneous penetration; Percutaneous permeation; Dermal drug levels; Dermatopharmacokinetic method; Microdialysis; Tape stripping; Drug delivery, topical; Metronidazole ID DERMATOLOGICAL DRUG PRODUCTS; CUTANEOUS MICRODIALYSIS; SKIN; FORMULATIONS; PENETRATION; STANDARDIZATION; BIOAVAILABILITY; PERSPECTIVES; ABSORPTION; DERMATITIS AB Aim: To evaluate the bioequivalence of 3 marketed topical metronidazole formulations by simultaneous dermal microdialysis and stratum corneum sampling by the tape stripping methodology, and to compare the techniques as tools for the determination of bioequivalence. Methods: Nine microdialysis probes were inserted in the volar aspect of the left forearm of 14 healthy volunteers and, following application of the 3 metronidazole creams, microdialysis samples were collected for 5 h. On the right forearm, tape strip sampling was performed 30 and 120 min after product application. At the end of the experiment, ultrasound scanning measurements confirmed that all probes were placed inside the dermis. Results:There was no statistical difference in penetration of the 3 topicals as determined by microdialysis. However, their bioequivalence could not be determined due to intersubject variability exceeding the criteria for bioequivalence evaluation. Tape strip sampling established a bio-equivalence between 2 of the creams, but rejected any bio-equivalence between these 2 formulations and the third. The third formulation was a generic formulation approved despite containing a lower concentration of metronidazole (0.75%) than the innovator formulation (1.0%). The result of the bioequivalence evaluation depends on the methodology employed. Conclusion: Whenever the dermis is the target tissue, microdialysis provides the most relevant information on drug bioavailability. Copyright (C) 2010 S. Karger AG, Basel C1 [Ortiz, P. Garcia; Benfeldt, E.] Univ Copenhagen, Gentofte Hosp, Dept Dermatoallergol, Hellerup, Denmark. [Sonne, J.] Univ Copenhagen, Gentofte Hosp, Clin Pharmacol Unit, Hellerup, Denmark. [Hansen, S. H.] Univ Copenhagen, Dept Pharmaceut & Analyt Chem, Pharmaceut Fac, Copenhagen, Denmark. [Shah, V. P.] US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Ortiz, PG (reprint author), Gentofte Univ Hosp, Dept Dermatol, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. EM patriciagarcia@dadlnet.dk FU Aage Bang's Foundation; Hans and Nora Buchards Foundation; Danish Hospital Foundation for Medical Research Region of Copenhagen; Faeroe Islands and Greenland; Leo Foundation; Mrs. Liv Bryhn's Foundation; Danish Psoriasis Foundation; Foundation for Scientific Research without Animal Experiments FX This study was supported by grants from Aage Bang's Foundation, Hans and Nora Buchards Foundation, the Danish Hospital Foundation for Medical Research Region of Copenhagen, the Faeroe Islands and Greenland, the Leo Foundation, Mrs. Liv Bryhn's Foundation, the Danish Psoriasis Foundation and the Foundation for Scientific Research without Animal Experiments. NR 34 TC 10 Z9 10 U1 1 U2 7 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-5527 J9 SKIN PHARMACOL PHYS JI Skin Pharmacol. Physiol. PY 2011 VL 24 IS 1 BP 44 EP 53 DI 10.1159/000320151 PG 10 WC Dermatology; Pharmacology & Pharmacy SC Dermatology; Pharmacology & Pharmacy GA 694AC UT WOS:000285265500007 ER PT J AU Rubin, DB AF Rubin, Daniel B. TI A Calibrated Multiclass Extension of AdaBoost SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE AdaBoost; boosting; multiclass classification ID CLASSIFICATION METHODS; BOOSTING ALGORITHMS; STATISTICAL VIEW; PREDICTION AB AdaBoost is a popular and successful data mining technique for binary classification. However, there is no universally agreed upon extension of the method for problems with more than two classes. Most multiclass generalizations simply reduce the problem to a series of binary classification problems. The statistical interpretation of AdaBoost is that it operates through loss-based estimation: by using an exponential loss function as a surrogate for misclassification loss, it sequentially minimizes empirical risk through fitting a base classifier to iteratively reweighted training data. While there are several extensions using loss-based estimation with multiclass base classifiers, these use multiclass versions of the exponential loss that are not classification calibrated: unless restrictions are placed on conditional class probabilities, it becomes possible to have optimal surrogate risk but poor misclassification risk. In this work, we introduce a new AdaBoost extension called AdaBoost. SL that does not reduce the problem into binary subproblems and that uses a classification-calibrated multiclass exponential loss function. Numerical experiments show the algorithm performs well on benchmark datasets. C1 US FDA, Rockville, MD 20857 USA. RP Rubin, DB (reprint author), US FDA, Rockville, MD 20857 USA. NR 31 TC 0 Z9 0 U1 0 U2 3 PU WALTER DE GRUYTER GMBH PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 2194-6302 EI 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PY 2011 VL 10 IS 1 AR 54 DI 10.2202/1544-6115.1731 PG 25 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 855TT UT WOS:000297588600004 ER PT J AU Yan, LK Liu, AY Li, ZH Zheng, G AF Yan, Lihan K. Liu, Aiyi Li, Zhaohai Zheng, Gang TI Optimal two-stage sequential robust design for gene-intervention studies SO STATISTICS AND ITS INTERFACE LA English DT Article DE Optimal two-stage design; MAX; Group sequential; Gene-intervention ID GENOME-WIDE ASSOCIATION; CLINICAL-TRIALS; SAMPLE-SIZE; TREND TESTS; PROPORTIONS; STATISTICS; MAXIMUM; MARKERS; POWER AB Gene-intervention studies investigate the responsiveness to therapies according to individuals' genetic profiles. We propose a two-stage sequential design for these studies and investigate the cost of the sample size versus the statistical power. In a typical sequential design, a single normally distributed test statistic is used. For a genetic study, the robust test is used because of the uncertainty of the underlying genetic model (e. g. the recessive, additive or dominant models). The robust test statistic that we consider in the two-stage sequential design is the maximum of three correlated normally distributed statistics, each which is optimal under the corresponding genetic model. We study various factors that affect minimizing the average sample number (ASN) or maximizing the power of a gene-intervention study under the two-stage sequential design and make recommendations for the optimal solutions under different scenarios. C1 [Yan, Lihan K.] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD USA. [Li, Zhaohai] George Washington Univ, Dept Stat, Washington, DC 20052 USA. [Zheng, Gang] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Yan, LK (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM lihan.yan@fda.hhs.gov; liua@mail.nih.gov; zli@gwu.edu; zhengg@nhlbi.nih.gov OI Liu, Aiyi/0000-0002-6618-5082 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX We would like to thank the reviewers for their helpful comments which strengthened the presentation of this paper. We would also like to thank Ms. Heather Liu for her editorial help. Research of A. Liu is supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. The opinions expressed in the article are those of the authors, not necessarily of the National Institutes of Health, nor the Food and Drug Administration. NR 36 TC 0 Z9 0 U1 0 U2 0 PU INT PRESS BOSTON, INC PI SOMERVILLE PA PO BOX 43502, SOMERVILLE, MA 02143 USA SN 1938-7989 EI 1938-7997 J9 STAT INTERFACE JI Stat. Interface PY 2011 VL 4 IS 4 BP 431 EP 441 PG 11 WC Mathematical & Computational Biology; Mathematics, Interdisciplinary Applications SC Mathematical & Computational Biology; Mathematics GA 861DY UT WOS:000298000500002 ER PT J AU Bolon, B Garman, RH Gundersen, HJG Johnson, GA Kaufmann, W Krinke, G Little, PB Makris, SL Mellon, RD Sulik, KK Jensen, K AF Bolon, Brad Garman, Robert H. Gundersen, Hans Jorgen G. Johnson, G. Allan Kaufmann, Wolfgang Krinke, Georg Little, Peter B. Makris, Susan L. Mellon, R. Daniel Sulik, Kathleen K. Jensen, Karl TI Continuing Education Course #3: Current Practices and Future Trends in Neuropathology Assessment for Developmental Neurotoxicity Testing SO TOXICOLOGIC PATHOLOGY LA English DT Article DE developmental neurotoxicity; neuropathology; risk assessment ID MAGNETIC-RESONANCE MICROSCOPY; INDUCED BRAIN ABNORMALITIES; RAT-BRAIN; ACUTE INSULT; EXPOSURE; SIZE AB The continuing education course on Developmental Neurotoxicity Testing (DNT) was designed to communicate current practices for DNT neuropathology, describe promising innovations in quantitative analysis and noninvasive imaging, and facilitate a discussion among experienced neuropathologists and regulatory scientists regarding suitable DNT practices. Conventional DNT neuropathology endpoints are qualitative histopathology and morphometric endpoints of particularly vulnerable sites (e. g., cerebral, cerebellar, or hippocampal thickness). Novel imaging and stereology measurements hold promise for automated analysis of factors that cannot be effectively examined in routinely processed specimens (e. g., cell numbers, fiber tract integrity). The panel recommended that dedicated DNT neuropathology data sets be acquired on a minimum of 8 sections (for qualitative assessment) or 3 sections (for quantitative linear and stereological analyses) using a small battery of stains to examine neurons and myelin. Where guidelines permit discretion, immersion fixation is acceptable for younger animals (postnatal day 22 or earlier), and peripheral nerves may be embedded in paraffin. Frequent concerns regarding DNT data sets include false-negative outcomes due to processing difficulties (e. g., lack of concordance among sections from different animals) and insensitive analytical endpoints (e. g., qualitative evaluation) as well as false-positive results arising from overinterpretation or misreading by inexperienced pathologists. C1 [Jensen, Karl] US EPA, NHEERL, ORD, Res Triangle Pk, NC 27711 USA. [Bolon, Brad] GEMpath Inc, Longmont, CO USA. [Garman, Robert H.] Consultants Vet Pathol, Murrysville, PA USA. [Gundersen, Hans Jorgen G.] Univ Aarhus, DK-8000 Aarhus, Denmark. [Johnson, G. Allan] Duke Univ, Durham, NC USA. [Kaufmann, Wolfgang] BASF, Ludwigshafen, Germany. [Little, Peter B.] Charles River Labs Inc, Durham, NC USA. [Makris, Susan L.] US EPA, Washington, DC 20460 USA. [Mellon, R. Daniel] US FDA, Silver Spring, MD USA. [Sulik, Kathleen K.] Univ N Carolina, Chapel Hill, NC USA. RP Jensen, K (reprint author), US EPA, NHEERL, ORD, Mail Drop B105-06, Res Triangle Pk, NC 27711 USA. EM jensen.karl@epa.gov OI Johnson, G.Allan/0000-0002-7606-5447 FU NCI NIH HHS [U24 CA092656]; NCRR NIH HHS [P41 RR005959] NR 32 TC 8 Z9 8 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2011 VL 39 IS 1 BP 289 EP 293 DI 10.1177/0192623310386247 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 800QU UT WOS:000293379600032 PM 21075916 ER PT J AU DeGrasse, SL DeGrasse, JA Reuter, K AF DeGrasse, Stacey L. DeGrasse, Jeffrey A. Reuter, Kevin TI Solid core column technology applied to HPLC-FD of paralytic shellfish toxins SO TOXICON LA English DT Article DE Column; HPLC; Oxidation; Paralytic shellfish toxins; Saxitoxin; Solid core; Fused core ID FUSED-CORE AB Pre-column oxidation liquid chromatography with fluorescence detection is a chemical method for analyzing paralytic shellfish toxins. In order to improve the sample throughput and efficiency of AOAC Method 2005.06, solid core particle column technology was evaluated. We demonstrate that supplanting the original fully porous particle column with a solid core particle column reduces sample analysis time from 15 to 5 min per sample and improves resolution. Published by Elsevier Ltd. C1 [DeGrasse, Stacey L.; DeGrasse, Jeffrey A.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem,Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA. [Reuter, Kevin] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP DeGrasse, SL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem,Spect & Mass Spectrometry Branch, 5100 Paint Branch Pkwy,HFS 707, College Pk, MD 20740 USA. EM Stacey.DeGrasse@fda.hhs.gov RI DeGrasse, Jeffrey/J-1151-2014; OI DeGrasse, Jeffrey/0000-0003-3178-6301; DeGrasse, Stacey/0000-0001-7808-4193 NR 15 TC 7 Z9 7 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JAN PY 2011 VL 57 IS 1 BP 179 EP 182 DI 10.1016/j.toxicon.2010.11.004 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 716TV UT WOS:000286997300024 PM 21078334 ER PT J AU Alam, SK Feleppa, EJ Rondeau, M Kalisz, A Garra, BS AF Alam, S. Kaisar Feleppa, Ernest J. Rondeau, Mark Kalisz, Andrew Garra, Brian S. TI Ultrasonic Multi-Feature Analysis Procedure for Computer-Aided Diagnosis of Solid Breast Lesions SO ULTRASONIC IMAGING LA English DT Article DE Breast cancer; computer-aided diagnosis (CAD); fractal analysis; tnorphometric analysis; multi-feature analysis; ROC; sonography; spectrum analysis; texture analysis; tissue characterization; tumor classification; ultrasonic imaging; ultrasound ID SELF-ORGANIZING MAP; TEXTURE ANALYSIS; TISSUE CHARACTERIZATION; DISCRIMINANT-ANALYSIS; SONOGRAPHIC FEATURES; SPECTRAL PARAMETERS; LOGISTIC-REGRESSION; CANCER; CLASSIFICATION; NODULES AB We have developed quantitative descriptors to provide an objective means of noninvasive identification of cancerous breast lesions. These descriptors include quantitative acoustic features assessed using spectrum analysis of ultrasonic radiofrequency (rt) echo signals and morphometric properties related to lesion shape. Acoustic features include measures of echogenicity, heterogeneity and shadowing, computed by generating spectral-parameter images of the lesion and surrounding tissue. Spectral-parameter values are derived from rf echo signals at each pixel using a sliding-window Fourier analysis. We derive quantitative acoustic features from spectral-parameter maps of the lesion and adjacent areas. We quantify morphometric features by geometric and fractal analysis of traced lesion boundaries. Initial results on biopsy-proven cases show that although a single parameter cannot reliably discriminate cancerous from noncancerous breast lesions, multi-feature analysis provides excellent discrimination for this data set. We have processed data for 130 biopsy-proven patients, acquired during routine ultrasonic examinations at three clinical sites and produced an area under the receiver-operating-characteristics (ROC) curve of 0.947 +/- 0.045. Among the quantitative descriptors, lesion-margin definition, spiculation and border irregularity are the most useful; some additional morphometric features (such as border irregularity) also are particularly effective in lesion classification. Our findings are consistent with many of the BI-RADS (Breast Imaging Reporting and Data System) breast-lesion-classification criteria in use today. C1 [Alam, S. Kaisar; Feleppa, Ernest J.; Rondeau, Mark; Kalisz, Andrew] Riverside Res, New York, NY 10038 USA. [Garra, Brian S.] US FDA, Silver Spring, MD 20903 USA. RP Alam, SK (reprint author), Riverside Res, 156 William St, New York, NY 10038 USA. EM kalam@riversideresearch.org FU US Army Medical Research and Materiel Command [DAMD17-98-1-8331]; Susan G. Komen for the Cure [KG081601]; Advanced Technology Laboratories FX This work was supported in part by US Army Medical Research and Materiel Command grant DAMD17-98-1-8331 and Susan G. Komen for the Cure grant KG081601. We are indebted to our late colleague Dr. Frederic Lizzi for his inspirational support and advice with the analysis. Data used in this study were acquired at the University of Cincinnati, Thomas Jefferson University, and Yale University. The original data provided by these three collaborating medical centers were acquired with funding provided by Advanced Technology Laboratories, which currently is a division of Philips Corporation. Ms. Rumana Huq and Ms. Stella Urban traced lesions using custom software. NR 55 TC 12 Z9 12 U1 2 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0161-7346 EI 1096-0910 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD JAN PY 2011 VL 33 IS 1 BP 17 EP 38 PG 22 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 765HW UT WOS:000290697100002 PM 21608446 ER PT S AU Botsis, T Ball, R AF Botsis, Taxiarchis Ball, Robert BE Moen, A Andersen, SK Aarts, J Hurlen, P TI Network Analysis of Possible Anaphylaxis Cases Reported to the US Vaccine Adverse Event Reporting System after H1N1 Influenza Vaccine SO USER CENTRED NETWORKED HEALTH CARE SE Studies in Health Technology and Informatics LA English DT Proceedings Paper CT 23 rd Conference of the European Federation of Medical Informatics (MIE) CY AUG 28-31, 2011 CL Forum Databehandling Helsesektoren, Oslo, NORWAY SP European Federat Med Informat HO Forum Databehandling Helsesektoren DE Spontaneous Reporting System; Network Analysis; VAERS; H1N1 AB The identification of signals from spontaneous reporting systems plays an important role in monitoring the safety of medical products. Network analysis (NA) allows the representation of complex interactions among the key elements of such systems. We developed a network for a subset of the US Vaccine Adverse Event Reporting System (VAERS) by representing the vaccines/adverse events (AEs) and their interconnections as the nodes and the edges, respectively; this subset we focused upon included possible anaphylaxis reports that were submitted for the H1N1 influenza vaccine. Subsequently, we calculated the main metrics that characterize the connectivity of the nodes and applied the island algorithm to identify the densest region in the network and, thus, identify potential safety signals. AEs associated with anaphylaxis formed a dense region in the `anaphylaxis' network demonstrating the strength of NA techniques for pattern recognition. Additional validation and development of this approach is needed to improve future pharmacovigilance efforts. C1 [Botsis, Taxiarchis; Ball, Robert] US FDA, OBE, CBER, Rockville, MD 20852 USA. RP Botsis, T (reprint author), US FDA, OBE, CBER, Woodmont Off Complex 1,Room 306N, Rockville, MD 20852 USA. EM Taxiarchis.Botsis@fda.hhs.gov NR 11 TC 4 Z9 4 U1 1 U2 2 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0926-9630 BN 978-1-60750-806-9 J9 STUD HEALTH TECHNOL PY 2011 VL 169 BP 564 EP 568 DI 10.3233/978-1-60750-806-9-564 PG 5 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA BA4DP UT WOS:000335401700110 PM 21893812 ER PT S AU Aidoo, A Manjanatha, MG AF Aidoo, Anane Manjanatha, Mugimane G. BE Mutanen, M Pajari, AM TI Influence of dietary Soy Isoflavones Genistein and Daidzein on Genotoxicity and Mammary Carcinogenicity in Rats Exposed to the Model Carcinogen 7,12-Dimethylbenz[a]anthracene (DMBA) SO VEGETABLES, WHOLE GRAINS, AND THEIR DERIVATIVES IN CANCER PREVENTION SE Diet and Cancer LA English DT Article; Book Chapter DE Estrogen replacement therapy; Phytoestrogens; Soy isoflavones - genistein and daidzein; Genotoxicity; Carcinogenicity; 7,12-dimethylbenz[a]anthracene ID SPRAGUE-DAWLEY RATS; CORONARY-HEART-DISEASE; BREAST-CANCER; POSTMENOPAUSAL WOMEN; TRANSGENIC MICE; FEMALE RATS; IN-VITRO; ESTROGEN; PHYTOESTROGENS; RISK AB Epidemiological studies provide evidence for the possibility of preventing cancer and/or forestalling the complications of menopause through the consumption of foods containing phytoestrogens such as soy isoflavones. Lifestyle changes in technologically advanced societies, however, limit the consumption of adequate foods to meet health needs; thus supplements of phytoestrogen including soy isoflavones daidzein (DZ) and genistein (GE), considered to be compounds in soy that impart beneficial effects, are ingested in large quantities on a regular basis. This raises health concern since isoflavones are structurally similar to steroidal hormones, and it is possible that they may alter endogenous hormone metabolism and influence the pathogenesis of steroid-dependent diseases such as breast and prostate cancer. Equally important, humans are consistently exposed to mutagenic carcinogens whose toxicities could be enhanced by interaction with ingested isoflavones. Recent report indicates that DZ and GE are not only mutagenic, but also they enhance chemical carcinogenesis in animal models. Here, we report the results of feeding rats with DZ and GE to determine whether the genotoxicity and mammary carcinogenesis induced by the potent rodent mammary carcinogen dimethylbenz[a]anthracene (DMBA) could be altered. The data obtained suggest that DZ and GE diets given separately did not significantly alter DMBA-induced mutagenicity in lymphocytes, liver, mammary and heart, and carcinogenicity in the mammary. The mixture of DZ and GE was effective in reducing DMBA effects, suggesting that consuming diets containing more than one soy isoflavones as opposed to taking supplements in isolation, could impart some benefits; these results are discussed together with other animal studies reported on soy isoflavones. C1 [Aidoo, Anane; Manjanatha, Mugimane G.] FDA Jefferson Labs, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Aidoo, A (reprint author), FDA Jefferson Labs, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. EM anane.aidoo@fda.hhs.gov; mugimane.manjanatha@fda.hhs.gov NR 78 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 1361-8075 BN 978-90-481-9799-6 J9 DIET CANCER JI Diet Cancer PY 2011 VL 2 BP 143 EP 171 DI 10.1007/978-90-481-9800-9_7 D2 10.1007/978-90-481-9800-9 PG 29 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA BRR13 UT WOS:000283462100007 ER PT J AU Peters, SM Yancy, H Bremer, E Monroe, J Paul, D Stubbs, JT Myers, MJ AF Peters, Sharla M. Yancy, Haile Bremer, Eric Monroe, Jason Paul, David Stubbs, John T., III Myers, Michael J. TI In vitro identification and verification of inflammatory biomarkers in swine SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Inflammation; qRT-PCR; Microarray ID PAS DOMAIN PROTEIN-1; MYCOBACTERIUM-TUBERCULOSIS; DENDRITIC CELL; MONOCYTE DIFFERENTIATION; GENE-EXPRESSION; ACTIVATION; S100A12; CD1; PATHWAYS; RECEPTOR AB Currently there are no non-steroidal anti-inflammatory drugs (NSAIDs) approved for the control of inflammation in swine due to a lack of validated animal models and suitable biomarkers to assess drug efficacy. This study investigates the differential expression of genes altered in response to Escherichia coli lipopolysaccharide (LPS) induced inflammation which may serve as indicators of NSAID efficacy. Unstimulated whole blood from swine was mixed with tissue culture media, stimulated with LPS, and RNA extracted at the following time points Oh, 1 h, 3 h, 24 h and 48 h. Total RNA was extracted and analyzed using a commercial swine DNA microarray. The DNA microarray was utilized as a screen to determine potential biomarkers, focusing on the genes that exhibited the greatest degree of differential expression. A master list of 57 genes was formed based on the differential expression as a result of the stimulation. Following analysis, 12 genes whose expressions were significantly altered (8 up- and 4 down-regulated) were chosen for verification via quantitative RT-PCR (qRT-PCR). The qRT-PCR analysis confirmed the differential expression of 11 of the 12 genes chosen via the microarray analyses. Specifically, traditional genes such as SAA, G-CSF, and IL-10 were up-regulated, while CD4 was down-regulated; all of the genes were altered by 24 h or 48 h post-stimulation. We demonstrate here that expression of these 11 genes is altered as a direct result of LPS stimulation and consequently inflammation. Published by Elsevier B.V. C1 [Peters, Sharla M.; Yancy, Haile; Myers, Michael J.] US FDA CVM, Laurel, MD 20708 USA. [Peters, Sharla M.; Stubbs, John T., III] Howard Univ, Dept Microbiol, Washington, DC 20059 USA. [Bremer, Eric; Monroe, Jason; Paul, David] Precis Biomarker Resources, Evanston, IL 60201 USA. RP Myers, MJ (reprint author), US FDA CVM, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM michael.myers@fda.hhs.gov NR 28 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JAN PY 2011 VL 139 IS 1 BP 67 EP 72 DI 10.1016/j.vetimm.2010.08.001 PG 6 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 715DK UT WOS:000286860400009 PM 20828834 ER PT J AU Johnson, TJ Thorsness, JL Anderson, CP Lynne, AM Foley, SL Han, J Fricke, WF McDermott, PF White, DG Khatri, M Stell, AL Flores, C Singer, RS AF Johnson, Timothy J. Thorsness, Jessica L. Anderson, Cole P. Lynne, Aaron M. Foley, Steven L. Han, Jing Fricke, W. Florian McDermott, Patrick F. White, David G. Khatri, Mahesh Stell, Adam L. Flores, Cristian Singer, Randall S. TI Horizontal Gene Transfer of a ColV Plasmid Has Resulted in a Dominant Avian Clonal Type of Salmonella enterica Serovar Kentucky SO PLOS ONE LA English DT Article ID PATHOGENIC ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; VIRULENCE PLASMIDS; DNA-SEQUENCE; PREVALENCE; STRAINS; CHICKENS; POULTRY; IMMUNOGENICITY; COLONIZATION AB Salmonella enterica continues to be a significant cause of foodborne gastrointestinal illness in humans. A wide variety of Salmonella serovars have been isolated from production birds and from retail poultry meat. Recently, though, S. enterica subsp. enterica serovar Kentucky has emerged as one of the prominent Salmonella serovars isolated from broiler chickens. Recent work suggests that its emergence apparently coincides with its acquisition of a ColV virulence plasmid. In the present study, we examined 902 Salmonella isolates belonging to 59 different serovars for the presence of this plasmid. Of the serovars examined, the ColV plasmid was found only among isolates belonging to the serovars Kentucky (72.9%), Typhimurium (15.0%) and Heidelberg (1.7%). We demonstrated that a single PFGE clonal type of S. Kentucky harbors this plasmid, and acquisition of this plasmid by S. Kentucky significantly increased its ability to colonize the chicken cecum and cause extraintestinal disease. Comparison of the completed sequences of three ColV plasmids from S. Kentucky isolated from different geographical locales, timepoints and sources revealed a nearly identical genetic structure with few single nucleotide changes or insertions/deletions. Overall, it appears that the ColV plasmid was recently acquired by a single clonal type S. Kentucky and confers to its host enhanced colonization and fitness capabilities. Thus, the potential for horizontal gene transfer of virulence and fitness factors to Salmonella from other enteric bacteria exists in poultry, representing a potential human health hazard. C1 [Johnson, Timothy J.; Thorsness, Jessica L.; Khatri, Mahesh; Stell, Adam L.; Flores, Cristian; Singer, Randall S.] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. [Anderson, Cole P.; Lynne, Aaron M.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77340 USA. [Foley, Steven L.; Han, Jing] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Fricke, W. Florian] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [McDermott, Patrick F.; White, David G.] US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. RP Johnson, TJ (reprint author), Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. EM joh04207@umn.edu FU Minnesota Agricultural Experiment Station [MINV-063-054]; Food Safety Research and Response Network [2005-35212-15287] FX This project was funded by the Minnesota Agricultural Experiment Station, grant MINV-063-054 and by the Food Safety Research and Response Network, which is supported by the National Research Initiative of the United States Department of Agriculture Cooperative State Research, Education and Extension Service, grant number # 2005-35212-15287. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 46 TC 33 Z9 34 U1 0 U2 13 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 DEC 22 PY 2010 VL 5 IS 12 AR e15524 DI 10.1371/journal.pone.0015524 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000033 PM 21203520 ER PT J AU Teferedegne, B Murata, H Quinones, M Peden, K Lewis, AM AF Teferedegne, Belete Murata, Haruhiko Quinones, Mariam Peden, Keith Lewis, Andrew M., Jr. TI Patterns of microRNA Expression in Non-Human Primate Cells Correlate with Neoplastic Development In Vitro SO PLOS ONE LA English DT Article ID HUMAN BREAST-CANCER; HUMAN TUMOR-CELLS; DOWN-REGULATION; VERO CELLS; MESENCHYMAL TRANSITION; EPITHELIAL-CELLS; NKG2D; METASTASIS; TRANSFORMATION; PROGRESSION AB MicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate gene expression post-transcriptionally. They play a critical role in developmental and physiological processes and have been implicated in the pathogenesis of several diseases including cancer. To identify miRNA signatures associated with different stages of neoplastic development, we examined the expression profile of 776 primate miRNAs in VERO cells (a neoplastically transformed cell line being used for the manufacture of viral vaccines), progenitor primary African green monkey kidney (pAGMK) cells, and VERO cell derivatives: spontaneously immortalized, non-tumorigenic, low-passage VERO cells (10-87 LP); tumorigenic, high-passage VERO cells (10-87 HP); and a cell line (10-87 T) derived from a 10-87 HP cell tumor xenograft in athymic nude mice. When compared with pAGMK cells, the majority of miRNAs were expressed at lower levels in 10-87 LP, 10-87 HP, and 10-87 T cells. We identified 10 up-regulated miRNAs whose level of expression correlated with VERO cell evolution from a non-tumorigenic phenotype to a tumorigenic phenotype. The overexpression of miR-376a and the polycistronic cluster of miR-376a, miR-376b and miR-376c conferred phenotypic changes to the non-tumorigenic 10-87 LP cells that mimic the tumorigenic 10-87 HP cells. Thirty percent of miRNAs that were components of the identified miRNAs in our spontaneously transformed AGMK cell model are also dysregulated in a variety of human tumors. These results may prove to be relevant to the biology of neoplastic development. In addition, one or more of these miRNAs could be biomarkers for the expression of a tumorigenic phenotype. C1 [Teferedegne, Belete; Murata, Haruhiko; Lewis, Andrew M., Jr.] US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Peden, Keith] US FDA, Lab Retrovirus Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Quinones, Mariam] NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20892 USA. RP Teferedegne, B (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM andrew.lewis@fda.hhs.gov FU Division of Microbiology and Infectious Diseases (DMID); National Institute of Allergy and Infectious Diseases (NIAID) through Biologics Evaluation and Research (CBER); Food and Drug Administration (FDA) FX This work is partially supported by a contract from the Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID) through an interagency agreement with Center for Biologics Evaluation and Research (CBER), Food and Drug Administration (FDA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 78 TC 13 Z9 13 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 DEC 22 PY 2010 VL 5 IS 12 AR e14416 DI 10.1371/journal.pone.0014416 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000017 PM 21203544 ER PT J AU Verthelyi, D Wang, VV AF Verthelyi, Daniela Wang, Vivian TI Trace Levels of Innate Immune Response Modulating Impurities (IIRMIs) Synergize to Break Tolerance to Therapeutic Proteins SO PLOS ONE LA English DT Article ID TOLL-LIKE RECEPTORS; B-CELL ACTIVATION; CPG OLIGODEOXYNUCLEOTIDES; DENDRITIC CELLS; BACTERIAL-DNA; IN-VIVO; MYD88-INDEPENDENT PATHWAYS; VACCINE ADJUVANTS; GENE-EXPRESSION; LIPOPOLYSACCHARIDE AB Therapeutic proteins such as monoclonal antibodies, replacement enzymes and toxins have significantly improved the therapeutic options for multiple diseases, including cancer and inflammatory diseases as well as enzyme deficiencies and inborn errors of metabolism. However, immune responses to these products are frequent and can seriously impact their safety and efficacy. Of the many factors that can impact protein immunogenicity, this study focuses on the role of innate immune response modulating impurities (IIRMIs) that could be present despite product purification and whether these impurities can synergize to facilitate an immunogenic response to therapeutic proteins. Using lipopolysaccharide (LPS) and CpG ODN as IIRMIs we showed that trace levels of these impurities synergized to induce IgM, IFN gamma, TNF alpha and IL-6 expression. In vivo, trace levels of these impurities synergized to increase antigen-specific IgG antibodies to ovalbumin. Further, whereas mice treated with human erythropoietin showed a transient increase in hematocrit, those that received human erythropoietin containing low levels of IIRMIs had reduced response to erythropoietin after the 1(st) dose and developed long-lasting anemia following subsequent doses. This suggests that the presence of IIRMIs facilitated a breach in tolerance to the endogenous mouse erythropoietin. Overall, these studies indicate that the risk of enhancing immunogenicity should be considered when establishing acceptance limits of IIRMIs for therapeutic proteins. C1 [Verthelyi, Daniela; Wang, Vivian] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Verthelyi, D (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM daniela.verthelyi@fda.hhs.gov NR 55 TC 13 Z9 13 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 DEC 22 PY 2010 VL 5 IS 12 AR e15252 DI 10.1371/journal.pone.0015252 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 698FG UT WOS:000285578000026 PM 21203556 ER PT J AU Jackson, RD Gabriel, S Pariser, A Feig, P AF Jackson, Rebecca D. Gabriel, Sherine Pariser, Anne Feig, Peter TI Training the Translational Scientist SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Editorial Material AB A Clinical and Translational Science Awards Industry Forum titled "Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry" was held in February 2010. A session at this forum was organized to address the training and skills needed to develop a biomedical scientific workforce that interfaces academia, government agencies, and industry to support the process of translating science into applicable means to improve health. By examining the requisite competencies and training resources for scientists in each of these sectors, opportunities for collaboration and adoption of new educational strategies were identified that could help to address barriers to translational research education and career development. C1 [Jackson, Rebecca D.] Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA. [Pariser, Anne] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Gabriel, Sherine] Mayo Clin, Off Strateg Alliance, Rochester, MN 55905 USA. [Feig, Peter] Merck Res Labs, Rahway, NJ 07065 USA. RP Jackson, RD (reprint author), Ohio State Univ, Ctr Clin & Translat Sci, Columbus, OH 43210 USA. EM jackson.20@osu.edu FU NCRR NIH HHS [UL1 RR025755] NR 0 TC 4 Z9 4 U1 1 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD DEC 22 PY 2010 VL 2 IS 63 AR 63mr2 DI 10.1126/scitranslmed.3001632 PG 3 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735UK UT WOS:000288444900005 PM 21178132 ER PT J AU Kamikawa, TL Mikolajczyk, MG Kennedy, M Zhang, P Wang, W Scott, DE Alocilja, EC AF Kamikawa, Tracy L. Mikolajczyk, Malgorzata G. Kennedy, Michael Zhang, Pei Wang, Wei Scott, Dorothy E. Alocilja, Evangelyn C. TI Nanoparticle-based biosensor for the detection of emerging pandemic influenza strains SO BIOSENSORS & BIOELECTRONICS LA English DT Article; Proceedings Paper CT World Congress on Biosensors CY MAY 26-28, 2010 CL Scotland, ENGLAND DE Influenza; Biosensor; Direct-charge transfer; Electrically active; Immunomagnetic; Polyaniline ID CHARGE TRANSFER BIOSENSOR; BACILLUS-ANTHRACIS SPORES; MAGNETIC-PROPERTIES; POLYANILINE; VIRUS; ELECTRODES; SENSITIVITY; BIOLOGY; HUMANS; ASSAY AB Electrically active magnetic (EAM) nanoparticles, consisting of aniline monomer polymerized around gamma iron(III) oxide (gamma-Fe(2)O(3)) cores, serve as the basis of a direct-charge transfer biosensor developed for detection of surface glycoprotein hemagglutinin (HA) from the Influenza A virus (FLUAV) H5N1 (A/Vietnam/1203/04). H5N1 preferentially binds alpha 2,3-linked host glycan receptors. EAM nanoparticles were immunofunctionalized with antibodies against target HA. Glycans preincubated with HA in 10% mouse serum were incubated with anti-HA-EAM complexes. The anti-HA-EAM complexes effectively acted as immunomagnetic separator of HA from mouse serum matrix. EAM nanoparticles served as the biosensor transducer for cyclic voltammetry measurements. The polyaniline was made electrically active by hydrochloric acid doping. Experimental results indicate that the biosensor is able to detect recombinant H5 HA at 1.4 mu M in 10% mouse serum, with high specificity for H5 as compared to H1 (H1N1 A/South Carolina/1/18). This novel design applies EAM nanoparticles in a sensitive, specific, affordable, and easy-to-use biosensor with applications in disease monitoring and biosecurity. (C) 2010 Elsevier B.V. All rights reserved. C1 [Kamikawa, Tracy L.; Alocilja, Evangelyn C.] Michigan State Univ, Dept Biosyst & Agr Engn, E Lansing, MI 48824 USA. [Kamikawa, Tracy L.; Mikolajczyk, Malgorzata G.; Kennedy, Michael; Zhang, Pei; Scott, Dorothy E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Wang, Wei] Michigan State Univ, Dept Crop & Soil Sci, E Lansing, MI 48824 USA. RP Alocilja, EC (reprint author), Michigan State Univ, Dept Biosyst & Agr Engn, 115 Farrall Hall, E Lansing, MI 48824 USA. EM alocilja@msu.edu RI Wang, Wei/F-6555-2011 NR 44 TC 21 Z9 22 U1 3 U2 33 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD DEC 15 PY 2010 VL 26 IS 4 SI SI BP 1346 EP 1352 DI 10.1016/j.bios.2010.07.047 PG 7 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 708ZQ UT WOS:000286403400030 PM 20729069 ER PT J AU Tong, WD Fan, XH AF Tong, Weida Fan, Xiaohui TI Statistical Evaluation of Clinical Usefulness of Microarrays for Cancer Prognosis Needs to be Placed in the Context of Clinical Reality-Response SO CLINICAL CANCER RESEARCH LA English DT Letter ID VALIDATION C1 [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Ctr Bioinformat, Jefferson, AR 72079 USA. [Fan, Xiaohui] Coll Pharmaceut Sci, Pharmaceut Informat Inst, Hangzhou, Zhejiang, Peoples R China. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Bioinformat, Jefferson, AR 72079 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2010 VL 16 IS 24 BP 6181 EP 6181 DI 10.1158/1078-0432.CCR-10-1921 PG 1 WC Oncology SC Oncology GA 695YJ UT WOS:000285408600037 ER PT J AU Doerge, DR Vanlandingham, M Twaddle, NC Delclos, KB AF Doerge, Daniel R. Vanlandingham, Michelle Twaddle, Nathan C. Delclos, K. Barry TI Lactational transfer of bisphenol A in Sprague-Dawley rats SO TOXICOLOGY LETTERS LA English DT Review DE Bisphenol A; Lactation; Neonatal; Mass spectrometry ID MEASURING ENVIRONMENTAL PHENOLS; TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; PERINATAL EXPOSURE; BREAST-MILK; FEMALE RATS; PHARMACOKINETICS; DISPOSITION; METABOLISM; EXCRETION AB Bisphenol A (BPA), an important industrial chemical to which humans are exposed on a daily basis, has long been associated with endocrine disruption in experimental animal models. Such exposures are of concern, particularly during fetal and early neonatal periods, because of greater vulnerability of developing organs to aberrant endocrine signaling. Although rarely reported, information about internal exposures to the receptor-active aglycone form of BPA during the perinatal period is essential to accurate assessment of potential risks. Lactating Sprague-Dawley dams were treated by daily gavage with 100 mu g/kg bw d6-BPA starting at birth. Conjugated and aglycone forms of BPA were then measured by using LC/MS/MS in milk from lactating dams on PND 7 and in serum from dams and their pups on PND 10. All samples were collected 1 h after dosing, a time selected to produce nearly maximal levels. While aglycone BPA was detected in all dam serum and milk samples, none was detected in pup serum (<0.2 nM). Doses delivered to pups lactationally, estimated from milk concentrations and body weights, were 300-fold lower than the dose administered to the dams. Similarly, serum concentrations of total BPA in pups were 300-fold lower than those in their dams. Furthermore, plasma concentrations of total BPA in PND 10 rat pups were 500-fold lower than peak levels achieved following direct oral delivery of the same dose to the same age pups. These findings of significant dose attenuation for the active aglycone form of BPA, relative to that of the dam, suggest high potency for toxicological effects derived exclusively from lactational transfer. Alternatively, studies that include lactational exposure and report minimal effects from BPA should consider the possibility that inadequate internal exposures were achieved during the critical postnatal period. Published by Elsevier Ireland Ltd. C1 [Doerge, Daniel R.; Vanlandingham, Michelle; Twaddle, Nathan C.; Delclos, K. Barry] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCRT Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU NCTR/FDA [224-07-0007]; National Institute for Environmental Health Sciences/National Toxicology Program [224-07-0007] FX This research was supported in part by Interagency Agreement #224-07-0007 between NCTR/FDA and the National Institute for Environmental Health Sciences/National Toxicology Program. This document has been reviewed in accordance with U.S. Food and Drug Administration (FDA) policy and approved for publication. Approval does not signify that the contents necessarily reflect the position or opinions of the FDA nor does mention of trade names or commercial products constitute endorsement or recommendation for use. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the FDA. The authors gratefully acknowledge helpful discussions with Dr. M.L. Camacho, NCTR. NR 36 TC 38 Z9 38 U1 1 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 15 PY 2010 VL 199 IS 3 BP 372 EP 376 DI 10.1016/j.toxlet.2010.09.022 PG 5 WC Toxicology SC Toxicology GA 694UT UT WOS:000285325200022 PM 20933065 ER PT J AU Boehmer, JL DeGrasse, JA McFarland, MA Tall, EA Shefcheck, KJ Ward, JL Bannerman, DD AF Boehmer, Jamie L. DeGrasse, Jeffrey A. McFarland, Melinda A. Tall, Elizabeth A. Shefcheck, Kevin J. Ward, Jeffrey L. Bannerman, Douglas D. TI The proteomic advantage: Label-free quantification of proteins expressed in bovine milk during experimentally induced coliform mastitis SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article; Proceedings Paper CT Annual Scientific Meeting on Cutting Edge Technologies - Animalomics/ Conference on Research Workers in Animal Diseases (CRWAD) CY DEC 07-09, 2009 CL Chicago, IL SP Amer Assoc Vet Immunologists DE Bovine milk proteome; Liquid chromatography/tandem mass spectrometry (LC-MS/MS); Coliform mastitis; Label-free quantification ID COMPLEMENT FRAGMENT C5A; INNATE IMMUNE-RESPONSES; SERUM AMYLOID-A; HEAVY-CHAIN 4; MASS-SPECTROMETRY; ESCHERICHIA-COLI; INTRAMAMMARY INFECTION; SHOTGUN PROTEOMICS; DAIRY-COWS; INFLAMMATORY CYTOKINES AB Coliform mastitis remains a primary focus of dairy cattle disease research due in part to the lack of efficacious treatment options for the deleterious side effects of exposure to LPS, including profound intra-mammary inflammation. To facilitate new veterinary drug approvals, reliable biomarkers are needed to evaluate the efficacy of adjunctive therapies for the treatment of inflammation associated with coliform mastitis. Most attempts to characterize the host response to LPS, however, have been accomplished using ELISAs. Because a relatively limited number of bovine-specific antibodies are commercially available, reliance on antibodies can be very limiting for biomarker discovery. Conversely, proteomic approaches boast the capability to analyze an unlimited number of protein targets in a single experiment, independent of antibody availability. Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS), a widely used proteomic strategy for the identification of proteins in complex mixtures, has gained popularity as a means to characterize proteins in various bovine milk fractions, both under normal physiological conditions as well as during clinical mastitis. The biological complexity of bovine milk has, however, precluded the complete annotation of the bovine milk proteome. Conventional approaches to reducing sample complexity, including fractionation and the removal of high abundance proteins, has improved proteome coverage, but the dynamic range of proteins present, and abundance of a relatively small number of proteins, continues to hinder comparative proteomic analyses of bovine milk. Nonetheless, advances in both liquid chromatography and mass spectrometry instrumentation, including nano-flow liquid chromatography (nano-LC), nano-spray ionization, and faster scanning speeds and ionization efficiency of mass spectrometers, have improved analyses of complex samples. In the current paper, we review the proteomic approaches used to conduct comparative analyses of milk from healthy cows and cows with clinical mastitis, as well as proteins related to the host response that have been identified in mastitic milk. Additionally, we present data that suggests the potential utility of LC-MS/MS label-free quantification as an alternative to costly labeling strategies for the relative quantification of individual proteins in complex mixtures. Temporal expression patterns generated using spectral counts, an LC-MS/MS label-free quantification strategy, corresponded well with ELISA data for acute phase proteins with commercially available antibodies. Combined, the capability to identify low abundance proteins, and the potential to generate temporal expression profiles, indicate the advantages of using proteomics as a screening tool in biomarker discovery analyses to assess biologically relevant proteins modulated during disease, including previously uncharacterized targets. Published by Elsevier B.V. C1 [Boehmer, Jamie L.; Tall, Elizabeth A.; Ward, Jeffrey L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [DeGrasse, Jeffrey A.; McFarland, Melinda A.; Shefcheck, Kevin J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Bannerman, Douglas D.] USDA ARS, Bovine Funct Genom Lab, Beltsville, MD 20705 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 63 TC 30 Z9 31 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD DEC 15 PY 2010 VL 138 IS 4 SI SI BP 252 EP 266 DI 10.1016/j.vetimm.2010.10.004 PG 15 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 697QX UT WOS:000285531500003 PM 21067814 ER PT J AU Kutanzi, KR Koturbash, I Bronson, RT Pogribny, IP Kovalchuk, O AF Kutanzi, Kristy R. Koturbash, Igor Bronson, Roderick T. Pogribny, Igor P. Kovalchuk, Olga TI Imbalance between apoptosis and cell proliferation during early stages of mammary gland carcinogenesis in ACI rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Cell proliferation; Breast carcinogenesis; Estrogen; Ionizing radiation; Apoptosis; p53 ID BREAST-CANCER; EPITHELIAL-CELLS; P53 PATHWAY; C-MYC; MDM2; DEATH; GENOME; OVEREXPRESSION; TRANSFORMATION; INSTABILITY AB Estrogen and ionizing radiation are well-documented human breast carcinogens yet the exact mechanisms of their deleterious effects on mammary gland remain to be discerned Here we analyze the balance between cellular proliferation and apoptosis in the mammary glands of rats exposed to estrogen and X-ray radiation and the combined action of these carcinogenic agents For the first time we show that combined exposure to estrogen and radiation has a synergistic effect on cell proliferation in the mammary glands of ACI rats as evidenced by a substantially greater magnitude of cell proliferation especially after 12 and 18 weeks of treatment when compared to mammary glands of rats exposed to estrogen or radiation alone We also demonstrate that an Imbalance between cell proliferation and apoptosis rather than enhanced cell proliferation or apoptosis suppression alone may be a driving force for carcinogenesis Our studies further suggest that compromised functional activity of p53 may be one of the mechanisms responsible for the proliferation/apoptosis imbalance In sum the results of our study indicate that evaluation of the extent of cell proliferation and apoptosis before the onset of preneoplastic lesions may be a potential biomarker of breast cancer risk after exposure to breast carcinogens (C) 2010 Elsevier B V All rights reserved C1 [Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Kutanzi, Kristy R.; Koturbash, Igor; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Bronson, Roderick T.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. FU Alberta Cancer Research Institute; Canadian Breast Cancer Foundation; Vanier Canada Graduate Scholarship; National Science and Engineering Research Council; Queen Elizabeth II Graduate Scholarship; Alberta Heritage for Medical Research Scholarship FX Work was supported by the Alberta Cancer Research Institute and Canadian Breast Cancer Foundation Operating grants to Olga Kovalchuk Kristy Kutanzi is a recipient of the Vanier Canada Graduate Scholarship National Science and Engineering Research Council Graduate Scholarship, Queen Elizabeth II Graduate Scholarship and the Alberta Heritage for Medical Research Scholarship We are thankful to Rocio Rodriguez-Juarez for technical assistance and to Dr Valentina Titova for careful proofreading of this manuscript NR 36 TC 2 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD DEC 10 PY 2010 VL 694 IS 1-2 BP 1 EP 6 DI 10.1016/j.mrfmmm.2010.07.006 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 699MQ UT WOS:000285667900001 PM 20659487 ER PT J AU Smoker, M Tran, K Smith, RE AF Smoker, Michael Tran, Kevin Smith, Robert E. TI Determination of Polycyclic Aromatic Hydrocarbons (PAHs) in Shrimp SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE PAHs; PhotoSpray; LC-MS/MS; shrimp ID ATMOSPHERIC-PRESSURE PHOTOIONIZATION; MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; IONIZATION; FLOW AB A simple and rapid method for determining polycyclic aromatic hydrocarbons (PAHs) in shrimp is described. For sample preparation, the quick and simple QuEChERS procedure was used. Reverse-phase chromatography using an octadecyl silica (C(18)) column and water/acetonitrile gradient elution was used to separate analyte mixtures. After separation, PAHs were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS) equipped with the atmospheric pressure photoionization (PhotoSpray APPI) source operating in the positive-ion mode. In this methodology, all 16 common PAHs were used and toluene served as a charged dopant to efficiently ionize analyte molecules through secondary reactions. Spikes were performed at 0.2 and 1 mu g/g with and without primary and secondary amine (PSA) sorbent cleanup. Recoveries of PAHs were good, with ion ratios that agreed well between the spikes and standards. Without cleanup at 0.2 mu g/mL, seven compounds had relatively low recovery (49-69%) and one compound, naphthalene, had a somewhat high recovery of 129%. At 1 mu g/mL without cleanup, only three compounds had slightly lower recovery (66--67%). When PSA cleanup was performed, all PAH recoveries were within 75-125% at both spike levels. C1 [Smoker, Michael; Tran, Kevin; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11630 W 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov NR 14 TC 28 Z9 28 U1 1 U2 47 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 DEC 8 PY 2010 VL 58 IS 23 BP 12101 EP 12104 DI 10.1021/jf1029652 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 686BW UT WOS:000284672800006 PM 21062062 ER PT J AU Kainz, W Guag, J Benkler, S Szczerba, D Neufeld, E Krauthamer, V Myklebust, J Bassen, H Chang, I Chavannes, N Kim, JH Sarntinoranont, M Kuster, N AF Kainz, W. Guag, J. Benkler, S. Szczerba, D. Neufeld, E. Krauthamer, V. Myklebust, J. Bassen, H. Chang, I. Chavannes, N. Kim, J. H. Sarntinoranont, M. Kuster, N. TI Development and validation of a magneto-hydrodynamic solver for blood flow analysis SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID FIELDS AB The objective of this study was to develop a numerical solver to calculate the magneto-hydrodynamic (MHD) signal produced by a moving conductive liquid, i.e. blood flow in the great vessels of the heart, in a static magnetic field. We believe that this MHD signal is able to non-invasively characterize cardiac blood flow in order to supplement the present non-invasive techniques for the assessment of heart failure conditions. The MHD signal can be recorded on the electrocardiogram (ECG) while the subject is exposed to a strong static magnetic field. The MHD signal can only be measured indirectly as a combination of the heart's electrical signal and the MHD signal. The MHD signal itself is caused by induced electrical currents in the blood due to the moving of the blood in the magnetic field. To characterize and eventually optimize MHD measurements, we developed a MHD solver based on a finite element code. This code was validated against literature, experimental and analytical data. The validation of the MHD solver shows good agreement with all three reference values. Future studies will include the calculation of the MHD signals for anatomical models. We will vary the orientation of the static magnetic field to determine an optimized location for the measurement of the MHD blood flow signal. C1 [Kainz, W.; Guag, J.; Krauthamer, V.; Myklebust, J.; Bassen, H.; Chang, I.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Benkler, S.; Chavannes, N.] Schmid & Partner Engn AG, Zurich, Switzerland. [Szczerba, D.; Neufeld, E.; Kuster, N.] Fdn Res Informat Technol Soc ITIS, Zurich, Switzerland. [Kim, J. H.; Sarntinoranont, M.] Univ Florida, Soft Tissue Mech & Drug Delivery Lab, Gainesville, FL 32611 USA. RP Kainz, W (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM wolfgang.kainz@fda.hhs.gov OI Myklebust, Joel/0000-0002-8709-9706 NR 10 TC 7 Z9 7 U1 1 U2 6 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 DEC 7 PY 2010 VL 55 IS 23 BP 7253 EP 7261 DI 10.1088/0031-9155/55/23/005 PG 9 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 680UN UT WOS:000284261000019 PM 21081822 ER PT J AU Hamburg, MA AF Hamburg, Margaret A. TI SHATTUCK LECTURE Innovation, Regulation, and the FDA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WOMEN C1 US FDA, Off Commissioner, Silver Spring, MD 20993 USA. RP Hamburg, MA (reprint author), US FDA, Off Commissioner, 10903 New Hampshire Ave,Bldg 1,Rm 2217, Silver Spring, MD 20993 USA. EM margaret.hamburg@fda.hhs.gov NR 12 TC 25 Z9 25 U1 0 U2 8 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 DEC 2 PY 2010 VL 363 IS 23 BP 2228 EP 2232 DI 10.1056/NEJMsa1007467 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 688EP UT WOS:000284832900010 PM 21121835 ER PT J AU Volpe, DA AF Volpe, Donna A. TI Application of Method Suitability for Drug Permeability Classification SO AAPS JOURNAL LA English DT Review DE artificial membranes; drug permeability; ex vivo perfusion; in situ perfusion; in vitro cell monolayers; method suitability ID IN-VITRO PERMEABILITY; INTESTINAL PERMEABILITY; CACO-2 MONOLAYERS; ABSORPTION MODELS; CELL-CULTURES; RAT; TRANSPORT; PREDICTION; VALIDATION; SYSTEM AB Experimental models of permeability in animals, excised tissues, cell monolayers, and artificial membranes are important during drug discovery and development as permeability is one of several factors affecting the intestinal absorption of oral drug products. The utility of these models is demonstrated by their ability to predict a drug's in vivo intestinal absorption. Within the various permeability models, there are differences in the performance of the assays, along with variability in animal species, tissue sources, and cell types, resulting in a variety of experimental permeability values for the same drug among laboratories. This has led to a need for assay standardization within laboratories to ensure applicability in the drug development process. Method suitability provides a generalized approach to standardize and validate a permeability model within a laboratory. First, assay methodology is optimized and validated for its various experimental parameters along with acceptance criteria for the assay. Second, the suitability of the model is demonstrated by a rank order relationship between experimental permeability values and human extent of absorption of known model compounds. Lastly, standard compounds are employed to classify a test drug's intestinal permeability and ensure assay reproducibility and quality. This review will provide examples of the different aspects method suitability for in situ (intestinal perfusions), ex vivo (everted intestinal sacs, diffusion chambers), and in vitro (cell monolayers, artificial membranes) experimental permeability models. Through assay standardization, reference standards, and acceptance criteria, method suitability assures the dependability of experimental data to predict a drug's intestinal permeability during discovery, development, and regulatory application. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.volpe@fda.hhs.gov NR 61 TC 27 Z9 28 U1 1 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD DEC PY 2010 VL 12 IS 4 BP 670 EP 678 DI 10.1208/s12248-010-9227-8 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735OF UT WOS:000288426100020 PM 20811966 ER PT J AU Nagavelli, LR Lionberger, RA Sayeed, VA Yu, L Allgire, J Smith, A Wokovich, A Westenberger, BJ Buhse, L AF Nagavelli, Laxma R. Lionberger, Robert A. Sayeed, Vilayat A. Yu, Lawrence Allgire, James Smith, Anjanette Wokovich, Anna Westenberger, Benjamin J. Buhse, Lucinda TI Analysis of Bead Sizes for MR Capsules Labeled for Sprinkle SO AAPS PHARMSCITECH LA English DT Article DE bead size; generic drugs; modified-release capsules; quality target product profile; sprinkle ID NATURAL FOODS; MASTICATION AB The bead sizes used in approved modified release capsules labeled for sprinkling on food was investigated to generate bead size guidelines for generic products labeled for sprinkling. The conclusions from a survey of FDA databases were corroborated with experimental data obtained by measuring the bead sizes of several reference-listed drugs on the market labeled for administration by sprinkling on food. The experimental data show that majority of the marketed products were found to have bead sizes of less than 1,500 mu m (1.5 mm). Based on this information, a bead size of less than 1,500 mu m should generally be considered acceptable for use in generic products labeled for sprinkling. C1 [Nagavelli, Laxma R.; Lionberger, Robert A.; Sayeed, Vilayat A.; Yu, Lawrence] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Rockville, MD 20855 USA. [Allgire, James; Smith, Anjanette; Wokovich, Anna; Westenberger, Benjamin J.; Buhse, Lucinda] US FDA, Div Pharmaceut Anal, Off Pharmaceut Sci, St Louis, MO 63101 USA. RP Sayeed, VA (reprint author), US FDA, Off Gener Drugs, Off Pharmaceut Sci, 7500 Standish Pl, Rockville, MD 20855 USA. EM Vilayat.sayeed@fda.hhs.gov NR 9 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD DEC PY 2010 VL 11 IS 4 BP 1508 EP 1510 DI 10.1208/s12249-010-9529-2 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 735PE UT WOS:000288428600003 PM 20936439 ER PT J AU Kligfield, P Green, CL Mortara, J Sager, P Stockbridge, N Li, M Zhang, J George, S Rodriguez, I Bloomfield, D Krucoff, MW AF Kligfield, Paul Green, Cynthia L. Mortara, Justin Sager, Philip Stockbridge, Norman Li, Michael Zhang, Joanne George, Samuel Rodriguez, Ignacio Bloomfield, Daniel Krucoff, Mitchell W. TI The Cardiac Safety Research Consortium electrocardiogram warehouse: Thorough QT database specifications and principles of use for algorithm development and testing SO AMERICAN HEART JOURNAL LA English DT Article ID IDENTIFICATION; PROLONGATION; QT/QTC AB This document examines the formation, structure, and principles guiding the use of electrocardiogram (ECG) data sets obtained during thorough QT studies that have been derived from the ECG Warehouse of the Cardiac Safety Research Consortium (CSRC). These principles are designed to preserve the fairness and public interest of access to these data, commensurate with the mission of the CSRC. The data sets comprise anonymized XML formatted digitized ECGs and descriptive variables from placebo and positive control arms of individual studies previously submitted on a proprietary basis to the US Food and Drug Administration by pharmaceutical sponsors. Sponsors permit the release of these studies into the public domain through the CSRC on behalf of the Food and Drug Administration's Critical Path Initiative and public health interest. For algorithm research protocols submitted to and approved by CSRC, unblinded "training" ECG data sets are provided for algorithm development and for initial evaluation, whereas separate blinded "testing" data sets are used for formal algorithm evaluation in cooperation with the CSRC according to methods detailed in this document. (Am Heart J 2010;160:1023-8.) C1 [Kligfield, Paul] Weill Cornell Med Coll, Div Cardiol, Dept Med, New York, NY USA. [Green, Cynthia L.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Durham, NC USA. [Green, Cynthia L.; Krucoff, Mitchell W.] Duke Clin Res Inst, Durham, NC USA. [Mortara, Justin] Mortara Instrument, Milwaukee, WI USA. [Sager, Philip] Sager Consulting Partners, San Francisco, CA USA. [Stockbridge, Norman; Li, Michael; Zhang, Joanne] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [George, Samuel] NewCardio Inc, Santa Clara, CA USA. [Rodriguez, Ignacio] Merck & Co Inc, Merck Res Labs, Rahway, NJ 07065 USA. [Bloomfield, Daniel] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. RP Kligfield, P (reprint author), Weill Cornell Med Ctr, 525 E 68th St, New York, NY 10065 USA. EM pkligfi@med.cornell.edu FU Clinical and Translational Sciences Award [UL1 RR024128] FX CLG was supported in part by a Clinical and Translational Sciences Award Grant to Duke University (UL1 RR024128). NR 9 TC 15 Z9 15 U1 0 U2 0 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 DEC PY 2010 VL 160 IS 6 BP 1023 EP 1028 DI 10.1016/j.ahj.2010.09.002 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 692WW UT WOS:000285187600010 PM 21146653 ER PT J AU Brustkern, AM Buhse, LF Nasr, M Al-Hakim, A Keire, DA AF Brustkern, Adam M. Buhse, Lucinda F. Nasr, Moheb Al-Hakim, Ali Keire, David A. TI Characterization of Currently Marketed Heparin Products: Reversed-Phase Ion-Pairing Liquid Chromatography Mass Spectrometry of Heparin Digests SO ANALYTICAL CHEMISTRY LA English DT Article ID OVERSULFATED CHONDROITIN SULFATE; ADVERSE CLINICAL EVENTS; CAPILLARY-ELECTROPHORESIS; DISACCHARIDE COMPOSITION; OLIGOSACCHARIDES; QUANTIFICATION; IDENTIFICATION; ISOMERS AB Here we report results from the analyses by enzymatic digestion and reversed-phase ion pairing liquid chromatography mass spectrometry (RPIP-LC-MS) of active pharmaceutical ingredient (API) unfractionated heparins (UFHs) from six different manufacturers and one USP standard sample We employed a reverse phase ionpairing chromatography method using a C(18) column and hexylamine as the ion pairing reagent with acetonitrile gradient elution to separate disaccharides generated from the digestion of the heparins by lyase I and III (E C 4 2 2 7 and 4 2 2 8) before introduction into an ion-trap mass spectrometer by an electrospray ionization (ESI) interface Extracted ion chromatograms (EICs) were used to determine the relative abundance of the disaccharides by mass spectrometry Eight disaccharides were observed and a similar composition profile was observed from digests of 20 UFH samples The compositional profile determined from these experiments provides a measure of the norm and range of variation in "good" heparin to which future preparations can be compared Furthermore, the profile obtained in the RPIP-LC-MS assay is sensitive to the presence of the contaminant, oversulfated chondroitin sulfate A (OSCS), in heparin C1 [Brustkern, Adam M.; Buhse, Lucinda F.; Keire, David A.] US FDA, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. [Nasr, Moheb; Al-Hakim, Ali] US FDA, Off New Drug Qual Assessment, CDER, Silver Spring, MD 20993 USA. RP Keire, DA (reprint author), US FDA, Div Pharmaceut Anal, CDER, St Louis, MO 63101 USA. NR 31 TC 32 Z9 35 U1 0 U2 17 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 DEC 1 PY 2010 VL 82 IS 23 BP 9865 EP 9870 DI 10.1021/ac102301j PG 6 WC Chemistry, Analytical SC Chemistry GA 686AG UT WOS:000284668600040 PM 21069966 ER PT J AU Lyn-Cook, BD Mohammed, SI Davis, C Word, B Haefele, A Wang, HG Hammons, G AF Lyn-Cook, Beverly D. Mohammed, Sulma I. Davis, Cornelius Word, Beverly Haefele, Aaron Wang, Honggang Hammons, George TI Gender Differences in Gemcitabine (Gemzar) Efficacy in Cancer Cells: Effect of Indole-3-Carbinol SO ANTICANCER RESEARCH LA English DT Article DE Sex differences; pancreatic cancer; gemcitabine; indole-3-carbinol ID FACTOR-KAPPA-B; PANCREATIC-CANCER; DNA METHYLATION; DIETARY INDOLE-3-CARBINOL; DEOXYCYTIDINE KINASE; TRANSCRIPTION FACTOR; RANDOMIZED-TRIAL; EXPRESSION; INHIBITION; CARCINOGENESIS AB Pancreatic cancer has a poor prognosis, mainly due to lack of effective therapies. This study demonstrated the ability of dietary agent, indole-3-carbinol (I3C), to lower the LD50 of gemcitabine (Gemzar) in decreasing growth of both male (MiaPaca2) and female (SU86.86) pancreatic cancer cells. Female pancreatic cancer cells were more resistant to gemcitabine alone. Additionally, RT-PCR analysis of MiaPaca2 cells treated with I, 10 or 100 mu M of I3C showed that I3C reactivated the tumor suppressor gene p16INK4a in pancreatic cancer cells. Methylated-specific PCR analysis indicated that I3C demethylated the promoter region of p16INK4a, which was methylated in the untreated cancer cells. p16INK4a inactivation through promoter hypermethylation is considered an early event in pancreatic carcinogenesis. A positive control using 5-azacytidine also reactivated p16INK4a. This study demonstrated the potential of I3C, a possible nontoxic hypomethylating agent, combined with the anticancer agent, gemcitabine, to be a powerful strategy for treating pancreatic cancer. C1 [Lyn-Cook, Beverly D.; Davis, Cornelius; Word, Beverly; Haefele, Aaron; Wang, Honggang; Hammons, George] US FDA, Off Regulatory Act, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mohammed, Sulma I.] Purdue Univ, Canc Res Ctr, W Lafayette, IN 47907 USA. RP Lyn-Cook, BD (reprint author), US FDA, Off Regulatory Act, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Beverly.lyn-cook@fda.hhs.gov NR 42 TC 5 Z9 5 U1 2 U2 5 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 DEC PY 2010 VL 30 IS 12 BP 4907 EP 4913 PG 7 WC Oncology SC Oncology GA 717BV UT WOS:000287018100016 PM 21187469 ER PT J AU Zhao, S Young, SR Tong, E Abbott, JW Womack, N Friedman, SL McDermott, PF AF Zhao, S. Young, S. R. Tong, E. Abbott, J. W. Womack, N. Friedman, S. L. McDermott, P. F. TI Antimicrobial Resistance of Campylobacter Isolates from Retail Meat in the United States between 2002 and 2007 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MACROLIDE RESISTANCE; JEJUNI INFECTIONS; COLI; SALMONELLA; QUINOLONE; POULTRY; FLUOROQUINOLONE; SURVEILLANCE; PREVALENCE AB The emergence of antimicrobial resistance in Campylobacter spp. has been a growing public health concern globally. The objectives of this study were to determine the prevalence, antimicrobial susceptibility, and genetic relatedness of Campylobacter spp. recovered by the National Antimicrobial Resistance Monitoring System (NARMS) retail meat program. Retail meat samples (n = 24,566) from 10 U.S. states collected between 2002 and 2007, consisting of 6,138 chicken breast, 6,109 ground turkey, 6,171 ground beef, and 6,148 pork chop samples, were analyzed. A total of 2,258 Campylobacter jejuni, 925 Campylobacter coli, and 7 Campylobacter lari isolates were identified. Chicken breast samples showed the highest contamination rate (49.9%), followed by ground turkey (1.6%), whereas both pork chops and ground beef had <0.5% contamination. The most common resistance was to doxycycline/tetracycline (46.6%), followed by nalidixic acid (18.5%), ciprofloxacin (17.4%), azithromycin and erythromycin (2.8%), telithromycin (2.4%), clindamycin (2.2%), and gentamicin (<0.1%). In a subset of isolates tested, no resistance to meropenem and florfenicol was seen. C. coli isolates showed higher resistance rates to antimicrobials, with the exception of doxycycline/tetracycline, than those seen for C. jejuni. Pulsed-field gel electrophoresis (PFGE) fingerprinting resulted in 1,226 PFGE profiles among the 2,318 isolates, with many clones being widely dispersed throughout the 6-year sampling period. C1 [Zhao, S.; Young, S. R.; Tong, E.; Abbott, J. W.; Womack, N.; Friedman, S. L.; McDermott, P. F.] US FDA, Res Off, CVM, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP Zhao, S (reprint author), US FDA, Res Off, CVM, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM shaohua.zhao@fda.hhs.gov NR 38 TC 45 Z9 47 U1 0 U2 10 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 DEC PY 2010 VL 76 IS 24 BP 7949 EP 7956 DI 10.1128/AEM.01297-10 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 688VO UT WOS:000284882800007 PM 20971875 ER PT J AU Savoie, N Garofolo, F van Amsterdam, P Bansal, S Beaver, C Bedford, P Booth, BP Evans, C Jemal, M Lefebvre, M de Silva, ALL Lowes, S Marini, JC Masse, R Mawer, L Ormsby, E Rocci, ML Viswanathan, CT Wakelin-Smith, J Welink, J White, JT Woolf, E AF Savoie, Natasha Garofolo, Fabio van Amsterdam, Peter Bansal, Surendra Beaver, Chris Bedford, Patrick Booth, Brian P. Evans, Christopher Jemal, Mohammed Lefebvre, Marc Lopes de Silva, Arthur Leonardo Lowes, Steve Marini, Joseph C. Masse, Robert Mawer, Louise Ormsby, Eric Rocci, Mario L., Jr. Viswanathan, C. T. Wakelin-Smith, Jason Welink, Jan White, Joleen T. Woolf, Eric TI 2010 White Paper on Recent Issues in Regulated Bioanalysis & Global Harmonization of Bioanalytical Guidance SO BIOANALYSIS LA English DT Article ID VALIDATION GROUP WORKSHOP; LIGAND-BINDING ASSAYS; CALIBRATION; RECOMMENDATIONS; FORUM AB The 4th Calibration and Validation Group Workshop on Recent Issues in Regulated Bioanalysis, a 2-day full immersion workshop, was organized by the Calibration and Validation Group. Contract research organizations, pharmaceutical companies and regulatory agencies came together to discuss several 'hot' topics concerning bioanalytical issues and regulatory challenges and to reach a consensus among panelists and attendees on many points regarding method validation of small and large molecules. C1 [Savoie, Natasha; Garofolo, Fabio; Lefebvre, Marc] Algorithme Pharma Inc, Montreal, PQ H7V 4B3, Canada. [van Amsterdam, Peter] Abbott Healthcare Prod BV, Weesp, Netherlands. [Bansal, Surendra] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Bedford, Patrick; Ormsby, Eric] Hlth Canada TPD, Ottawa, ON, Canada. [Booth, Brian P.; Viswanathan, C. T.] US FDA, CDER, Silver Spring, MD USA. [Evans, Christopher] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Jemal, Mohammed; White, Joleen T.] Bristol Myers Squibb Co, Princeton, NJ USA. [Lopes de Silva, Arthur Leonardo] ANVISA, Brasilia, DF, Brazil. [Lowes, Steve] Advion BioServ Inc, Ithaca, NY USA. [Marini, Joseph C.] Inc Johnson & Johnson, Centocor R&D, Radnor, PA USA. [Masse, Robert] Anapharm PharmaNet, Quebec City, PQ, Canada. [Mawer, Louise; Wakelin-Smith, Jason] Med & Healthcare Prod Regulatory Agcy, London, England. [Rocci, Mario L., Jr.] ICON Dev Solut, Whitesboro, NY USA. [Welink, Jan] Med Evaluat Board, The Hague, Netherlands. [Woolf, Eric] Merck Res Labs, West Point, PA USA. RP Garofolo, F (reprint author), Algorithme Pharma Inc, 575 Armand Frappier Blvd, Montreal, PQ H7V 4B3, Canada. EM fgarofolo@algopharm.com FU Anapharm; Cetero Research; Pharma Medica; Pharma Medica, PPD; Algorithme Pharma; Alta Analytical Laboratory; PerkinElmer; AB Sciex; ICON; Waters; Advion; Biovail; KCAS; ABC Labs; Maxxam; GYROS; ZefSci; Varian; Cedra; Tandem Labs FX Workshop sustaining sponsors: Anapharm, Cetero Research, Pharma Medica, PPD, Algorithme Pharma, Alta Analytical Laboratory, PerkinElmer, AB Sciex, ICON, Waters, Advion, Biovail Contract Research, KCAS, ABC Labs, Maxxam, GYROS, ZefSci, Varian, Cedra, Tandem Labs. NR 32 TC 68 Z9 70 U1 0 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD DEC PY 2010 VL 2 IS 12 BP 1945 EP 1960 DI 10.4155/BIO.10.164 PG 16 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 695WQ UT WOS:000285403700009 PM 21110739 ER PT J AU Hung, HMJ Wang, SJ AF Hung, H. M. James Wang, Sue-Jane TI Challenges to multiple testing in clinical trials SO BIOMETRICAL JOURNAL LA English DT Article; Proceedings Paper CT 6th International Conference on Multiple Comparison Procedures (MCP 2009) CY MAR 24-27, 2009 CL Tokyo Univ Sci, Tokyo, JAPAN HO Tokyo Univ Sci DE Composite endpoint; Familywise; Non-inferiority; Sequentially rejective; Studywise ID SECONDARY END-POINTS; CLEAR STATISTICAL SIGNIFICANCE; REGULATORY APPLICATIONS; IF AB Multiple testing problems are complex in evaluating statistical evidence in pivotal clinical trials for regulatory applications. However, a common practice is to employ a general and rather simple multiple comparison procedure to handle the problems. Applying multiple comparison adjustments is to ensure proper control of type I error rates. However, in many practices, the emphasis of the type I error rate control often leads to a choice of a statistically valid multiple test procedure but the common sense is overlooked. The challenges begin with confusions in defining a relevant family of hypotheses for which the type I error rates need to be properly controlled. Multiple testing problems are in a wide variety, ranging from testing multiple doses and endpoints jointly, composite endpoint, non-inferiority and superiority, to studying time of onset of a treatment effect, and searching for minimum effective dose or a patient subgroup in which the treatment effect lies. To select a valid and sensible multiple test procedure, the first step should be to tailor the selection to the study questions and to the ultimate clinical decision tree. Then evaluation of statistical power performance should come in to play in the next step to fine tune the selected procedure. C1 [Hung, H. M. James] US FDA, Div Biometr 1, OB OTS CDER, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] US FDA, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB OTS CDER, 10903 New Hampshire Ave,HFD 710, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 20 TC 17 Z9 17 U1 3 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2010 VL 52 IS 6 SI SI BP 747 EP 756 DI 10.1002/bimj.200900206 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 693XO UT WOS:000285258900005 ER PT J AU Wang, SJ Hung, HMJ O'Neill, RT AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert T. TI Impacts on type I error rate with inappropriate use of learn and confirm in confirmatory adaptive design trials SO BIOMETRICAL JOURNAL LA English DT Article; Proceedings Paper CT 6th International Conference on Multiple Comparison Procedures (MCP 2009) CY MAR 24-27, 2009 CL Tokyo Univ Sci, Tokyo, JAPAN HO Tokyo Univ Sci DE Adaptive design; Learn and confirm; Learning free type I error rate; Studywise type I error rate ID II/III CLINICAL-TRIALS; HYPOTHESES SELECTION; PREDICTIVE POWER; INTERIM AB A two-stage adaptive design trial is a single trial that combines the learning data from stage 1 (or phase II) and the confirming data in stage 2 (or phase III) for formal statistical testing. We call it a "Learn and Confirm" trial. The studywise type I error rate remains to be at issue in a "Learn and Confirm" trial. For studying multiple doses or multiple enpdoints, a "Learn and Confirm" adaptive design can be more attractive than a fixed design approach. This is because intuitively the learning data in stage 1 should not be subjected to type I error scrutiny if there is no formal interim analysis performed and only an adaptive selection of design parameters is made at stage 1. In this work, we conclude from extensive simulation studies that the intuition is most often misleading. That is, regardless of whether or not there is a formal interim analysis for making an adaptive selection, the type I error rates are always at risk of inflation. Inappropriate use of any "Learn and Confirm" strategy should not be overlooked. C1 [Wang, Sue-Jane; O'Neill, Robert T.] US FDA, Off Biostat, OTS CDER, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, OB OTS CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, OTS CDER, 10903 New Hampshire Ave,HFD 700, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 25 TC 10 Z9 11 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD DEC PY 2010 VL 52 IS 6 SI SI BP 798 EP 810 DI 10.1002/bimj.200900207 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 693XO UT WOS:000285258900009 PM 21154897 ER PT J AU Westfall, PH Troendle, JF Pennello, G AF Westfall, Peter H. Troendle, James F. Pennello, Gene TI Multiple McNemar Tests SO BIOMETRICS LA English DT Article DE Bonferroni-Holm; Bootstrap; Discreteness; Exact tests; Multiple comparisons; Postmarket surveillance; Predictive model ID BOOTSTRAP AB P>Methods for performing multiple tests of paired proportions are described. A broadly applicable method using McNemar's exact test and the exact distributions of all test statistics is developed; the method controls the familywise error rate in the strong sense under minimal assumptions. A closed form (not simulation-based) algorithm for carrying out the method is provided. A bootstrap alternative is developed to account for correlation structures. Operating characteristics of these and other methods are evaluated via a simulation study. Applications to multiple comparisons of predictive models for disease classification and to postmarket surveillance of adverse events are given. C1 [Westfall, Peter H.] Texas Tech Univ, Area ISQS, Lubbock, TX 79409 USA. [Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Bethesda, MD 20892 USA. [Pennello, Gene] US FDA, Epidemiol Branch, Ctr Devices & Radiol Hlth, HFZ 541, Rockville, MD 20850 USA. RP Westfall, PH (reprint author), Texas Tech Univ, Area ISQS, Lubbock, TX 79409 USA. EM peter.westfall@ttu.edu FU NIH, NICHD FX This research was supported in part by the Intramural Research Program of the NIH, NICHD. NR 20 TC 7 Z9 7 U1 2 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2010 VL 66 IS 4 BP 1185 EP 1191 DI 10.1111/j.1541-0420.2010.01408.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 693DN UT WOS:000285204900020 PM 20345498 ER PT J AU Reutter, D Schutzer, SE Craft, CM Fletcher, J Fricke, FL Holowachuk, SA Johnson, RC Keim, PS Pearson, JL Sibert, RW Velsko, S AF Reutter, Dennis Schutzer, Steven E. Craft, Charles M. Fletcher, Jacqueline Fricke, Frederick L. Holowachuk, Scott A. Johnson, Rudolph C. Keim, Paul S. Pearson, James L. Sibert, Robert W. Velsko, Steve TI PLANNING FOR EXERCISES OF CHEMICAL, BIOLOGICAL, RADIOLOGICAL, AND NUCLEAR (CBRN) FORENSIC CAPABILITIES SO BIOSECURITY AND BIOTERRORISM-BIODEFENSE STRATEGY PRACTICE AND SCIENCE LA English DT Article ID BIOTERRORISM; PREPAREDNESS; TOPOFF AB A forensic capability to help identify perpetrators and exclude innocent people should be an integral part of a strategy against terrorist attacks. Exercises have been conducted to increase our preparedness and response capabilities to chemical, biological, radiological, and nuclear (CBRN) terrorist attacks. However, incorporating forensic components into these exercises has been deficient. CBRN investigations rely on forensic results, so the need to integrate a forensic component and forensics experts into comprehensive exercises is paramount. This article provides guidance for planning and executing exercises at local, state, federal, and international levels that test the effectiveness of forensic capabilities for CBRN threats. The guidelines presented here apply both to situations where forensics is only a component of a more general exercise and where forensics is the primary focus of the exercise. C1 [Reutter, Dennis] Lawrence Livermore Natl Lab, Forens Sci Ctr, Livermore, CA 94551 USA. [Schutzer, Steven E.] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. [Craft, Charles M.] Sandia Natl Labs, Albuquerque, NM 87185 USA. [Fletcher, Jacqueline] Oklahoma State Univ, Natl Inst Microbial Forens & Food & Agr Biosecur, Dept Entomol & Plant Pathol, Stillwater, OK 74078 USA. [Fricke, Frederick L.] US FDA, Cincinnati, OH USA. [Holowachuk, Scott A.] Def Res & Dev Canada, Dept Natl Def, Forens Grp, Operat Support Sect, Suffield, AB, Canada. [Johnson, Rudolph C.] Ctr Dis Control & Prevent, Chem Terrorism Method Dev Grp, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA. [Keim, Paul S.] No Arizona Univ, Flagstaff, AZ 86011 USA. [Pearson, James L.] Virginia Dept Gen Serv, DCLS, Div Consolidated Lab Serv, Richmond, VA USA. [Sibert, Robert W.] Dept Homeland Secur, Sci & Technol Directorate, Chem Forens Program, Washington, DC USA. [Velsko, Steve] Lawrence Livermore Natl Lab, Global Secur Directorate, Livermore, CA USA. RP Reutter, D (reprint author), Lawrence Livermore Natl Lab, Forens Sci Ctr, POB 808,L-091, Livermore, CA 94551 USA. EM reutter1@llnl.gov RI Keim, Paul/A-2269-2010 NR 10 TC 2 Z9 2 U1 3 U2 14 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1538-7135 J9 BIOSECUR BIOTERROR JI Biosecur. Bioterror. PD DEC PY 2010 VL 8 IS 4 BP 343 EP 355 DI 10.1089/bsp.2010.0023 PG 13 WC Public, Environmental & Occupational Health; International Relations SC Public, Environmental & Occupational Health; International Relations GA 692WO UT WOS:000285186800006 PM 21142761 ER PT J AU Shao, Y Liu, Y Shao, C Hu, J Li, X Li, F Zhang, L Zhao, D Sun, L Zhao, X Kopecko, DJ Kalvakolanu, DV Li, Y Xu, DQ AF Shao, Y. Liu, Y. Shao, C. Hu, J. Li, X. Li, F. Zhang, L. Zhao, D. Sun, L. Zhao, X. Kopecko, D. J. Kalvakolanu, D. V. Li, Y. Xu, D. Q. TI Enhanced tumor suppression in vitro and in vivo by co-expression of survivin-specific siRNA and wild-type p53 protein SO CANCER GENE THERAPY LA English DT Article DE prostate cancer; p53; survivin; siRNA ID ACID-ACTIVATED REGULATOR; PROSTATE-CANCER; BREAST-CANCER; DOWN-REGULATION; TRANSCRIPTIONAL REPRESSION; TARGETING SURVIVIN; CELL-DEATH; IFN-BETA; AURORA-B; C-MYC AB The development of malignant prostate cancer involves multiple genetic alterations. For example, alterations in both survivin and p53 are reported to have crucial roles in prostate cancer progression. However, little is known regarding the interrelationships between p53 and survivin in prostate cancer. Our data demonstrate that the expression of survivin is inversely correlated with that of wtp53 protein (r(s)-0.548) in prostate cancer and in normal prostate tissues. We have developed a therapeutic strategy, in which two antitumor factors, small interfering RNA-survivin and p53 protein, are co-expressed from the same plasmid, and have examined their effects on the growth of PC3, an androgen-independent prostate cancer cell line. When p53 was expressed along with a survivin-specific short hairpin RNA (shRNA), tumor cell proliferation was significantly suppressed and apoptosis occurred. In addition, this combination also abrogated the expression of downstream target molecules such as cyclin-dependent kinase 4 and c-Myc, while enhancing the expression of GRIM19. These changes in gene expression occurred distinctly in the presence of survivin-shRNA/wtp53 compared with control or single treatment groups. Intratumoral injection of the co-expressed construct inhibited the growth and survival of tumor xenografts in a nude mouse model. These studies revealed evidence of an interaction between p53 and survivin proteins plus a complex signaling network operating downstream of the wtp53-survivin pathway that actively controls tumor cell proliferation, survival and apoptosis. Cancer Gene Therapy (2010) 17, 844-854; doi: 10.1038/cgt.2010.41; published online 13 August 2010 C1 [Shao, Y.; Liu, Y.; Shao, C.; Li, X.; Li, F.; Zhang, L.; Zhao, D.; Sun, L.; Zhao, X.; Li, Y.] Jilin Univ, Dis Prevent & Treatment Res Ctr, Dept Pathophysiol, Norman Bethune Coll Med & Prostate, Changchun 130021, Peoples R China. [Hu, J.] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Kopecko, D. J.; Xu, D. Q.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kalvakolanu, D. V.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Greene Baum Canc Ctr,Mol Biol Program, Baltimore, MD 21201 USA. RP Li, Y (reprint author), Jilin Univ, Dis Prevent & Treatment Res Ctr, Dept Pathophysiol, Norman Bethune Coll Med & Prostate, Changchun 130021, Peoples R China. EM lyang@jlu.edu.cnor; deqi.xu@fda.hhs.gov FU The Research Fund for the Doctoral Program of Higher Education China [20070183012]; NIH [CA105005, CA78282] FX This work was supported by 'The Research Fund for the Doctoral Program of Higher Education China' in 2007. Grant 20070183012. We thank Dr Ruijuan Gao, Tyler Bassett and Suqin Pan for providing valuable help and technical support. DVK is supported by the NIH grants CA105005 and CA78282. NR 46 TC 9 Z9 11 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2010 VL 17 IS 12 BP 844 EP 854 DI 10.1038/cgt.2010.41 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 680EC UT WOS:000284214200003 PM 20706288 ER PT J AU Kim, PW Nambiar, S AF Kim, Peter W. Nambiar, Sumathi TI Meta-Analysis of a Possible Signal of Increased Mortality Associated with Cefepime Use Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 [Kim, Peter W.; Nambiar, Sumathi] US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Silver Spring, MD 20993 USA. RP Kim, PW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM peter.kim@fda.hhs.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2010 VL 51 IS 11 BP 1351 EP 1352 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 675RZ UT WOS:000283850200025 ER PT J AU Lesko, LJ Zineh, I Huang, SM AF Lesko, L. J. Zineh, I. Huang, S-M TI What Is Clinical Utility and Why Should We Care? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PERSONALIZED MEDICINE; IMMINENT REALITY; DRUG DEVELOPMENT; ELUSIVE DREAM C1 [Lesko, L. J.; Zineh, I.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM lawrence.lesko@fda.hhs.gov; lssam.Zineh@fda.hhs.gov; ShiewMei.Huang@fda.hhs.gov NR 27 TC 37 Z9 39 U1 1 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 DEC PY 2010 VL 88 IS 6 BP 729 EP 733 DI 10.1038/clpt.2010.229 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 684BR UT WOS:000284522500001 PM 21081937 ER PT J AU Woodcock, J AF Woodcock, J. TI Assessing the Clinical Utility of Diagnostics Used in Drug Therapy SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID SURROGATE END-POINTS; COLORECTAL-CANCER; BIOMARKERS; QUANTITY; SURVIVAL; QUALITY; LIFE AB There is an ongoing debate over the evidentiary standards that should be applied for introduction of new diagnostics into routine clinical practice. Many call for evidence of "clinical utility," i.e., a positive impact on patient outcomes. A diagnostic, when used with a medicine, has clinical utility if it improves the outcomes of drug therapy. Improved outcomes may be defined broadly, including benefits, harm reduction, and patient-reported outcomes. Much of the controversy centers around the methods of demonstrating clinical utility. For instance, are randomized prospective trials the only acceptable source of data? Practically speaking, many sources of evidence-mechanistic, pharmacologic, and observational-can contribute to a finding of clinical utility, depending on the circumstances. Clinical utility is highly indication specific, and achieving it is dependent on good analytical and diagnostic test performance. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM janet.woodcock@fda.hhs.gov NR 22 TC 36 Z9 38 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2010 VL 88 IS 6 BP 765 EP 773 DI 10.1038/clpt.2010.230 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 684BR UT WOS:000284522500017 PM 20981005 ER PT J AU Temple, R AF Temple, R. TI Enrichment of Clinical Study Populations SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CORONARY-HEART-DISEASE; BREAST-CANCER; FAILURE; SUPPRESSION; PREVENTION; ENCAINIDE; MORTALITY; SURVIVAL; PLACEBO; EVENTS AB Those who conduct clinical trials "enrich" study populations in a variety of ways in order to identify a population of patients in whom a drug effect, if present, is more likely to be demonstrable. The principal ways to do this are as follows: (i) practical enrichment, i.e., generally seeking to reduce noise (variability of measurement) and heterogeneity (by avoiding the enrollment of patients with other diseases and individuals in whom the disease disappears spontaneously), (ii) prognostic enrichment, i.e., finding patients who are likely to have the event of interest when enrolling for risk-reduction studies, and (iii) predictive enrichment, i.e., finding the individuals who are more likely to respond. Enrichment fits well into the growing interest in "individualization" of therapy but creates some tension with another trend, namely, the desire for "real-world studies" with less restrictive entry criteria and other requirements. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Robert.Temple@fda.hhs.gov NR 15 TC 39 Z9 39 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2010 VL 88 IS 6 BP 774 EP 778 DI 10.1038/clpt.2010.233 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 684BR UT WOS:000284522500018 PM 20944560 ER PT J AU Brunelle, JK Zhang, BL AF Brunelle, Joslyn K. Zhang, Baolin TI Apoptosis assays for quantifying the bioactivity of anticancer drug products SO DRUG RESISTANCE UPDATES LA English DT Review DE Anticancer drugs; Bioactivity assays; Caspases; FRET ID INDEPENDENT CELL-DEATH; TUMOR-NECROSIS-FACTOR; BREAST-CANCER CELLS; BCL-2 FAMILY; ALAMAR-BLUE; P53 PATHWAY; PROTEIN-S; THERAPY; PHAGOCYTOSIS; RECEPTORS AB The goal of cancer therapy is to kill cancer cells Many anticancer drugs are designed to kill cells by inducing apoptosis However the potency assays used for measuring the bioactivity of these products are generally cell viability assays which do not distinguish between cell death and growth inhibition There are a number of commercial assays available to measure apoptosis however many of these assays are not appropriate for use in high throughput screening formats preferred by Industry to measure drug activity also known as potency due to their inherent low robustness and/or high variability This review outlines the strengths and weaknesses of current apoptosis assays and highlights new promising assay developments for evaluation of anticancer therapeutics such as the design of fluorescent and luminescent constructs to be applied as caspase substrates Published by Elsevier Ltd C1 [Brunelle, Joslyn K.; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Zhang, BL (reprint author), 29 Lincoln Dr,Bldg 29A,Rm 2A01,HFD 122, Bethesda, MD 20892 USA. NR 68 TC 23 Z9 24 U1 0 U2 9 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD DEC PY 2010 VL 13 IS 6 BP 172 EP 179 DI 10.1016/j.drup.2010.09.001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 699LU UT WOS:000285665700002 PM 20947411 ER PT J AU Diaz-Amigo, C AF Diaz-Amigo, Carmen TI Towards a Comprehensive Validation of ELISA Kits for Food Allergens: Case 1-Egg SO FOOD ANALYTICAL METHODS LA English DT Article; Proceedings Paper CT 5th Workshop on Food Allergen Methodologies CY MAY 11-14, 2008 CL Halifax, CANADA DE Egg; Allergy; ELISA; Validation; Reference Material ID EGG; PROTEINS AB There are several enzyme-linked immunosorbent assay (ELISA) kits in the market that have been proven to be useful for the determination of egg in foods. However, inconsistent results that are obtained when different kits are used make the selection of one kit over another very difficult. Two different approaches were used to help understand why results vary among kits. Different kits were used to analyze spiked egg material [NIST reference material (RM) 8445] in wheat flour (raw ingredients) and cookies containing egg as an ingredient baked for different periods of time (processed food). These results were compared with immunoblotting using conjugated antibodies from the commercial kits to determine the antibody specificity and sample extraction efficiency. ELISA results can be difficult to compare because reporting units differ among kits. Results from both ELISA and immunoblotting are in agreement regarding the decreased detection of proteins in baked cookie extracts. Moreover, immunoblotting showed that this reduction is due to reduced protein content in these extracts. However, a properly selected extraction solution may help improve the solubility of certain egg proteins in processed foods. Harmonization of the reporting unit system along with the use of a common reference material is recommended as the path forward in the standardization of detection methods for food allergens. This would assist the end user in making an informed decision regarding the selection of the most appropriate kit for his or her purpose. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Diaz-Amigo, C (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM carmen.westphal@fda.hhs.gov NR 11 TC 13 Z9 14 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-9751 J9 FOOD ANAL METHOD JI Food Anal. Meth. PD DEC PY 2010 VL 3 IS 4 SI SI BP 344 EP 350 DI 10.1007/s12161-009-9094-z PG 7 WC Food Science & Technology SC Food Science & Technology GA 680ST UT WOS:000284255400009 ER PT J AU Diaz-Amigo, C AF Diaz-Amigo, Carmen TI Towards a Comprehensive Validation of ELISA Kits for Food Allergens. Case 2-Milk SO FOOD ANALYTICAL METHODS LA English DT Article; Proceedings Paper CT 5th Workshop on Food Allergen Methodologies CY MAY 11-14, 2008 CL Halifax, CANADA DE Milk; Food Allergy; ELISA; Validation; Reference Material ID COWS MILK ALLERGY; ANAPHYLAXIS; TOLERANCE; CHILDREN AB Milk and milk derivatives are common ingredients in food products. Undeclared milk is one of the leading causes of recalls in many countries, including the USA, and cases of allergic reactions have been reported due to unexpected exposures. There are commercial enzyme-linked immunosorbent assay (ELISA) kits available to the food industry to comply with the law by ensuring label accuracy and to identify potential sources of cross-contact. These kits are also used by regulatory agencies as part of their compliance programs. However, none of the commercial ELISAs for milk have been validated. Performance of ELISA kits for food allergens is affected by matrix, food processing, and stability and solubility of target proteins, among others factors. The performance of different commercial kits for milk allergens was evaluated by comparing a standard [National Institute of Standards and Technology (NIST) SRM #1549] spiked in wheat flour. We also compared the effect of food processing on detectability of milk proteins from incurred peanut butter cookies baked at various times. Kits differed in their ability to detect heat-treated milk proteins in baked cookies. Immunoblots clearly showed differences in antibody specificities and in their ability to detect proteins in processed foods. Factors such as undefined antibody specificity and differences in sample extraction solutions, materials used for calibrators, and reporting units contribute to variability of results among test kits and, hence, to increased uncertainty regarding the most appropriate use of the kits. Moreover, the use of incurred vs. spiked samples may affect protein recovery and, therefore, jeopardize the quantitative nature of the kit. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Diaz-Amigo, C (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM carmen.westphal@fda.hhs.gov NR 9 TC 13 Z9 13 U1 0 U2 18 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1936-9751 J9 FOOD ANAL METHOD JI Food Anal. Meth. PD DEC PY 2010 VL 3 IS 4 SI SI BP 351 EP 356 DI 10.1007/s12161-009-9095-y PG 6 WC Food Science & Technology SC Food Science & Technology GA 680ST UT WOS:000284255400010 ER PT J AU Ravel, A Davidson, VJ Ruzante, JM Fazil, A AF Ravel, Andre Davidson, Valerie J. Ruzante, Juliana M. Fazil, Aamir TI Foodborne Proportion of Gastrointestinal Illness: Estimates from a Canadian Expert Elicitation Survey SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID UNITED-STATES; FOOD; INFECTIONS; DISEASE AB The study used a structured expert elicitation survey to derive estimates of the foodborne attributable proportion for nine illnesses caused by enteric pathogens in Canada. It was based on a similar study conducted in the United States and focused on Campylobacter, Escherichia coli O157:H7, Listeria monocytogenes, nontyphoidal Salmonella enterica, Shigella spp., Vibrio spp., Yersinia enterocolitica, Cryptosporidium parvum, and Norwalk-like virus. For each pathogen, experts were asked to provide their best estimate and low and high limits for the proportion of foodborne illness relative to total cases. In addition, they provided background information with regard to food safety experience, including self-evaluated expertise for each pathogen on a 5-point scale. A snowball approach was used to identify 152 experts within Canada. The experts' background details were summarized using descriptive statistics. Factor analysis was used to determine whether the variability in best estimates was related to self-assessed level of expertise or other background information. Cluster analysis followed by beta function fitting was undertaken on best estimates from experts who self-evaluated their expertise 3 or higher. In parallel, Monte Carlo resampling was run using triangular distributions based on each expert's best estimate and its limits. Sixty-six experts encompassing various academic backgrounds, fields of expertise, and experiences relevant to food safety provided usable data. Considerable variation between experts in their estimated foodborne attributable proportions was observed over all diseases, without any relationship to the expert's background. Uncertainty about their estimate (measured by the low and high limits) varied between experts and between pathogens as well. Both cluster analysis and Monte Carlo resampling clearly indicated disagreement between experts for Campylobacter, E. coli O157, L. monocytogenes, Salmonella, Vibrio, and Y. enterocolitica. In the absence of more reliable estimates, the observed discrepancy between experts must be explored and understood before one can judge which opinion is the best. C1 [Ravel, Andre] Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, Fac Med Vet, St Hyacinthe, PQ J2S 2M1, Canada. [Davidson, Valerie J.] Univ Guelph, Sch Engn, Guelph, ON N1G 2W1, Canada. [Ruzante, Juliana M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Fazil, Aamir] Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, Guelph, ON, Canada. RP Ravel, A (reprint author), Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, Fac Med Vet, Pavillon Sante Publ Vet 3190,Rue Sicotte, St Hyacinthe, PQ J2S 2M1, Canada. EM andre_ravel@phac-aspc.gc.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 thank all experts helping build the expert list and those answering the survey. The authors also thank Natalya Obushenko at the Laboratory for Foodborne Zoonoses, Guelph ON, who participated in the data analysis. 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 20 TC 17 Z9 17 U1 0 U2 6 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 DEC PY 2010 VL 7 IS 12 BP 1463 EP 1472 DI 10.1089/fpd.2010.0582 PG 10 WC Food Science & Technology SC Food Science & Technology GA 688GH UT WOS:000284837300004 PM 20704505 ER PT J AU Kaput, J Evelo, CT Perozzi, G van Ommen, B Cotton, R AF Kaput, Jim Evelo, Chris T. Perozzi, Giuditta van Ommen, Ben Cotton, Richard TI Connecting the Human Variome Project to nutrigenomics SO GENES AND NUTRITION LA English DT Editorial Material DE Nutrigenomics; Human Variome Project; Harmonization ID COPY NUMBER VARIATION; DEVELOPING-COUNTRIES; GLOBAL HEALTH; HUMAN GENOME; PARTICIPATORY RESEARCH; NUTRITIONAL GENOMICS; HUMAN-POPULATIONS; GENETIC-VARIATION; GRAND CHALLENGES; DISEASE AB Nutrigenomics is the science of analyzing and understanding gene-nutrient interactions, which because of the genetic heterogeneity, varying degrees of interaction among gene products, and the environmental diversity is a complex science. Although much knowledge of human diversity has been accumulated, estimates suggest that similar to 90% of genetic variation has not yet been characterized. Identification of the DNA sequence variants that contribute to nutrition-related disease risk is essential for developing a better understanding of the complex causes of disease in humans, including nutrition-related disease. The Human Variome Project (HVP; http://www.humanvariomeproject.org) is an international effort to systematically identify genes, their mutations, and their variants associated with phenotypic variability and indications of human disease or phenotype. Since nutrigenomic research uses genetic information in the design and analysis of experiments, the HVP is an essential collaborator for ongoing studies of gene-nutrient interactions. With the advent of next generation sequencing methodologies and the understanding of the undiscovered variation in human genomes, the nutrigenomic community will be generating novel sequence data and results. The guidelines and practices of the HVP can guide and harmonize these efforts. C1 [Kaput, Jim] US FDA, Div Personalised Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Evelo, Chris T.] Maastricht Univ, Dept Bioinformat BiGCaT, Maastricht, Netherlands. [Perozzi, Giuditta] INRAN Natl Res Inst Food & Nutr, I-00178 Rome, Italy. [van Ommen, Ben] TNO Qual Life, NL-3700 AJ Zeist, Netherlands. [Cotton, Richard] Genom Disorders Res Ctr, Melbourne, Vic 3053, Australia. RP Kaput, J (reprint author), US FDA, Div Personalised Nutr & Med, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM James.kaput@fda.hhs.gov RI Evelo, Chris/D-2914-2009; Perozzi, Giuditta/A-7460-2016 OI Evelo, Chris/0000-0002-5301-3142; Perozzi, Giuditta/0000-0003-1755-6104 NR 72 TC 1 Z9 2 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD DEC PY 2010 VL 5 IS 4 BP 275 EP 283 DI 10.1007/s12263-010-0186-6 PG 9 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 682SO UT WOS:000284423500001 PM 28300226 ER PT J AU van Ommen, B El-Sohemy, A Hesketh, J Kaput, J Fenech, M Evelo, CT McArdle, HJ Bouwman, J Lietz, G Mathers, JC Fairweather-Tait, S van Kranen, H Elliott, R Wopereis, S Ferguson, LR Meplan, C Perozzi, G Allen, L Rivero, D AF van Ommen, Ben El-Sohemy, Ahmed Hesketh, John Kaput, Jim Fenech, Michael Evelo, Chris T. McArdle, Harry J. Bouwman, Jildau Lietz, Georg Mathers, John C. Fairweather-Tait, Sue van Kranen, Henk Elliott, Ruan Wopereis, Suzan Ferguson, Lynnette R. Meplan, Catherine Perozzi, Giuditta Allen, Lindsay Rivero, Damariz CA Micronutrient Genomics Project Wor TI The Micronutrient Genomics Project: a community-driven knowledge base for micronutrient research SO GENES AND NUTRITION LA English DT Review DE Micronutrient; Bioinformatics; Database; Genomics ID BETA-CAROTENE; VITAMIN-A; STABLE-ISOTOPES; METABOLISM; RIBOFLAVIN; FOLATE; DEFICIENCY; DATABASE; DISEASE; BIOLOGY AB Micronutrients influence multiple metabolic pathways including oxidative and inflammatory processes. Optimum micronutrient supply is important for the maintenance of homeostasis in metabolism and, ultimately, for maintaining good health. With advances in systems biology and genomics technologies, it is becoming feasible to assess the activity of single and multiple micronutrients in their complete biological context. Existing research collects fragments of information, which are not stored systematically and are thus not optimally disseminated. The Micronutrient Genomics Project (MGP) was established as a community-driven project to facilitate the development of systematic capture, storage, management, analyses, and dissemination of data and knowledge generated by biological studies focused on micronutrient-genome interactions. Specifically, the MGP creates a public portal and open-source bioinformatics toolbox for all "omics" information and evaluation of micronutrient and health studies. The core of the project focuses on access to, and visualization of, genetic/genomic, transcriptomic, proteomic and metabolomic information related to micronutrients. For each micronutrient, an expert group is or will be established combining the various relevant areas (including genetics, nutrition, biochemistry, and epidemiology). Each expert group will (1) collect all available knowledge, (2) collaborate with bioinformatics teams towards constructing the pathways and biological networks, and (3) publish their findings on a regular basis. The project is coordinated in a transparent manner, regular meetings are organized and dissemination is arranged through tools, a toolbox web portal, a communications website and dedicated publications. C1 [van Ommen, Ben; Bouwman, Jildau; Wopereis, Suzan] TNO Qual Life, NL-3700 AJ Zeist, Netherlands. [El-Sohemy, Ahmed] Univ Toronto, Dept Nutr Sci, Toronto, ON M5S 3E2, Canada. [Hesketh, John; Meplan, Catherine] Newcastle Univ, Sch Med, Inst Cell & Mol Biosci, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. [Kaput, Jim] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Fenech, Michael] CSIRO Food & Nutr Sci, Adelaide Bc, SA 5000, Australia. [Evelo, Chris T.] Maastricht Univ, Dept Bioinformat BiGCaT, Maastricht, Netherlands. [McArdle, Harry J.] Univ Aberdeen, Rowett Inst Nutr & Hlth, Aberdeen AB21 9SB, Scotland. [Lietz, Georg] Newcastle Univ, Human Nutr Res Ctr, Sch Agr Food & Rural Dev, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Mathers, John C.] Newcastle Univ, Inst Ageing & Hlth, Human Nutr Res Ctr, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. RP van Ommen, B (reprint author), TNO Qual Life, POB 360, NL-3700 AJ Zeist, Netherlands. EM ben.vanommen@tno.nl; a.el.sohemy@utoronto.ca; j.e.hesketh@ncl.ac.uk; james.kaput@fda.hhs.gov; chris.evelo@bigcat.unimaas.nl; h.mcardle@abdn.ac.uk; jildau.bouwman@tno.nl; Georg.lietz@ncl.ac.uk; john.mathers@newcastle.ac.uk; Catherine.meplan@ncl.ac.uk RI Lietz, Georg/A-4084-2012; Fairweather-Tait, Susan/K-4251-2012; Evelo, Chris/D-2914-2009; Perozzi, Giuditta/A-7460-2016; OI Evelo, Chris/0000-0002-5301-3142; Perozzi, Giuditta/0000-0003-1755-6104; Mathers, John/0000-0003-3406-3002; El-Sohemy, Ahmed/0000-0002-8877-6414 FU Canadian Institutes of Health Research (CIHR); Office of Biotechnology, Genomics and Population Health of the Public Health Agency of Canada (BGPH/PHAC); United States Food and Drug Administration (FDA); European Nutrigenomics Organisation; Eurreca; Advanced Foods and Materials Network (AFMNet) FX Funding for the Vancouver planning workshop was provided by a Meetings, Planning and Dissemination Grant from the Canadian Institutes of Health Research (CIHR), as well as contributions from the Office of Biotechnology, Genomics and Population Health of the Public Health Agency of Canada (BGPH/PHAC), the United States Food and Drug Administration (FDA), the European Nutrigenomics Organisation (http://www.nugo.org), Eurreca (http://www.eurreca.org) and the Advanced Foods and Materials Network (AFMNet). This work has been approved for publication by the FDA but it does not necessarily reflect official agency policy. NR 48 TC 21 Z9 22 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1555-8932 J9 GENES NUTR JI Genes Nutr. PD DEC PY 2010 VL 5 IS 4 BP 285 EP 296 DI 10.1007/s12263-010-0192-8 PG 12 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 682SO UT WOS:000284423500002 PM 21189865 ER PT J AU Miller, HI AF Miller, Henry I. TI Benighted EC Politicians Reject Food from Cloned Animals 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.] 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 DEC PY 2010 VL 30 IS 21 BP 6 EP 8 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 693OU UT WOS:000285234200001 ER PT J AU Kohonen-Corish, MRJ Al-Aama, JY Auerbach, AD Axton, M Barash, CI Bernstein, I Beroud, C Burn, J Cunningham, F Cutting, GR den Dunnen, JT Greenblatt, MS Kaput, J Katz, M Lindblom, A Macrae, F Maglott, D Moslein, G Povey, S Ramesar, R Richards, S Seminara, D Sobrido, MJ Tavtigian, S Taylor, G Vihinen, M Winship, I Cotton, RGH AF Kohonen-Corish, Maija R. J. Al-Aama, Jumana Y. Auerbach, Arleen D. Axton, Myles Barash, Carol Isaacson Bernstein, Inge Beroud, Christophe Burn, John Cunningham, Fiona Cutting, Garry R. den Dunnen, Johan T. Greenblatt, Marc S. Kaput, Jim Katz, Michael Lindblom, Annika Macrae, Finlay Maglott, Donna Moeslein, Gabriela Povey, Sue Ramesar, Raj Richards, Sue Seminara, Daniela Sobrido, Maria-Jesus Tavtigian, Sean Taylor, Graham Vihinen, Mauno Winship, Ingrid Cotton, Richard G. H. CA Contributors Human Variome Project TI How to Catch All Those Mutations-The Report of the Third Human Variome Project Meeting, UNESCO Paris, May 2010 SO HUMAN MUTATION LA English DT Editorial Material DE mutation; variation; genomics; genetic disease ID RECOMMENDATIONS AB The third Human Variome Project (HVP) Meeting "Integration and Implementation" was held under UNESCO Patronage in Paris, France, at the UNESCO Headquarters May 10-14, 2010. The major aims of the HVP are the collection, curation, and distribution of all human genetic variation affecting health. The HVP has drawn together disparate groups, by country, gene of interest, and expertise, who are working for the common good with the shared goal of pushing the boundaries of the human variome and collaborating to avoid unnecessary duplication. The meeting addressed the 12 key areas that form the current framework of HVP activities: Ethics; Nomenclature and Standards; Publication, Credit and Incentives; Data Collection from Clinics; Overall Data Integration and Access-Peripheral Systems/Software; Data Collection from Laboratories; Assessment of Pathogenicity; Country Specific Collection; Translation to Healthcare and Personalized Medicine; Data Transfer, Databasing, and Curation; Overall Data Integration and Access-Central Systems; and Funding Mechanisms and Sustainability. In addition, three societies that support the goals and the mission of HVP also held their own Workshops with the view to advance disease-specific variation data collection and utilization: the International Society for Gastrointestinal Hereditary Tumours, the Micronutrient Genomics Project, and the Neurogenetics Consortium. Hum Mutat 31:1374-1381, 2010. (c) 2010 Wiley-Liss, Inc. C1 [Kohonen-Corish, Maija R. J.] Univ NSW, St Vincents Clin Sch, Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia. [Al-Aama, Jumana Y.] King Abdulaziz Univ, Dept Med Genet, Fac Med, Jeddah 21413, Saudi Arabia. [Al-Aama, Jumana Y.] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21413, Saudi Arabia. [Auerbach, Arleen D.] Rockefeller Univ, Program Human Genet & Hematol, New York, NY 10021 USA. [Axton, Myles] Nat Publishing Grp, New York, NY USA. [Barash, Carol Isaacson] Boston Univ, Dept Philosophy Genet Eth & Policy Consulting, Boston, MA 02215 USA. [Bernstein, Inge] Hvidovre Univ Hosp, Dept Surg Gastroenterol, Copenhagen, Denmark. [Beroud, Christophe] Univ Montpellier 1, Hop Arnaud Villeneuve, Genet Mol Lab, INSERM,U827, Montpellier, France. [Burn, John] Newcastle Univ, Inst Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. [Cunningham, Fiona] EBI, Cambridge CB10 1SD, England. [Cutting, Garry R.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. [den Dunnen, Johan T.] Leiden Univ, Med Ctr, Leiden, Netherlands. [Greenblatt, Marc S.] Univ Vermont, Coll Med, Burlington, VT USA. [Kaput, Jim] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. [Katz, Michael] March Dimes Fdn, White Plains, NY USA. [Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden. [Macrae, Finlay] Dept Colorectal Med & Genet, Parkville, Vic, Australia. [Macrae, Finlay] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Parkville, Vic, Australia. [Maglott, Donna] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [Moeslein, Gabriela] HELIOS St Josefs Hosp, Bochum, Germany. [Povey, Sue] UCL, Div Life Sci, London, England. [Ramesar, Raj] Univ Cape Town, Inst Infect Dis & Mol Med, Div Human Genet, MRC Human Genet Res Unit, ZA-7700 Rondebosch, South Africa. [Richards, Sue] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Seminara, Daniela] NCI, Bethesda, MD 20892 USA. [Sobrido, Maria-Jesus] Inst Hlth Carlos III, Ctr Biomed Network Res Rare Disorders CIBERER, Fdn Publ Galega Med Xenom, Madrid, Spain. [Tavtigian, Sean] Univ Utah, Sch Med, Huntsman Canc Inst, Dept Oncol Sci, Salt Lake City, UT USA. [Taylor, Graham] St James Univ Hosp, Leeds, W Yorkshire, England. [Vihinen, Mauno] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. [Vihinen, Mauno] Tampere Univ Hosp, Res Ctr, Tampere, Finland. [Winship, Ingrid] Univ Melbourne, Royal Melbourne Hosp, Melbourne, Vic 3050, Australia. [Cotton, Richard G. H.] Genom Disorders Res Ctr, Melbourne, Vic, Australia. RP Kohonen-Corish, MRJ (reprint author), Univ NSW, St Vincents Clin Sch, Garvan Inst Med Res, Canc Res Program, 384 Victoria St, Sydney, NSW 2010, Australia. EM m.corish@garvan.org.au RI Ramesar, Raj/I-6941-2015; BEROUD, Christophe/A-8381-2008; Vihinen, Mauno/A-8452-2012; LABO, U827/A-8632-2008 OI Ramesar, Raj/0000-0001-5688-1634; BEROUD, Christophe/0000-0003-2986-8738; Axton, J. Myles/0000-0002-8042-4131; Cunningham, Fiona/0000-0002-7445-2419; Auerbach, Arleen/0000-0002-6911-8379; Winship, Ingrid/0000-0001-8535-6003; Vihinen, Mauno/0000-0002-9614-7976; FU NIDDK NIH HHS [R37 DK044003, R37 DK044003-21] NR 7 TC 23 Z9 27 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD DEC PY 2010 VL 31 IS 12 BP 1374 EP 1381 DI 10.1002/humu.21379 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 693VG UT WOS:000285252900015 PM 20960468 ER PT J AU Hillyer, P Chen, A Navarro, M Schramm, LM Mane, VP Rabin, RL AF Hillyer, P. Chen, A. Navarro, M. Schramm, L. M. Mane, V. P. Rabin, R. L. TI Respiratory syncytial virus (RSV) strain dependent differences in induction of type I and III interferon subtypes and innate immune responses SO IMMUNOLOGY LA English DT Meeting Abstract CT Annual Congress of the British-Society-for-Immunology CY DEC 06-10, 2010 CL Liverpool, ENGLAND SP British Soc Immunol C1 [Hillyer, P.; Chen, A.; Navarro, M.; Schramm, L. M.; Mane, V. P.; Rabin, R. L.] USFDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD DEC PY 2010 VL 131 SU 1 BP 138 EP 138 PG 1 WC Immunology SC Immunology GA 689XL UT WOS:000284964100453 ER PT J AU Belay, ED Schonberger, LB Brown, P Priola, SA Chesebro, B Will, RG Asher, DM AF Belay, Ermias D. Schonberger, Lawrence B. Brown, Paul Priola, Suzette A. Chesebro, Bruce Will, Robert G. Asher, David M. TI Disinfection and Sterilization of Prion-Contaminated Medical Instruments SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID CREUTZFELDT-JAKOB-DISEASE; DECONTAMINATION; ENCEPHALOPATHIES; TRANSMISSION; INFECTIVITY; STEEL C1 [Belay, Ermias D.; Schonberger, Lawrence B.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Priola, Suzette A.; Chesebro, Bruce] NIH, Hamilton, MT USA. [Asher, David M.] US FDA, Silver Spring, MD USA. [Will, Robert G.] United Kingdom Natl Creutzfeldt Jakob Dis Surveil, Edinburgh, Midlothian, Scotland. RP Belay, ED (reprint author), 1600 Clifton Rd, Atlanta, GA 30333 USA. EM EBelay@cdc.gov RI Belay, Ermias/A-8829-2013 NR 15 TC 5 Z9 5 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD DEC PY 2010 VL 31 IS 12 BP 1304 EP 1306 DI 10.1086/657579 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 675PJ UT WOS:000283842300018 PM 21047181 ER PT J AU Hoffmann, M Fischer, M Ottesen, A McCarthy, PJ Lopez, JV Brown, EW Monday, SR AF Hoffmann, Maria Fischer, Markus Ottesen, Andrea McCarthy, Peter J. Lopez, Jose V. Brown, Eric W. Monday, Steven R. TI Population dynamics of Vibrio spp. associated with marine sponge microcosms SO ISME JOURNAL LA English DT Article DE 16S rRNA gene sequencing; 16S-23S rRNA intergenic spacer region; Phylum Porifera; speciation; Vibrio ID SEQUENCE DATA; ENVIRONMENT; ARB AB Vibrio is a diverse genus of marine-associated bacteria with at least 74 species and more expected as additional marine ecospheres are interrogated. This report describes a phylogenetic reconstruction of Vibrio isolates derived from one such unique ecosystem, marine sponges (Phylum Porifera) collected from depths of 150 to 1242 feet. 16S rRNA gene sequencing along with molecular typing of 16S-23S rRNA intergenic spacer regions clustered many sponge-associated Vibrio (spp) with current known species. That is, several benthic Vibrio species commensal with Porifera sponges seemed genetically linked to vibrios associated with coastal or shallow-water communities, signalling a panmictic population structure among seemingly ecologically disparate strains. Conversely, phylogenetic analysis provided evidence for at least two novel Vibrio speciation events within this specific sponge microcosm. Collectively, these findings earmark this still relatively unknown environment as a bastion of taxonomic and phylogenetic variability for the genus and probably other bacterial taxa. The ISME Journal (2010) 4, 1608-1612; doi:10.1038/ismej.2010.85; published online 1 July 2010 C1 [Hoffmann, Maria; Ottesen, Andrea; Brown, Eric W.; Monday, Steven R.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hoffmann, Maria; Fischer, Markus] Univ Hamburg, Dept Chem, Inst Food Chem, Hamburg, Germany. [McCarthy, Peter J.] Florida Atlantic Univ, Ctr Marine Biomed & Biotechnol Res, Harbor Branch, Oceanog Inst, Ft Pierce, FL USA. [Lopez, Jose V.] Nova SE Univ, Oceanog Ctr, Dania, FL USA. RP Hoffmann, M (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, Mailstop HFS-711,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM maria.hoffman@fda.hhs.gov RI Fischer, Markus/G-9477-2012; OI McCarthy, Peter/0000-0002-2396-7463; Lopez, Jose/0000-0002-1637-4125 FU Center for Food Safety and Applied Nutrition FX We would like to thank Marianna Naum for her assistance with the maximum likelihood analyses. This project was supported by an appointment of MH to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities. This work denotes HBOI contribution number 1805. NR 20 TC 11 Z9 11 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1751-7362 J9 ISME J JI ISME J. PD DEC PY 2010 VL 4 IS 12 BP 1608 EP 1612 DI 10.1038/ismej.2010.85 PG 5 WC Ecology; Microbiology SC Environmental Sciences & Ecology; Microbiology GA 701SW UT WOS:000285844700012 PM 20596073 ER PT J AU Boyce, JA Assa'ad, A Burks, AW Jones, SM Sampson, HA Wood, RA Plaut, M Cooper, SF Fenton, MJ Arshad, SH Bahna, SL Beck, LA Byrd-Bredbenner, C Camargo, CA Eichenfield, L Furuta, GT Hanifin, JM Jones, C Kraft, M Levy, BD Lieberman, P Luccioli, S McCall, KM Schneider, LC Simon, RA Simons, FER Teach, SJ Yawn, BP Schwaninger, JM AF Boyce, Joshua A. Assa'ad, Amal Burks, A. Wesley Jones, Stacie M. Sampson, Hugh A. Wood, Robert A. Plaut, Marshall Cooper, Susan F. Fenton, Matthew J. Arshad, S. Hasan Bahna, Sami L. Beck, Lisa A. Byrd-Bredbenner, Carol Camargo, Carlos A., Jr. Eichenfield, Lawrence Furuta, Glenn T. Hanifin, Jon M. Jones, Carol Kraft, Monica Levy, Bruce D. Lieberman, Phil Luccioli, Stefano McCall, Kathleen M. Schneider, Lynda C. Simon, Ronald A. Simons, F. Estelle R. Teach, Stephen J. Yawn, Barbara P. Schwaninger, Julie M. TI Guidelines for the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAID-Sponsored Expert Panel Report SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article C1 [Plaut, Marshall; Cooper, Susan F.; Fenton, Matthew J.; Schwaninger, Julie M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. [Boyce, Joshua A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy,Dept Med, Boston, MA 02115 USA. [Assa'ad, Amal] Univ Cincinnati, Div Allergy & Immunol, Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Dept Pediat, Div Allergy & Immunol, Durham, NC 27710 USA. [Jones, Stacie M.] Univ Arkansas Med Sci, Div Allergy & Immunol, Dept Pediat, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. [Sampson, Hugh A.] Mt Sinai Sch Med, Elliot & Roslyn Jaffe Food Allergy Inst, Div Allergy & Immunol, Dept Pediat, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Allergy & Immunol, Baltimore, MD USA. [Arshad, S. Hasan] Univ Southampton, Sch Med, Southampton, Hants, England. [Arshad, S. Hasan] St Marys Hosp, David Hide Asthma & Allergy Res Ctr, Newport, Wight, England. [Arshad, S. Hasan] Southampton Univ Hosp NHS Trust, Southampton, Hants, England. [Bahna, Sami L.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, Allergy & Immunol Sect, Shreveport, LA 71105 USA. [Beck, Lisa A.] Univ Rochester, Dept Dermatol, Med Ctr, Rochester, NY 14627 USA. [Byrd-Bredbenner, Carol] Rutgers State Univ, Dept Nutr Sci, New Brunswick, NJ 08903 USA. [Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Camargo, Carlos A., Jr.] Harvard Univ, Sch Med, Dept Med, Div Rheumatol Allergy & Immunol,Massachusetts Gen, Boston, MA USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. [Eichenfield, Lawrence] Rady Childrens Hosp, Div Pediat & Adolescent Dermatol, San Diego, CA USA. [Furuta, Glenn T.] Childrens Hosp Denver, Sect Pediat Gastroenterol Hepatol & Nutr, Digest Hlth Inst, Aurora, CO USA. [Furuta, Glenn T.] Univ Colorado, Dept Pediat, Denver Sch Med, Aurora, CO USA. [Furuta, Glenn T.] Natl Jewish Hlth, Dept Pediat, Denver, CO USA. [Hanifin, Jon M.] Oregon Hlth & Sci Univ, Dept Dermatol, Portland, OR 97201 USA. [Jones, Carol] Allergy & Asthma Network Mothers Asthmat, Mclean, VA USA. [Kraft, Monica] Duke Univ, Med Ctr, Dept Med, Div Pulm Allergy & Crit Care Med, Durham, NC 27710 USA. [Levy, Bruce D.] Brigham & Womens Hosp, Partners Asthma Ctr, Div Pulm & Crit Care Med, Boston, MA 02115 USA. [Levy, Bruce D.] Harvard Univ, Sch Med, Boston, MA USA. [Lieberman, Phil] Univ Tennessee, Dept Med, Div Allergy & Immunol, Coll Med, Memphis, TN 38104 USA. [Luccioli, Stefano] US FDA, Off Food Addit Safety, College Pk, MD USA. [McCall, Kathleen M.] Childrens Hosp Orange Cty, Orange, CA USA. [Schneider, Lynda C.] Childrens Hosp Boston, Div Immunol, Boston, MA USA. [Simon, Ronald A.] Scripps Clin, Div Allergy Asthma & Immunol, San Diego, CA USA. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Pediat, Winnipeg, MB, Canada. [Simons, F. Estelle R.] Univ Manitoba, Fac Med, Dept Child Hlth & Immunol, Winnipeg, MB, Canada. [Teach, Stephen J.] Childrens Natl Med Ctr, Div Emergency Med, Washington, DC 20010 USA. [Yawn, Barbara P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. [Yawn, Barbara P.] Univ Minnesota, Sch Med, Dept Family & Community Hlth, Minneapolis, MN 55455 USA. RP Fenton, MJ (reprint author), NIAID, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Room 3105, Bethesda, MD 20892 USA. EM fentonm@niaid.nih.gov RI Byrd-Bredbenner, Carol/F-8064-2015 OI Byrd-Bredbenner, Carol/0000-0002-8010-3987 FU National Institutes of Health; GlaxoSmithKline; Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson; Dyax Corp; Food Allergy and Anaphylaxis Network, Mead Johnson; National Peanut Board; Food Allergy Initiative; National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine); Phadia AB; Genentech; National Institutes of Health (National Institute of Allergy and Infectious Diseases); National Institute of Health Research, UK; American Academy of Allergy, Asthma, and Immunology; National Eczema Association; US Department of Agriculture; Canned Food Alliance; New Jersey Department of Health and Senior Services; Dey; Novartis; Astellas; Ferndale; Johnson Johnson; Sinclair; Stiefel; Therapeutics Inc.; American Gastrointestinal Association; ALZA; Astellas Pharma US, Inc; Asubio Pharmaceuticals, Inc; Centocor, Inc; Corgentech; Nucryst Pharmaceuticals; Seattle Genetics; Shionogi USA; Merck; Sepracor; Dey Laboratories; Schering-Plough; AstraZenica; TEVA; Pfizer; MEDA; Alcon; Intelliject; US Food and Drug Administration; AllerGen; Canadian Allergy; Asthma and Immunology Foundation/Anaphylaxis Canada; Canadian Institutes of Health Research; AstraZeneca Foundation; Aventis; Child Health Center Board; CNMC Research Advisory Council; National Association of Chain Drug Stores Foundation; National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute); Novartis/Genentech; Robert Woods Johnson Foundation; US Centers for Disease Control and Prevention; US Public Health Service; Washington, DC, Department of Health FX J. A. Boyce has served on the Advisory Board of GlaxoSmithKline. He has served as a consultant and/or speaker for Altana, GlaxoSmithKline, and Merck. He has received funding/grant support from the National Institutes of Health.; A. Assa'ad holds, or is listed as an inventor on, US patent application #10/566903, entitled "Genetic markers of food allergy." She has served as a consultant for GlaxoSmithKline and as a speaker for the American College of Allergy, Asthma, and Immunology, the North East Allergy Society, the Virginia Allergy Society, the New England Allergy Society, and the American Academy of Pediatrics. Dr Assa'ad has received funding/grant support from GlaxoSmithKline.; A. W. Burks holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein and MastCell, Inc, and is a minority stockholder in Dannon Co Probiotics. He has served as a consultant for ActoGeniX NV, McNeil Nutritionals, Mead Johnson, and Novartis. He has served on the speaker's bureau for EpiPen/Dey, LP, and has served on the data monitoring committee for Genentech. He has served on an expert panel for Nutricia. Dr Burks has received funding/grant support from the Food Allergy and Anaphylaxis Network, Gerber, Mead Johnson, and the National Institutes of Health.; S. M. Jones has served as a speaker and grant reviewer and has served on the medical advisory committee for the Food Allergy and Anaphylaxis Network. She has received funding/grant support from Dyax Corp, the Food Allergy and Anaphylaxis Network, Mead Johnson, the National Peanut Board, and the National Institutes of Health.; H. A. Sampson holds, or is listed as an inventor on, multiple US patents related to food allergy. He owns stock in Allertein Therapeutics. He is the immediate past president of the American Academy of Allergy, Asthma, and Immunology. He has served as a consultant for Allertein Therapeutics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy Initiative, and Schering Plough. He has received funding/grant support for research projects from the Food Allergy Initiative, the National Institutes of Health (Division of Receipt and Referral, National Institute of Allergy and Infectious Diseases, National Center for Complementary and Alternative Medicine), and Phadia AB. He is a co-owner of Herbal Spring, LLC.; R. A. Wood has served as a speaker/advisory board member for GlaxoSmithKline, Merck, and Dey. He has received funding/grant support from Genentech and the National Institutes of Health (National Institute of Allergy and Infectious Diseases).; S. H. Arshad has received funding/grant support from the National Institutes of Health and the National Institute of Health Research, UK.; S. L. Bahna has received funding/grant support from Genentech.; L. A. Beck has received funding/grant support from the American Academy of Allergy, Asthma, and Immunology, the National Eczema Association, and the National Institutes of Health.; C. Byrd-Bredbenner owns stock in Johnson & Johnson. She has received funding/grant support from the US Department of Agriculture, the Canned Food Alliance, and the New Jersey Department of Health and Senior Services.; C. A. Camargo Jr has consulted for Dey and Novartis. He has received funding/grant support from a variety of government agencies and not-for-profit research foundations, as well as Dey and Novartis.; L. Eichenfield has received funding/grant support from a variety of not-for-profit foundations, as well as Astellas, Ferndale, Johnson & Johnson, Novartis, Sinclair, Stiefel, and Therapeutics Inc.; G. T. Furuta has served as a consultant and/or speaker to Ception Therapeutics and TAP. He has received funding/grant support from the American Gastrointestinal Association and the National Institutes of Health.; J. M. Hanifin has served as served as a consultant for ALZA, Anesiva, Inc, Barrier Therapeutics, Inc, Milliken & Company, Nordic Biotech, Novartis Pharmaceuticals Corporation, Shionogi USA, Taisho Pharmaceutical R&D, Inc, Teikoku Pharma USA, Inc, UCB, York Pharma, ZARS, Inc, and ZymoGenetics. He has served as an investigator or received research funding from ALZA, Astellas Pharma US, Inc, Asubio Pharmaceuticals, Inc, Centocor, Inc, Corgentech, Novartis, Nucryst Pharmaceuticals, Seattle Genetics, and Shionogi USA.; M. Kraft has served as a consultant and/or speaker for Astra-Zeneca, Genentech, GlaxoSmithKline, Merck, Novartis, and Sepracor. She has received funding/grant support from Genentech, GlaxoSmithKline, the National Institutes of Health and Novartis.; B. D. Levy holds, or is listed as an inventor on, US patent applications #20080064746 entitled "Lipoxins and aspirin-triggered lipoxins and their stable analogs in the treatment of asthma and inflammatory airway diseases" and #20080096961 entitled "Use of docosatrienes, resolvins and their stable analogs in the treatment of airway diseases and asthma." He owns stock in Resolvyx Pharmaceuticals. He has served as a consultant for Bayer Healthcare and Resolvyx Pharmaceuticals. Dr Levy has received funding/grant support from the National Institutes of Health.; P. Lieberman has served as a consultant and/or speaker to Dey Laboratories, Novartis, Schering-Plough, AstraZenica, Merck, TEVA, Pfizer, MEDA, Alcon, Genentech, Intelliject, and the Food Allergy and Anaphylaxis Network. He is past president of the American Academy of Allergy, Asthma, and Immunology.; L. C. Schneider has served as a consultant/clinical advisor for the Food Allergy Initiative. She has received funding/grant support from a variety of not-for-profit research foundations, as well as Novartis and the National Institutes of Health.; R. A. Simon has served as a speaker for Dey Laboratories, Genentech, GlaxoSmithKline, Merck, Novartis, and the US Food and Drug Administration.; F. E. R. Simons holds a patent on "Fast-disintegrating epinephrine tablets for sublingual administration." She is a past-president of the American Academy of Allergy, Asthma, and Immunology and of the Canadian Society of Allergy and Clinical Immunology. She is a member of the advisory boards of Dey, Intelliject, and ALK-Abello. She has received funding/grant support from AllerGen, the Canadian Allergy, Asthma and Immunology Foundation/Anaphylaxis Canada, and the Canadian Institutes of Health Research.; S. J. Teach has served as a speaker for AstraZeneca. He has received funding/grant support from the AstraZeneca Foundation, Aventis, the Child Health Center Board, the CNMC Research Advisory Council, the National Association of Chain Drug Stores Foundation, the National Institutes of Health (National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute), Novartis/Genentech, the Robert Woods Johnson Foundation, the US Centers for Disease Control and Prevention, the US Public Health Service, and the Washington, DC, Department of Health. NR 1 TC 399 Z9 409 U1 12 U2 36 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 EI 1097-6825 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD DEC PY 2010 VL 126 IS 6 BP 1105 EP 1118 DI 10.1016/j.jaci.2010.10.008 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 689RZ UT WOS:000284947800005 PM 21134568 ER PT J AU Melendez, SN Hanning, I Han, J Nayak, R Clement, AR Wooming, A Hererra, P Jones, FT Foley, SL Ricke, SC AF Melendez, S. N. Hanning, I. Han, J. Nayak, R. Clement, A. R. Wooming, A. Hererra, P. Jones, F. T. Foley, S. L. Ricke, S. C. TI Salmonella enterica isolates from pasture-raised poultry exhibit antimicrobial resistance and class I integrons SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE integron; pasture; poultry; resistance; Salmonella ID FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; ANTIBIOTIC-RESISTANCE; VIRULENCE PLASMIDS; ORGANIC CHICKENS; UNITED-STATES; SEROVAR HEIDELBERG; CAMPYLOBACTER SPP.; RETAIL STORES; ENTERITIDIS AB Aims: While considerable foodborne pathogen research has been conducted on conventionally produced broilers and turkeys, few studies have focused on free-range (organic) or pastured poultry. The current surveillance study was designed to isolate, identify and genetically characterize Salmonella from pastured poultry farm environment and from retail samples. Methods and Results: In this study, 59 isolates were collected from two pastured poultry farms (n = 164; pens, feed, water and insect traps) and retail carcasses (n = 36) from a local natural foods store and a local processing plant. All isolates were serotyped and analysed phenotypically (antimicrobial resistance profiles) and genotypically (DNA fingerprints, plasmid profiles and integron analysis). Salmonella enterica was detected using standard microbiological methods. Salmonella Kentucky was the most prevalent serotype detected from the sampled sources (53%), followed by Salmonella Enteritidis (24%), Bareilly (10%), Mbandaka (7%), Montevideo (5%) or Newport (2%). All isolates were resistant to sulfisoxazole and novobiocin, and the majority (40/59) possessed class I integrons shown by PCR detection. Each Salmonella serotype elicited a distinct pulsed-field gel electrophoresis fingerprint profile, and unique differences were observed among the serotypes. Conclusions: The findings of this study show that Salmonella serotypes isolated from pasture-raised poultry exhibit antimicrobial resistance and class I integrons. Significance and Impact of the Study: This study demonstrates that despite the cessation of antibiotic usage in poultry production, antibiotic resistant Salmonella may still be recovered from the environment and poultry products. C1 [Hanning, I.] Univ Arkansas, Dept Food Sci, Div Agr, Fayetteville, AR 72704 USA. [Han, J.; Nayak, R.; Foley, S. L.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, F. T.] Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. RP Hanning, I (reprint author), Univ Arkansas, Dept Food Sci, Div Agr, 2650 N Young Ave, Fayetteville, AR 72704 USA. EM ihanning@uark.edu FU USDA/CSREES NIFSI [406-2008 51110] FX This study was funded by the USDA/CSREES NIFSI grant no. 406-2008 51110. NR 60 TC 30 Z9 31 U1 1 U2 16 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 DEC PY 2010 VL 109 IS 6 BP 1957 EP 1966 DI 10.1111/j.1365-2672.2010.04825.x PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 679OI UT WOS:000284170300012 PM 20722876 ER PT J AU Sangal, V Harbottle, H Mazzoni, CJ Helmuth, R Guerra, B Didelot, X Paglietti, B Rabsch, W Brisse, S Weill, FX Roumagnac, P Achtman, M AF Sangal, Vartul Harbottle, Heather Mazzoni, Camila J. Helmuth, Reiner Guerra, Beatriz Didelot, Xavier Paglietti, Bianca Rabsch, Wolfgang Brisse, Sylvain Weill, Francois-Xavier Roumagnac, Philippe Achtman, Mark TI Evolution and Population Structure of Salmonella enterica Serovar Newport SO JOURNAL OF BACTERIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; HORIZONTAL GENE-TRANSFER; SEQUENCE TYPING DATA; AMPC BETA-LACTAMASE; MULTIDRUG-RESISTANT; SEROTYPE NEWPORT; SUBSPECIES-I; SPECTRUM CEPHALOSPORINS; STAPHYLOCOCCUS-AUREUS; PHYLOGENETIC NETWORKS AB Salmonellosis caused by Salmonella enterica serovar Newport is a major global public health concern, particularly because S. Newport isolates that are resistant to multiple drugs (MDR), including third-generation cephalosporins (MDR-AmpC phenotype), have been commonly isolated from food animals. We analyzed 384 S. Newport isolates from various sources by a multilocus sequence typing (MLST) scheme to study the evolution and population structure of the serovar. These were compared to the population structure of S. enterica serovars Enteritidis, Kentucky, Paratyphi B, and Typhimurium. Our S. Newport collection fell into three lineages, Newport-I, Newport-II, and Newport-III, each of which contained multiple sequence types (STs). Newport-I has only a few STs, unlike Newport-II or Newport-III, and has possibly emerged recently. Newport-I is more prevalent among humans in Europe than in North America, whereas Newport-II is preferentially associated with animals. Two STs of Newport-II encompassed all MDR-AmpC isolates, suggesting recent global spread after the acquisition of the bla(CMY-2) gene. In contrast, most Newport-III isolates were from humans in North America and were pansusceptible to antibiotics. Newport was intermediate in population structure to the other serovars, which varied from a single monophyletic lineage in S. Enteritidis or S. Typhimurium to four discrete lineages within S. Paratyphi B. Both mutation and homologous recombination are responsible for diversification within each of these lineages, but the relative frequencies differed with the lineage. We conclude that serovars of S. enterica provide a variety of different population structures. C1 [Mazzoni, Camila J.; Achtman, Mark] Natl Univ Ireland Univ Coll Cork, Environm Res Inst, Cork, Ireland. [Mazzoni, Camila J.; Achtman, Mark] Natl Univ Ireland Univ Coll Cork, Dept Microbiol, Cork, Ireland. [Sangal, Vartul; Mazzoni, Camila J.; Roumagnac, Philippe; Achtman, Mark] Max Planck Inst Infect Biol, Dept Mol Biol, D-10117 Berlin, Germany. [Sangal, Vartul] Univ Strathclyde, Strathclyde Inst Pharm & Biomed Sci, Glasgow G4 0RE, Lanark, Scotland. [Harbottle, Heather] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Helmuth, Reiner; Guerra, Beatriz] BfR Fed Inst Risk Assessment, Natl Salmonella Reference Lab, Berlin, Germany. [Didelot, Xavier] Univ Oxford, Dept Stat, Oxford OX1 3TG, England. [Paglietti, Bianca] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. [Rabsch, Wolfgang] Robert Koch Inst, Natl Reference Ctr Salmonellae & Other Enter, Wernigerode, Germany. [Weill, Francois-Xavier] Inst Pasteur, Unite Bacteries Pathogenes Enter, F-75724 Paris, France. [Roumagnac, Philippe] Ctr Cooperat Int Rech Agron Dev, UMR BGPI, F-34398 Montpellier 5, France. RP Achtman, M (reprint author), Natl Univ Ireland Univ Coll Cork, Environm Res Inst, Lee Rd, Cork, Ireland. EM m.achtman@ucc.ie RI Didelot, Xavier/H-1608-2013; Mazzoni, Camila/L-3441-2014; OI Didelot, Xavier/0000-0003-1885-500X; Sangal, Vartul/0000-0002-7405-8446; PAGLIETTI, Bianca/0000-0002-2568-0642; Weill, Francois-Xavier/0000-0001-9941-5799 FU Science Foundation of Ireland [05/FE1/B882]; National Institutes of Health [R01 GM084318-01A1]; Federal Institute for Risk Assessment [BfR-45-004]; Med-Ved-Net (European Union) FX This work was partly supported by grants 05/FE1/B882 (Science Foundation of Ireland), R01 GM084318-01A1 (National Institutes of Health), and BfR-45-004 (Federal Institute for Risk Assessment) and by the Med-Ved-Net (European Union-funded Network of Excellence for the Prevention and Control of Zoonoses). NR 67 TC 48 Z9 48 U1 2 U2 13 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 DEC PY 2010 VL 192 IS 24 BP 6465 EP 6476 DI 10.1128/JB.00969-10 PG 12 WC Microbiology SC Microbiology GA 686IQ UT WOS:000284690400018 PM 20935094 ER PT J AU Joseph, F AF Joseph, Francesca TI Pediatric Cardiovascular Device Registries-The Need for Such Data And The Potential Impact SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Editorial Material ID CARDIOLOGY C1 US FDA, Silver Spring, MD 20993 USA. RP Joseph, F (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM francesca.joseph@fda.hhs.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2010 VL 3 IS 6 SI SI BP 597 EP 599 DI 10.1007/s12265-010-9196-4 PG 3 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 687LK UT WOS:000284779800001 PM 20585915 ER PT J AU Patel-Raman, SM Chen, EA AF Patel-Raman, Sonna M. Chen, Eric A. TI Past, Present, and Future Regulatory Aspects of Ventricular Assist Devices SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH LA English DT Article DE Ventricular assist devices; Mechanical circulatory support; FDA; Regulatory ID HEART-TRANSPLANTATION; SUPPORT; NOVACOR; SYSTEM; THORATEC; BRIDGE AB The development of ventricular assist devices (VADs) for the treatment of heart failure has been ongoing since the National Heart Lung and Blood Institute (NHLBI) initiated the artificial heart program in 1964. The primary goal was to develop VADs and total artificial hearts for both temporary (short-term) and long-term use. Due to a small target population and the inability to blind patients and clinicians, the Food and Drug Administration (FDA) has recognized the challenges of conducting trials with these invasive devices. In an effort to address those challenges, FDA has accepted a variety of clinical trial designs to collect the data required to evaluate safety and effectiveness data in different patient groups. This article will provide a detailed discussion of the past, present, and future FDA regulatory considerations for VADs. C1 [Patel-Raman, Sonna M.; Chen, Eric A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Patel-Raman, SM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-1255, Silver Spring, MD 20993 USA. EM sonna.patel@fda.hhs.gov NR 8 TC 3 Z9 3 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1937-5387 J9 J CARDIOVASC TRANSL JI J. Cardiovasc. Transl. Res. PD DEC PY 2010 VL 3 IS 6 SI SI BP 600 EP 603 DI 10.1007/s12265-010-9225-3 PG 4 WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental SC Cardiovascular System & Cardiology; Research & Experimental Medicine GA 687LK UT WOS:000284779800002 PM 21046301 ER PT J AU Koutchma, T Song, Y Setikaite, I Juliano, P Barbosa-Canovas, GV Dunne, CP Patazca, E AF Koutchma, Tatiana Song, Yoonseok Setikaite, Ilona Juliano, Pablo Barbosa-Canovas, Gustavo V. Dunne, C. Patrick Patazca, Eduardo TI PACKAGING EVALUATION FOR HIGH-PRESSURE HIGH-TEMPERATURE STERILIZATION OF SHELF-STABLE FOODS SO JOURNAL OF FOOD PROCESS ENGINEERING LA English DT Article ID BARRIER AB The integrity of flexible packages during high-pressure (HP) sterilization is of critical importance to the safety and shelf life of food products. For HP-sterilization, packaged products need to be preheated to a target temperature before HP processing. Preheating efficiency can be affected by the packaging material utilized. The objectives were to quantify the impact of packaging materials on the rate of heat penetration into foods during preheating, and to evaluate the effects of preheating and HP processing (at 688 MPa and 121C) on package integrity, oxygen permeability and mechanical properties for commercially available packaging materials. Commercial scrambled egg patties were vacuum-sealed in pouches. Four plastic-laminated materials (nylon/coextruded ethylene-vinyl alcohol, nylon/polypropylene [PP], polyethylene terephthalate [PET]/aluminum oxide/casted PP [CPP] and PET/polyethylene) and two aluminum foil-laminated pouches (PET/aluminum [Al]/CPP and nylon/Al/PP) were tested. Selected packaging materials also were evaluated after thermal retort (TR) treatment and HP low temperature processing. The results demonstrated that foil-laminated materials provided shorter preheating time than thinner polymeric materials. HP treatment at high temperatures (HP-HT) increased seal strength of foil-laminated pouches. However, the HP-HT process did not significantly contribute to changes in seal strength of plastic-laminated pouches. It was found that the HP-HT process altered the oxygen barrier of the composite packaging materials. However, the increase in permeability observed during the HP-HT process was attributed to thermal damage occurring during preheating. TR processing increased oxygen permeability to a higher extent than HP-HT processing. It was concluded that the selected packaging materials could provide the required oxygen barrier for HP-HT treated shelf-stable foods. C1 [Koutchma, Tatiana; Setikaite, Ilona; Patazca, Eduardo] IIT, Summit Argo, IL 60501 USA. [Song, Yoonseok] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Setikaite, Ilona] Quaker Tropicana Gatorade PepsiCo, Barrington, IL USA. [Juliano, Pablo; Barbosa-Canovas, Gustavo V.] Washington State Univ, Dept Biol Syst Engn, Pullman, WA 99164 USA. [Juliano, Pablo] Food Sci Australia, Innovat Foods Ctr, Werribee, Vic 3030, Australia. [Dunne, C. Patrick] USA, Res Dev & Engn Command, Natick, MA 01760 USA. RP Koutchma, T (reprint author), Agr & Agri Food Canada, 93 Stone Rd W, Guelph, ON N1G 5C9, Canada. EM koutchmat@agr.gc.ca RI Juliano, Pablo/H-9251-2013 OI Juliano, Pablo/0000-0002-7425-8085 NR 19 TC 14 Z9 15 U1 4 U2 26 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-8876 J9 J FOOD PROCESS ENG JI J. Food Process Eng. PD DEC PY 2010 VL 33 IS 6 BP 1097 EP 1114 DI 10.1111/j.1745-4530.2008.00328.x PG 18 WC Engineering, Chemical; Food Science & Technology SC Engineering; Food Science & Technology GA 689XH UT WOS:000284963700008 ER PT J AU Fleischman, GJ Badvela, MK Rehkopf, A Stewart, CM AF Fleischman, Gregory J. Badvela, Mani K. Rehkopf, Andre Stewart, Cynthia M. TI Thermal Death Time Measurement Using Thin Flexible Sleeves: A New Experimental Approach for Determining Microbial Destruction Kinetics in Fluids of Arbitrary Viscosity SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The thermal death time kinetics of Salmonella Enteritidis (SE) was measured in buffer, egg yolk, and albumen using thin layer plastic sleeves. The sleeves allowed for the loading and sampling of liquids of high or unusual viscosity, as in the case of yolk and albumen, and accepted relatively large volumes (2 to 3 ml) of fluid. The sleeves maintained the volume of the fluid in a thin layer and could be easily handled for heat exposure. The thin layer maintained one-dimensional heat transfer and minimized temperature gradients, thus preventing parts of the fluid from experiencing different heating rates. A representative strain of SE associated with an egg-based salmonellosis outbreak was used in this study. The D- and z-values of the chosen strain, H7037, were measured in buffer, yolk, and albumen. In buffer, SE had the following mean (+/- standard deviation) D-values: D(55 degrees C) = 3.51 +/- 0.30 min, D(57 degrees C) = 1.75 +/- 0.13 min, and D(60 degrees C) = 0.25 +/- 0.06 min. In yolk, D(58 degrees C) = 0.90 +/- 0.05, D(60 degrees C) = 0.26 +/- 0.03, and D(62 degrees C) = 0.20 +/- 0.02. In albumen, D(55 degrees C) = 1.26 +/- 0.31, D(56 degrees C) = 0.68 +/- 0.10, and D(57 degrees C) = 0.44 +/- 0.04. The z-values for for SE calculated from these D-values were 4.29 +/- 0.39 degrees C in buffer, 6.12 +/- 0.26 degrees C in yolk, and 4.63 +/- 1.14 degrees C in albumen. The sleeves allowed one consistent approach to determining thermal death time kinetics regardless of viscosity. C1 [Fleischman, Gregory J.] US FDA, Summit Argo, IL 60501 USA. [Badvela, Mani K.; Rehkopf, Andre; Stewart, Cynthia M.] Natl Ctr Food Safety & Technol, IIT, Summit Argo, IL 60501 USA. RP Fleischman, GJ (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM gregory.fleischman@fda.hhs.gov FU U.S. Food and Drug Administration [FD-000431]; National Center for Food Safety and Technology [FD-000431] FX The authors gratefully acknowledge the efforts of Claudia Rodriguez in overseeing the microbiological aspects of this work. This paper was supported by Cooperative Agreement FD-000431 from the U.S. Food and Drug Administration and the National Center for Food Safety and Technology. NR 7 TC 1 Z9 1 U1 1 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD DEC PY 2010 VL 73 IS 12 BP 2301 EP 2305 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 692RJ UT WOS:000285172500023 PM 21219753 ER PT J AU Ohmann, EL Brooks, MM Webber, SA Girnita, DM Ferrell, RE Burckart, GJ Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, JK Naftel, DC Zeevi, A AF Ohmann, Erin L. Brooks, Maria M. Webber, Steven A. Girnita, Diana M. Ferrell, Robert E. Burckart, Gilbert J. Chinnock, Richard Canter, Charles Addonizio, Linda Bernstein, Daniel Kirklin, James K. Naftel, David C. Zeevi, Adriana TI Association of genetic polymorphisms and risk of Late post-transplantation infection in pediatric heart recipients SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Article DE pediatric heart transplant; bacteria infection; viral infection; genetic polymorphism ID GRANZYME-B; TRANSPLANT RECIPIENTS; INTERFERON-GAMMA; ACUTE REJECTION; OTITIS-MEDIA; FREQUENCY; GENOTYPE; CHILDREN; SUSCEPTIBILITY; ARTHRITIS AB BACKGROUND Late infections are common causes of morbidity and mortality after pediatric heart transplantation In this multicenter study from 6 centers we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients METHODS Late infection was defined as a clinical infectious process occuring >60 days after transplantation and requiring hospitalization intravenous antimicrobial therapy or a life-threatening infection requiring oral therapy All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor and effector molecule genes by single specific pnmer-polymerase chain reaction and/or sequencing Significant associations in univariable analyses were tested m multivariable Cox regression models RESULTS Late infection was common, with 48 7% of patients expenencing >= 1 late infection 25 2% had >= 1 late bacterial infection and 30 5% had >= 1 late viral infection Older age at transplantation was a protective factor for late infection, both bactenal and viral (hazard ratio [HR] 0 89-092 per 1 year age increase, p < 0 001) Adjusting for age, race and transplant etiology, late bactenal infection was associated with HMOX1 A + 326G AG and GG genotypes (HR 241 95% confidence interval [CI] 1 35-430 p = 0 003) and GZMB A-295G AA genotype (HR 1 47, 95% CI, 1 03-2 1, p = 0 036) Late viral mfection was associated with FAS A-670G GG genotype (FIR 1 42,95% CI, 1 00-2 00, p = 0 050) in the adjusted model and with CTL44 A+49G AA and AG genotypes (HR, 1 49 95% CI 1 02-2 19 p = 0 041) m umvariable analysis CONCLUSION We found an association between late bacterial infection and GP of HMOX1 which may control macrophage activation A weaker association was also found between late viral infection and GP of CTL44 a regulator of T-cell activation This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation J Heart Lung Transplant 2010 29 1342-51 (C) 2010 International Society for Heart and Lung Transplantation All rights reserved C1 [Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Div Transplant Pathol, Pittsburgh, PA 15261 USA. [Ohmann, Erin L.; Webber, Steven A.] Univ Pittsburgh, Dept Pediat, Div Cardiol, Pittsburgh, PA 15261 USA. [Brooks, Maria M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Burckart, Gilbert J.] US FDA, Off Translat Sci, Off Clin Pharmacol, Silver Spring, MD USA. [Chinnock, Richard] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Canter, Charles] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Pediat Cardiol, St Louis, MO 63110 USA. [Addonizio, Linda] Columbia Univ, Dept Pediat, Div Cardiol, New York Presbyterian Hosp, New York, NY 10027 USA. [Bernstein, Daniel] Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Cardiol, Palo Alto, CA 94304 USA. [Kirklin, James K.; Naftel, David C.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Zeevi, A (reprint author), Univ Pittsburgh, Dept Pathol, Div Transplant Pathol, W1551 Biomed Sci Tower, Pittsburgh, PA 15261 USA. OI Chinnock, Richard/0000-0002-9814-1762; Brooks, Maria/0000-0002-2030-7873 FU National Heart Lung and Blood Institute, National Institutes of Health [5P50 HL 074 732-05]; University of Pittsburgh School of Medicine; Dons Duke Clinical Research Fellowship FX This work was supported by grant 5P50 HL 074 732-05 from the National Heart Lung and Blood Institute, National Institutes of Health Erin L Ohmann is supported by funding from Dean Arthur S Levine, MD, and the Clinical Scientist Training Program at the University of Pittsburgh School of Medicine, and by the Dons Duke Clinical Research Fellowship program NR 35 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD DEC PY 2010 VL 29 IS 12 BP 1342 EP 1351 DI 10.1016/j.healun.2010.07.013 PG 10 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 693JP UT WOS:000285220700004 PM 20869265 ER PT J AU Zhang, HH Song, KM Rabin, RL Hill, BJ Perfetto, SP Roederer, M Douek, DC Siegel, RM Farber, JM AF Zhang, Hongwei H. Song, Kaimei Rabin, Ronald L. Hill, Brenna J. Perfetto, Stephen P. Roederer, Mario Douek, Daniel C. Siegel, Richard M. Farber, Joshua M. TI CCR2 Identifies a Stable Population of Human Effector Memory CD4(+) T Cells Equipped for Rapid Recall Response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; CYTOMEGALOVIRUS-SPECIFIC CD4(+); PRIMARY IMMUNE-RESPONSE; VIRUS TYPE-1 INFECTION; EPSTEIN-BARR-VIRUS; LYMPH-NODE; L-SELECTIN; PHENOTYPIC CHARACTERIZATION; DIFFERENTIAL REGULATION; INTERLEUKIN (IL)-2 AB Because T cells act primarily through short-distance interactions, homing receptors can identify colocalizing cells that serve common functions. Expression patterns for multiple chemokine receptors on CD4(+) T cells from human blood suggested a hierarchy of receptors that are induced and accumulate during effector/memory cell differentiation. We characterized CD4(+)CD45RO(+) T cells based on expression of two of these receptors, CCR5 and CCR2, the principal subsets being CCR5(-)CCR2(-) (similar to 70%), CCR5(+)CCR2(-) (similar to 25%), and CCR5(+)CCR2(+) (similar to 5%). Relationships among expression of CCR5 and CCR2 and CD62L, and the subsets' proliferation histories, suggested a pathway of progressive effector/memory differentiation from the CCR5(-)CCR2(-) to CCR5(+)CCR2(-) to CCR5(+)CCR2(+) cells. Sensitivity and rapidity of TCR-mediated activation, TCR signaling, and effector cytokine production by the subsets were consistent with such a pathway. The subsets also showed increasing responsiveness to IL-7, and the CCR5(+)CCR2(+) cells were CD127(bright) and invariably showed the greatest response to tetanus toxoid. CCR5(+)CCR2(+) cells also expressed the largest repertoire of chemokine receptors and migrated to the greatest number of chemokines. By contrast, the CCR5(+)CCR2(-) cells had the greatest percentages of regulatory T cells, activated/cycling cells, and CMV-reactive cells, and were most susceptible to apoptosis. Our results indicate that increasing memory cell differentiation can be uncoupled from susceptibility to death, and is associated with an increase in chemokine responsiveness, suggesting that vaccination (or infection) can produce a stable population of effector-capable memory cells that are highly enriched in the CCR5(+)CCR2(+) subset and ideally equipped for rapid recall responses in tissue. The Journal of Immunology, 2010, 185: 6646-6663. C1 [Siegel, Richard M.; Farber, Joshua M.] NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. [Zhang, Hongwei H.; Song, Kaimei; Farber, Joshua M.] NIAID, Inflammat Biol Sect, Lab Mol Immunol, Bethesda, MD 20892 USA. [Hill, Brenna J.; Douek, Daniel C.] NIAID, Human Immunol Sect, Bethesda, MD 20892 USA. [Perfetto, Stephen P.; Roederer, Mario] NIAID, Vaccine Res Ctr, ImmunoTechnol Sect, Bethesda, MD 20892 USA. [Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), NIAMSD, Autoimmun Branch, NIH, Bldg 10,Room 11N-112,10 Ctr Dr, Bethesda, MD 20892 USA. EM jfarber@niaid.nih.gov OI Siegel, Richard/0000-0001-5953-9893 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This work was supported by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health. NR 80 TC 17 Z9 19 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 1 PY 2010 VL 185 IS 11 BP 6646 EP 6663 DI 10.4049/jimmunol.0904156 PG 18 WC Immunology SC Immunology GA 681KJ UT WOS:000284311500030 PM 20980630 ER PT J AU Marcelin, G Bland, HM Negovetich, NJ Sandbulte, MR Ellebedy, AH Webb, AD Griffin, YS DeBeauchamp, JL McElhaney, JE Webby, RJ AF Marcelin, Glendie Bland, Hilliary M. Negovetich, Nicholas J. Sandbulte, Matthew R. Ellebedy, Ali H. Webb, Ashley D. Griffin, Yolanda S. DeBeauchamp, Jennifer L. McElhaney, Janet E. Webby, Richard J. TI Inactivated Seasonal Influenza Vaccines Increase Serum Antibodies to the Neuraminidase of Pandemic Influenza A(H1N1) 2009 Virus in an Age-Dependent Manner SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID H1N1; ASSOCIATION; PROTECTION; INFECTION; MICE AB Levels of preexisting antibodies to the hemagglutinin of pandemic influenza A(H1N1) 2009 (hereafter pandemic H1N1) virus positively correlate with age. The impact of contemporary seasonal influenza vaccines on establishing immunity to other pandemic H1N1 proteins is unknown. We measured serum antibodies to the neuraminidase (NA) of pandemic H1N1 in adults prior to and after vaccination with seasonal trivalent inactivated influenza vaccines. Serum antibodies to pandemic H1N1 NA were observed in all age groups; however, vaccination elevated levels of pandemic H1N1 NA antibodies predominately in elderly individuals (age, >= 60 years). Therefore, contemporary seasonal vaccines likely contribute to reduction of pandemic H1N1-associated disease in older individuals. C1 [Marcelin, Glendie; Bland, Hilliary M.; Negovetich, Nicholas J.; Ellebedy, Ali H.; Webb, Ashley D.; Griffin, Yolanda S.; DeBeauchamp, Jennifer L.; Webby, Richard J.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Sandbulte, Matthew R.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [McElhaney, Janet E.] Univ Connecticut, Sch Med, Dept Immunol, Farmington, CT USA. [McElhaney, Janet E.] Univ British Columbia, Dept Med, Vancouver, BC, Canada. RP Webby, RJ (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 262 Danny Thomas Pl,Mail Stop 330, Memphis, TN 38105 USA. EM richard.webby@stjude.org FU National Institute of Allergy and Infectious Diseases [HHSN266200700005C, R01 AI68265]; Canadian Institutes of Health Research; American Lebanese Syrian Associated Charities; GlaxoSmithKline; University of Connecticut Health Center; Vancouver Coastal Health Research Institute FX Financial support: National Institute of Allergy and Infectious Diseases (contract HHSN266200700005C and grant R01 AI68265); Canadian Institutes of Health Research; American Lebanese Syrian Associated Charities; GlaxoSmithKline (investigator-initiated contract to J.E.M.).; We acknowledge Adrianus C. M. Boon for editorial assistance and the research teams supporting the influenza projects at the University of Connecticut Health Center and Vancouver Coastal Health Research Institute. We thank the World Health Oranization Global Influenza Surveillance Network for providing the H1N1 viruses. NR 15 TC 29 Z9 29 U1 0 U2 1 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 DEC 1 PY 2010 VL 202 IS 11 BP 1634 EP 1638 DI 10.1086/657084 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 675BU UT WOS:000283799900004 PM 20979454 ER PT J AU Dair, BJ Saylor, DM Cargal, TE French, GR Kennedy, KM Casas, RS Guyer, JE Warren, JA Kim, CS Pollack, SK AF Dair, Benita J. Saylor, David M. Cargal, T. Eric French, Grace R. Kennedy, Kristen M. Casas, Rachel S. Guyer, Jonathan E. Warren, James A. Kim, Chang-Soo Pollack, Steven K. TI The Effect of Substrate Material on Silver Nanoparticle Antimicrobial Efficacy SO JOURNAL OF NANOSCIENCE AND NANOTECHNOLOGY LA English DT Article DE Nanoparticle; Antimicrobial; Medical Device; Coating; Polymer ID ION AB With the advent of nanotechnology, silver nanoparticles increasingly are being used in coatings, especially in medical device applications, to capitalize on their antimicrobial properties. The attractiveness of nanoparticulate silver systems is the expected increased antimicrobial efficacy relative to their bulk counterparts, which may be attributed to an increased silver ion (Ag(+)) solubility, and hence availability, that arises from capillarity effects in small, nanometer-sized particles. However, a change of the material upon which the antimicrobial nanoparticulate silver is deposited (herein called "substrate") may affect the availability of Ag+ ions and the intended efficacy of the device. We utilize both theory and experiment to determine the effect of substrate on ion release from silver particles in electrochemical environments and find that substrate surface charge, chemical reactivity or affinity of the surface for Ag+ ions, and wettability of the surface all affect availability of Ag+ ions, and hence antimicrobial efficacy. It is also observed that with time of exposure to deionized water, Ag+ ion release increases to a maximum value at 5 min before decreasing to undetectable levels, which is attributed to coarsening of the nanoparticles, and which subsequently reduces the solubility and availability of Ag+ ions. This coarsening phenomenon is also predicted by the theoretical considerations and has been confirmed experimentally by transmission electron microscopy. C1 [Dair, Benita J.; Saylor, David M.; Cargal, T. Eric; French, Grace R.; Kennedy, Kristen M.; Casas, Rachel S.; Kim, Chang-Soo; Pollack, Steven K.] FDA Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, Silver Spring, MD 20993 USA. [Guyer, Jonathan E.; Warren, James A.] NIST, Mat Sci & Engn Labs, Div Met, Gaithersburg, MD 20899 USA. RP Dair, BJ (reprint author), FDA Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Chem & Mat Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. RI Warren, James/B-1698-2008; Guyer, Jonathan/M-5165-2016; OI Warren, James/0000-0001-6887-1206; Guyer, Jonathan/0000-0002-1407-6589; Casas, Rachel/0000-0003-2848-3107 NR 15 TC 12 Z9 13 U1 1 U2 12 PU AMER SCIENTIFIC PUBLISHERS PI STEVENSON RANCH PA 25650 NORTH LEWIS WAY, STEVENSON RANCH, CA 91381-1439 USA SN 1533-4880 J9 J NANOSCI NANOTECHNO JI J. Nanosci. Nanotechnol. PD DEC PY 2010 VL 10 IS 12 BP 8456 EP 8462 DI 10.1166/jnn.2010.3566 PG 7 WC Chemistry, Multidisciplinary; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 672XQ UT WOS:000283621400080 PM 21121354 ER PT J AU Stumbo, PJ Weiss, R Newman, JW Pennington, JA Tucker, KL Wiesenfeld, PL Illner, AK Klurfeld, DM Kaput, J AF Stumbo, Phyllis J. Weiss, Rick Newman, John W. Pennington, Jean A. Tucker, Katherine L. Wiesenfeld, Paddy L. Illner, Anne-Kathrin Klurfeld, David M. Kaput, Jim TI Web-Enabled and Improved Software Tools and Data Are Needed to Measure Nutrient Intakes and Physical Activity for Personalized Health Research SO JOURNAL OF NUTRITION LA English DT Article ID HEART-RATE-VARIABILITY; FOOD FREQUENCY QUESTIONNAIRE; DIETARY ASSESSMENT; HUMAN METABOLOME; SYSTEMS BIOLOGY; HIGH-THROUGHPUT; FATTY-ACIDS; IDENTIFICATION; NUTRIGENOMICS; CHALLENGES AB Food intake physical activity (PA) and genetic makeup each affect health and each factor influences the impact of the other 2 factors Nutrigenomics describes interactions between genes and environment Knowledge about the interplay between environment and genetics would be improved if experimental designs included measures of nutrient intake and PA Lack of familiarity about how to analyze environmental variables and ease of access to tools and measurement instruments are 2 deterrents to these combined studies This article describes the state of the art for measuring food intake and PA to encourage researchers to make their tools better known and more available to workers in other fields Information presented was discussed during a workshop on this topic sponsored by the USDA NIH and FDA in the spring of 2009 J Nutr 140 2104-2115 2010 C1 [Stumbo, Phyllis J.] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA 52242 USA. [Weiss, Rick] Viocare Inc, Princeton, NJ 08542 USA. [Newman, John W.] ARS, USDA, Western Human Nutr Res Ctr, Davis, CA 95616 USA. [Pennington, Jean A.] NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. [Tucker, Katherine L.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA. [Wiesenfeld, Paddy L.] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Illner, Anne-Kathrin] German Inst Human Nutr, Dept Epidemiol, D-14558 Potsdam, Nuthetal, Germany. [Klurfeld, David M.] USDA ARS, Beltsville, MD 20705 USA. [Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Stumbo, PJ (reprint author), Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA 52242 USA. RI Tucker, Katherine/A-4545-2010; OI Tucker, Katherine/0000-0001-7640-662X FU FDA/National Center for Toxicological Research/Division of Personalized Nutrition and Medicine NIH; USDA FX Supported by FDA/National Center for Toxicological Research/Division of Personalized Nutrition and Medicine NIH and USDA NR 91 TC 16 Z9 16 U1 1 U2 4 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD DEC PY 2010 VL 140 IS 12 BP 2104 EP 2115 DI 10.3945/jn.110.128371 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 692AG UT WOS:000285123300001 PM 20980656 ER PT J AU Wang, C Daniels, MJ Scharfstein, DO Land, S AF Wang, C. Daniels, M. J. Scharfstein, D. O. Land, S. TI A Bayesian Shrinkage Model for Incomplete Longitudinal Binary Data With Application to the Breast Cancer Prevention Trial SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Informative drop-out; Intermittent missingness; Prior elicitation ID PATTERN-MIXTURE-MODELS; SEMIPARAMETRIC NONRESPONSE MODELS; LOGISTIC-REGRESSION MODELS; INFORMATIVE DROP-OUT; MISSING DATA; REPEATED OUTCOMES; SELECTION BIAS; NONIGNORABLE NONRESPONSE; SENSITIVITY-ANALYSIS; RESPONSE DATA AB We consider inference in randomized longitudinal studies with missing data that is generated by skipped clinic visits and loss to followup. In this setting, it is well known that full data estimands are not identified unless unverified assumptions are imposed. We assume a non-future dependence model for the drop-out mechanism and partial ignorability for the intermittent missingness. We posit an exponential tilt model that links nonidentifiable distributions and distributions identified under partial ignorability. This exponential tilt model is indexed by nonidentified parameters, which are assumed to have an informative prior distribution, elicited from subject-matter experts. Under this model, full data estimands are shown to be expressed as functionals of the distribution of the observed data. To avoid the curse of dimensionality, we model the distribution of the observed data using a Bayesian shrinkage model. In a simulation study, we compare our approach to a fully parametric and a fully saturated model for the distribution of the observed data. Our methodology is motivated by, and applied to, data from the Breast Cancer Prevention Trial. C1 [Wang, C.; Daniels, M. J.] Univ Florida, Dept Stat, Gainesville, FL 32611 USA. [Wang, C.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Scharfstein, D. O.] Johns Hopkins Univ, Dept Biostat, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Land, S.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15213 USA. RP Wang, C (reprint author), Univ Florida, Dept Stat, Gainesville, FL 32611 USA. EM mdaniels@stat.ufl.edu FU NIH [R01-CA85295, U10-CA37377, U10-CA69974, R01 AI078835, P30MH086043, R01HL79457] FX C. Wang was Ph.D. Student, Department of Statistics, University of Florida, Gainesville, FL 32611, and is Mathematical Statistician, Division of Biostatistics, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD 20993. M. J. Daniels is Professor and Chair, Department of Statistics, University of Florida, Gainesville, FL 32611 (E-mail: mdaniels@stat.ufl.edu). D. O. Scharfstein is Professor, Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205. S. Land is Research Associate Professor, Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA 15213. This research was supported by NIH grants R01-CA85295, U10-CA37377, U10-CA69974, R01 AI078835, P30MH086043, and R01HL79457. The authors are grateful to oncologist Patricia Ganz at UCLA for providing her expertise for the MNAR analysis. NR 66 TC 9 Z9 9 U1 0 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2010 VL 105 IS 492 BP 1333 EP 1346 DI 10.1198/jasa.2010.ap09321 PG 14 WC Statistics & Probability SC Mathematics GA 710VU UT WOS:000286545900005 PM 21516191 ER PT J AU Zuurbier, L Homminga, I Calvert, V Winkel, MLT Buijs-Gladdines, JGCAM Kooi, C Smits, WK Sonneveld, E Veerman, AJP Kamps, WA Horstmann, M Petricoin, EF Pieters, R Meijerink, JPP AF Zuurbier, L. Homminga, I. Calvert, V. Winkel, M. L. Te Buijs-Gladdines, J. G. C. A. M. Kooi, C. Smits, W. K. Sonneveld, E. Veerman, A. J. P. Kamps, W. A. Horstmann, M. Petricoin, E. F., III Pieters, R. Meijerink, J. P. P. TI NOTCH1 and/or FBXW7 mutations predict for initial good prednisone response but not for improved outcome in pediatric T-cell acute lymphoblastic leukemia patients treated on DCOG or COALL protocols SO LEUKEMIA LA English DT Article DE pediatric T-ALL; NOTCH1; FBXW7; TLX3; prednisone response; outcome AB Aberrant activation of the NOTCH1 pathway by inactivating and activating mutations in NOTCH1 or FBXW7 is a frequent phenomenon in T-cell acute lymphoblastic leukemia (T-ALL). We retrospectively investigated the relevance of NOTCH1/FBXW7 mutations for pediatric T-ALL patients enrolled on Dutch Childhood Oncology Group (DCOG) ALL7/8 or ALL9 or the German Co-Operative Study Group for Childhood Acute Lymphoblastic Leukemia study (COALL-97) protocols. NOTCH1-activating mutations were identified in 63% of patients. NOTCH1 mutations affected the heterodimerization, the juxtamembrane and/or the PEST domains, but not the RBP-J-kappa-associated module, the ankyrin repeats or the transactivation domain. Reverse-phase protein microarray data confirmed that NOTCH1 and FBXW7 mutations resulted in increased intracellular NOTCH1 levels in primary T-ALL biopsies. Based on microarray expression analysis, NOTCH1/FBXW7 mutations were associated with activation of NOTCH1 direct target genes including HES1, DTX1, NOTCH3, PTCRA but not cMYC. NOTCH1/FBXW7 mutations were associated with TLX3 rearrangements, but were less frequently identified in TAL1- or LMO2-rearranged cases. NOTCH1-activating mutations were less frequently associated with mature T-cell developmental stage. Mutations were associated with a good initial in vivo prednisone response, but were not associated with a superior outcome in the DCOG and COALL cohorts. Comparing our data with other studies, we conclude that the prognostic significance for NOTCH1/FBXW7 mutations is not consistent and may depend on the treatment protocol given. Leukemia (2010) 24, 2014-2022; doi:10.1038/leu.2010.204; published online 23 September 2010 C1 [Meijerink, J. P. P.] Erasmus Univ, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Med Ctr,ZH, NL-3015 GJ Rotterdam, Netherlands. [Calvert, V.; Petricoin, E. F., III] George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. [Sonneveld, E.; Veerman, A. J. P.; Kamps, W. A.] Dutch Childhood Oncol Grp, The Hague, Netherlands. [Kamps, W. A.] Univ Groningen, Univ Med Ctr Groningen, Beatrix Childrens Hosp, Dept Pediat Oncol, Groningen, Netherlands. [Horstmann, M.] German Cooperat Study Grp Childhood Acute Lymphob, Hamburg, Germany. [Horstmann, M.] Univ Med Ctr Hamburg Eppendorf, Res Inst Childrens Canc Ctr Hamburg, Clin Pediat Hematol & Oncol, Hamburg, Germany. [Petricoin, E. F., III] NCI, FDA Clin Prote Program, US FDA, Bethesda, MD USA. RP Meijerink, JPP (reprint author), Erasmus Univ, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Med Ctr,ZH, Room Sp2456,Dr Molewaterpl 60, NL-3015 GJ Rotterdam, Netherlands. EM j.meijerink@erasmusmc.nl RI Meijerink, Jules/D-4393-2017 OI Meijerink, Jules/0000-0002-6860-798X FU Stichting Kinderen Kankervrij (KiKa) [KiKa 2007-012, KiKa 2008-029]; Dutch Cancer Society Dutch Cancer Society (KWF-EMCR) [2006-3500]; German Jose Carreras Leukemia Foundation [SP 04/03] FX LZ and WKS were financed by the Stichting Kinderen Kankervrij (KiKa; Grant no. KiKa 2007-012). IH was financed by the Dutch Cancer Society Dutch Cancer Society (KWF-EMCR 2006-3500) CK was financed by KiKa (Grant no. KiKa 2008-029). We thank the German Jose Carreras Leukemia Foundation (Grant no. SP 04/03 to MH). NR 44 TC 64 Z9 66 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 EI 1476-5551 J9 LEUKEMIA JI Leukemia PD DEC PY 2010 VL 24 IS 12 BP 2014 EP 2022 DI 10.1038/leu.2010.204 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 695OF UT WOS:000285380900005 PM 20861909 ER PT J AU Park, S Jennings, R Liu, HM Badano, A Myers, K AF Park, Subok Jennings, Robert Liu, Haimo Badano, Aldo Myers, Kyle TI A statistical, task-based evaluation method for three-dimensional x-ray breast imaging systems using variable-background phantoms SO MEDICAL PHYSICS LA English DT Article ID POWER-LAW NOISE; CONE-BEAM CT; DIGITAL TOMOSYNTHESIS; COMPUTER-SIMULATION; SIGNAL-DETECTION; MONTE-CARLO; MODEL; OBSERVER; OPTIMIZATION; MAMMOGRAPHY AB Purpose: For the last few years, development and optimization of three-dimensional (3D) x-ray breast imaging systems, such as digital breast tomosynthesis (DBT) and computed tomography, have drawn much attention from the medical imaging community, either academia or industry. However, there is still much room for understanding how to best optimize and evaluate the devices over a large space of many different system parameters and geometries. Current evaluation methods, which work well for 2D systems, do not incorporate the depth information from the 3D imaging systems. Therefore, it is critical to develop a statistically sound evaluation method to investigate the usefulness of inclusion of depth and background-variability information into the assessment and optimization of the 3D systems. Methods: In this paper, we present a mathematical framework for a statistical assessment of planar and 3D x-ray breast imaging systems. Our method is based on statistical decision theory, in particular, making use of the ideal linear observer called the Hotelling observer. We also present a physical phantom that consists of spheres of different sizes and materials for producing an ensemble of randomly varying backgrounds to be imaged for a given patient class. Lastly, we demonstrate our evaluation method in comparing laboratory mammography and three-angle DBT systems for signal detection tasks using the phantom's projection data. We compare the variable phantom case to that of a phantom of the same dimensions filled with water, which we call the uniform phantom, based on the performance of the Hotelling observer as a function of signal size and intensity. Results: Detectability trends calculated using the variable and uniform phantom methods are different from each other for both mammography and DBT systems. Conclusions: Our results indicate that measuring the system's detection performance with consideration of background variability may lead to differences in system performance estimates and comparisons. For the assessment of 3D systems, to accurately determine trade offs between image quality and radiation dose, it is critical to incorporate randomness arising from the imaging chain including background variability into system performance calculations. (C) 2010 American Association of Physicists in Medicine. [DOI: 10.1118/1.3488910] C1 [Park, Subok; Jennings, Robert; Badano, Aldo; Myers, Kyle] OSEL CDRH FDA, Div Imaging Appl Math, Silver Spring, MD 20993 USA. [Liu, Haimo] Univ Maryland, College Pk, MD 20742 USA. RP Park, S (reprint author), OSEL CDRH FDA, Div Imaging Appl Math, Silver Spring, MD 20993 USA. EM subok.park@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health FX The authors would like to thank Robert Leimbach and Hugo de las Heras, respectively, for initial and additional phantom measurements, Rongping Zeng for her help on implementing analytical x-ray projections of the 3D spheres, and Iacovos Kyprianou for his support on the use of the cone beam laboratory. This work was supported in part by the National Institute of Biomedical Imaging and Bioengineering at the National Institutes of Health through an intramural grant to the Center for Devices and Radiological Health, FDA, as well as the FDA's Office of Women's Health. NR 48 TC 29 Z9 29 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 DEC PY 2010 VL 37 IS 12 BP 6253 EP 6270 DI 10.1118/1.3488910 PG 18 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 701UR UT WOS:000285849400016 PM 21302782 ER PT J AU Sun, JC Schnackenberg, LK Pence, L Bhattacharyya, S Doerge, DR Bowyer, JF Beger, RD AF Sun, Jinchun Schnackenberg, Laura K. Pence, Lisa Bhattacharyya, Sudeepa Doerge, Daniel R. Bowyer, John F. Beger, Richard D. TI Metabolomic analysis of urine from rats chronically dosed with acrylamide using NMR and LC/MS SO METABOLOMICS LA English DT Article DE Metabolomics; Acrylamide; Pattern Recognition; Energy Metabolism; Glutathione Biosynthesis ID DNA ADDUCT FORMATION; FISCHER-344 RATS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; DRINKING-WATER; GLYCIDAMIDE; TOXICITY; MICE; GENOTOXICITY; TOXICOKINETICS; SPECTROSCOPY AB Acrylamide (AA) is known to cause neurotoxicity, genotoxicity, reproductive, and carcinogenic effects in rodents and neurotoxicity in humans. A metabolomics study of urine samples from rats dosed with acrylamide for 14 days was undertaken to understand the mechanisms of and develop biomarkers for acrylamide-induced toxicity. NMR-based and LC/MS-based metabolomics methods were used to analyze metabolites in urine samples. Three mercapturic acid conjugates of acrylamide were detected using exact mass and principal component analysis (PCA) of urine samples. NMR analysis showed an increase in creatine and a decrease in taurine throughout the dosing period. Results showed that citric acid cycle metabolites were down-regulated later in the dosing period. Further, many amino acids were also up-regulated during the study and may be related to the weight loss observed in this study. Taken together, the data suggest that both LC/MS-based and NMR-based metabolomics analysis can detect changes in endogenous metabolites related to glutathione, TCA cycle, and amino acid metabolism induced by AA administration over a 2 week dosing period. C1 [Sun, Jinchun; Schnackenberg, Laura K.; Pence, Lisa; Bhattacharyya, Sudeepa; Beger, Richard D.] US FDA, Ctr Metabol, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Bowyer, John F.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Ctr Metabol, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 43 TC 6 Z9 8 U1 1 U2 27 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD DEC PY 2010 VL 6 IS 4 BP 550 EP 563 DI 10.1007/s11306-010-0225-8 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 676UO UT WOS:000283944300009 ER PT J AU Valentine, CR Delongchamp, RR Pearce, MG Rainey, HF Dobrovolsky, VN Malling, HV Heflich, RH AF Valentine, Carrie R. Delongchamp, Robert R. Pearce, Mason G. Rainey, Heather F. Dobrovolsky, Vasily N. Malling, Heinrich V. Heflich, Robert H. TI In vivo mutation analysis using the Phi X174 transgenic mouse and comparisons with other transgenes and endogenous genes SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE Transgenic mice; Somatic cell mutation; Germ cell mutation; Mutation frequency; Single-burst analysis ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; MISMATCH REPAIR DEFICIENCY; ENU-INDUCED MUTATION; BIG BLUE(R) MICE; ESCHERICHIA-COLI; SPLENIC LYMPHOCYTES; MUTANT FREQUENCIES; MAMMALIAN-CELLS; NUCLEOTIDE-SEQUENCE; INDUCED MUTAGENESIS AB The Phi X174 transgenic mouse was first developed as an in vivo Ames test, detecting base pair substitution (bps) at a single bp in a reversion assay. A forward mutational assay was also developed, which is a gain of function assay that also detects bps exclusively. Later work with both assays focused on establishing that a mutation was fixed in vivo using single-burst analysis: determining the number of mutant progeny virus from an electroporated cell by dividing the culture into aliquots before scoring mutants. We review results obtained from single-burst analysis, including testing the hypothesis that high mutant frequencies (MFs) of G:C to A:T mutation recovered by transgenic targets include significant numbers of unrepaired G:T mismatches. Comparison between the Phi X174 and lad transgenes in mouse spleen indicates that the spontaneous bps mutation frequency per nucleotide (mf(n)) is not significantly lower for Phi X174 than for lacl; the response to ENU is also comparable. For the lad transgene, the spontaneous bps mf(n) is highly age-dependent up to 12 weeks of age and the linear trend extrapolates at conception to a frequency close to the human bps mf(n) per generation of 1.7 x 10(-8). Unexpectedly, we found that the lad somatic (spleen) bps mf(n) per cell division at early ages was estimated to be the same as for the human germ-line. The bps mf(n) in bone marrow for the gpt transgene is comparable to spleen for the lad and Phi X174 transgenes. We conclude that the G:C to A:T transition is characteristic of spontaneous in vivo mutation and that the MFs measured in these transgenes at early ages reflect the expected accumulation of in vivo mutation typical of endogenous mammalian mutation rates. However, spontaneous and induced mf(n)s per nucleotide for the cif gene in spleen are 5-10 times higher than for these other transgenes. Published by Elsevier B.V. C1 [Valentine, Carrie R.; Pearce, Mason G.; Rainey, Heather F.; Dobrovolsky, Vasily N.; Heflich, Robert H.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Dept Epidemiol, Coll Publ Hlth, Little Rock, AR 72205 USA. [Malling, Heinrich V.] NIEHS, Mammalian Mutagenesis Grp, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Heflich, RH (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov NR 87 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD DEC PY 2010 VL 705 IS 3 BP 205 EP 216 DI 10.1016/j.mrrev.2010.07.001 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 701HF UT WOS:000285808300006 PM 20637298 ER PT J AU Cote, TR Xu, K Pariser, AR AF Cote, Timothy R. Xu, Kui Pariser, Anne R. TI Accelerating orphan drug development SO NATURE REVIEWS DRUG DISCOVERY LA English DT Editorial Material C1 [Cote, Timothy R.; Xu, Kui] US FDA, Off Commissioner, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. [Pariser, Anne R.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD 20993 USA. RP Cote, TR (reprint author), US FDA, Off Commissioner, Off Orphan Prod Dev, Silver Spring, MD 20993 USA. EM timothy.cote@fda.hhs.gov NR 6 TC 19 Z9 19 U1 0 U2 12 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 DEC PY 2010 VL 9 IS 12 BP 901 EP 902 DI 10.1038/nrd3340 PG 2 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 688SE UT WOS:000284871900001 PM 21119719 ER PT J AU Banoo, S Bell, D Bossuyt, P Herring, A Mabey, D Poole, F Smith, PG Sriram, N Wongsrichanalai, C Linke, R O'Brien, R Perkins, M Cunningham, J Matsoso, P Nathanson, CM Olliaro, P Peeling, RW Ramsay, A AF Banoo, Shabir Bell, David Bossuyt, Patrick Herring, Alan Mabey, David Poole, Freddie Smith, Peter G. Sriram, N. Wongsrichanalai, Chansuda Linke, Ralf O'Brien, Rick Perkins, Mark Cunningham, Jane Matsoso, Precious Nathanson, Carl Michael Olliaro, Piero Peeling, Rosanna W. Ramsay, Andy CA TDR Diagnostics Evaluation Expert TI Evaluation of diagnostic tests for infectious diseases: general principles SO NATURE REVIEWS MICROBIOLOGY LA English DT Article ID ACCURACY; MEDICINE C1 [Banoo, Shabir] Med Control Council S Africa, Pretoria, South Africa. [Bell, David] WHO, Reg Off Western Pacific, Manila, Philippines. [Bossuyt, Patrick] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands. [Herring, Alan] Univ Bristol, Sch Vet, Bristol, Avon, England. [Mabey, David] London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England. [Poole, Freddie] US FDA, Div Microbiol Devices, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Smith, Peter G.] London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, London WC1, England. [Sriram, N.] Tulip Grp Co, Goa, India. [Wongsrichanalai, Chansuda] US Naval Med Res Unit 2, Jakarta, Indonesia. [Linke, Ralf; O'Brien, Rick; Perkins, Mark] Fdn Innovat Diagnost FIND, Geneva, Switzerland. [Cunningham, Jane; Matsoso, Precious; Nathanson, Carl Michael; Olliaro, Piero; Peeling, Rosanna W.; Ramsay, Andy] WHO, UNICEF UNDP World Bank WHO Special Programme Res, CH-1211 Geneva, Switzerland. RP Banoo, S (reprint author), Med Control Council S Africa, Pretoria, South Africa. EM peelingr@who.int RI Bossuyt, Patrick/B-4557-2016 OI Bossuyt, Patrick/0000-0003-4427-0128 NR 16 TC 34 Z9 34 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD DEC PY 2010 SU S BP S17 EP S27 DI 10.1038/nrmicro1523 PG 11 WC Microbiology SC Microbiology GA 687BM UT WOS:000284748800004 ER PT J AU Cohen, MH Johnson, JR Chattopadhyay, S Tang, SH Justice, R Sridhara, R Pazdur, R AF Cohen, Martin H. Johnson, John R. Chattopadhyay, Somesh Tang, Shenghui Justice, Robert Sridhara, Rajeshwari Pazdur, Richard TI Approval Summary: Erlotinib Maintenance Therapy of Advanced/Metastatic Non-Small Cell Lung Cancer (NSCLC) SO ONCOLOGIST LA English DT Article DE Erlotinib; Non-small cell lung cancer; Maintenance treatment ID III RANDOMIZED-TRIAL; PHASE-III; THYMIDYLATE SYNTHASE; PLUS CARBOPLATIN; 1ST-LINE TREATMENT; BEVACIZUMAB; PACLITAXEL; GEMCITABINE AB On April 16, 2010, the U. S. Food and Drug Administration (FDA) approved erlotinib tablets (Tarceva (R); OSI Pharmaceuticals, Inc., Melville, NY) for maintenance treatment of patients with stage IIIB/IV non-small cell lung cancer (NSCLC) whose disease had not progressed after four cycles of platinum-based first-line chemotherapy. In total, 889 patients received either erlotinib (150 mg) or placebo once daily. Progression-free survival (PFS), in all patients and in patients with epidermal growth factor receptor (EGFR)(+) tumors by immuno-histochemistry (IHC), was the primary efficacy endpoint. Overall survival (OS) was a secondary sponsor endpoint but was the primary regulatory endpoint. Median PFS times were 2.8 months and 2.6 months in the erlotinib and placebo arms, respectively (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.62-0.82; p < .001). Median OS times were 12.0 months and 11.0 months, favoring erlotinib (HR, 0.81; 95% CI, 0.70-0.95). The PFS and OS HRs in patients with EGFR(+) tumors by IHC were 0.69 (95% CI, 0.58-0.82) and 0.77 (95% CI, 0.64-0.93), respectively. The PFS and OS HRs in patients with EGFR(-) tumors by IHC were 0.77 (95% CI, 0.51-1.14) and 0.91 (95% CI, 0.59-1.38), respectively. Following disease progression, 57% of placebo-treated patients received additional chemotherapy, compared with 47% of erlotinib-treated patients. Fourteen percent of placebo-treated patients received erlotinib or gefitinib, 31% received docetaxel, and 14% received pemetrexed. In total, 59% of placebo-treated patients who received treatment received FDA approved second-line NSCLC drugs. The most common adverse reactions in patients receiving erlotinib were rash and diarrhea. The Oncologist 2010;15:1344-1351 C1 [Cohen, Martin H.; Johnson, John R.; Chattopadhyay, Somesh; Tang, Shenghui; Justice, Robert; Sridhara, Rajeshwari; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov FU AstraZeneca; Lilly; Pfizer; ImClone FX Reviewer "A" discloses research funding from AstraZeneca, Lilly, Pfizer, and ImClone. NR 21 TC 32 Z9 32 U1 1 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD DEC PY 2010 VL 15 IS 12 BP 1344 EP 1351 DI 10.1634/theoncologist.2010-0257 PG 8 WC Oncology SC Oncology GA 699SK UT WOS:000285682900013 PM 21148614 ER PT J AU Cohen, MH Cortazar, P Justice, R Pazdur, R AF Cohen, Martin H. Cortazar, Patricia Justice, Robert Pazdur, Richard TI Approval Summary: Pemetrexed Maintenance Therapy of Advanced/Metastatic Nonsquamous, Non-Small Cell Lung Cancer (NSCLC) SO ONCOLOGIST LA English DT Article DE Pemetrexed; Non-small cell lung cancer; Maintenance treatment ID PHASE-III TRIAL; THYMIDYLATE SYNTHASE; RANDOMIZED TRIAL; CHEMOTHERAPY; CISPLATIN; GEMCITABINE; HISTOLOGY; DURATION AB On July 2, 2009, the U.S. Food and Drug Administration approved pemetrexed injection (Alimta (R) Injection; Eli Lilly and Company, Indianapolis, IN) for maintenance treatment of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer whose disease has not progressed after four cycles of platinumbased doublet induction chemotherapy. A double-blind study of pemetrexed plus best supportive care versus placebo plus best supportive care was conducted. Pemetrexed, 500 mg/m(2) i.v., was administered every 21 days until disease progression. Folic acid, vitamin B12, and a corticosteroid were given to all study patients. There were 663 randomized patients (pemetrexed, 441; placebo, 222). Treatments were well balanced with respect to baseline disease characteristics and stratification factors. The median overall survival (OS) time for intent-to-treat (ITT) patients was 13.4 months for patients receiving pemetrexed and 10.6 months for those receiving placebo (hazard ratio [HR] 0.79; 95% confidence interval [CI], 0.65-0.95; p = .012). Median OS times were 15.5 months versus 10.3 months for patients with nonsquamous histologies receiving pemetrexed and placebo, respectively (HR, 0.70; 95% CI, 0.56-0.88). The median OS time in patients with squamous histology receiving pemetrexed was 9.9 months, versus 10.8 months for those receiving placebo (HR, 1.07; 95% CI, 0.77-1.50). A significantly longer progression- free survival interval for both the ITT and nonsquamous patient populations receiving pemetrexed maintenance therapy was also observed. The most common (>5%) adverse reactions in patients receiving pemetrexed were hematologic toxicity, an increase in hepatic enzymes, fatigue, gastrointestinal toxicity, sensory neuropathy, and skin rash. The Oncologist 2010;15:1352-1358 C1 [Cohen, Martin H.; Cortazar, Patricia; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 23 TC 27 Z9 27 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD DEC PY 2010 VL 15 IS 12 BP 1352 EP 1358 DI 10.1634/theoncologist.2010-0224 PG 7 WC Oncology SC Oncology GA 699SK UT WOS:000285682900014 PM 21148615 ER PT J AU Dal Pan, GJ AF Dal Pan, Gerald J. TI Commentary on "Secondary Use of Electronic Health Record Data: Spontaneous Triggered Adverse Drug Event Reporting" by Linder et al. SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material C1 US FDA, Silver Spring, MD USA. RP Dal Pan, GJ (reprint author), US FDA, Silver Spring, MD USA. EM gerald.dalpan@fda.hhs.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2010 VL 19 IS 12 BP 1216 EP 1217 DI 10.1002/pds.2050 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 699JO UT WOS:000285659900002 PM 20981885 ER PT J AU Shaw, PM Zineh, I AF Shaw, Peter M. Zineh, Issam TI Generating and weighing evidence in drug development and regulatory decision making: 5th US FDA-DIA workshop on pharmacogenomics SO PHARMACOGENOMICS LA English DT Article DE co-development; diagnostics; DNA sampling; drug labels; pharmaceutical company; pharmacogenetics; pharmacogenomics; prospective/retrospective analysis; regulatory; US FDA; workshop AB The 5th US FDA-Drug Industry Association (DIA) workshop in a series on pharmacogenomics entitled: 'Generating and Weighing Evidence in Drug Development and Regulatory Decision Making', contained four major topics (tracks): 'Learning from Labels and Label Changes: How to Build Pharmacogenomics into Drug Development Programs'; 'Enabling Pharmacogenomic Clinical Trials Through Sampling'; 'Designing Pharmacogenomics Studies to be Fit for Purpose'; and 'Co-Development of Drugs and Diagnostics'. The meeting was attended by approximately 200 professionals, primarily involved in drug development and healthcare delivery. Several critical elements drove the success of the meeting: it was recognized that the enriched conversation at this workshop between regulators and drug developers was driven with less inhibition than before and with a greater scientific focus on the issues. Multiple examples in the field and broader collective experience helped more in-depth thinking of the pros and cons of implementing pharmacogenetic/genetic approaches during drug development, in the current environment. It was also noted that this field is still developing and nascent as illustrated by the paucity of actual diagnostic drug co-development examples. Furthermore, the complexities of conducting pharmacogenetic research in global drug-development programs was acknowledged as was the need for rigorous research designs and methodologies despite these challenges. C1 [Shaw, Peter M.] Merck & Co Inc, Pharmacogenet & Mol Profiling, West Point, PA 19486 USA. [Zineh, Issam] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Shaw, PM (reprint author), Merck & Co Inc, Pharmacogenet & Mol Profiling, POB 4,770 Sumneytown Pike,WP53B-120, West Point, PA 19486 USA. EM peter_show3@merck.com NR 4 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 DEC PY 2010 VL 11 IS 12 SI SI BP 1629 EP 1635 DI 10.2217/PGS.10.142 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742VS UT WOS:000288974000001 PM 21142905 ER PT J AU Surh, LC Pacanowski, MA Haga, SB Hobbs, S Lesko, LJ Gottlieb, S Papaluca-Amati, M Patterson, SD Hughes, AR Kim, MJ Close, SL Mosteller, M Zineh, I Dechairo, B Cohen, NA AF Surh, Linda C. Pacanowski, Michael A. Haga, Susanne B. Hobbs, Stuart Lesko, Lawrence J. Gottlieb, Scott Papaluca-Amati, Marisa Patterson, Scott D. Hughes, Arlene R. Kim, Myong-Jin Close, Sandra L. Mosteller, Michael Zineh, Issam Dechairo, Bryan Cohen, Nadine A. TI Learning from product labels and label changes: how to build pharmacogenomics into drug-development programs SO PHARMACOGENOMICS LA English DT Article DE biomarkers; genetic tests; pharmacogenetics; pharmacogenomics; product label; summary of product characteristics; US prescribing information ID COLORECTAL-CANCER; WARFARIN AB The 2010 US FDA-Drug Industry Association (DIA) Pharmacogenomics (PGx) Workshop follows a series that began in 2002 bringing together multidisciplinary experts spanning regulatory authorities, medical research, healthcare and industry. This report summarizes the 'Building PGx into Labels' sessions from the workshop, which discussed the critical elements in developing PGx outcomes leading to product labels that inform efficacy and/or safety. Examples were drawn from US prescribing information, which integrated PGx knowledge into medical decisions (e.g., panitumumab, warfarin and clopidogrel). Attendees indicated the need for broader dialog and for guidelines on evidentiary considerations for PGx to be included into product labels. Also discussed was the understanding of appropriate PGx placement on labels; how to encourage adoption by medical communities of label recommendations on PGx tests; and, given the global nature of drug development, worldwide considerations including European Summary of Product Characteristics. C1 [Surh, Linda C.] GlaxoSmithKline Inc, Global Regulatory Affairs, Res Triangle Pk, NC 27709 USA. [Pacanowski, Michael A.; Lesko, Lawrence J.; Kim, Myong-Jin; Zineh, Issam] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Haga, Susanne B.] Duke Univ, Inst Genome Sci & Policy, Durham, NC 27706 USA. [Hughes, Arlene R.; Mosteller, Michael] GlaxoSmithKline Inc, Genet, Res Triangle Pk, NC USA. [Gottlieb, Scott] Amer Enterprise Inst Publ Policy Res, Washington, DC 20036 USA. [Papaluca-Amati, Marisa] European Med Agcy, London, England. [Patterson, Scott D.] Amgen Inc, Mol Sci, Thousand Oaks, CA USA. [Close, Sandra L.] Eli Lilly & Co, BioMed, Indianapolis, IN USA. RP Surh, LC (reprint author), GlaxoSmithKline Inc, Global Regulatory Affairs, Res Triangle Pk, NC 27709 USA. EM lcsurh@gmail.com NR 8 TC 11 Z9 11 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD DEC PY 2010 VL 11 IS 12 SI SI BP 1637 EP 1647 DI 10.2217/PGS.10.138 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742VS UT WOS:000288974000002 PM 21142906 ER PT J AU Warner, A Nelsen, A Bhathena, A FitzGerald, K Gilardi, S Kelso, E Knoppers, B McLeod, HL Nelson, R Uyama, Y Weisman, J Rudman, A AF Warner, Amelia Nelsen, Anita Bhathena, Anahita FitzGerald, Kevin Gilardi, Sandra Kelso, Ellen Knoppers, Bartha McLeod, Howard L. Nelson, Robert Uyama, Yoshi Weisman, Jennifer Rudman, Allen TI Enabling pharmacogenomic clinical trials through sampling SO PHARMACOGENOMICS LA English DT Article DE clinical trials; drug development; international coordination; pharmacogenomics; regulatory; sample collection AB Discussion and output from the US FDA and the pharmaceutical industry from the Drug Information Association/FDA 5th Workshop in a series on pharmacogenomics entitled: 'Generating and Weighing Evidence in Drug Development and Regulatory Decision Making'. A major topic area at the 5th FDA/Industry Workshop on Pharmacogenomics, February 2-4, 2010 in Bethseda (MD, USA), was enabling pharmacogenomic clinical trials through collection of future use samples. The importance of the collection of samples with permission for future analyses was affirmed by both industry and the FDA. In addition, current barriers for the collection of such samples were detailed and possible solutions for overcoming barriers at sites, as well as globally within countries, were discussed. The importance of international concordance on collection of these samples was emphasized, and potential areas for industry to harmonize sample collection practices. A standalone workshop on issues related to sampling was determined to be a key step for solving issues related to future use sample collection during drug development. C1 [Warner, Amelia] Merck Res Labs, N Wales, PA 19454 USA. [Nelsen, Anita] GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. [Bhathena, Anahita] Abbott Labs, Abbott Pk, IL 60064 USA. [FitzGerald, Kevin] Georgetown Univ, Washington, DC 20057 USA. [Gilardi, Sandra] Bristol Myers Squibb Co, Pennington, NJ 08534 USA. [Kelso, Ellen] Goodwyn Inst Review Board, Cincinnati, OH 45242 USA. [Knoppers, Bartha] McGill Univ, Montreal, PQ H3A 1A4, Canada. [McLeod, Howard L.] Univ N Carolina, Chapel Hill, NC 27599 USA. [Nelson, Robert; Rudman, Allen] US FDA, Silver Spring, MD 20993 USA. [Uyama, Yoshi] Japanese Pharmaceut & Med Devices Agcy, Tokyo 1000013, Japan. [Weisman, Jennifer] Off Civil Rights, Silver Spring, MD 20993 USA. RP Warner, A (reprint author), Merck Res Labs, 351 N Sumneytown Pike,UG4D-34, N Wales, PA 19454 USA. EM amelia.warner@merck.com NR 2 TC 3 Z9 3 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD DEC PY 2010 VL 11 IS 12 SI SI BP 1649 EP 1654 DI 10.2217/PGS.10.139 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742VS UT WOS:000288974000003 PM 21142907 ER PT J AU Burns, DK Hughes, AR Power, A Wang, SJ Patterson, SD AF Burns, Daniel K. Hughes, Arlene R. Power, Aidan Wang, Sue-Jane Patterson, Scott D. TI Designing pharmacogenomic studies to be fit for purpose SO PHARMACOGENOMICS LA English DT Article DE abacavir; biomarkers; cetuximab; HLA-B*5701; KRAS; panitumumab; pharmacogenomics; prospective-retrospective ID METASTATIC COLORECTAL-CANCER; HUMAN-LEUKOCYTE ANTIGEN-B-ASTERISK-5701; ABACAVIR HYPERSENSITIVITY REACTIONS; HLA-B REGION; K-RAS; GENETIC-VARIATIONS; CLINICAL-OUTCOMES; ASSOCIATION; HLA-B-ASTERISK-5701; MUTATIONS AB The 2010 US FDA-Drug Industry Association (DIA) Pharmacogenomics Workshop, the fifth in a series of meetings that begun in 2002, brought together multidisciplinary experts from regulatory authorities, medical research, healthcare and drug development. This article summarizes the 'Designing Pharmacogenomic Studies to be Fit for Purpose' track in which considerations regarding the use of retrospective and prospective studies were examined in relation to their ability to influence treatment decisions and labeling for drugs. The aim of the session, using real-world examples (KRAS/panitumumab and HLA-B*5701/abacavir), was to identify good scientific principles that would guide the design of studies to identify subgroups of responders during development programs (including marketed drugs), which could subsequently be used to guide treatment decisions. C1 [Patterson, Scott D.] Amgen Inc, Med Sci, Thousand Oaks, CA 91320 USA. [Burns, Daniel K.] Duke Univ, Deane Drug Discovery Inst, R David Thomas Execut Training Ctr, Durham, NC 27708 USA. [Hughes, Arlene R.] Genet GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. [Power, Aidan] Pfizer Inc, Mol Med, PharmaTherapeut Res, Groton, CT 06340 USA. [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Patterson, SD (reprint author), Amgen Inc, Med Sci, 1 Amgen Ctr Dr,MS 38-3-A, Thousand Oaks, CA 91320 USA. EM spatters@amgen.com NR 46 TC 5 Z9 5 U1 0 U2 2 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 DEC PY 2010 VL 11 IS 12 SI SI BP 1657 EP 1667 DI 10.2217/PGS.10.140 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742VS UT WOS:000288974000004 PM 21142908 ER PT J AU Hinman, LM Carl, KM Spear, BB Salerno, RA Becker, RL Abbott, BM Kelly, JF Mansfield, E Katz, RG Harper, C Day, SP Pacanowski, MA Pignato, W AF Hinman, Lois M. Carl, Kevin M. Spear, Brian B. Salerno, Ronald A. Becker, Robert L. Abbott, Brian M. Kelly, James F. Mansfield, Elizabeth Katz, Russell G. Harper, Courtney Day, Stephen P. Pacanowski, Michael A. Pignato, William TI Development and regulatory strategies for drug and diagnostic co-development SO PHARMACOGENOMICS LA English DT Article DE biomarkers; co-development pharmacogenomics; companion diagnostics; drug/diagnostic ID LUMIRACOXIB AB At the 5th FDA-Drug Industry Association (DIA) Workshop on 'Pharmacogenomics in Drug Development and Regulatory Decision Making', track four focused on the current thinking and issues in the co-development of therapeutic drugs or biologics, and their companion diagnostic products. Identification and validation of genomic and other biomarkers are becoming important components of drug-development strategies, and recent successes show the power of personalized approaches to change the benefit risk paradigm for new drugs. C1 [Hinman, Lois M.] Novartis Pharmaceut, E Hanover, NJ 07939 USA. Abbott Labs, Abbott Pk, IL 60064 USA. US FDA, CDRH, Rockville, MD 20857 USA. AstraZeneca, Wilmington, DE USA. Roche Mol Systs, Alameda, CA USA. [Pignato, William] Novartis Mol Diagnost, Cambridge, MA USA. RP Hinman, LM (reprint author), Novartis Pharmaceut, 1 Hth Plaza, E Hanover, NJ 07939 USA. EM lois.hinman@novartis.com NR 6 TC 9 Z9 9 U1 1 U2 5 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 DEC PY 2010 VL 11 IS 12 SI SI BP 1669 EP 1675 DI 10.2217/PGS.10.141 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742VS UT WOS:000288974000005 PM 21142909 ER PT J AU Soldin, OP Soldin, SJ Vinks, AA Younis, I Landy, HJ AF Soldin, Offie P. Soldin, Steven J. Vinks, Alexander A. Younis, Islam Landy, Helain J. TI Longitudinal Comparison of Thyroxine Pharmacokinetics Between Pregnant and Nonpregnant Women: A Stable Isotope Study SO THERAPEUTIC DRUG MONITORING LA English DT Article DE levothyroxine LT4; Thyroid; gestation; clinical pharmacology; thyroid disorder/drug therapy/physiopathology/hypothyroidism ID TANDEM MASS-SPECTROMETRY; THYROID-HORMONE TRANSPORTERS; REFERENCE INTERVALS; MENSTRUAL-CYCLE; DISEASE; TRIIODOTHYRONINE; REPLACEMENT; BRAIN; HYPOTHYROIDISM; DEFICIENCY AB The treatment of maternal hypothyroidism presents clinicians with a unique challenge, because dosing regimens previously developed and validated for nonpregnant women cannot be easily extrapolated to dosing in pregnancy. Thyroid hormone requirement increases by 20% to 40% early during pregnancy, persisting throughout gestation. Accordingly, women with treated hypothyroidism need to increase their levothyroxine dose to prevent maternal hypothyroidism and the associated impaired cognitive development and increased fetal mortality. We investigated the pharmacokinetic properties of levothyroxine during pregnancy through the use of a novel, traceable form of levothyroxine. The objective was to conduct a longitudinal study to determine whether levothyroxine pharmacokinetics differ in the pregnant versus nonpregnant state. We used a unique C-13-levothyroxine-tracer method to distinguish between endogenous and exogenous levothyroxine and studied the pharmacokinetics of a single oral dose of levothyroxine using tandem mass spectrometry. Moreover, we were able to detect single dose amounts of the drug, in picogram/mL concentrations. The area under the curve was 23.0 ng*h/mL in pregnancy and 14.8 ng*h/mL in nonpregnant women (P < 0.03) with median serum half-lives of 32.1 hours and 24.1 hours, respectively (P < 0.04). Further research involves the measurement of free thyroxine on these samples using tandem mass spectrometry. Future work should focus on the mechanisms responsible for the gestational differences in pharmacokinetics and whether these should necessitate dose schedule changes in pregnancy. C1 [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Med, Washington, DC 20007 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Physiol, Washington, DC 20007 USA. [Soldin, Offie P.] Georgetown Univ, Med Ctr, Dept Biophys, Washington, DC 20007 USA. [Soldin, Steven J.] Georgetown Univ, Dept Pharmacol, Washington, DC USA. [Soldin, Steven J.] Georgetown Univ, Bioanalyt Core Lab, Washington, DC USA. [Vinks, Alexander A.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH USA. [Vinks, Alexander A.] Univ Cincinnati, Cincinnati Childrens Hosp Med Ctr, Pediat Pharmacol Res Unit, Cincinnati, OH USA. [Vinks, Alexander A.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Younis, Islam] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Landy, Helain J.] Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Soldin, OP (reprint author), Lombardi Comprehens Canc Ctr, Dept Med, LL S-166, Washington, DC 20057 USA. EM os35@georgetown.edu FU National Institutes of Health/National Institute of Child Health and Human Development (NIH/NICHD) [5U10HD0478925]; Office of Research on Women's Health; GCRC at Georgetown University Medical Center; NIH/NICHD Pediatric Pharmacology Research Unit [5U10HD037249-10]; National Institutes of Health National Center for Research Resources [M01RR-023942] FX O.P.S. is supported by a National Institutes of Health/National Institute of Child Health and Human Development (NIH/NICHD) supplement to the Obstetric-Fetal Pharmacology Research Unit Network Grant 5U10HD0478925, funds from the Office of Research on Women's Health, and by the GCRC at Georgetown University Medical Center. A.A.V.'s contribution was supported in part by NIH/NICHD Pediatric Pharmacology Research Unit grant 5U10HD037249-10 (AAV).; This project was conducted through the General Clinical Research Center at Georgetown University and supported by the National Institutes of Health National Center for Research Resources, Grant M01RR-023942. NR 35 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0163-4356 EI 1536-3694 J9 THER DRUG MONIT JI Ther. Drug Monit. PD DEC PY 2010 VL 32 IS 6 BP 767 EP 773 DI 10.1097/FTD.0b013e3181f12fe5 PG 7 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 678TI UT WOS:000284103400015 PM 20962709 ER PT J AU Boorman, GA Wolf, DC Francke-Carroll, S Maronpot, RR AF Boorman, Gary A. Wolf, Douglas C. Francke-Carroll, Sabine Maronpot, Robert R. TI Pathology Peer Review SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material DE toxicologic pathology; safety assessment; quality assurance C1 [Boorman, Gary A.] Covance Inc, Vienna, VA USA. [Wolf, Douglas C.] US EPA, Res Triangle Pk, NC 27711 USA. [Francke-Carroll, Sabine] US FDA, College Pk, MD USA. [Maronpot, Robert R.] Maronpot Consulting LLC, Raleigh, NC USA. RP Boorman, GA (reprint author), Covance Inc, Vienna, VA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD DEC PY 2010 VL 38 IS 7 BP 1009 EP 1010 DI 10.1177/0192623310385361 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 800QM UT WOS:000293378600001 PM 21248323 ER PT J AU Soni, MG Thurmond, TS Miller, ER Spriggs, T Bendich, A Omaye, ST AF Soni, Madhu G. Thurmond, T. Scott Miller, Edgar R., III Spriggs, Tracey Bendich, Adrianne Omaye, Stanley T. TI Safety of Vitamins and Minerals: Controversies and Perspective SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE antioxidants; safety; vitamins; minerals; supplements; toxicity ID RANDOMIZED CONTROLLED-TRIAL; LONG-TERM SUPPLEMENTATION; BETA-CAROTENE; CARDIOVASCULAR-DISEASE; ALPHA-TOCOPHEROL; WOMENS HEALTH; LUNG-CANCER; ANTIOXIDANT; PREVENTION; FLAVONOIDS AB Available information suggests that currently over 47% of males and 59% of females use dietary supplements for health benefits, and the number of users is rapidly increasing. However, numerous studies published over more than a decade have linked some supplements (including vitamins E, C, D, A, and B, as well as selenium) to no health benefits or even to adverse health effects. Recent studies with negative results, which drew media attention, include the following: a 2008 study on the ability of vitamin E and selenium to lower the risk of prostate cancer was halted amidst fear of potential harm; vitamin C may do more harm than good as it may protect cancer cells; intake of vitamins E and C by 15,000 male physicians for 10 years had no health benefits. In contrast, there are compelling cause and effect data linking the use of folic acid with consistent and significant reductions in fetal adverse pregnancy outcomes, demonstrating no beneficial effects of calcium and vitamin D supplements in improving bone strength and reducing fractures. These equivocal and conflicting findings on the effects of supplements on health outcomes have left consumers confused about their benefits and wary of the possible adverse effects of vitamin and mineral supplementation. The objectives of this session are to characterize the current state of the science as it relates to the impact of vitamin and mineral supplementation on human health, review the statutory and regulatory perspective of vitamin use from a safety perspective, assess the credibility of meta-analysis in the safety assessment of vitamins, and elicit the mechanisms of these interactions-pro-oxidant versus antioxidant effects and beneficial versus adverse effects. C1 [Omaye, Stanley T.] Univ Nevada, Dept Nutr, Reno, NV 89557 USA. [Soni, Madhu G.] Soni & Associates Inc, Vero Beach, FL USA. [Thurmond, T. Scott] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Miller, Edgar R., III] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Spriggs, Tracey; Bendich, Adrianne] GlaxoSmithkline Consumer Healthcare, Parsippany, NJ USA. RP Omaye, ST (reprint author), Univ Nevada, Dept Nutr, Mail Stop 142, Reno, NV 89557 USA. EM omaye@unr.edu NR 49 TC 28 Z9 30 U1 3 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2010 VL 118 IS 2 BP 348 EP 355 DI 10.1093/toxsci/kfq293 PG 8 WC Toxicology SC Toxicology GA 682WB UT WOS:000284432600003 PM 20861067 ER PT J AU Wang, T Jacobson-Kram, D Pilaro, AM Lapadula, D Jacobs, A Brown, P Lipscomb, J McGuinn, WD AF Wang, Tao Jacobson-Kram, David Pilaro, Anne M. Lapadula, Daniel Jacobs, Abigail Brown, Paul Lipscomb, John McGuinn, William David TI ICH Guidelines: Inception, Revision, and Implications for Drug Development SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material ID TOXICITY; ASSAY; TRANSFORMATION; CARCINOGENS C1 [Wang, Tao] Nova Pharmaceut Corp, Preclin Safety, Emeryville, CA 94608 USA. [Jacobson-Kram, David; Pilaro, Anne M.; Jacobs, Abigail; Brown, Paul; McGuinn, William David] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lapadula, Daniel] Novartis Pharmaceut, Preclin Safety, E Hanover, NJ 07936 USA. [Lipscomb, John] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA. RP Wang, T (reprint author), Nova Pharmaceut Corp, Preclin Safety, 4560 Horton St,M-S 4-6, Emeryville, CA 94608 USA. EM tao.wang@novartis.com NR 16 TC 8 Z9 8 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2010 VL 118 IS 2 BP 356 EP 367 DI 10.1093/toxsci/kfq286 PG 12 WC Toxicology SC Toxicology GA 682WB UT WOS:000284432600004 PM 20861066 ER PT J AU Yu, XF Dhakal, IB Beggs, M Edavana, VK Williams, S Zhang, XM Mercer, K Ning, BT Lang, NP Kadlubar, FF Kadlubar, S AF Yu, Xinfeng Dhakal, Ishwori B. Beggs, Marjorie Edavana, Vineetha Koroth Williams, Suzanne Zhang, Xuemei Mercer, Kelly Ning, Baitang Lang, Nicholas P. Kadlubar, Fred F. Kadlubar, Susan TI Functional Genetic Variants in the 3 '-Untranslated Region of Sulfotransferase Isoform 1A1 (SULT1A1) and Their Effect on Enzymatic Activity SO TOXICOLOGICAL SCIENCES LA English DT Article DE SULT1A1; genotype; phenotype; pharmacogenetics ID BREAST-CANCER PATIENTS; PHENOL SULFOTRANSFERASE; HUMAN GENOME; HUMAN-LIVER; HAPLOTYPE RECONSTRUCTION; LINKAGE DISEQUILIBRIUM; PARTIAL-PURIFICATION; ASSAY CONDITIONS; PST ACTIVITY; ASSOCIATION AB Sulfotransferase isoform 1A1 (SULT1A1) is the most highly expressed hepatic sulfotransferase and is involved in the biotransformation of a wide variety of endo- and xenobiotics. A common single nucleotide polymorphism (SNP) in the coding region of SULT1A1, several proximal promoter SNPs, and copy number variation (CNV) are associated with altered enzymatic activity, but these variants do not fully account for the observed variation of SULT1A1 activity in human populations. In order to identify additional SNPs modulating SULT1A1 activity, we examined the 3'-untranslated region (UTR) of SULT1A1 in 97 liver samples. Direct sequencing revealed that two SNPs in the 3'-UTR (902A > G [rs6839] and 973C > T [rs1042157]) and one SNP in the 3'-flanking region (1307G > A [rs4788068]) were common. These SNPs are in absolute linkage disequilibrium with each other and in tight linkage with SULT1A1*1/2 (linkage coefficient D' 0.83) and are significantly associated with SULT1A1 messenger RNA (p = 0.001, 0.029, 0.021) and enzymatic activity (p = 0.022, 0.012, 0.027). We then examined the collective effects of 3'-UTR SNPs, SULT1A1*1/2, and CNV on SULT1A1 activity in 498 Caucasian and 127 African-American subjects by haplotype analysis. This analysis revealed that SULT1A1*1/2 does not contribute to the variation in SULT1A1 enzymatic activity when the 3'-UTR SNPs are included in the statistical model. Two major haplotypes (ACG and GTA) were significantly correlated with SULT1A1 activity, and when stratified by copy number, the SULT1A1 3'-UTR SNPs remain significantly associated with SULT1A1 enzymatic activity in Caucasians, but not in African-Americans. Subsequent functional characterization revealed that a microRNA, miR-631, regulates SULT1A1 expression in a genotype-specific manner. C1 [Yu, Xinfeng; Dhakal, Ishwori B.; Beggs, Marjorie; Edavana, Vineetha Koroth; Williams, Suzanne; Zhang, Xuemei; Mercer, Kelly; Kadlubar, Fred F.; Kadlubar, Susan] Univ Arkansas Med Sci, Coll Med, Div Med Genet, Little Rock, AR 72205 USA. [Ning, Baitang] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Lang, Nicholas P.] Univ Arkansas Med Sci, Coll Med, Dept Surg, Little Rock, AR 72205 USA. RP Kadlubar, S (reprint author), Univ Arkansas Med Sci, Coll Med, Div Med Genet, 4301 W Markham,580, Little Rock, AR 72205 USA. EM sakadlubar@uams.edu FU National Cancer Institute at the National Institutes of Health [R01CA128897]; National Center for Research Resources [1UL1RR029884]; Susan G. Komen for the Cure [BCTR0707584] FX National Cancer Institute at the National Institutes of Health (R01CA128897); National Center for Research Resources (award number 1UL1RR029884); Susan G. Komen for the Cure (BCTR0707584). NR 42 TC 30 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD DEC PY 2010 VL 118 IS 2 BP 391 EP 403 DI 10.1093/toxsci/kfq296 PG 13 WC Toxicology SC Toxicology GA 682WB UT WOS:000284432600007 PM 20881232 ER PT J AU Fux, E Gonzalez-Gil, S Lunven, M Gentien, P Hess, P AF Fux, Elie Gonzalez-Gil, Sonsoles Lunven, Michel Gentien, Patrick Hess, Philipp TI Production of diarrhetic shellfish poisoning toxins and pectenotoxins at depths within and below the euphotic zone SO TOXICON LA English DT Article DE Marine toxins; Dinophysis acuta; LC-MS; Passive sampling; SPATT; Okadaic acid; Dinophysistoxin-2; Pectenotoxin-2 ID DINOFLAGELLATE DINOPHYSIS-ACUMINATA; LC-MS/MS ANALYSIS; OKADAIC ACID; NEW-ZEALAND; LIQUID-CHROMATOGRAPHY; MARINE-PHYTOPLANKTON; MASS-SPECTROMETRY; LIPOPHILIC TOXINS; BALTIC SEA; ACUTA AB During a 10 day survey in the CelticSea near the Irish South-West coast (July 2007), Dinophysis acuta was observed in large numbers. The deployment of a profiler allowed for the identification of a D. acuta thin layer that reached 1910 cells/L The aim of the study was to investigate if the bloom that occurred in low light environment was viable, dividing, actively producing toxins and if the toxin profile changed over a short term period. Several large concentrates of phytoplankton samples were obtained over a 14 h period, from evening to morning, by pumping Dinophysis from specific depths. In addition, D. acuta was collected in complete darkness at 81 m depth by concentrating 120 L of water. The cells were extracted and their toxin profiles were established by liquid chromatography - mass spectrometry (LC-MS). Passive samplers were deployed in a nearby location for 6 days at 30, 50, 70 and 110 m depth, and the toxin profiles were determined by LC-MS as above. The toxin profiles obtained in phytoplankton samples and in the SPATT were compared and correlated well. Sample concentrates and SPATT results suggested that toxic D. acuta occurred and produced similar toxin profiles at all water depths, including below the euphotic zone. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Fux, Elie; Hess, Philipp] Biotoxin Chem Marine Inst, Galway, Ireland. [Gonzalez-Gil, Sonsoles] Inst Espanol Oceanog, Ctr Oceanog Vigo, Vigo, Spain. [Lunven, Michel; Gentien, Patrick] IFREMER, Ctr Brest, F-29280 Plouzane, France. RP Fux, E (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM elie.fux@marine.ie RI Hess, Philipp/G-1761-2010; Gonzalez-Gil, Sonsoles/M-2515-2014 OI Hess, Philipp/0000-0002-9047-1345; FU Marine Institute; BIOTOX; EU [514074] FX The Marine Institute and BIOTOX (EU funded project 514074 under FP 6) have provided funds for this study. The authors also would like Dr Juliette Smith from Woods Hole Oceanographic Institute for her valuable comments on this manuscript. NR 34 TC 11 Z9 11 U1 1 U2 17 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC PY 2010 VL 56 IS 8 BP 1487 EP 1496 DI 10.1016/j.toxicon.2010.09.007 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 685YQ UT WOS:000284664400021 PM 20888853 ER PT J AU Boada, LD Zumbado, M Luzardo, OR Almeida-Gonzalez, M Plakas, SM Granade, HR Abraham, A Jester, ELE Dickey, RW AF Boada, Luis D. Zumbado, Manuel Luzardo, Octavio R. Almeida-Gonzalez, Maira Plakas, Steven M. Granade, Hudson R. Abraham, Ann Jester, Edward L. E. Dickey, Robert W. TI Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary Islands (Spain) SO TOXICON LA English DT Article DE Ciguatera; Outbreak; Ciguatoxins; Lesser amberjack; Canary Islands ID NEUROTOXINS; TOXINS AB Ciguatera fish poisoning (CFP) is endemic in certain tropical and subtropical regions of the world. CFP had not been described on the West Africa Coast until a 2004 outbreak in the Canary Islands. In 2008-2009, two additional outbreaks of ciguatera occurred. Individuals afflicted had consumed lesser amberjack (Seriola rivoliana) captured from nearby waters. Caribbean ciguatoxin-1 (C-CTX-1) was confirmed in fish samples by LC-MS/MS. Ciguatoxic fish in this region may pose a new health risk for the seafood consumer. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Boada, Luis D.; Zumbado, Manuel; Luzardo, Octavio R.; Almeida-Gonzalez, Maira] Univ Las Palmas Gran Canaria, Hlth Sci Ctr, Dept Clin Sci, Toxicol Unit, Las Palmas Gran Canaria 35080, Spain. [Plakas, Steven M.; Granade, Hudson R.; Abraham, Ann; Jester, Edward L. E.; Dickey, Robert W.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Boada, LD (reprint author), Univ Las Palmas Gran Canaria, Hlth Sci Ctr, Dept Clin Sci, Toxicol Unit, POB 550, Las Palmas Gran Canaria 35080, Spain. EM ldominguez@dcc.ulpgc.es RI Zumbado, Manuel/B-4495-2010; Dominguez-Boada, Luis/L-5577-2015; OI Almeida Gonzalez, Maira/0000-0003-2410-4659; Dominguez-Boada, Luis/0000-0002-0195-4565; P. Luzardo, Octavio/0000-0002-4153-3028 NR 17 TC 21 Z9 22 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD DEC PY 2010 VL 56 IS 8 BP 1516 EP 1519 DI 10.1016/j.toxicon.2010.07.021 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 685YQ UT WOS:000284664400025 PM 20692274 ER PT J AU Kwekel, JC Desai, VG Moland, CL Branham, WS Fuscoe, JC AF Kwekel, Joshua C. Desai, Varsha G. Moland, Carrie L. Branham, William S. Fuscoe, James C. TI Age and sex dependent changes in liver gene expression during the life cycle of the rat SO BMC GENOMICS LA English DT Article ID DRUG-METABOLIZING-ENZYMES; TRANSCRIPTION FACTORS; MOUSE-LIVER; CLINICAL-PHARMACOLOGY; UNITED-STATES; GROWTH; INJURY; CYTOCHROME-P450; CARCINOGENICITY; POLYMORPHISMS AB Background: Age-and sex-related susceptibility to adverse drug reactions and disease is a key concern in understanding drug safety and disease progression. We hypothesize that the underlying suite of hepatic genes expressed at various life cycle stages will impact susceptibility to adverse drug reactions. Understanding the basal liver gene expression patterns is a necessary first step in addressing this hypothesis and will inform our assessments of adverse drug reactions as the liver plays a central role in drug metabolism and biotransformation. Untreated male and female F344 rats were sacrificed at 2, 5, 6, 8, 15, 21, 52, 78, and 104 weeks of age. Liver tissues were collected for histology and gene expression analysis. Whole-genome rat microarrays were used to query global expression profiles. Results: An initial list of differentially expressed genes was selected using criteria based upon p-value (p < 0.05) and fold-change (+/- 1.5). Three dimensional principal component analyses revealed differences between males and females beginning at 2 weeks with more divergent profiles beginning at 5 weeks. The greatest sex-differences were observed between 8 and 52 weeks before converging again at 104 weeks. K-means clustering identified groups of genes that displayed age-related patterns of expression. Various adult aging-related clusters represented gene pathways related to xenobiotic metabolism, DNA damage repair, and oxidative stress. Conclusions: These results suggest an underlying role for genes in specific clusters in potentiating age-and sex-related differences in susceptibility to adverse health effects. Furthermore, such a comprehensive picture of life cycle changes in gene expression deepens our understanding and informs the utility of liver gene expression biomarkers. C1 [Kwekel, Joshua C.; Desai, Varsha G.; Moland, Carrie L.; Branham, William S.; Fuscoe, James C.] US FDA, Ctr Funct Genom, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kwekel, JC (reprint author), US FDA, Ctr Funct Genom, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM joshua.kwekel@fda.hhs.gov; james.fuscoe@fda.hhs.gov FU U.S. Department of Energy; U.S. Food and Drug Administration FX The thoughtful comments and critical reviews from Drs. Tao Han, Leming Shi, and William Salminen are greatly appreciated. JCK was supported in part 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 findings and conclusions presented in this article are the authors and do not necessarily reflect those of the Food and Drug Administration. NR 58 TC 28 Z9 29 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD NOV 30 PY 2010 VL 11 AR 675 DI 10.1186/1471-2164-11-675 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 700TD UT WOS:000285766300001 PM 21118493 ER PT J AU Hammad, TA Mosholder, AD AF Hammad, Tarek A. Mosholder, Andrew D. TI Suicide and antidepressants Beware extrapolation from ecological data SO BRITISH MEDICAL JOURNAL LA English DT Letter ID WARNINGS C1 [Hammad, Tarek A.; Mosholder, Andrew D.] Food & Drug Adm, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol, Silver Spring, MD 20993 USA. RP Hammad, TA (reprint author), Food & Drug Adm, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Tarek.Hammad@fda.hhs.gov NR 5 TC 1 Z9 1 U1 1 U2 4 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1756-1833 J9 BRIT MED J JI Br. Med. J. PD NOV 30 PY 2010 VL 341 AR c6844 DI 10.1136/bmj.c6844 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 691OG UT WOS:000285090100003 PM 21118884 ER PT J AU Zhao, N Zidan, A Tawakkul, M Sayeed, VA Khan, M AF Zhao, Na Zidan, Ahmed Tawakkul, Mobin Sayeed, Vilayat A. Khan, Mansoor TI Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Tablet splitting; Quality assessment; Near infrared mapping ID NEAR-INFRARED SPECTROSCOPY; NIR SPECTROSCOPY; PHARMACEUTICAL APPLICATIONS; REFLECTANCE SPECTRA; CONTENT UNIFORMITY; BLEND UNIFORMITY; IDENTIFICATION; CHEMOMETRICS; VARIABILITY; EXCIPIENTS AB Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets. Published by Elsevier B.V. C1 [Zhao, Na; Zidan, Ahmed; Tawakkul, Mobin; Khan, Mansoor] US FDA, Div Prod Qual Res, Off Testing & Res, CDER, Rockville, MD 20857 USA. [Sayeed, Vilayat A.] US FDA, Div Chem Review, Off Gener Drugs, CDER, Rockville, MD 20857 USA. [Zidan, Ahmed] Zagazig Univ, Fac Pharm, Zagazig, Egypt. RP Khan, M (reprint author), 10903 New Hampshire Ave,WO 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 FU critical path programs; Office of Generic Drugs FX Funding from critical path programs and Office of Generic Drugs is gratefully acknowledged. NR 29 TC 10 Z9 10 U1 1 U2 16 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 NOV 30 PY 2010 VL 401 IS 1-2 BP 25 EP 31 DI 10.1016/j.ijpharm.2010.09.004 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 693KJ UT WOS:000285222700004 PM 20849940 ER PT J AU Zhou, Y Li, N Choi, FFK Qiao, CF Song, JZ Li, SL Liu, X Cai, ZW Fu, PP Lin, G Xu, HX AF Zhou, Yan Li, Na Choi, Franky Fung-Kei Qiao, Chun-Feng Song, Jing-Zheng Li, Song-Lin Liu, Xin Cai, Zong-Wei Fu, Peter P. Lin, Ge Xu, Hong-Xi TI A new approach for simultaneous screening and quantification of toxic pyrrolizidine alkaloids in some potential pyrrolizidine alkaloid-containing plants by using ultra performance liquid chromatography-tandem quadrupole mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article DE Pyrrolizidine alkaloids (PAs); UPLC-TQ-MS; Precursor ion scan (PIS); Multiple reaction monitoring (MRM); Parasenecio species; Senecio species ID MEDICINAL-PLANTS; N-OXIDES AB A rapid, but sensitive and selective method for simultaneous screening and quantification of toxic pyrrolizidine alkaloids (PAs) by ultra performance liquid-chromatography (UPLC) coupled with tandem mass spectrometry (MS/MS) on a tandem quadrupole mass spectrometer (TQ-MS) is described. This was accomplished by incorporating the precursor ion scan (PIS) acquisition and multiple reaction monitoring (MRM) acquisition in the same UPLC-MS/MS run. Notably, the developed PIS approach for detecting two pairs of characteristic product ions at m/z 120/138 or 168/150, allowed specific identification of toxic retronecine and otonecine types PAs. This PIS method is highly sensitive with over 10-fold sensitivity improvement upon previously published LC-MS method. Moreover, this new approach is suitable for high sample throughput and was applied to the screening and quantifying toxic PAs in 22 samples collected from seven Parasenecio species and four Senecio species. In addition, coupling the MRM with PIS approach generated quantitative results equivalent to those obtained by conventional MRM-only approach. This coupled MRM with PIS approach could provide both qualitative and quantitative results without the need of repetitive analyses. (C) 2010 Elsevier B.V. All rights reserved. C1 [Li, Na; Lin, Ge] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. [Zhou, Yan; Choi, Franky Fung-Kei; Qiao, Chun-Feng; Song, Jing-Zheng; Li, Song-Lin; Liu, Xin; Xu, Hong-Xi] Hong Kong Jockey Club Inst Chinese Med, Shatin, Hong Kong, Peoples R China. [Cai, Zong-Wei] Hong Kong Baptist Univ, Dept Chem, Hong Kong, Hong Kong, Peoples R China. [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 linge@cuhk.edu.hk; xuhongxi@hkjcicm.org OI Cai, Zongwei/0000-0002-8724-7684 FU Hong Kong Jockey Club Charities Trust [JCICM-15-07] FX This research was supported by the Hong Kong Jockey Club Charities Trust (JCICM-15-07). The authors are grateful to Dr. Karl Lo of Waters Corp. The contents of this article do not necessarily reflect the views and policies of the U.S. Food & Drug Administration. The mentioning of trade names and commercial products does not constitute endorsement or recommendation for use. NR 26 TC 33 Z9 38 U1 6 U2 39 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 NOV 29 PY 2010 VL 681 IS 1-2 BP 33 EP 40 DI 10.1016/j.aca.2010.09.011 PG 8 WC Chemistry, Analytical SC Chemistry GA 682GO UT WOS:000284389600005 PM 21035600 ER PT J AU Le Nouen, C Hillyer, P Munir, S Winter, CC McCarty, T Bukreyev, A Collins, PL Rabin, RL Buchholz, UJ AF Le Nouen, Cyril Hillyer, Philippa Munir, Shirin Winter, Christine C. McCarty, Thomas Bukreyev, Alexander Collins, Peter L. Rabin, Ronald L. Buchholz, Ursula J. TI Effects of Human Respiratory Syncytial Virus, Metapneumovirus, Parainfluenza Virus 3 and Influenza Virus on CD4+T Cell Activation by Dendritic Cells SO PLOS ONE LA English DT Article ID T-HELPER TYPE-1; IN-VITRO; YOUNG-CHILDREN; DIFFERENTIAL RESPONSE; FLOW-CYTOMETRY; CILIATED CELLS; TRACT DISEASE; HUMAN NAIVE; INFECTION; LYMPHOCYTES AB Background: Human respiratory syncytial virus (HRSV), and to a lesser extent human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), re-infect symptomatically throughout life without antigenic change, suggestive of incomplete immunity. One causative factor is thought to be viral interference with dendritic cell (DC)-mediated stimulation of CD4+ T cells. Methodology, Principal Findings: We infected human monocyte-derived DC with purified HRSV, HMPV, HPIV3, or influenza A virus (IAV) and compared their ability to induce activation and proliferation of autologous CD4+ T cells in vitro. IAV was included because symptomatic re-infection without antigenic change is less frequent, suggesting that immune protection is more complete and durable. We examined virus-specific memory responses and superantigen-induced responses by multiparameter flow cytometry. Live virus was more stimulatory than inactivated virus in inducing DC-mediated proliferation of virus-specific memory CD4+ T cells, suggesting a lack of strong suppression by live virus. There were trends of increasing proliferation in the order: HMPV, HRSV, HPIV3, IAV, and greater production of interferon-gamma c and tumor necrosis factor-alpha by proliferating cells in response to IAV, but differences were not significant. Exposure of DC to HRSV, HPIV3, or IAV reduced CD4+ T cell proliferation in response to secondary stimulus with superantigen, but the effect was transitory and greatest for IAV. T cell cytokine production was similar, with no evidence of Th2 or Th17 skewing. Conclusions, Significance: Understanding the basis for the ability of HRSV in particular to symptomatically re-infect without significant antigenic change is of considerable interest. The present results show that these common respiratory viruses are similar in their ability to induce DC to activate CD4+ T cells. Thus, the results do not support the common model in which viral suppression of CD4+ T cell activation and proliferation by HRSV, HMPV, and HPIV3 is a major factor in the difference in re-infectability compared to IAV. C1 [Le Nouen, Cyril; Munir, Shirin; Winter, Christine C.; McCarty, Thomas; Bukreyev, Alexander; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Le Nouen, C (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov OI Tripp, Ralph/0000-0002-2924-9956 FU NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. Disclaimer: The views expressed in this report are the personal opinions of the authors and are not the official opinion of the U.S. Food and Drug Administration, the National Institutes of Health, or the Department of Health and Human Services. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 60 TC 18 Z9 18 U1 1 U2 7 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 29 PY 2010 VL 5 IS 11 AR e15017 DI 10.1371/journal.pone.0015017 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 686HD UT WOS:000284686500016 PM 21124776 ER PT J AU Hadwiger, ME Trehy, ML Ye, W Moore, T Allgire, J Westenberger, B AF Hadwiger, Michael E. Trehy, Michael L. Ye, Wei Moore, Terry Allgire, James Westenberger, Benjamin TI Identification of amino-tadalafil and rimonabant in electronic cigarette products using high pressure liquid chromatography with diode array and tandem mass spectrometric detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE E-cigarettes; Electronic cigarettes; HPLC; Mass spectrometry; Multi mode ionization; MS; Rimonabant; Amino tadalafil ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; HERBAL DIETARY-SUPPLEMENT; LC-ESI-MS; STRUCTURE ELUCIDATION; ADULTERANT; ANALOG AB A high-pressure liquid chromatography-diode array detection and multi-mode ionization tandem mass spectrometry (HPLC-DAD-MMI-MS/MS) method was used to identify amino-tadalafil and rimonabant in electronic cigarette (e-cigarette) cartridges Amino-tadalafil is a drug analogue of the commercially approved Cialis (TM) (i e tadalafil) Rimonabant is a drug that was at one time approved for weight loss in Europe (although approval has been retracted) but not in the United States In addition poor quality control over the e-cigarette products analyzed here is shown by the presence of nicotine in products labeled as containing no nicotine or by the presence of significant amounts of rimonabant oxidative degradant in e-cigarette products containing rimonabant Identification was accomplished by comparing the retention time of relevant peaks in the sample with those of standard compounds in addition to comparison of the UV spectra mass spectra and/or product ion mass spectra Published by Elsevier B V C1 [Hadwiger, Michael E.; Trehy, Michael L.; Ye, Wei; Moore, Terry; Allgire, James; Westenberger, Benjamin] Food & Drug Adm, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Hadwiger, ME (reprint author), Food & Drug Adm, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. NR 11 TC 46 Z9 49 U1 2 U2 43 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 26 PY 2010 VL 1217 IS 48 BP 7547 EP 7555 DI 10.1016/j.chroma.2010.10.018 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 686BS UT WOS:000284672400012 PM 20980012 ER PT J AU Kim, DH Ilev, IK AF Kim, D. -H. Ilev, I. K. TI Simple confocal thickness gauge based on fibre-optic confocal sensor for non-contact measurement SO ELECTRONICS LETTERS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; REFRACTIVE-INDEX; TISSUE AB A simple non-contact thickness measurement method based on a dual-confocal microscope has been developed and tested. A reference comparison method was adapted for calibration of the system. The high accuracy potential of the method was demonstrated by measuring the thickness of transparent samples and a non-transparent soft biological sample. Lensed-tip fibre-optic confocal sensors were tested for the method. C1 [Kim, D. -H.; Ilev, I. K.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 7 TC 3 Z9 3 U1 0 U2 1 PU INST ENGINEERING TECHNOLOGY-IET PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 0013-5194 J9 ELECTRON LETT JI Electron. Lett. PD NOV 25 PY 2010 VL 46 IS 24 BP 1594 EP 1595 DI 10.1049/el.2010.3048 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 684WB UT WOS:000284584600012 ER PT J AU Wang, W Castelan-Vega, JA Jimenez-Alberto, A Vassell, R Ye, ZP Weiss, CD AF Wang, Wei Castelan-Vega, Juan A. Jimenez-Alberto, Alicia Vassell, Russell Ye, Zhiping Weiss, Carol D. TI A mutation in the receptor binding site enhances infectivity of 2009 H1N1 influenza hemagglutinin pseudotypes without changing antigenicity SO VIROLOGY LA English DT Article DE hemagglutinin; influenza A 2009 H1N1 virus; pseudotype neutralization; hemagglutinin pseudotypes; influenza A antigenicity; influenza infectivity ID PANDEMIC INFLUENZA; AVIAN INFLUENZA; IN-VIVO; MOLECULAR-DYNAMICS; LENTIVIRAL VECTOR; GENE DELIVERY; VIRUS ENTRY; NEURAMINIDASE; SPECIFICITY; MICE AB The 2009 H1N1 pandemic highlights the need to better understand influenza A infectivity and antigenicity. Relative to other recent seasonal H1N1 influenza strains, the 2009 H1N1 virus grew less efficiently in eggs, which hindered efforts to rapidly supply vaccine. Using lentiviral pseudotypes bearing influenza hemagglutinin (HA-pseudotypes) we evaluated a glutamine to arginine mutation at position 223 (Q223R) and glycosylation at residue 276 in HA for their effects on infectivity and neutralization. Q223R emerged during propagation in eggs and lies in the receptor binding site. We found that the Q223R mutation greatly enhanced infectivity of HA-pseudotypes in human cells, which was further augmented by inclusion of the viral neuraminidase (NA) and M2 proteins. Loss of glycosylation at residue 276 did not alter infectivity. None of these modifications affected neutralization. These findings provide information for increasing 2009 H1N1HA-pseudotype titers without altering antigenicity and offer insights into receptor use. Published by Elsevier Inc. C1 [Weiss, Carol D.] US FDA, Immunoregulat Lab, CBER, HFM 466, Bethesda, MD 20892 USA. [Ye, Zhiping] US FDA, Ctr Biol Evaluat & Res, Lab Resp Viral Dis, Bethesda, MD 20892 USA. RP Weiss, CD (reprint author), US FDA, Immunoregulat Lab, CBER, HFM 466, Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. EM carol.weiss@fda.hhs.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU FDA; CDW; COTEPABE (Instituto Politecnico Nacional, Mexico); CONACYT FX We thank the following persons for generously supplying key reagents for these studies: Galina Vodieko and Christine Anderson (FDA, Bethesda, MD) for sheep reference antisera; Dr. Kanta Subbarao (NIH, Bethesda, MD) for ferret A/California/04/2009 antiserum; and Dr. Gary Nabel (NIH, Bethesda, MD) for CMV/R 8 kappa B and HIV-luciferase expression vectors. We are also grateful to Drs. Vladimir Lugostev and Judy Beeler (FDA, Bethesda, MD) for critical review of the manuscript and Dr. Juan Luis Arciniega (FDA, Bethesda, MD) for providing laboratory space for some of this research. This work was supported by institutional research funds from the FDA for WW, JC-V, AJ-A, RV, ZY, and CDW and from COTEPABE (Instituto Politecnico Nacional, Mexico) and CONACYT for JC-V and AJ-A. NR 42 TC 17 Z9 18 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 25 PY 2010 VL 407 IS 2 BP 374 EP 380 DI 10.1016/j.virol.2010.08.027 PG 7 WC Virology SC Virology GA 671DJ UT WOS:000283480100023 PM 20869738 ER PT J AU Glierova, H Panigaj, M Semberova, J Janouskova, O Dvorakova, E Zivny, J Holada, K AF Glierova, Hana Panigaj, Martin Semberova, Jana Janouskova, Olga Dvorakova, Eva Zivny, Jan Holada, Karel TI Impairment of Erythropoiesis In Inbred Cellular Prion Protein Deficient Mice SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Glierova, Hana; Panigaj, Martin; Janouskova, Olga; Dvorakova, Eva; Holada, Karel] Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Prague, Czech Republic. [Semberova, Jana] CBER FDA, Div Hematol, Rockville, MD USA. [Zivny, Jan] Charles Univ Prague, Inst Pathol Physiol, Fac Med 1, Prague, Czech Republic. RI Panigaj, Martin/G-6492-2013; Janouskova, Olga/H-4110-2014 OI Janouskova, Olga/0000-0002-1365-6274 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2010 VL 116 IS 21 BP 844 EP 844 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662202255 ER PT J AU Kimchi-Sarfaty, C Simhadri, VL Kopelman, D Friedman, A Edwards, N Javaid, A Okunji, C Komar, A Sauna, Z Katagiri, N AF Kimchi-Sarfaty, Chava Simhadri, Vijaya L. Kopelman, David Friedman, Adam Edwards, Nathan Javaid, Atiq Okunji, Chinyere Komar, Anton Sauna, Zuben Katagiri, Nobuko TI The Synonymous V107V Mutation In Factor IX Is Not So Silent and May Cause Hemophilia R In Patients SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Kimchi-Sarfaty, Chava; Simhadri, Vijaya L.; Kopelman, David; Friedman, Adam; Edwards, Nathan; Javaid, Atiq; Okunji, Chinyere; Sauna, Zuben; Katagiri, Nobuko] US FDA, Div Hematol, CBER, Bethesda, MD 20014 USA. [Komar, Anton] Cleveland State Univ, Cleveland, OH 44115 USA. NR 0 TC 1 Z9 1 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 19 PY 2010 VL 116 IS 21 BP 906 EP 906 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662202420 ER PT J AU Entin, I Yaccoby, S Zhining, W Shaughnessy, J Barlogie, B Epstein, J AF Entin, Igor Yaccoby, Shmuel Zhining, Wen Shaughnessy, John, Jr. Barlogie, Bart Epstein, Joshua TI Myeloma Cell Interaction with Osteoclasts and Mesenchymal Stem Cells Reveals Genes Associated with Post Relapse Survival SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Entin, Igor; Yaccoby, Shmuel; Shaughnessy, John, Jr.; Barlogie, Bart; Epstein, Joshua] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Zhining, Wen] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2010 VL 116 IS 21 BP 1220 EP 1220 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662203289 ER PT J AU Lacerda, SH Semberova, J Holada, K Simakova, O Simak, J AF Lacerda, Silvia H. Semberova, Jana Holada, Karel Simakova, Olga Simak, Jan TI Carbon Nanotubes Activate Store Operated Calcium Entry (SOCE) In Human Platelets Manifested by STIM1 Capping SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Lacerda, Silvia H.; Simak, Jan] US FDA, Lab Cellular Hematol, CBER, Rockville, MD 20857 USA. [Semberova, Jana] Inst Care Mother & Child, Prague, Czech Republic. [Holada, Karel] Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Prague, Czech Republic. [Simakova, Olga] 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 19 PY 2010 VL 116 IS 21 BP 1311 EP 1311 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662203521 ER PT J AU Gelderman-Fuhrmann, M Farrell, J Panigaj, M Holada, K Vostal, J AF Gelderman-Fuhrmann, Monique Farrell, John Panigaj, Martin Holada, Karel Vostal, Jaroslav TI Deletion of the Prion Protein Does not Affect Erythropoiesis in a Mouse Model of Beta-Thalassemia. SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Gelderman-Fuhrmann, Monique; Farrell, John; Vostal, Jaroslav] FDA CBER OBRR, Lab Cellular Hematol, Rockville, MD USA. [Panigaj, Martin; Holada, Karel] Charles Univ Prague, Inst Immunol & Microbiol, Fac Med 1, Prague, Czech Republic. RI Panigaj, Martin/G-6492-2013 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 19 PY 2010 VL 116 IS 21 BP 1318 EP 1318 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662203544 ER PT J AU Gelderman-Fuhrmann, M Chi, X Zhi, L Vostal, J AF Gelderman-Fuhrmann, Monique Chi, Xuan Zhi, Li Vostal, Jaroslav TI UVB Light Exposed Human Platelets Mediate Acute Lung Injury In a Two-Event Mouse Model of Transfusion. SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Gelderman-Fuhrmann, Monique; Chi, Xuan; Zhi, Li; Vostal, Jaroslav] FDA CBER OBRR, Lab Cellular Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2010 VL 116 IS 21 BP 1374 EP 1374 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662203685 ER PT J AU Rao, SS Ketha, KMV Atreya, CD AF Rao, Shilpakala Sainath Ketha, Krishna Mohan V. Atreya, Chintamani D. TI Staphylococcus Aureus Detection In Platelets Using Short Synthetic Peptides Derived From Phage-Displayed Random Peptide Libraries Coupled with Quantum-Dot Nanocrystals. SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Rao, Shilpakala Sainath; Ketha, Krishna Mohan V.] US FDA, Lab Cellular Hematol, CBER, Bethesda, MD 20014 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 19 PY 2010 VL 116 IS 21 BP 1375 EP 1376 PG 2 WC Hematology SC Hematology GA 752BH UT WOS:000289662203690 ER PT J AU Ketha, KMV Rao, SS Atreya, CD AF Ketha, Krishna Mohan V. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Combinatorial Antimicrobicidal Peptides Exhibit Enhanced Activity Against Bacterial Contaminants In Stored Platelet Concentrates (PCs) SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Ketha, Krishna Mohan V.; Atreya, Chintamani D.] CBER Food & Drug Adm, Lab Cellular Hematol, Bethesda, MD 20014 USA. [Rao, Shilpakala Sainath] CBER FDA, Div Hematol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2010 VL 116 IS 21 BP 488 EP 489 PG 2 WC Hematology SC Hematology GA 752BH UT WOS:000289662201227 ER PT J AU Zhi, L Chi, X Gelderman-Fuhrmann, M Vostal, J AF Zhi, Li Chi, Xuan Gelderman-Fuhrmann, Monique Vostal, Jaroslav TI Protein Kinase C Mediates UVB Light Induced Changes in Human Platelets that Lead to Inflammation In a Two-Event Animal Model of Transfusion Mediated Acute Lung Injury. SO BLOOD LA English DT Meeting Abstract CT 52nd Annual Meeting of the American-Society-of-Hematology (ASH) CY DEC 04-07, 2010 CL Orlando, FL SP Amer Soc Hematol C1 [Zhi, Li; Chi, Xuan; Gelderman-Fuhrmann, Monique; Vostal, Jaroslav] FDA CBER OBRR, Lab Cellular Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 19 PY 2010 VL 116 IS 21 BP 1375 EP 1375 PG 1 WC Hematology SC Hematology GA 752BH UT WOS:000289662203689 ER PT J AU Neverov, A Chumakov, K AF Neverov, Alexander Chumakov, Konstantin TI Massively parallel sequencing for monitoring genetic consistency and quality control of live viral vaccines SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mutant quantification; quasispecies; sequence heterogeneity; vaccine safety; neurovirulence ID ORAL POLIOVIRUS VACCINE; GEL-ELECTROPHORESIS; NEUROVIRULENCE TEST; IN-VITRO; VIRUS; RNA; STRAIN; POLIOMYELITIS; POPULATIONS; MICROEVOLUTION AB Intrinsic genetic instability of RNA viruses may lead to the accumulation of revertants during manufacture of live viral vaccines, requiring rigorous quality control to ensure vaccine safety. Each lot of oral poliovirus vaccine (OPV) is tested for neurovirulence in animals and also for the presence of neurovirulent revertants. Mutant analysis by PCR and restriction enzyme cleavage (MAPREC) is used to measure the frequency of neurovirulent mutations at the 5' untranslated region (UTR) of the viral genome that correlate with the level of neurovirulence determined by the monkey neurovirulence test. However, MAPREC can only monitor mutations at a few genomic loci and miss mutations at other sites that could adversely affect vaccine quality. Here we propose to use massively parallel sequencing (MPS) for sensitive detection and quantification of all mutations in the entire genome of attenuated viruses. Analysis of vaccine samples and reference preparations demonstrated a perfect agreement with MAPREC results. Quantitative MPS analysis of validated reference preparations tested by MAPREC produced identical results, suggesting that the method could take advantage of the existing reference materials and be used as a replacement for the MAPREC procedure in lot release of OPV. Patterns of mutations present at a low level in vaccine preparations were characteristic of seed viruses used for their manufacture and could be used for identification of individual batches. This approach may represent the ultimate tool for monitoring genetic consistency of live viral vaccines. C1 [Neverov, Alexander; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU Food and Drug Administration FX We thank Dr. Ellie Ehrenfeld, Dr. Steven Rubin, and Dr. Keith Peden for reading the manuscript. The work was supported by funds from the Food and Drug Administration's intramural research program. NR 39 TC 28 Z9 30 U1 0 U2 3 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 NOV 16 PY 2010 VL 107 IS 46 BP 20063 EP 20068 DI 10.1073/pnas.1012537107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 680UT UT WOS:000284261800083 PM 21041640 ER PT J AU Rahman, Z Zidan, AS Khan, MA AF Rahman, Ziyaur Zidan, Ahmed S. Khan, Mansoor A. TI Risperidone solid dispersion for orally disintegrating tablet: Its formulation design and non-destructive methods of evaluation SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Risperidone; Methyl-beta-cyclodextrin; Solid dispersion; Orally disintegrating tablet ID NEAR-INFRARED SPECTROSCOPY; DRY EMULSION TABLET; REFLECTANCE SPECTRA; BETA-CYCLODEXTRIN; IN-VITRO; COMPLEXATION; DISSOLUTION; BIOAVAILABILITY; REGRESSION; DELIVERY AB The focus of present investigation was to assess the utility of non-destructive techniques in the evaluation of risperidone solid dispersions (SD) with methyl-beta-cyclodextrin (MBCD) and subsequent incorporation of the SD into orally disintegrating tablets (ODT) for a faster release of risperidone. The SD was prepared by a solvent evaporation method and evaluated by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), near infrared spectroscopy (NIR), NIR-chemical imaging (NIR-CI), powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC). DSC and XRD analysis indicated that crystallinity of SD has reduced significantly. FTIR showed no interaction between risperidone and MBCD. Partial least square (PLS) was applied to the NIR data for the construction of chemometric models to determine both components of the SD. Good correlations were obtained for calibration and prediction as indicated by correlation coefficients >0.9965. The model was more accurate and less biased in predicting the MBCD than risperidone as indicated by its lower mean accuracy and mean bias values. SD-3 (risperidone:MBCD, 1:3) was incorporated into ODT tablets containing diluent (D-mannitol, FlowLac (R) 100 or galenIQ (TM)-721) and superdisintegrant (Kollidon (R) CL-SF, Ac-Di-Sol or sodium starch glycolate). Disintegration time, T(50) and T(90) were decreased in the formulations containing mannitol and Kollidon (R) CL-SF, but increased with galenIQ (TM)-721 and sodium starch glycolate, respectively. NIR-CI images confirmed the homogeneity of SD and ODT formulations. Published by Elsevier B.V. C1 [Rahman, Ziyaur; Zidan, Ahmed S.; Khan, Mansoor A.] US FDA, DPQR, CDER, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, DPQR, CDER, 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) FX The authors would like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting post doctoral research program. NR 49 TC 29 Z9 30 U1 1 U2 20 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 NOV 15 PY 2010 VL 400 IS 1-2 BP 49 EP 58 DI 10.1016/j.ijpharm.2010.08.025 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 675KP UT WOS:000283829900008 PM 20801200 ER PT J AU Hailemariam, K Iwasaki, K Huang, BW Sakamoto, K Tsuji, Y AF Hailemariam, Kiros Iwasaki, Kenta Huang, Bo-Wen Sakamoto, Kensuke Tsuji, Yoshiaki TI Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress SO JOURNAL OF CELL SCIENCE LA English DT Article DE HIPK2; ATF1; Phosphorylation; Ferritin; Genotoxic stress; Transcription ID INTERACTING PROTEIN KINASE-2; ELEMENT-BINDING PROTEIN; INDUCIBLE FACTOR-I; RESPONSIVE ELEMENT; OXIDATIVE STRESS; H-GENE; ACTIVATES TRANSCRIPTION; MEDIATED TRANSCRIPTION; INDUCED APOPTOSIS; HYPOXIC RESPONSE AB ATF1 (activating transcription factor 1), a stimulus-induced CREB family transcription factor, plays important roles in cell survival and proliferation. Phosphorylation of ATF1 at Ser63 by PKA (cAMP-dependent protein kinase) and related kinases was the only known post-translational regulatory mechanism of ATF1. Here, we found that HIPK2 (homeodomain-interacting protein kinase 2), a DNA-damage-responsive nuclear kinase, is a new ATF1 kinase that phosphorylates Ser198 but not Ser63. ATF1 phosphorylation by HIPK2 activated ATF1 transcription function in the GAL4-reporter system. ATF1 is a transcriptional repressor of ferritin H, the major intracellular iron storage gene, through an ARE (antioxidant-responsive element). HIPK2 overrode the ATF1-mediated ARE repression in a kinase-activity-dependent manner in HepG2 cells. Furthermore, DNA-damage-inducing agents doxorubicin, etoposide and sodium arsenite induced ferritin H mRNA expression in HIPK2(+/+) MEF cells, whereas it was significantly impaired in HIPK2(-/-) MEF cells. Induction of other ARE-regulated detoxification genes such as NQO1 (NADPH quinone oxidoreductase 1), GST (glutathione S-transferase) and HO1 (heme oxygenase 1) by genotoxic stress was also decreased in HIPK2-deficient cells. Taken together, these results suggest that HIPK2 is a new ATF1 kinase involved in the regulation of ferritin H and other antioxidant detoxification genes in genotoxic stress conditions. C1 [Hailemariam, Kiros; Iwasaki, Kenta; Huang, Bo-Wen; Sakamoto, Kensuke; Tsuji, Yoshiaki] N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. [Hailemariam, Kiros] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Iwasaki, Kenta] Nagoya Univ, Sch Med, Dept Appl Immunol, Showa Ku, Nagoya, Aichi 4668550, Japan. RP Tsuji, Y (reprint author), N Carolina State Univ, Dept Environm & Mol Toxicol, Campus Box 7633, Raleigh, NC 27695 USA. EM yoshiaki_tsuji@ncsu.edu FU National Institutes of Health [DK-60007, ES-007046, DK-60007S]; North Carolina State University FX We are grateful to Eric J. Huang at University of California San Francisco for providing us with the HIPK2 wild-type and knockout MEF cells. We thank M. Lienhard Schmitz at Justus-Liebig University, Germany for HIPK2 plasmids. We thank Jun Ninomiya-Tsuji at North Carolina State University for plasmids and discussion. This work was supported in part by National Institutes of Health research grant DK-60007 to Y.T. K.H. was supported by the National Institutes of Health training grant ES-007046 and the National Institutes of Health minority supplement grant DK-60007S. B.-W.H. was supported by North Carolina State University Research Assistant Fellowship. Deposited in PMC for release after 12 months. NR 68 TC 21 Z9 23 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2010 VL 123 IS 22 BP 3863 EP 3871 DI 10.1242/jcs.073627 PG 9 WC Cell Biology SC Cell Biology GA 675BM UT WOS:000283798600005 PM 20980392 ER PT J AU Heather, A Nina, R Emilio, P Dwight, F Rashmi, R Derese, G Paul, P Svetlana, G Yi-Wen, C Ingrid, L Kanneboyina, N AF Heather M, Alger Nina, Raben Emilio, Pistilli Dwight, Francia Rashmi, Rawat Derese, Getnet Paul, Plotz Svetlana, Ghimbovschi Yi-Wen, Chen Ingrid, Lundberg Kanneboyina, Nagaraju TI The role of Tumor Necrosis Factor-alpha-Related Apoptosis Inducing Ligand (TRAIL) in mediating muscle fiber damage in myositis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Meeting Abstract CT 10th Congress of the International-Society-of-Neuroimmunology (ISNI) CY OCT 26-30, 2010 CL Sitges, SPAIN SP Int Soc Neuroimmunol C1 [Heather M, Alger; Dwight, Francia; Svetlana, Ghimbovschi; Yi-Wen, Chen; Kanneboyina, Nagaraju] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. [Nina, Raben; Paul, Plotz] NIAMSD, NIH, Bethesda, MD 20892 USA. [Emilio, Pistilli] Univ Penn, Penn Muscle Inst, Philadelphia, PA 19104 USA. [Rashmi, Rawat] US FDA, Silver Spring, MD USA. [Derese, Getnet] Johns Hopkins Univ, Baltimore, MD USA. [Ingrid, Lundberg] Karolinska Univ Hosp Solna, Dept Med, Rheumatol Unit, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV 15 PY 2010 VL 228 IS 1-2 SI SI BP 206 EP 206 PG 1 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 673WH UT WOS:000283694400585 ER PT J AU Southworth, MR Temple, R AF Southworth, Mary Ross Temple, Robert TI Interaction of Clopidogrel and Omeprazole SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Southworth, Mary Ross; Temple, Robert] US FDA, Silver Spring, MD USA. RP Southworth, MR (reprint author), US FDA, Silver Spring, MD USA. NR 1 TC 9 Z9 9 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 11 PY 2010 VL 363 IS 20 BP 1977 EP 1977 DI 10.1056/NEJMc1012022 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 678CR UT WOS:000284047600036 PM 21067412 ER PT J AU Schlessinger, S Kokko, K Fratkin, J Butt, F Hawxby, A Todaro, M Henderson, H Seawright, A Parker, C Byers, P Gonzalez-Peralta, R Kayler, L Fauerbach, L Lawrence, R Haafiz, A Stanek, D Hammond, R Thoroughman, D Pippen, T Johnson, S Mahle, W Lyon, G Laporte, K Kanter, K Ivey, M Arnold, K Lance, S Navarro-Almario, E Farnon, E Kuehnert, M Shieh, W Paddock, C Zaki, S Drew, C Schmitz, A Sejvar, J Sriram, R Visvesvara, G Beach, M Yoder, J Roy, S Qvarnstrom, Y Bandea, R daSilva, A Bosserman, E Budge, P Lutterloh, E AF Schlessinger, S. Kokko, K. Fratkin, J. Butt, F. Hawxby, A. Todaro, M. Henderson, H. Seawright, A. Parker, C. Byers, P. Gonzalez-Peralta, R. Kayler, L. Fauerbach, L. Lawrence, R. Haafiz, A. Stanek, D. Hammond, R. Thoroughman, D. Pippen, T. Johnson, S. Mahle, W. Lyon, G., III Laporte, K. Kanter, K. Ivey, M. Arnold, K. Lance, S. Navarro-Almario, E. Farnon, E. Kuehnert, M. Shieh, W. Paddock, C. Zaki, S. Drew, C. Schmitz, A. Sejvar, J. Sriram, R. Visvesvara, G. Beach, M. Yoder, J. Roy, S. Qvarnstrom, Y. Bandea, R. daSilva, A. Bosserman, E. Budge, P. Lutterloh, E. TI Balamuthia mandrillaris Transmitted Through Organ Transplantation-Mississippi, 2009 (Reprinted from vol 59, pg 1165-1170, 2010) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 [Schlessinger, S.] Mississippi Organ Recovery Agcy, Flowood, MS USA. [Kokko, K.; Fratkin, J.; Butt, F.; Hawxby, A.; Todaro, M.; Henderson, H.; Seawright, A.; Parker, C.] Univ Mississippi, Med Ctr, University, MS 38677 USA. [Gonzalez-Peralta, R.; Kayler, L.; Fauerbach, L.; Lawrence, R.; Haafiz, A.] Univ Florida, Shands Hosp, Gainesville, FL 32611 USA. [Mahle, W.; Lyon, G., III; Laporte, K.; Kanter, K.] Emory Univ, Childrens Healthcare Atlanta, Atlanta, GA 30322 USA. [Navarro-Almario, E.] US FDA, Rockville, MD 20857 USA. [Budge, P.; Lutterloh, E.] CDC, EIS, Atlanta, GA 30333 USA. RP Schlessinger, S (reprint author), Mississippi Organ Recovery Agcy, Flowood, MS USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 2010 VL 304 IS 18 BP 2008 EP 2012 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 677OB UT WOS:000284000600010 ER PT J AU Resnic, FS Gross, TP Marinac-Dabic, D Loyo-Berrios, N Donnelly, S Normand, SLT Matheny, ME AF Resnic, Frederic S. Gross, Thomas P. Marinac-Dabic, Danica Loyo-Berrios, Nilsa Donnelly, Sharon Normand, Sharon-Lise T. Matheny, Michael E. TI Automated Surveillance to Detect Postprocedure Safety Signals of Approved Cardiovascular Devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTERVENTIONAL CARDIOLOGY; RANDOMIZED-TRIAL; MEDICAL DEVICE; STENTS; CATHETERIZATION; COMPLICATIONS; METAANALYSIS; REGISTRY; HOLES; RISK AB Context Ensuring the safety of medical devices challenges current surveillance approaches, which rely heavily on voluntary reporting of adverse events. Automated surveillance of clinical registries may provide early warnings in the postmarket evaluation of medical device safety. Objective To determine whether automated safety surveillance of clinical registries using a computerized tool can provide early warnings regarding the safety of new cardiovascular devices. Design, Setting, and Patients Prospective propensity-matched cohort analysis of 7 newly introduced cardiovascular devices, using clinical data captured in the Massachusetts implementation of the National Cardiovascular Data Repository CathPCI Registry for all adult patients undergoing percutaneous coronary intervention from April 2003 through September 2007 in Massachusetts. Main Outcome Measure Presence of any safety alert, triggered if the cumulative observed risk for a given device exceeded the upper 95% confidence interval (CI) of comparator control device. Predefined sensitivity analyses assessed robustness of alerts when triggered. Results We evaluated 74 427 consecutive interventional coronary procedures. Three of 21 safety analyses triggered sustained alerts in 2 implantable devices. Patients receiving Taxus Express2 drug-eluting stents experienced a 1.28-fold increased risk of post-procedural myocardial infarction (2.87% vs 2.25%; absolute risk increase, 0.62% [95% CI, 0.25%-0.99%]) and a 1.21-fold increased risk of major adverse cardiac events (4.24% vs 3.50%; absolute increase, 0.74% [95% CI, 0.29%-1.19%]) compared with those receiving alternative drug-eluting stents. Patients receiving Angio-Seal STS vascular closure devices experienced a 1.51-fold increased risk of major vascular complications (1.09% vs 0.72%; absolute increased risk, 0.37% [95% CI, 0.03%-0.71%]) compared with those receiving alternative vascular closure devices. Sensitivity analyses confirmed increased risk following use of the Taxus Express2 stent but not the Angio-Seal STS device. Conclusion Automated prospective surveillance of clinical registries is feasible and can identify low-frequency safety signals for new cardiovascular devices. JAMA. 2010;304(18):2019-2027 www.jama.com C1 [Resnic, Frederic S.; Donnelly, Sharon] Brigham & Womens Hosp, Boston, MA 02115 USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Gross, Thomas P.; Marinac-Dabic, Danica; Loyo-Berrios, Nilsa] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Normand, Sharon-Lise T.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Matheny, Michael E.] Tennessee Valley Healthcare Syst, Vet Adm Med Ctr, Nashville, TN USA. [Matheny, Michael E.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Resnic, FS (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM fresnic@partners.org FU Boston Scientific Inc; Abbott Vascular Inc; Cordis Corp; St Jude Medical; Medicines Company; National Library of Medicine [NIH R01-LM008142]; US Food and Drug Administration [HHSF 223200830058C]; Veterans Administration Health Services Research and Development Service [CDP 09-387]; Division of Healthcare Quality and Statistics, Massachusetts Department of Public Health FX Dr Resnic and Dr Matheny reported filing a patent application, currently under review at the US Patent Office, for several key analytic components of the DELTA surveillance system; the intellectual property rights of Drs Resnic and Matheny (current and former employees of Brigham and Women's Hospital) related to the development of DELTA are assigned to the institution, and Partners Healthcare, the parent organization of Brigham and Women's Hospital, retains partial rights for DELTA use and licensing. Neither Dr Resnic nor Dr Matheny have previously received or anticipate any financial compensation, stock options, income, or ownership in DELTA, Coping Systems, or any other related commercial entity. Dr Resnic reported receiving modest consulting income from Boston Scientific Inc, Abbott Vascular Inc, Cordis Corp, and St Jude Medical and receiving research grants from The Medicines Company. No other authors reported dislosures.; This study was funded, in part, by grants from the National Library of Medicine (NIH R01-LM008142) and the US Food and Drug Administration (HHSF 223200830058C) as well as from the Veterans Administration Health Services Research and Development Service (CDP 09-387).; The National Institutes of Health, the Veterans Administration Health Services Research and Development Service, and the US Food and Drug Administration had no role in the design and conduct of the study; the collection, management, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. However, the preliminary proposed study protocol was provided to the Veterans Administration Health Services Research and Development Service and the US Food and Drug Administration as part of the original grant and contract application process.; We acknowledge the significant system development and technical contributions of Richard Cope, BS, and Susan Robbins, BS, of Coping Systems Inc, Andover, Massachusetts. Coping Systems was a subcontractor to Brigham and Women's Hospital, and neither Mr Cope nor Ms Robbins received extra compensation for their contributions; Mr Cope is part owner of Coping Systems and is also named on the patent application filed by Dr Resnic and Dr Matheny. We also acknowledge the support of the Division of Healthcare Quality and Statistics, Massachusetts Department of Public Health. NR 33 TC 35 Z9 35 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 10 PY 2010 VL 304 IS 18 BP 2019 EP 2027 DI 10.1001/jama.2010.1633 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 677OB UT WOS:000284000600020 PM 21063011 ER PT J AU Nakashima, H Fujisawa, T Husain, SR Puri, RK AF Nakashima, Hideyuki Fujisawa, Toshio Husain, Syed R. Puri, Raj K. TI Interleukin-13 receptor alpha 2 DNA prime boost vaccine induces tumor immunity in murine tumor models SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID THERAPEUTIC CANCER VACCINES; REGULATORY T-CELLS; IL-13 RECEPTOR; FUNCTIONAL-CHARACTERIZATION; PSEUDOMONAS EXOTOXIN; MAMMARY-TUMOR; CLASS-II; IN-VIVO; PROTEIN; CHAIN AB Background: DNA vaccines represent an attractive approach for cancer treatment by inducing active T cell and B cell immune responses to tumor antigens. Previous studies have shown that interleukin-13 receptor alpha 2 chain (IL-13R alpha 2), a tumor-associated antigen is a promising target for cancer immunotherapy as high levels of IL-13R alpha 2 are expressed on a variety of human tumors. To enhance the effectiveness of DNA vaccine, we used extracellular domain of IL-13R alpha 2 (ECD alpha 2) as a protein-boost against murine tumor models. Methods: We have developed murine models of tumors naturally expressing IL-13R alpha 2 (MCA304 sarcoma, 4T1 breast carcinoma) and D5 melanoma tumors transfected with human IL-13R alpha 2 in syngeneic mice and examined the antitumor activity of DNA vaccine expressing IL-13R alpha 2 gene with or without ECD alpha 2 protein mixed with CpG and IFA adjuvants as a boost vaccine. Results: Mice receiving IL-13R alpha 2 DNA vaccine boosted with ECD alpha 2 protein were superior in exhibiting inhibition of tumor growth, compared to mice receiving DNA vaccine alone, in both prophylactic and therapeutic vaccine settings. In addition, prime-boost vaccination significantly prolonged the survival of mice compared to DNA vaccine alone. Furthermore, ECD alpha 2 booster vaccination increased IFN-gamma production and CTL activity against tumor expressing IL-13R alpha 2. The immunohistochemical analysis showed the infiltration of CD4 and CD8 positive T cells and IFN-gamma-induced chemokines (CXCL9 and CXCL10) in regressing tumors of immunized mice. Finally, the prime boost strategy was able to reduce immunosuppressive CD4(+) CD25(+) Foxp3(+) regulatory T cells (Tregs) in the spleen and tumor of vaccinated mice. Conclusion: These results suggest that immunization with IL-13R alpha 2 DNA vaccine followed by ECD alpha 2 boost mixed with CpG and IFA adjuvants inhibits tumor growth in T cell dependent manner. Thus our results show an enhancement of efficacy of IL-13R alpha 2 DNA vaccine with ECD alpha 2 protein boost and offers an exciting approach in the development of new DNA vaccine targeting IL-13R alpha 2 for cancer immunotherapy. C1 [Nakashima, Hideyuki; Fujisawa, Toshio; Husain, Syed R.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov NR 44 TC 9 Z9 10 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD NOV 10 PY 2010 VL 8 AR 116 DI 10.1186/1479-5876-8-116 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 686NH UT WOS:000284702500001 PM 21067607 ER PT J AU Rao, VA Klein, SR Bonar, SJ Zielonka, J Mizuno, N Dickey, JS Keller, PW Joseph, J Kalyanaraman, B Shacter, E AF Rao, V. Ashutosh Klein, Sarah R. Bonar, Spencer J. Zielonka, Jacek Mizuno, Naoko Dickey, Jennifer S. Keller, Paul W. Joseph, Joy Kalyanaraman, Balaraman Shacter, Emily TI The Antioxidant Transcription Factor Nrf2 Negatively Regulates Autophagy and Growth Arrest Induced by the Anticancer Redox Agent Mitoquinone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBSTRATE ADAPTER PROTEIN; MALIGNANT GLIOMA-CELLS; CANCER-CELLS; TARGETED ANTIOXIDANTS; OXIDATIVE DAMAGE; ARSENIC TRIOXIDE; TOPOISOMERASE-I; DT-DIAPHORASE; MCF-7 CELLS; DNA-DAMAGE AB Mitoquinone (MitoQ) is a synthetically modified, redox-active ubiquinone compound that accumulates predominantly in mitochondria. We found that MitoQ is 30-fold more cytotoxic to breast cancer cells than to healthy mammary cells. MitoQ treatment led to irreversible inhibition of clonogenic growth of breast cancer cells through a combination of autophagy and apoptotic cell death mechanisms. Relatively limited cytotoxicity was seen with the parent ubiquinone coenzyme Q(10). Inhibition of cancer cell growth by MitoQ was associated with G(1)/S cell cycle arrest and phosphorylation of the checkpoint kinases Chk1 and Chk2. The possible role of oxidative stress in MitoQ activity was investigated by measuring the products of hydroethidine oxidation. Increases in ethidium and dihydroethidium levels, markers of one-electron oxidation of hydroethidine, were observed at cytotoxic concentrations of MitoQ. Keap1, an oxidative stress sensor protein that regulates the antioxidant transcription factor Nrf2, underwent oxidation, degradation, and dissociation from Nrf2 in MitoQ-treated cells. Nrf2 protein levels, nuclear localization, and transcriptional activity also increased following MitoQ treatment. Knockdown of Nrf2 caused a 2-fold increase in autophagy and an increase in G(1) cell cycle arrest in response to MitoQ but had no apparent effect on apoptosis. The Nrf2-regulated enzyme NQO1 is partly responsible for controlling the level of autophagy. Keap1 and Nrf2 act as redox sensors for oxidative perturbations that lead to autophagy. MitoQ and similar compounds should be further evaluated for novel anticancer activity. C1 [Rao, V. Ashutosh; Klein, Sarah R.; Bonar, Spencer J.; Dickey, Jennifer S.; Shacter, Emily] US FDA, Biochem Lab, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Zielonka, Jacek; Joseph, Joy; Kalyanaraman, Balaraman] Med Coll Wisconsin, Free Radical Res Ctr, Milwaukee, WI 53226 USA. [Mizuno, Naoko; Keller, Paul W.] NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Rao, VA (reprint author), 29 Lincoln Dr,Bldg 29A,Rm 2A-09,HFD-122, Bethesda, MD 20892 USA. EM ashutosh.rao@fda.hhs.gov; emily.shacter@fda.hhs.gov RI Zielonka, Jacek/N-9546-2014 OI Zielonka, Jacek/0000-0002-2524-0145 FU NIAMS; NCI; National Institutes of Health [RO1CA125112, RO1CA136799] FX This work was supported in part by National Institutes of Health Intramural Research Programs of NIAMS and NCI and by National Institutes of Health Grants RO1CA125112 and RO1CA136799. NR 58 TC 62 Z9 63 U1 0 U2 12 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 5 PY 2010 VL 285 IS 45 BP 34447 EP 34459 DI 10.1074/jbc.M110.133579 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 673KL UT WOS:000283659100019 PM 20805228 ER PT J AU Jha, KN Wong, L Zerfas, PM De Silva, RS Fan, YX Spiridonov, NA Johnson, GR AF Jha, Kula N. Wong, Lily Zerfas, Patricia M. De Silva, Rukman S. Fan, Ying-Xin Spiridonov, Nikolay A. Johnson, Gibbes R. TI Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HSP90 CHAPERONE MACHINERY; MOLECULAR CHAPERONES; SIGNAL-TRANSDUCTION; MALE-INFERTILITY; PROTEIN-KINASES; CO-CHAPERONE; BINDING; CELL; SPERMATOGENESIS; RECEPTOR AB We previously reported the identification of small serine/threonine kinase (SSTK) that is expressed in postmeiotic germ cells, associates with HSP90, and is indispensable for male fertility. Sperm from SSTK-null mice cannot fertilize eggs in vitro and are incapable of fusing with eggs that lack zona pellucida. Here, using the yeast two-hybrid screen, we have discovered a novel SSTK-interacting protein (SIP) that is expressed exclusively in testis. The gene encoding SIP is restricted to mammals and encodes a 125-amino acid polypeptide with a predicted tetratricopeptide repeat domain. SIP is co-localized with SSTK in the cytoplasm of spermatids as they undergo restructuring and chromatin condensation, but unlike SSTK, is not retained in the mature sperm. SIP binds to SSTK with high affinity (K-d similar to 10 nM), and the proteins associate with each other when co-expressed in cells. In vitro, SIP inhibited SSTK kinase activity, whereas the presence of SIP in cells resulted in enzymatic activation of SSTK without affecting Akt or MAPK activity. SIP was found to be associated with cellular HSP70, and analyses with purified proteins revealed that SIP directly bound HSP70. Importantly, SSTK recruited SIP onto HSP90, and treatment of cells with the specific HSP90 inhibitor, 17-allylamino-17-demethoxygeldanamycin, completely abolished SSTK catalytic activity. Hence, these findings demonstrate that HSP90 is essential for functional maturation of the kinase and identify SIP as a cochaperone that is critical to the HSP90-mediated activation of SSTK. C1 [Jha, Kula N.; Wong, Lily; De Silva, Rukman S.; Fan, Ying-Xin; Spiridonov, Nikolay A.; Johnson, Gibbes R.] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Zerfas, Patricia M.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. RP Johnson, GR (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,HFD 122, Bethesda, MD 20892 USA. EM gibbes.johnson@fda.hhs.gov RI Spiridonov, Nikolay/B-6287-2014 NR 39 TC 3 Z9 6 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 NOV 5 PY 2010 VL 285 IS 45 BP 35180 EP 35187 DI 10.1074/jbc.M110.134767 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 673KL UT WOS:000283659100091 PM 20829357 ER PT J AU Kilcoyne, J Fux, E AF Kilcoyne, Jane Fux, Elie TI Strategies for the elimination of matrix effects in the liquid chromatography tandem mass spectrometry analysis of the lipophilic toxins okadaic acid and azaspiracid-1 in molluscan shellfish SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Lipophilic marine biotoxins; Azaspiracid; Okadaic acid; LC-MS; On-line SPE; Matrix effects ID SINGLE-LABORATORY VALIDATION; MYTILUS-EDULIS; SPORTS DRINKS; SOFT DRINKS; PERFORMANCE; MUSSELS; RESIDUES AB Considerable efforts are being made worldwide to replace in vivo assays with instrumental methods of analysis for the monitoring of marine biotoxins in shellfish Analysis of these compounds by the preferred technique of liquid chromatography tandem mass spectrometry (LC-MS/MS) is challenged by matrix effects associated with the shellfish tissues In methods validation assessment of matrix interferences is imperative to ensure the validity and accuracy of results being produced Matrix Interferences for the analysis of okadaic acid (OA) and azaspiracid 1 (AZA1) were assessed using acidic methods on electrospray triple stage quadrupole (TSQ) and hybrid quadrupole time of flight (QToF) instruments by the use of matrix matched standards for different tissue types Using an acidic method no matrix interference and suppression was observed on the TSQ for OA and AZA1 respectively whilst the opposite was observed on the QToF matrix enhancement for OA and no matrix interference for AZA1 The suppression of AZAs on the TSQ was found to be due to interfering compounds being carried over from previous injections The degree of suppression is very much dependant on the tissue type ranging from 15 to 70% Several strategies were evaluated to eliminate these interferences including the partitioning of the extract with hexane optimisation of the chromatographic method and the use of on-line SPE Hexane clean up did not have any impact on matrix effects The use of an alkaline method and a modified acidic method eliminated matrix suppression for AZA1 on the TSQ instrument while an on-line SPE method proved to be effective for matrix enhancement of OA on the QToF (C) 2010 Elsevier B V All rights reserved C1 [Kilcoyne, Jane] Marine Inst Renville, Oranmore, Galway, Ireland. [Fux, Elie] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Kilcoyne, J (reprint author), Marine Inst Renville, Oranmore, Galway, Ireland. OI Kilcoyne, Jane/0000-0002-1219-7731 FU Department of Agriculture Fisheries and Food FX This work was carried out as part of the national Irish biotoxin monitoring programme which is funded by the Department of Agriculture Fisheries and Food NR 39 TC 29 Z9 30 U1 3 U2 26 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 5 PY 2010 VL 1217 IS 45 BP 7123 EP 7130 DI 10.1016/j.chroma.2010.09.020 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 677EX UT WOS:000283973000015 PM 20926091 ER PT J AU Stang, PE Ryan, PB Racoosin, JA Overhage, JM Hartzema, AG Reich, C Welebob, E Scarnecchia, T Woodcock, J AF Stang, Paul E. Ryan, Patrick B. Racoosin, Judith A. Overhage, J. Marc Hartzema, Abraham G. Reich, Christian Welebob, Emily Scarnecchia, Thomas Woodcock, Janet TI Advancing the Science for Active Surveillance: Rationale and Design for the Observational Medical Outcomes Partnership SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID SAFETY SURVEILLANCE; CLAIMS DATA; EVENTS; CARE; ALGORITHMS; DATABASE; NETWORK; RECORDS AB The U.S. Food and Drug Administration (FDA) Amendments Act of 2007 mandated that the FDA develop a system for using automated health care data to identify risks of marketed drugs and other medical products. The Observational Medical Outcomes Partnership is a public-private partnership among the FDA, academia, data owners, and the pharmaceutical industry that is responding to the need to advance the science of active medical product safety surveillance by using existing observational databases. The Observational Medical Outcomes Partnership's transparent, open innovation approach is designed to systematically and empirically study critical governance, data resource, and methodological issues and their interrelationships in establishing a viable national program of active drug safety surveillance by using observational data. This article describes the governance structure, data-access model, methods-testing approach, and technology development of this effort, as well as the work that has been initiated. C1 [Stang, Paul E.] Johnson & Johnson, Pharmaceut Res & Dev, Titusville, NJ 08560 USA. Fdn Natl Inst Hlth, Bethesda, MD USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Regenstrief Inst Hlth Care, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Florida, Coll Pharm, Gainesville, FL USA. Digital Aurora, Manchester, VT USA. RP Stang, PE (reprint author), Johnson & Johnson, Pharmaceut Res & Dev, 1125 Trenton Harbourton Rd,POB 200,MS K304, Titusville, NJ 08560 USA. EM PStang@its.jnj.com OI Overhage, Joseph/0000-0003-0223-0195 FU Foundation for the National Institutes of Health FX The OMOP is funded by the Foundation for the National Institutes of Health, with contributions from a consortium of 17 organizations (Appendix Table, available at www.annals.org). Three members of the research team (Dr. Stang, Mr. Ryan, and Dr. Racoosin) serve in-kind and are not compensated for their participation. NR 35 TC 133 Z9 134 U1 1 U2 15 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD NOV 2 PY 2010 VL 153 IS 9 BP 600 EP 606 DI 10.7326/0003-4819-153-9-201011020-00010 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 673MH UT WOS:000283667000007 PM 21041580 ER PT J AU Abbasi, F Degheidy, HA Marti, GE AF Abbasi, Fatima Degheidy, Heba A. Marti, Gerald E. TI CONSENSUS DESCRIPTION OF BICLONAL MBL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 25th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 01-05, 2010 CL Houston, TX SP Int Clin Cytometry Soc C1 [Abbasi, Fatima; Degheidy, Heba A.; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2010 VL 78B IS 6 BP 390 EP 390 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100006 ER PT J AU Degheidy, HA Venzon, DJ Farooqui, MZH Abbasi, F Arthur, DC Wiestner, A Stevenson, MAS Marti, GE AF Degheidy, Heba A. Venzon, David J. Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Dian C. Wiestner, Adrian Stevenson, M. A. Stetler Marti, Gerald E. TI ONE STEP METHOD TOWARD STANDARDIZATION OF ZAP-70 EXPRESSION ANALYSIS IN CLL. SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 25th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 01-05, 2010 CL Houston, TX SP Int Clin Cytometry Soc C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Dian C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2010 VL 78B IS 6 BP 393 EP 393 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100016 ER PT J AU Degheidy, HA Venzon, D Farooqui, MZH Abbasi, F Arthur, DC Wiestner, A Stevenson, MAS Marti, GE AF Degheidy, Heba A. Venzon, David Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Diane C. Wiestner, Adrian Stevenson, M. A. Stetler Marti, Gerald E. TI COMBINED ANALYSIS OF ZAP-70,CD38,CD69,CD26,CD49D,CD27 AS A PREDICTOR FOR IGVH MUTATIONAL STATUS IN CLL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 25th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 01-05, 2010 CL Houston, TX SP Int Clin Cytometry Soc C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Venzon, David] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2010 VL 78B IS 6 BP 393 EP 394 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100017 ER PT J AU Degheidy, HA Venzon, DJ Farooqui, MZH Abbasi, F Arthur, DC Wiestner, A Stevenson, MAS Marti, GE AF Degheidy, Heba A. Venzon, David J. Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Diane C. Wiestner, Adrian Stevenson, M. A. Stetler Marti, Gerald E. TI ZAP-70 ANALYSIS IN CLL USING TWO DIFFERENT MONOCLONAL ANTIBODIES SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 25th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 01-05, 2010 CL Houston, TX SP Int Clin Cytometry Soc C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Venzon, David J.] NCI, Biostat & Data Management Sect, Rockville, MD USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2010 VL 78B IS 6 BP 394 EP 394 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100018 ER PT J AU Degheidy, HA Gadalla, SM Farooqui, MZH Abbasi, F Arthur, DC Wiestner, A Stevenson, MAS Marti, GE AF Degheidy, Heba A. Gadalla, Shahinaz M. Farooqui, Mohammed Z. H. Abbasi, Fatima Arthur, Diane C. Wiestner, Adrian Stevenson, M. A. Stetler Marti, Gerald E. TI BCL-2: BIOMARKER FOR 13Q14 DELETION STATUS IN CLL SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 25th Annual Meeting of the International-Clinical-Cytometry-Society CY OCT 01-05, 2010 CL Houston, TX SP Int Clin Cytometry Soc C1 [Degheidy, Heba A.; Abbasi, Fatima; Arthur, Diane C.; Stevenson, M. A. Stetler; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Gadalla, Shahinaz M.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2010 VL 78B IS 6 BP 394 EP 395 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 677BW UT WOS:000283965100019 ER PT J AU Justice, R Ibrahim, A Murgo, A Pazdur, R AF Justice, R. Ibrahim, A. Murgo, A. Pazdur, R. TI The point of view of FDA SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY NOV 16-19, 2010 CL Berlin, GERMANY C1 [Justice, R.; Ibrahim, A.; Murgo, A.; Pazdur, R.] US FDA, Off Oncol Drug Prod, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2010 VL 8 IS 7 BP 20 EP 20 DI 10.1016/S1359-6349(10)71736-5 PG 1 WC Oncology SC Oncology GA 735ZU UT WOS:000288460100034 ER PT J AU Dunne, J Margaryants, L Murphy, MD Myers, AM Avant, D Rodriguez, WJ AF Dunne, Julia Margaryants, Lala Murphy, M. Dianne Myers, Ann M. Avant, Debbie Rodriguez, William J. TI Globalization Facilitates Pediatric Drug Development in the 21st Century SO DRUG INFORMATION JOURNAL LA English DT Article DE Globalization; Pediatric clinical trial; FDA ID OFF-LABEL; CHILDREN; TRIALS AB Introduction: US legislation, supported by strengthened ethical frameworks and improved trial design, has produced significant increases in the number of pediatric clinical trials. This has global implications. Method: We reviewed all submissions of pediatric data received by the US FDA from 2002 to 2007 in response to new FDA pediatric initiatives. Results: Although 54% of the trials were multinational, the US dominated as a trial location. The European Union and Latin America followed. Few trials specifically studied neonates, infants, and toddlers. Conclusion: Although most pediatric drug programs are global, the United States remains the dominant location for pediatric trials. This distribution differs for adult trials. The balance may change in the future. EU and FDA regulators should continue to discuss coordinated approaches to minimize unnecessary pediatric trials and to optimize trial design, safety, and conduct so that the limited pediatric populations available are enrolled only in ethically implemented, scientifically important trials. C1 [Dunne, Julia; Murphy, M. Dianne; Myers, Ann M.; Avant, Debbie; Rodriguez, William J.] US FDA, Off Pediat Therapeut, Silver Spring, MD 20993 USA. [Margaryants, Lala] Sci Ctr Drug & Med Technol Expertise, Yerevan, Armenia. RP Dunne, J (reprint author), US FDA, Off Pediat Therapeut, 10903 New Hampshire Ave,Bldg 32,Room 5154, Silver Spring, MD 20993 USA. EM julia.dunne@fda.hhs.gov NR 16 TC 4 Z9 5 U1 0 U2 2 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 2010 VL 44 IS 6 BP 757 EP 765 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 678ZV UT WOS:000284130100012 ER PT J AU Oakley, MS Majam, V Majajan, B McCutchan, T Aravind, L Kumar, S AF Oakley, Miranda S. Majam, Victoria Majajan, Babita McCutchan, Thomas Aravind, L. Kumar, Sanjai TI MOLECULAR DETERMINANTS OF EXPERIMENTAL CEREBRAL MALARIA IN THE BRAIN AND CIRCULATION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Oakley, Miranda S.; Majam, Victoria; Majajan, Babita; Kumar, Sanjai] US FDA, Rockville, MD 20857 USA. [McCutchan, Thomas; Aravind, L.] NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 425 BP 127 EP 127 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700426 ER PT J AU Anez, G Chancey, CJ Grinev, A Morales-Betoulle, ME Rios, M AF Anez, German Chancey, Caren J. Grinev, Andriyan Morales-Betoulle, Maria E. Rios, Maria TI PHYLOGENETIC ANALYSIS OF AN ISOLATE OF DENGUE VIRUS TYPE 2 FROM GUATEMALA, 2009 SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Anez, German; Chancey, Caren J.; Grinev, Andriyan; Rios, Maria] US FDA, Bethesda, MD 20014 USA. [Morales-Betoulle, Maria E.] Univ Valle Guatemala, Guatemala City, Guatemala. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 512 BP 154 EP 154 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819700513 ER PT J AU Chancey, C Lee-Stroka, A Rios, M AF Chancey, Caren Lee-Stroka, Agnes Rios, Maria TI WEST NILE VIRUS BINDS TO RED BLOOD CELLS OF SEVERAL VERTEBRATE SPECIES SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH) CY NOV 03-07, 2010 CL Atlanta, GA SP Amer Soc Trop Med & Hyg (ASTMH) C1 [Chancey, Caren; Rios, Maria] Food & Drug Adm CBER, Bethesda, MD USA. [Lee-Stroka, Agnes] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2010 VL 83 IS 5 SU S MA 1060 BP 316 EP 316 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 832QF UT WOS:000295819701427 ER PT J AU deVore, NC Huynh, S Dobrovolskaia, EN Slater, JE AF deVore, Nicolette C. Huynh, Susan Dobrovolskaia, Ekaterina N. Slater, Jay E. TI Multiplex microbead measurements for the characterization of cat and ragweed allergen extracts SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID FEL-D-I; POTENCY; IGE; STABILITY; POLLEN; PURIFICATION; INFORMATION; REACTIVITY; ANTIBODIES; EXPOSURE AB Background: Current assays for allergen extracts can measure either overall potency or the levels of individual allergens. Objective: To develop a multiplex allergen extract potency assay (MAEPA) for allergen extracts that can concurrently measure individual allergens and characterize the overall allergen levels in the mixture. Methods: Six anti-Fel d 1 and 6 anti-Amb a 1 recombinant antibodies were generated and were covalently bound to carboxy-labeled beads. Antibody-bound beads were then used to measure Fel d 1 and Amb a 1 levels in commercial cat hair and short ragweed pollen (SRP) extracts, respectively, using bead-based flow cytometry. These major allergen levels were compared with those obtained using a conventional antibody-based method. Allergen levels were calculated by comparing the half-maximal effective concentrations of dose-response curves analyzed using 4-parameter fits. Bead-antibody pairs were tested to determine whether the presence of additional bead-antibody pairs affected the apparent potency of the extract. Results: Allergen contents of cat hair and SRP extracts determined using the MAEPA and anti-Fel d 1 and anti-Amb a 1 antibodies were comparable with potencies determined using conventional methods. Cross-interference from the concurrent use of multiple beads was minimal. Six lots of cat hair extract and 6 lots of SRP extract were tested. Conclusions: The MAEPA, a bead-based assay using recombinant antibodies, accurately determined Fel d 1 levels in cat hair allergenic extracts and Amb a 1 levels in SRP extracts. The results of this assay are reproducible and are consistent with data obtained using conventional methods. Ann Allergy Asthma Immunol. 2010;105:351-358. C1 [deVore, Nicolette C.; Huynh, Susan; Dobrovolskaia, Ekaterina N.; Slater, Jay E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. EM Jay.Slater@fda.hhs.gov FU Center for Biologics Evaluation and Research, US Food and Drug Administration FX This study was supported by the Center for Biologics Evaluation and Research, US Food and Drug Administration. NR 26 TC 5 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2010 VL 105 IS 5 BP 351 EP 358 DI 10.1016/j.anai.2010.09.026 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 701PO UT WOS:000285834000006 PM 21055660 ER PT J AU Gnjidic, D Le Couteur, DG Abernethy, DR Hilmer, SN AF Gnjidic, Danijela Le Couteur, David G. Abernethy, Darrell R. Hilmer, Sarah N. TI A Pilot Randomized Clinical Trial Utilizing the Drug Burden Index to Reduce Exposure to Anticholinergic and Sedative Medications in Older People SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE anticholinergic and sedative medications; older adults; prescribing practices ID RISK-INCREASING DRUGS; PRESCRIPTION DRUGS; PHYSICAL FUNCTION; WITHDRAWAL; FALLS; PERCEPTIONS; POPULATION; DECLINE; ADULTS; WOMEN AB BACKGROUND: The drug burden index (DBI) is an evidence-based tool that utilizes pharmacologic principles to calculate an individual's total exposure to anticholinergic and sedative medications. Higher DBI has been associated with functional impairment in observational studies of older people. OBJECTIVE: To assess the impact of providing information about DBI to general practitioners (GPs) on prescribing for older people. METHODS: This was a cluster randomized controlled trial with 3 months of follow-up. Participants were volunteers aged >= 70 years, living in self-care retirement villages in Sydney, Australia. The study intervention involved a letter and phone call to GPs, using DBI to prompt them to consider cessation or dose reduction of anticholinergic and sedative medications. The primary study outcome was to assess the impact of information about DBI on prescribing practices of the GPs. RESULTS: A total of 115 participants were enrolled, 57 in the intervention group (from 6 sites) and 58 in the control group (from 6 sites). At baseline, 19 of 57 participants in the intervention group and 31 of 58 participants in the control group had a DBI >0 (p < 0.05). At follow-up, a DBI change was observed in 16 participants. DBI decreased in 12 participants, 6 (32%) in the intervention group, and 6 (19%) in the control group. GPs identified the following barriers to reducing anticholinergic and sedative drugs: uncomfortable altering prescriptions initiated by specialists; unable to influence patients' attitudes; unaware of patients' medications and strong clinical indication. CONCLUSIONS: The intervention targeting GPs' prescribing practices was less effective than anticipated in reducing anticholinergic and sedative drug exposure, and barriers were identified. Future studies should explore multidisciplinary interventions, engaging patients, specialists, GPs, and pharmacists. C1 [Gnjidic, Danijela] Univ Sydney, Dept Clin Pharmacol, Sydney Med Sch, St Leonards, NSW, Australia. [Le Couteur, David G.] Concord Hosp, Ctr Educ & Res Ageing, Concord, NSW, Australia. [Abernethy, Darrell R.] US FDA, Silver Spring, MD USA. RP Gnjidic, D (reprint author), Univ Sydney, Dept Clin Pharmacol, Sydney Med Sch, St Leonards, NSW, Australia. EM dgnjidic@med.usyd.edu.au OI Hilmer, Sarah/0000-0002-5970-1501 FU Geoff and Elaine Penney Ageing Research Unit FX This study was supported by Geoff and Elaine Penney Ageing Research Unit. NR 28 TC 26 Z9 27 U1 1 U2 7 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2010 VL 44 IS 11 BP 1725 EP 1732 DI 10.1345/aph.1P310 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 679XX UT WOS:000284195200004 PM 20876826 ER PT J AU Johnson, CN Flowers, AR Noriea, NF Zimmerman, AM Bowers, JC DePaola, A Grimes, DJ AF Johnson, C. N. Flowers, A. R. Noriea, N. F., III Zimmerman, A. M. Bowers, J. C. DePaola, A. Grimes, D. J. TI Relationships between Environmental Factors and Pathogenic Vibrios in the Northern Gulf of Mexico SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID OYSTERS CRASSOSTREA-VIRGINICA; PARAHAEMOLYTICUS DENSITIES; CHESAPEAKE BAY; TDH-GENE; VULNIFICUS; WATER; CHOLERAE; COAST; COEFFICIENT; TEMPERATURE AB Although autochthonous vibrio densities are known to be influenced by water temperature and salinity, little is understood about other environmental factors associated with their abundance and distribution. Densities of culturable Vibrio vulnificus containing vvh (V. vulnificus hemolysin gene) and V. parahaemolyticus containing tlh (thermolabile hemolysin gene, ubiquitous in V. parahaemolyticus), tdh (thermostable direct hemolysin gene, V. parahaemolyticus pathogenicity factor), and trh (tdh-related hemolysin gene, V. parahaemolyticus pathogenicity factor) were measured in coastal waters of Mississippi and Alabama. Over a 19-month sampling period, vibrio densities in water, oysters, and sediment varied significantly with sea surface temperature (SST). On average, tdh-to-tlh ratios were significantly higher than trh-to-tlh ratios in water and oysters but not in sediment. Although tlh densities were lower than vvh densities in water and in oysters, the opposite was true in sediment. Regression analysis indicated that SST had a significant association with vvh and tlh densities in water and oysters, while salinity was significantly related to vibrio densities in the water column. Chlorophyll a levels in the water were correlated significantly with vvh in sediment and oysters and with pathogenic V. parahaemolyticus (tdh and trh) in the water column. Furthermore, turbidity was a significant predictor of V. parahaemolyticus density in all sample types (water, oyster, and sediment), and its role in predicting the risk of V. parahaemolyticus illness may be more important than previously realized. This study identified (i) culturable vibrios in winter sediment samples, (ii) niche-based differences in the abundance of vibrios, and (iii) predictive signatures resulting from correlations between environmental parameters and vibrio densities. C1 [Flowers, A. R.; Noriea, N. F., III; Zimmerman, A. M.; Grimes, D. J.] Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. [Johnson, C. N.] Louisiana State Univ, Dept Environm Sci, Baton Rouge, LA 70803 USA. [Bowers, J. C.] US FDA, College Pk, MD USA. [DePaola, A.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. RP Grimes, DJ (reprint author), Univ So Mississippi, Gulf Coast Res Lab, 703 E Beach Dr, Ocean Springs, MS 39564 USA. EM jay.grimes@usm.edu FU NOAA Oceans and Human Health Initiative [NA-04-OAR4600214]; NSF [EF-0813285]; NSF-NIH; NASA [NNX09AR57G] FX This research was supported by a NOAA Oceans and Human Health Initiative grant (NA-04-OAR4600214), by NSF grant EF-0813285 as part of the joint NSF-NIH Ecology of Infectious Diseases program, and by a NASA grant (NNX09AR57G). NR 40 TC 78 Z9 78 U1 1 U2 25 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2010 VL 76 IS 21 BP 7076 EP 7084 DI 10.1128/AEM.00697-10 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 670PM UT WOS:000283439800013 PM 20817802 ER PT J AU David, DE Lynne, AM Han, J Foley, SL AF David, Donna E. Lynne, Aaron M. Han, Jing Foley, Steven L. TI Evaluation of Virulence Factor Profiling in the Characterization of Veterinary Escherichia coli Isolates SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ANTIMICROBIAL RESISTANCE; GENES; STRAINS; CALVES; IDENTIFICATION; BACTERIA; ONTARIO; TRAITS; CATTLE; PIGS AB Escherichia coli has been used as an indicator organism for fecal contamination of water and other environments and is often a commensal organism in healthy animals, yet a number of strains can cause disease in young or immunocompromised animals. In this study, 281 E. coli isolates from bovine, porcine, chicken, canine, equine, feline, and other veterinary sources were analyzed by BOXA1R PCR and by virulence factor profiling of 35 factors to determine whether they had utility in identifying the animal source of the isolates. The results of BOXA1R PCR analysis demonstrated a high degree of diversity; less than half of the isolates fell into one of 27 clusters with at least three isolates (based on 90% similarity). Nearly 60% of these clusters contained isolates from more than one animal source. Conversely, the results of virulence factor profiling demonstrated clustering by animal source. Three clusters, named Bovine, Chicken, and Porcine, based on discriminant components analysis, were represented by 90% or more of the respective isolates. A fourth group, termed Companion, was the most diverse, containing at least 84% of isolates from canine, feline, equine, and other animal sources. Based on these results, it appears that virulence factor profiling may have utility, helping identify the likely animal host species sources of certain E. coli isolates. C1 [Han, Jing] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [David, Donna E.; Lynne, Aaron M.; Foley, Steven L.] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Lynne, Aaron M.; Foley, Steven L.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX USA. RP Foley, SL (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM steven.foley@fda.hhs.gov FU Marshfield Clinic Research Foundation; U.S. Food and Drug Administration; Oak Ridge Institute for Science and Education FX We thank the Marshfield Clinic Research Foundation and the U.S. Food and Drug Administration for financial support of the research. Jing Han is supported through the Oak Ridge Institute for Science and Education. NR 30 TC 6 Z9 6 U1 1 U2 4 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 NOV PY 2010 VL 76 IS 22 BP 7509 EP 7513 DI 10.1128/AEM.00726-10 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 675PX UT WOS:000283843900018 PM 20889790 ER PT J AU Sachdeva, A Defibaugh-Chavaz, SLH Day, JB Zink, D Sharma, SK AF Sachdeva, Amita Defibaugh-Chavaz, Stephanie L. H. Day, James B. Zink, Donald Sharma, Shashi K. TI Detection and Confirmation of Clostridium botulinum in Water Used for Cooling at a Plant Producing Low-Acid Canned Foods SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID NEUROTOXIN; STRAIN; TOXIN AB Our laboratory tested water samples used for cooling low-acid canned foods at a canning facility under investigation by the U. S. Food and Drug Administration. We used an enzyme-linked immunosorbent assay with digoxigenin-labeled antibodies (DIG-ELISA) and real-time PCR as screening methods and confirmed the presence of neurotoxin-producing Clostridium botulinum in the samples by mouse bioassay. C1 [Sachdeva, Amita; Defibaugh-Chavaz, Stephanie L. H.; Day, James B.; Zink, Donald; Sharma, Shashi K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Sharma, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, CPK1,HFS 712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM shashi.sharma@fda.hhs.gov NR 14 TC 6 Z9 6 U1 0 U2 10 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 NOV PY 2010 VL 76 IS 22 BP 7653 EP 7657 DI 10.1128/AEM.00820-10 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 675PX UT WOS:000283843900037 PM 20889791 ER PT J AU Mossoba, MM Al-Khaldi, SF Schoen, B Yakes, BJ AF Mossoba, Magdi M. Al-Khaldi, Sufian F. Schoen, Brianna Yakes, Betsy Jean TI Nanoparticle Probes and Mid-Infrared Chemical Imaging for DNA Microarray Detection SO APPLIED SPECTROSCOPY LA English DT Article DE DNA microarrays; Mid-infrared chemical imaging; Nanoparticles ID SINGLE-STRANDED-DNA; CLOSTRIDIUM-PERFRINGENS; GENE-EXPRESSION; GOLD SURFACES; HYBRIDIZATION; SPECTROSCOPY; IDENTIFICATION; AMPLIFICATION; ALKANETHIOLS; ATTACHMENT AB To date most mid-infrared spectroscopic studies have been limited, due to lack of sensitivity, to the structural characterization of a single oligonucleotide probe immobilized over the entire surface of a gold-coated slide or other infrared substrate. By contrast, widely used and commercially available glass slides and a microarray spotter that prints approximately 120-mu m-diameter DNA spots were employed in the present work. To our knowledge, mid-infrared chemical imaging (IRCI) in the external reflection mode has been applied in the present study for the first time to the detection of nanostructure-based DNA microarrays spotted on glass slides. Alkyl amine-modified oligonucleotide probes were immobilized on glass slides that had been prefunctionalized with succinimidyl ester groups. This molecular fluorophore-free method entailed the binding of gold-nanoparticle-streptavidin conjugates to biotinylated DNA targets. Hybridization was visualized by the silver enhancement of gold nanoparticles. The adlayer of silver, selectively hound only to hybridized spots in a microarray, formed the external reflective infrared substrate that was necessary for the detection of DNA hybridization by IRCI in the present proof-of-concept study. IRCI made it possible to discriminate between diffuse and specular external reflection modes. The promising qualitative results are presented herein, and the implications for quantitative determination of DNA microarrays are discussed. C1 [Mossoba, Magdi M.; Yakes, Betsy Jean] US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Al-Khaldi, Sufian F.; Schoen, Brianna] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Mossoba, MM (reprint author), US FDA, Div Analyt Chem, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov RI Yakes, Betsy/K-2646-2012 NR 50 TC 3 Z9 3 U1 3 U2 14 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD NOV PY 2010 VL 64 IS 11 BP 1191 EP 1198 DI 10.1366/000370210793335007 PG 8 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 681FO UT WOS:000284297000001 PM 21073786 ER PT J AU Grajkowski, A Cieslak, J Gapeev, A Schindler, C Beaucage, SL AF Grajkowski, Andrzej Cieslak, Jacek Gapeev, Alexei Schindler, Christian Beaucage, Serge L. TI Convenient Synthesis of a Propargylated Cyclic (3 '-5 ') Diguanylic Acid and Its "Click" Conjugation to a Biotinylated Azide SO BIOCONJUGATE CHEMISTRY LA English DT Article ID C-DI-GMP; I INTERFERON RESPONSE; ACETOBACTER-XYLINUM; CELLULOSE SYNTHESIS; TERMINAL ALKYNES; PROTECTING GROUP; SOLID-PHASE; ANALOGS; MOLECULE; DNA AB The ribonucleoside building block, N(2)-isobutyryl-2'-O-propargyl-3'-O-levulinyl guanosine, was prepared from commercial N(2)-isobutyryl-5'-O-(4,4'-dimethoxytrityl)-2'-O-propargyl guanosine in a yield of 91%. The propargylated guanylyl(3'-5')guanosine phosphotriester was synthesized from the reaction of N(2)-isobutyryl-2'-O-propargyl-3'-O-levulinyl guanosine with N(2)-isobutyryl-5'-O-(4,4'-dimethoxytrityl)-2'-O-tert-butyldimethylsilyl-3'-O-[(2-cyanoethyl)-N, N-diisopropylaminophosphinyl] guanosine and isolated in a yield of 88% after P(III) oxidation, 3'-/5'-deprotection, and purification. The propargylated guanylyl(3'-5')guanosine phosphotriester was phosphitylated using 2-cyanoethyl tetraisopropylphosphordiamidite and 1H-tetrazole and was followed by an in situ intramolecular cyclization to give a propargylated c-di-GMP triester, which was isolated in a yield of 40% after P(III) oxidation and purification. Complete N-deacylation of the guanine bases and removal of the 2-cyanoethyl phosphate protecting groups from the propargylated c-di-GMP triester were performed by treatment with aqueous ammonia at ambient temperature. The final 2'-desilylation reaction was effected by exposure to triethylammonium trihydrofluoride affording the desired propargylated c-di-GMP diester, the purity of which exceeded 95%. Biotinylation of the propargylated c-di-GMP diester was easily accomplished through its cycloaddition reaction with a biotinylated azide derivative under click conditions to produce the biotinylated c-di-GMP conjugate of interest in an isolated yield of 62%. C1 [Grajkowski, Andrzej; Cieslak, Jacek; Beaucage, Serge L.] Ctr Drug Evaluat & Res, Food & Drug Adm, Div Therapeut Prot, Bethesda, MD 20892 USA. [Schindler, Christian] Columbia Univ, Dept Microbiol & Immunol, New York, NY 10032 USA. [Gapeev, Alexei] Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. RP Grajkowski, A (reprint author), Ctr Drug Evaluat & Res, Food & Drug Adm, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Andrzej.Grajkowski@fda.hhs.gov FU NIH [R21 ES016835, RO1 AI058211] FX This work was supported in part by NIH grants R21 ES016835 and RO1 AI058211 (CS.). NR 26 TC 12 Z9 13 U1 2 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV PY 2010 VL 21 IS 11 BP 2147 EP 2152 DI 10.1021/bc1003857 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 680AT UT WOS:000284203200025 PM 20942415 ER PT J AU Antunes, AMM Godinho, ALA Martins, IL Oliveira, MC Gomes, RA Coelho, AV Beland, FA Marques, MM AF Antunes, Alexandra M. M. Godinho, Ana L. A. Martins, Ines L. Oliveira, M. Conceicao Gomes, Ricardo A. Coelho, Ana V. Beland, Frederick A. Marques, M. Matilde TI Protein Adducts As Prospective Biomarkers of Nevirapine Toxicity SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE INHIBITOR; INDUCED SKIN RASH; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; TO-CHILD TRANSMISSION; METABOLIC-ACTIVATION; COVALENT BINDING; DRUG-REACTIONS; HUMAN-ALBUMIN; SINGLE AB Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor used against human immunodeficiency virus type-1 (HIV-1), mostly to prevent mother-to-child HIV-1 transmission in developing countries. Despite its clinical efficacy, NVP administration is associated with a variety of toxic responses that include hepatotoxicity and skin rash. Although the reasons for the adverse effects of NVP administration are still unclear, increasing evidence supports the involvement of metabolic activation to reactive electrophiles. In particular, Phase II activation of the NVP metabolite 12-hydroxy-NVP is thought to mediate NVP binding to bionucleophiles, which may be at the onset of toxicity. In the present study, we investigated the nature and specific locations of the covalent adducts produced in human serum albumin and human hemoglobin by reaction in vitro with the synthetic model electrophile 12-mesyloxy-NVP, used as a surrogate for the Phase II metabolite 12-sulfoxy-NVP. Multiple sites of modification were identified by two different mass spectrometry-based methodologies, liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) and matrix-assisted laser desorption ionization tandem mass spectrometry (MALDI-TOF-TOF-MS). These two distinct methodologies, which in some instances afforded complementary information, allowed the identification of multiple adducts involving cysteine, lysine, tryptophan, histidine, serine, and the N-terminal valine of hemoglobin. Tryptophan, which is not a common site of covalent protein modification, was the NVP-modified amino acid residue detected in the two proteins and consistently identified by both LC-ESI-MS/MS and MALDI-TOF-TOF-MS. The propensity of tryptophan to react with the NVP-derived electrophile is further emphasized by the fact that human serum albumin possesses a single tryptophan residue, which suggests a remarkable selectivity that may be useful for biomonitoring purposes. Likewise, the NVP adduct with the terminal valine of hemoglobin, detected by LC-ESI-MS/MS after N-alkyl Edman degradation, appears as an easily assessed marker of NVP binding to proteins. Our results demonstrate the merits and complementarity of the two MS-based methodologies for the characterization of protein binding by NVP and suggest a series of plausible biomarkers of NVP toxicity that should be useful in the monitoring of toxicity effects in patients administered NVP. C1 [Antunes, Alexandra M. M.; Godinho, Ana L. A.; Martins, Ines L.; Oliveira, M. Conceicao; Marques, M. Matilde] Univ Tecn Lisbon, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. [Gomes, Ricardo A.; Coelho, Ana V.] Univ Nova Lisboa, Inst Tecnol Quim & Biol, P-2781901 Oeiras, Portugal. [Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Antunes, AMM (reprint author), Univ Tecn Lisbon, Inst Super Tecn, Ctr Quim Estrutural, Complexo 1,Av Rovisco Pais, P-1049001 Lisbon, Portugal. EM alexandra.antunes@ist.utl.pt; matilde.marques@ist.utl.pt RI Gomes, Ricardo/E-8379-2012; Oliveira, Maria Conceicao/H-8263-2012; Coelho, Ana/H-8885-2012; Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009; Varela Coelho, Ana/O-3977-2014; OI Gomes, Ricardo/0000-0001-7155-0059; Oliveira, Maria Conceicao/0000-0002-3068-4920; Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369; Varela Coelho, Ana/0000-0001-8700-8934; Lanca Martins, Ines/0000-0003-0797-7642; Coelho, Ana/0000-0002-6143-4203 FU Fundacao para a Ciencia e a Tecnologia (FCT), Portugal; FEDER [POCI/56582/QUI/2004, PPCDT/QUI/56582/2004]; FCT [SFRH/BPD/41037/2007]; National Center for Toxicological Research/Food and Drug Administration [224-93-0001]; National Institute for Environmental Health Sciences [224-93-0001] FX This work was supported in part by a research grant from Fundacao para a Ciencia e a Tecnologia (FCT), Portugal and FEDER (POCI/56582/QUI/2004; PPCDT/QUI/56582/2004), by a postdoctoral fellowship from FCT to R.A.G. (SFRH/BPD/41037/2007), and by Interagency Agreement No. 224-93-0001 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program. The LC-MS equipment used in this work is located at the IST-UTL node of the Portuguese National Mass Spectrometry Network (RNEM) and was acquired within the framework of the National Re-equipment Program sponsored by FCT. The opinions expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration. NR 52 TC 32 Z9 32 U1 0 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2010 VL 23 IS 11 BP 1714 EP 1725 DI 10.1021/tx100186t PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 681DJ UT WOS:000284290500011 PM 20809596 ER EF